|
1
|
Tavares V, Lopes C, Macedo-Silva C, Farinha M, Costa J, Vilas-Boas MI, Pinelas S, Assis J, Dinis-Ribeiro M, Pereira D, Pereira C, Medeiros R. Genetic markers of thrombophilia as predictors of outcome in colorectal cancer. J Thromb Thrombolysis 2025:10.1007/s11239-025-03106-1. [PMID: 40425987 DOI: 10.1007/s11239-025-03106-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/28/2025] [Indexed: 05/29/2025]
Abstract
Colorectal cancer (CRC) is the second leading cause of malignancy-related death worldwide, representing a significant health concern. Understanding the disease pathogenesis and identifying potential prognostic biomarkers is critical for improving patients' clinical outcomes. Haemostatic components implicated in cancer-associated thrombosis (CAT) seem to favour CRC progression. As such, genetic markers of thrombophilia might be potential prognostic biomarkers among patients with this malignant disease. To offer perspectives, a retrospective cohort study with 204 CRC patients was conducted to investigate the impact of seven germline haemostatic gene determinants on patient prognosis. A sex-stratified analysis was performed as the variants seem to have a distinct influence depending on the patient's sex. Genomic DNA was extracted from FFPE samples enriched in tumour cells. While the polymorphisms CNTN6 rs6764623 (CC/CA vs. AA; adjusted hazard ratio (aHR) = 0.44; 95% confidence interval (CI), 0.20-0.96; P = 0.040), PTGS2 rs20417 (GG vs. CC/CG; aHR = 2.88; 95%CI, 1.10-7.51; P = 0.031) and RGS7 rs2502448 (TT vs. CT/CC; aHR = 2.35; 95%CI, 1.20-4.61; P = 0.013) were associated with the five-year risk of cancer recurrence, ITGB3 rs5918 was a predictor of the risk of death due to all causes, particularly among male patients (TT vs. CT/CC; aHR = 2.05; 95% confidence interval (CI), 1.13-3.72; P = 0.019). While a sex-specific impact of the SNPs was observed, further investigation in larger cohorts, particularly with an increased representation of female patients, is required to confirm these associations. Collectively, these markers could help improve the prognosis assessment of CRC patients towards a more personalised intervention.
Collapse
Affiliation(s)
- Valéria Tavares
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Pathology and Laboratory Medicine Department/Clinical Pathology/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072, Porto, Portugal
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313, Porto, Portugal
- FMUP, Faculty of Medicine, University of Porto, 4200-072, Porto, Portugal
| | - Catarina Lopes
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313, Porto, Portugal
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072, Porto, Portugal
- CINTESIS - Center for Health Technology and Services Research, University of Porto, 4200-450, Porto, Portugal
| | - Catarina Macedo-Silva
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Group)/Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072, Porto, Portugal
| | - Mónica Farinha
- Pathology Department, Portuguese Institute of Oncology of Porto (IPOP), 4200-072, Porto, Portugal
| | - João Costa
- Pathology Department, Portuguese Institute of Oncology of Porto (IPOP), 4200-072, Porto, Portugal
| | - Maria Isabel Vilas-Boas
- Oncology Department, Portuguese Institute of Oncology of Porto (IPOP), 4200-072, Porto, Portugal
| | - Sofia Pinelas
- Oncology Department, Portuguese Institute of Oncology of Porto (IPOP), 4200-072, Porto, Portugal
| | - Joana Assis
- Clinical Research Unit, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072, Porto, Portugal
| | - Mário Dinis-Ribeiro
- FMUP, Faculty of Medicine, University of Porto, 4200-072, Porto, Portugal
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072, Porto, Portugal
| | - Deolinda Pereira
- Oncology Department, Portuguese Institute of Oncology of Porto (IPOP), 4200-072, Porto, Portugal
| | - Carina Pereira
- Precancerous Lesions and Early Cancer Management Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Group), Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072, Porto, Portugal
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Pathology and Laboratory Medicine Department/Clinical Pathology/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), 4200-072, Porto, Portugal.
- ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313, Porto, Portugal.
- FMUP, Faculty of Medicine, University of Porto, 4200-072, Porto, Portugal.
- CEBIMED, Faculty of Health Sciences, Fernando Pessoa University, 4200-150, Porto, Portugal.
- Research Department, Portuguese League Against Cancer (NRNorte), 4200-172, Porto, Portugal.
| |
Collapse
|
|
2
|
Zanif U, Parks J, Tai I, Yip S, Babinszky S, Milne K, Watson P, Murphy RA, Bhatti P. Pre-diagnostic Demographic, Lifestyle, and Health History Factors in Association with Secreted Protein Acidic and Rich in Cysteine (SPARC) Expression in Colorectal Cancer Tissue. Biomark Insights 2025; 20:11772719251339955. [PMID: 40417350 PMCID: PMC12099143 DOI: 10.1177/11772719251339955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 02/21/2025] [Indexed: 05/27/2025] Open
Abstract
Background Demographic, health history, and lifestyle factors have been associated with prognosis of colorectal cancer (CRC), but mechanisms underlying these associations remain poorly understood. A compelling mechanism involves changes in expression of tumor markers that influence treatment outcomes, such as secreted protein acidic and rich in cysteine (SPARC), lower levels of which have previously been associated with poorer CRC prognosis. Objective We explored the association of factors that have been previously associated with CRC prognosis with expression of SPARC in tumor tissues. Design We conducted a prospective evaluation of 50 participants of a longitudinal cohort study that went on to develop CRC. Methods Tumor and normal tissue cores were taken from formalin-fixed paraffin-embedded (FFPE) blocks of incident CRC cases and were used to create tissue microarrays (TMAs). Slides created from the TMAs were stained with SPARC antibodies and analyzed to calculate H-scores for both epithelial and non-epithelial components of tumor and normal tissues. H-scores were ln-transformed and analyzed in association with demographic, lifestyle, and health history factors assessed before cancer diagnosis using linear regression models. Results In CRC tumor epithelium, smoking was associated with a 0.53-fold lower level of SPARC expression (P = .054). Higher income was associated with a 1.33-fold greater level of SPARC expression in tumor non-epithelial tissue (P = .041). Higher cancer stage was associated with a 0.74-fold lower level of non-epithelial tumor SPARC expression (P = .040). In the epithelial component of normal colorectal tissues, higher fruit consumption was associated with a 2.74-fold greater SPARC H-score (P = .002). Conclusions The associations we observed for smoking, income, and cancer stage with SPARC in tumor tissue are consistent with previously established associations of these factors with CRC prognosis. Larger studies with prognostic data are needed, but our results suggest that differences in SPARC expression may contribute to previously observed impacts of various factors on CRC prognosis.
Collapse
Affiliation(s)
- Umaimah Zanif
- Cancer Control Research, BC Cancer Research Institute, Vancouver, Canada
| | - Jaclyn Parks
- Cancer Control Research, BC Cancer Research Institute, Vancouver, Canada
| | - Isabella Tai
- Genome Sciences Centre, BC Cancer Research Institute, Vancouver, Canada
- Division of Gastroenterology, University of British Columbia, Vancouver, Canada
| | - Stephen Yip
- Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
- Molecular Oncology, BC Cancer Research Institute, Vancouver, Canada
| | | | - Katy Milne
- Deeley Research Centre, BC Cancer, Victoria, BC, Canada
| | - Peter Watson
- Deeley Research Centre, BC Cancer, Victoria, BC, Canada
| | - Rachel A. Murphy
- Cancer Control Research, BC Cancer Research Institute, Vancouver, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, Canada
| | - Parveen Bhatti
- Cancer Control Research, BC Cancer Research Institute, Vancouver, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, Canada
| |
Collapse
|
|
3
|
Afify AY, Ashry MH, Hassan H. Sex differences in survival outcomes of early-onset colorectal cancer. Sci Rep 2024; 14:22041. [PMID: 39327445 PMCID: PMC11427454 DOI: 10.1038/s41598-024-71999-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 09/02/2024] [Indexed: 09/28/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most fatal cancers in the United States. Although the overall incidence and mortality rates are declining, an alarming rise in early-onset colorectal cancer (EOCRC), defined as CRC diagnosis in patients aged < 50 years, was previously reported. Our study focuses on analyzing sex-specific differences in survival among EOCRC patients and comparing sex-specific predictors of survival in both males and females in the United States. We retrieved and utilized data from the Surveillance, Epidemiology, and End Results (SEER) program. EOCRC patients, between the ages of 20 and 49, were exclusively included. We conducted thorough survival analyses using Kaplan-Meier curves, log-rank tests, Cox regression models, and propensity score matching to control for potential biases. Our study included 58,667 EOCRC patients (27,662 females, 31,005 males) diagnosed between 2000 and 2017. The baseline characteristics at the time of diagnosis were significantly heterogeneous between males and females. Males exhibited significantly worse overall survival (OS), cancer-specific survival (CSS), and noncancer-specific survival (NCSS) in comparison to females in both the general cohort, and the matched cohort. Predictors of survival outcomes generally followed a similar pattern in both sexes except for minor differences. In conclusion, we identified sex as an independent prognostic factor of EOCRC, suggesting disparities in survival between sexes. Further understanding of the epidemiological and genetic bases of these differences could facilitate targeted, personalized therapeutic approaches for EOCRC.
Collapse
Affiliation(s)
- Abdelrahman Yousry Afify
- School of Medicine, New Giza University (NGU), Giza, Egypt.
- Internal Medicine Department, Cairo University Hospitals, Cairo, Egypt.
| | - Mohamed Hady Ashry
- School of Medicine, New Giza University (NGU), Giza, Egypt
- Medical Research Platform, Giza, Egypt
| | - Hamsa Hassan
- Medical Research Platform, Giza, Egypt
- Egypt-Japan University of Science and Technology (EJUST), New Borg El Arab, Alexandria, Egypt
- Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| |
Collapse
|
|
4
|
Okamoto K, Sasaki K, Nozawa H, Murono K, Emoto S, Yamauchi S, Sugihara K, Ishihara S. Poor prognosis of young male patients with stage III colorectal cancer: A multicenter retrospective study. J Surg Oncol 2024; 129:785-792. [PMID: 38115553 DOI: 10.1002/jso.27557] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 11/15/2023] [Accepted: 11/30/2023] [Indexed: 12/21/2023]
Abstract
BACKGROUND AND OBJECTIVES The number of young patients with colorectal cancer (CRC) is increasing. However, sex-dependent differences in the prognosis of young CRC remain unknown. METHODS We investigated patients aged <70 years with stage III CRC treated between January 2000 and December 2010 in 24 Japanese referral hospitals. Patients were divided into subgroups by age of 50 years (early-onset and late-onset groups) and sex, and clinical characteristics and survival outcomes were compared. Risk factors associated with poor survival outcomes were also analyzed. RESULTS Among 4758 consecutive patients, 771 (16%) were <50 years. Regardless of sex, there were more patients with rectal cancer and treated with adjuvant chemotherapy in the early-onset group. Among males, tumors in the early-onset group were poorly differentiated (p < 0.001), and patients were diagnosed at an advanced N stage (p = 0.010). Among females, there were more patients with left-sided cancer in the early-onset group (p < 0.001). Relapse-free survival (RFS) and overall survival (OS) were worse in the early-onset group than in the late-onset group (5-year RFS rates: 58% and 63%, p = 0.024; 5-year OS rates: 76% and 81%, p = 0.041, respectively), while there were no age-dependent differences in the survival outcomes of female CRC patients. A multivariate analysis identified age <50 years as one of the independent risk factors associated with poor RFS in male stage III CRC patients (p = 0.032) CONCLUSIONS: Young male patients with stage III CRC showed poorer survival outcomes than their older counterparts. Therefore, age- and sex-related differences in the incidence of CRC recurrence need to be considered.
Collapse
Affiliation(s)
- Kazuaki Okamoto
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Kazuhito Sasaki
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Nozawa
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Koji Murono
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Shigenobu Emoto
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Shinichi Yamauchi
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kenichi Sugihara
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Soichiro Ishihara
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| |
Collapse
|
|
5
|
Aliyev V, Piozzi GN, Huseynov E, Mustafayev TZ, Kayku V, Goksel S, Asoglu O. Robotic male and laparoscopic female sphincter-preserving total mesorectal excision of mid-low rectal cancer share similar specimen quality, complication rates and long-term oncological outcomes. J Robot Surg 2023; 17:1637-1644. [PMID: 36943657 DOI: 10.1007/s11701-023-01558-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 03/01/2023] [Indexed: 03/23/2023]
Abstract
The aim of this study was to compare perioperative and long-term oncological outcomes between laparoscopic sphincter-preserving total mesorectal excision in female patients (F-Lap-TME) and robotic sphincter-preserving total mesorectal excision in male patients (M-Rob-TME) with mid-low rectal cancer (RC). A retrospective analysis of a prospectively maintained database was performed. 170 cases (F-Lap-TME: 60 patients; M-Rob-TME: 110 patients) were performed by a single surgeon (January 2011-January 2020). Clinical characteristics did not differ significantly between the two groups. Operating time was longer in M-Rob-TME than in F-Lap-TME group (185.3 ± 28.4 vs 124.5 ± 35.8 min, p < 0.001). There was no conversion to open surgery in both groups. Quality of mesorectum was complete/near-complete in 58 (96.7%) and 107 (97.3%) patients of F-Lap-TME and M-Rob-TME (p = 0.508), respectively. Circumferential radial margin involvement was observed in 2 (3.3%) and 3 (2.9%) in F-Lap-TME and M-Rob-TME patients (p = 0.210), respectively. Median length of follow-up was 62 (24-108) months in the F-Lap-TME and 64 (24-108) months in the M-Rob-TME group. Five-year overall survival rates were 90.5% in the F-Lap-TME and 89.6% in the M-Rob-TME groups (p = 0.120). Disease-free survival rates in F-Lap-TME and M-Rob-TME groups were 87.5% and 86.5% (p = 0.145), respectively. Local recurrence rates were 5% (n = 3) and 5.5% (n = 6) (p = 0.210), in the F-Lap-TME and M-Rob-TME groups, respectively. The robotic technique can potentially overcome some technical challenges related to the pelvic anatomical difference between sex compared to laparoscopy. Laparoscopic and robotic approach, respectively in female and male patients provide similar surgical specimen quality, perioperative outcomes, and long-term oncological results.
Collapse
Affiliation(s)
- Vusal Aliyev
- Bogazici Academy for Clinical Sciences, Istanbul, Turkey
| | - Guglielmo Niccolò Piozzi
- Department of Colorectal Surgery, Portsmouth Hospitals University NHS Trust, Portsmouth, United Kingdom
| | - Elnur Huseynov
- Department of General Surgery, Avrupa Safak Hospital, Istanbul, Turkey
| | | | - Vildan Kayku
- Department of Medical Oncology, Maslak Acibadem Hospital, Istanbul, Turkey
| | - Suha Goksel
- Department of Pathology, Maslak Acibadem Hospital, Istanbul, Turkey
| | - Oktar Asoglu
- Bogazici Academy for Clinical Sciences, Istanbul, Turkey.
| |
Collapse
|
|
6
|
Zaki TA, Liang PS, May FP, Murphy CC. Racial and Ethnic Disparities in Early-Onset Colorectal Cancer Survival. Clin Gastroenterol Hepatol 2023; 21:497-506.e3. [PMID: 35716905 PMCID: PMC9835097 DOI: 10.1016/j.cgh.2022.05.035] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 05/18/2022] [Accepted: 05/24/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND Young adults diagnosed with colorectal cancer (CRC) comprise a growing, yet understudied, patient population. We estimated 5-year relative survival of early-onset CRC and examined disparities in survival by race-ethnicity in a population-based sample. METHODS We used the National Cancer Institute's Surveillance, Epidemiology, and End Results program of cancer registries to identify patients diagnosed with early-onset CRC (20-49 years of age) between January 1, 1992, and December 31, 2013. For each racial-ethnic group, we estimated 5-year relative survival, overall and by sex, tumor site, and stage at diagnosis. To illustrate temporal trends, we compared 5-year relative survival in 1992-2002 vs 2003-2013. We also used Cox proportional hazards regression models to examine the association of race-ethnicity and all-cause mortality, adjusting for age at diagnosis, sex, county type (urban vs rural), county-level median household income, tumor site, and stage at diagnosis. RESULTS We identified 33,777 patients diagnosed with early-onset CRC (58.5% White, 14.0% Black, 13.0% Asian, 14.5% Hispanic). Five-year relative survival ranged from 57.6% (Black patients) to 69.1% (White patients). Relative survival improved from 1992-2002 to 2003-2013 for White patients only; there was no improvement for Black, Asian, or Hispanic patients. This pattern was similar by sex, tumor site, and stage at diagnosis. In adjusted analysis, Black (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [CI], 1.36-1.49), Asian (aHR, 1.06; 95% CI, 1.01-1.12), and Hispanic (aHR, 1.16; 95% CI, 1.10-1.21) race-ethnicity were associated with all-cause mortality. CONCLUSION Our study adds to the well-documented disparities in CRC in older adults by demonstrating persistent racial-ethnic disparities in relative survival and all-cause mortality in patients with early-onset CRC.
Collapse
Affiliation(s)
- Timothy A. Zaki
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Peter S. Liang
- Department of Medicine, New York University Langone Health, New York, New York,Department of Medicine, VA New York Harbor Health Care System, New York, New York
| | - Folasade P. May
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Caitlin C. Murphy
- Department of Health Promotion and Behavioral Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas
| |
Collapse
|
|
7
|
Levy L, Smiley A, Latifi R. Adult and Elderly Risk Factors of Mortality in 23,614 Emergently Admitted Patients with Rectal or Rectosigmoid Junction Malignancy. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19159203. [PMID: 35954556 PMCID: PMC9368534 DOI: 10.3390/ijerph19159203] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 07/24/2022] [Accepted: 07/25/2022] [Indexed: 02/05/2023]
Abstract
Background: Colorectal cancer, among which are malignant neoplasms of the rectum and rectosigmoid junction, is the fourth most common cancer cause of death globally. The goal of this study was to evaluate independent predictors of in-hospital mortality in adult and elderly patients undergoing emergency admission for malignant neoplasm of the rectum and rectosigmoid junction. Methods: Demographic and clinical data were obtained from the National Inpatient Sample (NIS), 2005−2014, to evaluate adult (age 18−64 years) and elderly (65+ years) patients with malignant neoplasm of the rectum and rectosigmoid junction who underwent emergency surgery. A multivariable logistic regression model with backward elimination process was used to identify the association of predictors and in-hospital mortality. Results: A total of 10,918 non-elderly adult and 12,696 elderly patients were included in this study. Their mean (standard deviation (SD)) age was 53 (8.5) and 77.5 (8) years, respectively. The odds ratios (95% confidence interval, P-value) of some of the pertinent risk factors for mortality for operated adults were 1.04 for time to operation (95%CI: 1.02−1.07, p < 0.001), 2.83 for respiratory diseases (95%CI: 2.02−3.98), and 1.93 for cardiac disease (95%CI: 1.39−2.70), among others. Hospital length of stay was a significant risk factor as well for elderly patients—OR: 1.02 (95%CI: 1.01−1.03, p = 0.002). Conclusions: In adult patients who underwent an operation, time to operation, respiratory diseases, and cardiac disease were some of the main risk factors of mortality. In patients who did not undergo a surgical procedure, malignant neoplasm of the rectosigmoid junction, respiratory disease, and fluid and electrolyte disorders were risk factors of mortality. In this patient group, hospital length of stay was only significant for elderly patients.
Collapse
Affiliation(s)
- Lior Levy
- School of Medicine, New York Medical College, Valhalla, NY 10595, USA;
| | - Abbas Smiley
- Westchester Medical Center, New York Medical College, Valhalla, NY 10595, USA;
| | - Rifat Latifi
- Department of Surgery, University of Arizona, Tucson, AZ 85721, USA
- Correspondence:
| |
Collapse
|
|
8
|
Chen X, Hu M, Chen Y, Li A, Hua Y, Jiang H, Li H, Lin M. Targeted deep sequencing reveals APC mutations as predictors of overall survival in Chinese colorectal patients receiving adjuvant chemotherapy. Scand J Gastroenterol 2022; 57:465-472. [PMID: 34978498 DOI: 10.1080/00365521.2021.2022189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objective: Targeted deep sequencing was used to characterize the mutational spectrum of APC in Chinese colorectal tumors in comparison to that in Caucasians from The Cancer Genome Atlas (TCGA) and to investigate whether APC mutations can predict overall survival in CRC patients receiving adjuvant chemotherapy.Methods: A total of 315 Chinese CRC patients including 241 stage II/III patients receiving fluorouracil-based adjuvant chemotherapy were included in this study. Next generation sequencing was carried out to detect somatic mutations on all APC exons. The associations between APC mutations and overall survival were determined by the Cox proportional hazards model.Results:APC was mutated in 221 of 315 colorectal tumors (70.2%). Chinese CRC had a much higher frequency of missense mutations (16.2% vs. 2.4%), but a lower frequency of nonsense (41.0% vs. 54.2%) and frameshift mutations (10.5% vs. 18.4%) than Caucasian CRC. Among stage II/III patients receiving fluorouracil-based adjuvant chemotherapy, APC mutations showed a significant association with worse survival (HR = 1.69; 95% CI, 1.10-2.62; p = .0179). Of the mutation types, frameshift mutations conferred the highest risk of death (HR = 2.88; 95% CI, 1.54-5.37; p =.0009). Among individual mutation sites, Arg232Ter, the most frequent mutation in Chinese CRC, exhibited the strongest negative impact on survival (HR = 2.65; 95% CI, 1.16-6.03; p =.0202).Conclusion:APC overall mutation was an independent predictor for overall survival of stage II/III CRC patients receiving fluorouracil-based chemotherapy.
Collapse
Affiliation(s)
- Xin Chen
- Department of General Surgery, Yangpu Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China
| | - Mengjun Hu
- Department of Pathology, Zhuji People's Hospital, Shaoxing, China
| | - Ying Chen
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.,Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China
| | - Ajian Li
- Department of General Surgery, Yangpu Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China
| | - Yutong Hua
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.,Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China
| | - Huihong Jiang
- Department of General Surgery, Yangpu Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China
| | - Huaguang Li
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.,Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China
| | - Moubin Lin
- Department of General Surgery, Yangpu Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China.,Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.,Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China
| |
Collapse
|
|
9
|
Yamamoto Y, Miyagawa Y, Kitazawa M, Koyama M, Nakamura S, Tokumaru S, Muranaka F, Soejima Y. Sex differences in non-strangulated postoperative adhesive small bowel obstruction: A retrospective cohort study. ANZ J Surg 2021; 91:2074-2080. [PMID: 34339097 DOI: 10.1111/ans.17103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 07/10/2021] [Accepted: 07/17/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Adhesive small bowel obstruction (ASBO) is one of the major causes of postoperative morbidity. Non-surgical management is generally applied to non-strangulated ASBO. Several factors have been reported to affect the response to non-surgical management in patients with ASBO. However, the association between sex differences and non-strangulated ASBO remains unclear. This study aimed to elucidate the effect of sex differences in non-strangulated postoperative ASBO. METHODS We divided 139 patients with a first episode of non-strangulated postoperative ASBO into two groups: male group (n = 83) and female group (n = 56). Clinical features and prognosis were compared between the two groups. RESULTS Female patients had lower proportions of oesophageal/gastric malignancies (P = 0.044) and colorectal malignancies (P = 0.030) and a higher proportion of uterine/ovarian malignancies (P < 0.001) than male patients did. More female patients required surgical management than male patients (P = 0.003) did. Hospital length of stay (LOS) was longer (P = 0.046) in the female group than in the male group. Multiple logistic regression analysis showed that the female sex was associated with an increased risk of the need for surgical management (odds ratio 5.318, P = 0.006). Cox proportional hazards regression analysis revealed that the female sex was positively associated with increased LOS (hazard ratio 0.687, P = 0.045). CONCLUSION Female sex was associated with failure of non-surgical management and increased LOS in patients with non-strangulated postoperative ASBO.
Collapse
Affiliation(s)
- Yuta Yamamoto
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Paediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Yusuke Miyagawa
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Paediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Masato Kitazawa
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Paediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Makoto Koyama
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Paediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Satoshi Nakamura
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Paediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Shigeo Tokumaru
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Paediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Futoshi Muranaka
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Paediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Yuji Soejima
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Paediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| |
Collapse
|
|
10
|
Illuminati G, Pasqua R, D'Ermo G, Girolami M, Cerbelli B, D'Amati G, Carboni F, Fiori E. Results of Adrenalectomy for Isolated, Metachronous Metastasis of Breast Cancer: A Retrospective Cohort Study. Front Surg 2021; 8:671424. [PMID: 34179068 PMCID: PMC8219849 DOI: 10.3389/fsurg.2021.671424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 05/17/2021] [Indexed: 11/23/2022] Open
Abstract
Background and Aim: Metachronous, isolated adrenal metastases from breast cancer are extremely rare. The aim of this study was to evaluate the results of adrenalectomy as a treatment of this uncommon condition. Methods: Twelve female patients (median age: 68 years) underwent 13 adrenalectomies for isolated, metachronous metastases of breast cancer. Ten resections were performed thorugh open surgery and two were preformed through a laparoscopic approach. As main study endpoints, postoperative mortality, postoperative morbidity and disease-free survival were considered. Median length of follow-up was 40 months. Results: Postoperative mortality was absent. Postoperative morbidity was 17%: one patient presented a postoperative pneumothorax requiring drainage and one patient required re-hospitalization 8 days after contralateral adrenalectomy for electrolyte imbalance. Two patients died of recurrent metastatic disease, 28 and 33 months respectively after adrenalectomy. One patient remained alive with hepatic metastases at 32 months from resection of adrenal recurrence. All in all, disease-free survival at 48 months was 75%. Conclusions: Adrenalectomy for metachronous, isolated metastases of breast cancer can be performed with no postoperative mortality and minimal postoperative morbidity, enabling good long-term disease-free survival.
Collapse
Affiliation(s)
- Giulio Illuminati
- Department of Surgical Sciences, University of Rome “La Sapienza”, Rome, Italy
| | - Rocco Pasqua
- Department of Surgical Sciences, University of Rome “La Sapienza”, Rome, Italy
| | - Giuseppe D'Ermo
- Department of Surgery, “Pietro Valdoni”, University of Rome “La Sapienza”, Rome, Italy
| | - Marco Girolami
- Department of Surgical Sciences, University of Rome “La Sapienza”, Rome, Italy
| | - Bruna Cerbelli
- Department of Medical-Surgical Sciences, Biotechnologies and Pathology, University of Rome “La Sapienza”, Rome, Italy
| | - Giulia D'Amati
- Department of Medical-Surgical Sciences, Biotechnologies and Pathology, University of Rome “La Sapienza”, Rome, Italy
| | - Fabio Carboni
- Department of Surgery, Regina Elena Cancer Institute, Rome, Italy
| | - Enrico Fiori
- Department of Surgery, “Pietro Valdoni”, University of Rome “La Sapienza”, Rome, Italy
| |
Collapse
|
|
11
|
Limam M, Matthes KL, Pestoni G, Michalopoulou E, Held L, Dehler S, Korol D, Rohrmann S. Are there sex differences among colorectal cancer patients in treatment and survival? A Swiss cohort study. J Cancer Res Clin Oncol 2021; 147:1407-1419. [PMID: 33661394 PMCID: PMC8021518 DOI: 10.1007/s00432-021-03557-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 02/04/2021] [Indexed: 10/25/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) is among the three most common incident cancers and causes of cancer death in Switzerland for both men and women. To promote aspects of gender medicine, we examined differences in treatment decision and survival by sex in CRC patients diagnosed 2000 and 2001 in the canton of Zurich, Switzerland. METHODS Characteristics assessed of 1076 CRC patients were sex, tumor subsite, age at diagnosis, tumor stage, primary treatment option and comorbidity rated by the Charlson Comorbidity Index (CCI). Missing data for stage and comorbidities were completed using multivariate imputation by chained equations. We estimated the probability of receiving surgery versus another primary treatment using multivariable binomial logistic regression models. Univariable and multivariable Cox proportional hazards regression models were used for survival analysis. RESULTS Females were older at diagnosis and had less comorbidities than men. There was no difference with respect to treatment decisions between men and women. The probability of receiving a primary treatment other than surgery was nearly twice as high in patients with the highest comorbidity index, CCI 2+, compared with patients without comorbidities. This effect was significantly stronger in women than in men (p-interaction = 0.010). Survival decreased with higher CCI, tumor stage and age in all CRC patients. Sex had no impact on survival. CONCLUSION The probability of receiving any primary treatment and survival were independent of sex. However, female CRC patients with the highest CCI appeared more likely to receive other therapy than surgery compared to their male counterparts.
Collapse
Affiliation(s)
- Manuela Limam
- Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
- Cancer Registry Zurich, Zug, Schaffhausen and Schwyz, University Hospital Zurich, Zurich, Switzerland
| | - Katarina Luise Matthes
- Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
- Cancer Registry Zurich, Zug, Schaffhausen and Schwyz, University Hospital Zurich, Zurich, Switzerland
| | - Giulia Pestoni
- Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
- Cancer Registry Zurich, Zug, Schaffhausen and Schwyz, University Hospital Zurich, Zurich, Switzerland
| | | | - Leonhard Held
- Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
| | - Silvia Dehler
- Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
- Cancer Registry Zurich, Zug, Schaffhausen and Schwyz, University Hospital Zurich, Zurich, Switzerland
| | - Dimitri Korol
- Cancer Registry Zurich, Zug, Schaffhausen and Schwyz, University Hospital Zurich, Zurich, Switzerland
| | - Sabine Rohrmann
- Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
- Cancer Registry Zurich, Zug, Schaffhausen and Schwyz, University Hospital Zurich, Zurich, Switzerland.
| |
Collapse
|
|
12
|
Bong JW, Ju Y, Seo J, Lee JA, Kang SH, Lee SI, Min BW. Clinical characteristics of rectal cancer patients with neoadjuvant chemoradiotherapy: a nationwide population-based cohort study in South Korea. Ann Surg Treat Res 2021; 100:282-290. [PMID: 34012946 PMCID: PMC8103159 DOI: 10.4174/astr.2021.100.5.282] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 02/12/2021] [Accepted: 02/26/2021] [Indexed: 01/04/2023] Open
Abstract
Purpose Neoadjuvant chemoradiotherapy has been accepted as a standard treatment for stage II–III rectal cancer. This study aimed to evaluate the clinical characteristics of patients who underwent neoadjuvant chemoradiotherapy for rectal cancer and effects on overall survival (OS) of neoadjuvant chemoradiotherapy in South Korea. Methods Patients who underwent curative resection for rectal cancer from 2014 to 2016 were retrospectively reviewed from the database of the National Quality Assessment program in South Korea. Patients were categorized into the upfront surgery group and neoadjuvant chemoradiotherapy group. We evaluated factors associated with the administration of neoadjuvant chemoradiotherapy and its effects on OS. Inverse probability of treatment weighting was performed to account for baseline differences between subgroups. Results A total of 6,141 patients were categorized into the upfront surgery group (n = 4,237) and neoadjuvant chemoradiotherapy group (n = 1,904). The neoadjuvant chemoradiotherapy was more frequently administered to male, midrectal cancer, and younger patients. In the neoadjuvant chemoradiotherapy group, old age, underweight, and pathologic stage were significant risk factors of OS, and male sex, the level of tumor and clinical stages were not associated with OS. After adjustment, the OS of the neoadjuvant chemoradiotherapy group followed the OS of the upfront surgery group of the same pathologic stage. Conclusion Male sex and the level of tumor were not related to the OS of rectal cancer patients with neoadjuvant chemoradiotherapy. The OS of patients who underwent neoadjuvant chemoradiotherapy was decided by their pathologic stages regardless of clinical stages.
Collapse
Affiliation(s)
- Jun Woo Bong
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Yeonuk Ju
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Jihyun Seo
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Jung Ae Lee
- Department of Radiation Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Sang Hee Kang
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Sun Il Lee
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| | - Byung Wook Min
- Division of Colon and Rectal Surgery, Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea
| |
Collapse
|
|
13
|
Indukuri R, Hases L, Archer A, Williams C. Estrogen Receptor Beta Influences the Inflammatory p65 Cistrome in Colon Cancer Cells. Front Endocrinol (Lausanne) 2021; 12:650625. [PMID: 33859619 PMCID: PMC8042384 DOI: 10.3389/fendo.2021.650625] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 03/05/2021] [Indexed: 11/15/2022] Open
Abstract
Inflammation is a primary component of both initiation and promotion of colorectal cancer (CRC). Cytokines secreted by macrophages, including tumor necrosis factor alpha (TNFα), activates the pro-survival transcription factor complex NFκB. The precise mechanism of NFκB in CRC is not well studied, but we recently reported the genome-wide transcriptional impact of TNFα in two CRC cell lines. Further, estrogen signaling influences inflammation in a complex manner and suppresses CRC development. CRC protective effects of estrogen have been shown to be mediated by estrogen receptor beta (ERβ, ESR2), which also impacts inflammatory signaling of the colon. However, whether ERβ impacts the chromatin interaction (cistrome) of the main NFκB subunit p65 (RELA) is not known. We used p65 chromatin immunoprecipitation followed by sequencing (ChIP-Seq) in two different CRC cell lines, HT29 and SW480, with and without expression of ERβ. We here present the p65 colon cistrome of these two CRC cell lines. We identify that RELA and AP1 motifs are predominant in both cell lines, and additionally describe both common and cell line-specific p65 binding sites and correlate these to transcriptional changes related to inflammation, migration, apoptosis and circadian rhythm. Further, we determine that ERβ opposes a major fraction of p65 chromatin binding in HT29 cells, but enhances p65 binding in SW480 cells, thereby impacting the p65 cistrome differently in the two cell lines. However, the biological functions of the regulated genes appear to have similar roles in both cell lines. To our knowledge, this is the first time the p65 CRC cistrome is compared between different cell lines and the first time an influence by ERβ on the p65 cistrome is investigated. Our work provides a mechanistic foundation for a better understanding of how estrogen influences inflammatory signaling through NFκB in CRC cells.
Collapse
Affiliation(s)
- Rajitha Indukuri
- Science for Life Laboratory, Department of Protein Science, KTH Royal Institute of Technology, Solna, Sweden
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
| | - Linnea Hases
- Science for Life Laboratory, Department of Protein Science, KTH Royal Institute of Technology, Solna, Sweden
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
| | - Amena Archer
- Science for Life Laboratory, Department of Protein Science, KTH Royal Institute of Technology, Solna, Sweden
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
| | - Cecilia Williams
- Science for Life Laboratory, Department of Protein Science, KTH Royal Institute of Technology, Solna, Sweden
- Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
- *Correspondence: Cecilia Williams, ;
| |
Collapse
|
|
14
|
Mahmoodzadeh H, Omranipour R, Borjian A, Borjian MA. Study of therapeutic results, lymph node ratio, short-term and long-term complications of lateral lymph node dissection in rectal cancer patients. Turk J Surg 2020; 36:224-228. [PMID: 33015568 DOI: 10.5578/turkjsurg.4593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 12/30/2019] [Indexed: 11/15/2022]
Abstract
Objectives This study aimed to assess disease free survival, lymph node ratio (LNR) and complication rate among advanced mid to low rectal cancer patients (stage 2-3) who underwent total mesorectal excision (TME) and lateral lymph node dissection (LLND) at the Iran Cancer Institute in 2016-2018. Material and Methods The study was carried out on 32 patients treated by curative surgery and lateral lymph node dissection at the Iran Cancer Institute from 2016 March to 2018 March. Chi-square test was used to assess the distribution of dichotomous clinical outcomes by sex. We also used Breslow test in Kaplan-Meier approach to estimate 1-year disease free survival and corresponding 95% confidence intervals (CI). Results Of the 279 dissected lymph nodes by TME, 42 nodes (in mesorectal) and of the 232 dissected lymph nodes by LLND, 7 nodes (in iliac, para-iliac and obturator) were positive for metastasis. Higher local recurrence was observed in men (three patients) compared to women (one patient) which was not statistically significant (p= 0.878). We also observed higher 1-year disease free survival rate in women (1-year disease free survival= 93.3%) compared to men (1-year disease free survival= 82.4%), which also was not statistically significant (p= 0.356). 1-year disease free survival rate in patient with negative lymph nodes was 95.5% while respective number in patients with positive lymph nodes was 70% (p= 0.047). Conclusion TME with LLND could prolong survival and reduce local recurrence in patients with advanced low rectal cancer. However, large-scale clinical trials are required to evaluate such procedure as a standard in Iran.
Collapse
Affiliation(s)
| | - Ramesh Omranipour
- Tehran University of Medical Science, Cancer Institute, Tehran, Iran
| | - Anahita Borjian
- Tehran University of Medical Science, Cancer Institute, Tehran, Iran
| | | |
Collapse
|
|
15
|
Li CH, Prokopec SD, Sun RX, Yousif F, Schmitz N, Boutros PC. Sex differences in oncogenic mutational processes. Nat Commun 2020; 11:4330. [PMID: 32859912 PMCID: PMC7455744 DOI: 10.1038/s41467-020-17359-2] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 01/30/2020] [Indexed: 02/03/2023] Open
Abstract
Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.
Collapse
Affiliation(s)
- Constance H Li
- Computational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
- Department of Human Genetics, University of California, Los Angeles, CA, USA
| | - Stephenie D Prokopec
- Computational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada
| | - Ren X Sun
- Computational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada
- Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada
| | - Fouad Yousif
- Computational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada
| | - Nathaniel Schmitz
- Computational Biology Program, Ontario Institute for Cancer Research, Toronto, ON, Canada
| | - Paul C Boutros
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
- Department of Human Genetics, University of California, Los Angeles, CA, USA.
- Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada.
- Vector Institute for Artificial Intelligence, Toronto, Canada.
- Department of Urology, University of California, Los Angeles, CA, USA.
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA.
- Institute for Precision Health, University of California, Los Angeles, CA, USA.
| |
Collapse
|
|
16
|
Zengin M, Karahan İ. The role of cancer-related inflammation for prediction of poor survival in postmenopausal female patients with stage II/III colon cancer. Int Immunopharmacol 2020; 85:106624. [PMID: 32492626 DOI: 10.1016/j.intimp.2020.106624] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 04/11/2020] [Accepted: 05/19/2020] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Cancer-related inflammation (CRI) is thought to be a successful predictor of prognosis in colon cancers (CC), but opinions on how to use it are highly variable. In this study, the role of CRI cells in survival for CC patients was investigated by considering gender and menopausal status. METHODS 163 stage II/III CC patients who underwent curative surgery between 1995 and 2015 were included in the study. The relationship between CRI cells was examined using a standard methodology. RESULTS High neutrophil-lymphocyte ratio (NLR) had a better relationship with prognostic factors, especially in postmenopausal women (gender, p = 0.037, positive surgical margin, p = 0.001; MSI, p < 0.001; Crohn's-like reaction, p = 0.001, etc). Also, the reproducibility of the study was better in postmenopausal women (intra-observer agreement = 0.72, intra-class correlation = 0.722, correlation of estimates = 0.718). In univariate analysis, 5-year survival was worse in postmenopausal women with high NLR (OS, p = 0.001; RFS, p < 0.001). In multivariate analysis, high NLR was independently a worse biomarker for OS (hazard ratio [HR], 1.29; 95% CI, 1.18-2.12; p = 0.001) and RFS (HR, 1.30; 95% CI, 1.21-2.59; p < 0.001) in postmenopausal women. CONCLUSIONS NLR had an independent poor prognostic significance in postmenopausal female patients, and the use of a standard approach for methodology improved successful results.
Collapse
Affiliation(s)
- Mehmet Zengin
- Kırıkkale University, Faculty of Medicine, Department of Pathology, Kırıkkale, Turkey.
| | - İrfan Karahan
- Kırıkkale University, Faculty of Medicine, Department of Internal Medicine, Kırıkkale, Turkey
| |
Collapse
|
|
17
|
Yang W, Giovannucci EL, Hankinson SE, Chan AT, Ma Y, Wu K, Fuchs CS, Lee IM, Sesso HD, Lin JH, Zhang X. Endogenous sex hormones and colorectal cancer survival among men and women. Int J Cancer 2020; 147:920-930. [PMID: 31863463 DOI: 10.1002/ijc.32844] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 12/10/2019] [Accepted: 12/11/2019] [Indexed: 02/06/2023]
Abstract
Although previous studies have suggested a potential role of sex hormones in the etiology of colorectal cancer (CRC), no study has yet examined the associations between circulating sex hormones and survival among CRC patients. We prospectively assessed the associations of prediagnostic plasma concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone and sex hormone-binding globulin (SHBG) with CRC-specific and overall mortality among 609 CRC patients (370 men and 239 postmenopausal women not taking hormone therapy at blood collection) from four U.S. cohorts. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression. We identified 174 deaths (83 CRC-specific deaths) in men and 106 deaths (70 CRC-specific deaths) in women. In men, higher circulating level of free testosterone was associated with lower risk of overall (the highest vs. lowest tertiles, HR = 0.66, 95% CI, 0.45-0.99, ptrend = 0.04) and possibly CRC-specific mortality (HR = 0.73, 95% CI, 0.41-1.29, ptrend = 0.27). We generally observed nonsignificant inverse associations for other sex steroids, and a positive association for SHBG with CRC-specific mortality among male patients. In women, however, we found a suggestive positive association of estrone with overall (HR = 1.54, 95% CI, 0.92-2.60, ptrend = 0.11) and CRC-specific mortality (HR = 1.96, 95% CI, 1.01-3.84, ptrend = 0.06). Total estradiol, free estradiol and free testosterone were generally suggestively associated with higher risk of mortality among female patients, although not statistically significant. These findings implicated a potential role of endogenous sex hormones in CRC prognosis, which warrant further investigation.
Collapse
Affiliation(s)
- Wanshui Yang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.,Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Edward L Giovannucci
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Susan E Hankinson
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA
| | - Andrew T Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.,Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA.,Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA
| | - Yanan Ma
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.,Department of Biostatistics and Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Charles S Fuchs
- Department of Medical Oncology, Yale Cancer Center, New Haven, CT.,Department of Medicine, Yale School of Medicine, New Haven, CT.,Department of Medical Oncology, Smilow Cancer Hospital, New Haven, CT
| | - I-Min Lee
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Division of Preventive Medicine, Department of Medicine Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Howard D Sesso
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Division of Preventive Medicine, Department of Medicine Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | | | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
| |
Collapse
|
|
18
|
Nikbakht HA, Hassanipour S, Shojaie L, Vali M, Ghaffari-fam S, Ghelichi-ghojogh M, Maleki Z, Arab-Zozani M, Abdzadeh E, Delam H, Salehiniya H, Shafiee M, Mohammadi S. Survival Rate of Colorectal Cancer in Eastern Mediterranean Region Countries: A Systematic Review and Meta-Analysis. Cancer Control 2020; 27:1073274820964146. [PMID: 33074714 PMCID: PMC7791530 DOI: 10.1177/1073274820964146] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Colorectal cancer (CRC) is the second most common cause of cancer-related deaths worldwide. Survival rates are among the most important factors in quality control and assessment of treatment protocols. This study was aimed to assess the survival rate of colorectal cancer in Eastern Mediterranean Region Countries. In the present study we comprehensively searched 6 international databases including PubMed/Medline, ProQuest, Scopus, Embase, Web of Knowledge and Google Scholar for published articles until November 2018. The Newcastle-Ottawa Quality Assessment Form for Cohort Studies was applied to evaluate the quality of included studies. The heterogeneity of papers was assessed with the Cochran Test and I-Square statistics. Meta-regression test was performed based on publication year, sample size and Human Development Index (HDI) of each study. Among the total of 1023 titles found in the systematic search, 43 studies were eligible to be included in the present meta-analysis. According to the results, the 1-year, 3-year and 5-year survival rate of patients with Colorectal Cancer was 88.07% (95% CI, 83.22-92.92), 70.67% (95% CI, 66.40-74.93) and, 57.26% (95% CI, 50.43-64.10); respectively. Furthermore, Meta-regressions did not show significant correlations between survival rate and year, sample size or Human Development Index. Survival rates, especially the 5-year survival rate in the EMRO were less than European countries and the USA. Documented and comprehensive evidence-based findings of the present meta-analysis can be used to enhance policies and outcomes of different medical areas including prophylaxis, treatment and health related objectives in colorectal cancer.
Collapse
Affiliation(s)
- Hossein-Ali Nikbakht
- Social Determinants of Health Research Center, Health Research
Institute, Babol University of Medical Sciences, Babol, Iran
| | - Soheil Hassanipour
- Gastrointestinal and Liver Diseases Research Center, Guilan
University of Medical Sciences, Rasht, Iran
| | - Layla Shojaie
- Division of GI/Liver, Department of Medicine, Keck school of
Medicine, University of Southern California, Los Angeles, CA, USA
| | - Mohebat Vali
- Student Research Committee, Shiraz University of Medical Sciences,
Shiraz, Iran
| | - Saber Ghaffari-fam
- School of Nursing of Miyandoab, Urmia University of Medical
Sciences, Urmia, Iran
| | | | - Zahra Maleki
- Student Research Committee, Shiraz University of Medical Sciences,
Shiraz, Iran
| | - Morteza Arab-Zozani
- Social Determinants of Health Research Center, Birjand University of
Medical Sciences, Birjand, Iran
| | - Elham Abdzadeh
- GI Cancer Screening and Prevention Research Center, Guilan
University of Medical Sciences, Rasht, Iran
| | - Hamed Delam
- Student Research Committee, Larestan University of Medical Sciences,
Larestan, Iran
| | - Hamid Salehiniya
- Social Determinants of Health Research Center, Birjand University of
Medical Sciences, Birjand, Iran
| | - Maryam Shafiee
- Assistant Professor of Medicine, Shiraz Nephro-Urology Research
Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Salman Mohammadi
- Nutrition Research Center, Shiraz University of Medical Sciences,
Shiraz, Iran
| |
Collapse
|
|
19
|
Li CH, Haider S, Shiah YJ, Thai K, Boutros PC. Sex Differences in Cancer Driver Genes and Biomarkers. Cancer Res 2019; 78:5527-5537. [PMID: 30275052 DOI: 10.1158/0008-5472.can-18-0362] [Citation(s) in RCA: 107] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 05/18/2018] [Accepted: 06/26/2018] [Indexed: 11/16/2022]
Abstract
Cancer differs significantly between men and women; even after adjusting for known epidemiologic risk factors, the sexes differ in incidence, outcome, and response to therapy. These differences occur in many but not all tumor types, and their origins remain largely unknown. Here, we compare somatic mutation profiles between tumors arising in men and in women. We discovered large differences in mutation density and sex biases in the frequency of mutation of specific genes; these differences may be associated with sex biases in DNA mismatch repair genes or microsatellite instability. Sex-biased genes include well-known drivers of cancer such as β-catenin and BAP1 Sex influenced biomarkers of patient outcome, where different genes were associated with tumor aggression in each sex. These data call for increased study and consideration of the molecular role of sex in cancer etiology, progression, treatment, and personalized therapy.Significance: This study provides a comprehensive catalog of sex differences in somatic alterations, including in cancer driver genes, which influence prognostic biomarkers that predict patient outcome after definitive local therapy. Cancer Res; 78(19); 5527-37. ©2018 AACR.
Collapse
Affiliation(s)
- Constance H Li
- Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. .,Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
| | - Syed Haider
- Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada
| | - Yu-Jia Shiah
- Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.,Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
| | - Kevin Thai
- Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada
| | - Paul C Boutros
- Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. .,Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.,Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
| |
Collapse
|
|
20
|
Delitto D, George TJ, Loftus TJ, Qiu P, Chang GJ, Allegra CJ, Hall WA, Hughes SJ, Tan SA, Shaw CM, Iqbal A. Prognostic Value of Clinical vs Pathologic Stage in Rectal Cancer Patients Receiving Neoadjuvant Therapy. J Natl Cancer Inst 2019; 110:460-466. [PMID: 29165692 DOI: 10.1093/jnci/djx228] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 09/28/2017] [Indexed: 12/15/2022] Open
Abstract
Background Neoadjuvant chemoradiation is currently standard of care in stage II-III rectal cancer, resulting in tumor downstaging for patients with treatment-responsive disease. However, the prognosis of the downstaged patient remains controversial. This work critically analyzes the relative contribution of pre- and post-therapy staging to the anticipated survival of downstaged patients. Methods The National Cancer Database (NCDB) was queried for patients with rectal cancer treated with transabdominal resection between 2004 and 2014. Stage II-III patients downstaged with neoadjuvant radiation were compared with stage I patients treated with definitive resection alone. Patients with positive surgical margins were excluded. Overall survival was evaluated using both Kaplan-Meier analyses and Cox proportional hazards models. All statistical tests were two-sided. Results A total of 44 320 patients were eligible for analysis. Survival was equivalent for patients presenting with cT1N0 disease undergoing resection (mean survival = 113.0 months, 95% confidence interval [CI] = 110.8 to 115.3 months) compared with those downstaged to pT1N0 from both cT3N0 (mean survival = 114.9 months, 95% CI = 110.4 to 119.3 months, P = .12) and cT3N1 disease (mean survival = 115.4 months, 95% CI = 110.1 to 120.7 months, P = .22). Survival statistically significantly improved in patients downstaged to pT2N0 from cT3N0 disease (mean survival = 109.0 months, 95% CI = 106.7 to 111.2 months, P < .001) and cT3N1 (mean survival = 112.8 months, 95% CI = 110.0 to 115.7 months, P < .001), compared with cT2N0 patients undergoing resection alone (mean survival = 100.0 months, 95% CI = 97.5 to 102.5 months). Multiple survival analysis confirmed that final pathologic stage dictated long-term outcomes in patients undergoing neoadjuvant radiation (hazard ratio [HR] of pT2 = 1.24, 95% CI = 1.10 to 1.41; HR of pT3 = 1.81, 95% CI = 1.61 to 2.05; HR of pT4 = 2.72, 95% CI = 2.28 to 3.25, all P ≤ .001 vs pT1; HR of pN1 = 1.50, 95% CI = 1.41 to 1.59; HR of pN2 = 2.17, 95% CI = 2.00 to 2.35, both P < .001 vs pN0); while clinical stage at presentation had little to no predictive value (HR of cT2 = 0.81, 95% CI = 0.69 to 0.95, P = .008; HR of cT3 = 0.83, 95% CI = 0.72 to 0.96, P = .009; HR of cT4 = 1.02, 95% CI = 0.85 to 1.21, P = .87 vs cT1; HR of cN1 = 0.96, 95% CI = 0.91 to 1.02, P = .19; HR of cN2 = 0.96, 95% CI = 0.86 to 1.08, P = .48 vs cN0). Conclusions Survival in patients with rectal cancer undergoing neoadjuvant radiation is driven by post-therapy pathologic stage, regardless of pretherapy clinical stage. These data will further inform prognostic discussions with patients.
Collapse
Affiliation(s)
- Daniel Delitto
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Thomas J George
- Division of Hematology and Oncology, Department of Medicine, University of Florida College of Medicine, Gainesville, FL
| | - Tyler J Loftus
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Peihua Qiu
- Department of Biostatistics, University of Florida College of Medicine, Gainesville, FL
| | - George J Chang
- Department of Surgical Oncology and Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Carmen J Allegra
- Division of Hematology and Oncology, Department of Medicine, University of Florida College of Medicine, Gainesville, FL
| | - William A Hall
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI
| | - Steven J Hughes
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Sanda A Tan
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Christiana M Shaw
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Atif Iqbal
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| |
Collapse
|
|
21
|
Yu Y, Carey M, Pollett W, Green J, Dicks E, Parfrey P, Yilmaz YE, Savas S. The long-term survival characteristics of a cohort of colorectal cancer patients and baseline variables associated with survival outcomes with or without time-varying effects. BMC Med 2019; 17:150. [PMID: 31352904 PMCID: PMC6661748 DOI: 10.1186/s12916-019-1379-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 06/27/2019] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Colorectal cancer is the third most common cancer in the world. In this study, we assessed the long-term survival characteristics and prognostic associations and potential time-varying effects of clinico-demographic variables and two molecular markers (microsatellite instability (MSI) and BRAF Val600Glu mutation) in a population-based patient cohort followed up to ~ 19 years. METHODS The patient cohort included 738 incident cases diagnosed between 1999 and 2003. Cox models were used to analyze the association between the variables and a set of survival outcome measures (overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), metastasis-free survival (MFS), recurrence/metastasis-free survival (RMFS), and event-free survival (EFS)). Cox proportional hazard (PH) assumption was tested for all variables, and Cox models with time-varying effects were used if any departure from the PH assumption was detected. RESULTS During the follow-up, ~ 61% patients died from any cause, ~ 26% died from colorectal cancer, and ~ 10% and ~ 20% experienced recurrences and distant metastases, respectively. Stage IV disease and post-diagnostic recurrence or metastasis were strongly linked to risk of death from colorectal cancer. If a patient had survived the first 6 years without any disease-related event (i.e., recurrence, metastasis, or death from colorectal cancer), their risks became very minimal after this time period. Distinct sets of markers were associated with different outcome measures. In some cases, the effects by variables were constant throughout the follow-up. For example, MSI-high tumor phenotype and older age at diagnosis predicted longer MFS times consistently over the follow-up. However, in some other cases, the effects of the variables varied with time. For example, adjuvant radiotherapy treatment was associated with increased risk of metastasis in patients who received this treatment after 5.5 years post-diagnosis, but not before that. CONCLUSIONS This study describes the long-term survival characteristics of a prospective cohort of colorectal cancer patients, relationships between baseline variables and a detailed set of patient outcomes over a long time, and time-varying effects of a group of variables. The results presented advance our understanding of the long-term prognostic characteristics in colorectal cancer and are expected to inspire future studies and clinical care strategies.
Collapse
Affiliation(s)
- Yajun Yu
- Discipline of Genetics, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, New Medical Education Building, St. John's, NL, A1B 3V6, Canada
| | - Megan Carey
- Discipline of Genetics, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, New Medical Education Building, St. John's, NL, A1B 3V6, Canada
| | - William Pollett
- Discipline of Surgery, Faculty of Medicine, Memorial University, St. John's, NL, Canada
| | - Jane Green
- Discipline of Genetics, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, New Medical Education Building, St. John's, NL, A1B 3V6, Canada
| | - Elizabeth Dicks
- Discipline of Medicine, Faculty of Medicine, Memorial University, St. John's, NL, Canada
| | - Patrick Parfrey
- Discipline of Medicine, Faculty of Medicine, Memorial University, St. John's, NL, Canada
| | - Yildiz E Yilmaz
- Discipline of Genetics, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, New Medical Education Building, St. John's, NL, A1B 3V6, Canada.,Discipline of Medicine, Faculty of Medicine, Memorial University, St. John's, NL, Canada.,Department of Mathematics and Statistics, Faculty of Science, Memorial University, St. John's, NL, Canada
| | - Sevtap Savas
- Discipline of Genetics, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, New Medical Education Building, St. John's, NL, A1B 3V6, Canada. .,Discipline of Oncology, Faculty of Medicine, Memorial University, St. John's, NL, Canada.
| |
Collapse
|
|
22
|
Lee JW, You NY, Kim Y, Kim Y, Kim J, Kang HT. Statin use and site-specific risk of colorectal cancer in individuals with hypercholesterolemia from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). Nutr Metab Cardiovasc Dis 2019; 29:701-709. [PMID: 31133496 DOI: 10.1016/j.numecd.2019.04.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 02/18/2019] [Accepted: 04/02/2019] [Indexed: 01/11/2023]
Abstract
BACKGROUND AND AIMS We investigated the association between statin use and site-specific risk of colorectal cancer in individuals with hypercholesterolemia. METHODS AND RESULTS This study is based on the National Health Insurance Service-National Health Screening Cohort, conducted during 2002-2015. Statin users were classified as high and low users according to medication possession ratio (MPR). Statin nonusers comprised participants who did not use statins during the entire follow-up period. In total, 17,737 statin users and 13,412 statin nonusers were included in the analysis, with a median follow-up period of 12.7 years. Cox proportional hazards regression models were adopted after stepwise adjustment for confounders to investigate prospective association between statin usage and colorectal cancer risk. In total, 378 (2.3%) of 16,588 male participants and 239 (1.6%) of 14,561 female participants had colorectal cancer during the follow-up period. Compared to nonusers, fully adjusted hazard ratios (HRs) (95% confidence intervals [95% CIs]) for colorectal cancer risk in high statin users were 0.56 (0.42-0.75) in men and 0.64 (0.46-0.90) in women. In men, the fully adjusted HRs for proximal and rectal cancer for high users were 0.29 (0.15-0.56) and 0.52 (0.35-0.78), respectively, compared to those for nonusers. In women, statistical significance was seen only in rectal cancer (HR 0.43 [0.25-0.72]) but not in proximal or distal colon cancer. CONCLUSIONS High statin users with hypercholesterolemia were associated with lower risk of overall colorectal cancer, especially proximal colon cancer in men and rectal cancer in both sexes.
Collapse
Affiliation(s)
- Jae-Woo Lee
- Department of Family Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea
| | - Na-Young You
- Department of Information & Statistics, Chungbuk National University, Cheongju, Republic of Korea
| | - Yeseul Kim
- Department of Family Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea
| | - Yonghwan Kim
- Department of Family Medicine, Yonsei University College of medicine, Seoul, Republic of Korea
| | - Joungyoun Kim
- Department of Information & Statistics, Chungbuk National University, Cheongju, Republic of Korea.
| | - Hee-Taik Kang
- Department of Family Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea; Department of Family Medicine, Chungbuk National University College of Medicine, Cheongju, Chungbuk, Republic of Korea.
| |
Collapse
|
|
23
|
Adam S, van de Poll-Franse LV, Mols F, Ezendam NPM, de Hingh IHJT, Arndt V, Thong MSY. The association of cancer-related fatigue with all-cause mortality of colorectal and endometrial cancer survivors: Results from the population-based PROFILES registry. Cancer Med 2019; 8:3227-3236. [PMID: 31012272 PMCID: PMC6558477 DOI: 10.1002/cam4.2166] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 04/03/2019] [Accepted: 04/03/2019] [Indexed: 11/10/2022] Open
Abstract
Purpose Cancer‐related fatigue (CRF) is one of the most prevalent symptoms experienced by cancer survivors. However, researchers are only beginning to elucidate the risk factors, underlying mechanism(s), and its association with other outcomes. Research on the association between CRF and mortality is limited. Methods The study sample comprised 2059 short‐term (<5 years postdiagnosis) cancer survivors from four PROFILES registry studies. Survivors diagnosed with stage I‐III colorectal cancer (CRC) or stage I‐III endometrial cancer (EC), with no evidence of disease, were identified and followed‐up by the Netherlands Cancer Registry. Fatigue was assessed with the Fatigue Assessment Scale. Cox proportional hazards models adjusted for demographic, clinical, and lifestyle characteristics were performed to assess the association of CRF with all‐cause mortality. Date of censoring was February 1, 2017. Results Prevalence of CRF varied between 35.8% (male CRC) and 43.6% (female CRC). After a median follow‐up period of 9.0 years, a total of 408 survivors (20%) had died. CRF was associated with increased all‐cause mortality in male CRC survivors (HRadj = 1.75, 95% CI [1.31‐2.33]). This association remained statistically significant after excluding survivors experiencing anhedonia. For female CRC (HRadj = 1.32, 95% CI [0.90‐1.97]) and EC (HRadj = 1.27, 95% CI [0.84‐1.90]) survivors, there was no significant association with all‐cause mortality for the fatigued group in multivariable analyses. Conclusion Our study found that CRF is significantly associated with all‐cause mortality in male CRC survivors, irrespective of potential confounders. This result suggests that clinicians should increase their attention towards the recognition and treatment of CRF.
Collapse
Affiliation(s)
- Salome Adam
- Netherlands Comprehensive Cancer Organisation, Utrecht, the Netherlands.,Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Switzerland
| | - Lonneke V van de Poll-Franse
- Netherlands Comprehensive Cancer Organisation, Utrecht, the Netherlands.,Department of Medical and Clinical Psychology, CoRPS-Center of Research on Psychology in Somatic Diseases, Tilburg University, Tilburg, the Netherlands.,Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Floortje Mols
- Department of Medical and Clinical Psychology, CoRPS-Center of Research on Psychology in Somatic Diseases, Tilburg University, Tilburg, the Netherlands
| | - Nicole P M Ezendam
- Netherlands Comprehensive Cancer Organisation, Utrecht, the Netherlands.,Department of Medical and Clinical Psychology, CoRPS-Center of Research on Psychology in Somatic Diseases, Tilburg University, Tilburg, the Netherlands
| | | | - Volker Arndt
- Unit of Cancer Survivorship, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Melissa S Y Thong
- Unit of Cancer Survivorship, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Medical Psychology, Amsterdam Public Health Research Institute, Location AMC, Amsterdam UMC, Amsterdam, the Netherlands
| |
Collapse
|
|
24
|
Lim H, Kim SY, Lee E, Lee S, Oh S, Jung J, Kim KS, Moon A. Sex-Dependent Adverse Drug Reactions to 5-Fluorouracil in Colorectal Cancer. Biol Pharm Bull 2019; 42:594-600. [DOI: 10.1248/bpb.b18-00707] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Hyesol Lim
- Duksung Innovative Drug Center, College of Pharmacy, Duksung Women’s University
| | - Sun Young Kim
- Department of Chemistry, College of Natural Sciences, Duksung Women’s University
| | - Eunhye Lee
- Duksung Innovative Drug Center, College of Pharmacy, Duksung Women’s University
| | - Seungeun Lee
- Duksung Innovative Drug Center, College of Pharmacy, Duksung Women’s University
| | - Sungryong Oh
- Duksung Innovative Drug Center, College of Pharmacy, Duksung Women’s University
| | - Joohee Jung
- Duksung Innovative Drug Center, College of Pharmacy, Duksung Women’s University
| | - Kwi Suk Kim
- Department of Pharmacy, Seoul National University Hospital
| | - Aree Moon
- Duksung Innovative Drug Center, College of Pharmacy, Duksung Women’s University
| |
Collapse
|
|
25
|
Saito T, Tanaka K, Ebihara Y, Kurashima Y, Murakami S, Shichinohe T, Hirano S. Novel prognostic score of postoperative complications after transthoracic minimally invasive esophagectomy for esophageal cancer: a retrospective cohort study of 90 consecutive patients. Esophagus 2019; 16:155-161. [PMID: 30178429 DOI: 10.1007/s10388-018-0645-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 08/29/2018] [Indexed: 02/03/2023]
Abstract
BACKGROUND Esophagectomy is the standard treatment for esophageal cancer, but has a high rate of postoperative complications. Some studies reported the various scoring system to estimate the postoperative complications. However, there were according to various surgical methods and included intra- and post-operative factors. Recently, minimally invasive esophagectomy (MIE) is becoming the first-line treatment for esophageal cancer. The aim of this study was to investigate the risk factors of postoperative complications and to establish a useful system for predicting postoperative complications after transthoracic MIE. METHODS From 2007 to 2015, 90 patients who underwent transthoracic MIE at our department were enrolled. Patients were divided into two groups according to postoperative complication: patients with major complications (n = 32) and without major complications (n = 58). Major complication was defined as ≥ IIIa in the Clavien-Dindo classification. RESULTS Multivariate analysis identified four independent risk factors for predicting postoperative complications: age [≥ 70 years; odd ratio (OR) 6.88; p = 0.001]; sex (male; OR 5.24; p = 0.031); total protein level (< 6.7 mg/dl; OR 6.51; p = 0.002), and C-reactive protein level (≥ 0.15; OR, 6.58; p = 0.001). These four factors were used to establish a score. The complication rate for scores 0-4 were 0, 11, 36, 71, 100%, respectively. The frequency of major complications was significantly associated with the score (p < 0.001). Receiver operator characteristic curves to predict the score with regard to major complications showed an area under the curve value of 0.798 (95% confidence interval: 0.696-0.871, P < 0.001). CONCLUSIONS Our novel score may help to decide surgical intervention for esophagectomy and provide appropriate resources for perioperative management.
Collapse
Affiliation(s)
- Takahiro Saito
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, N-15, W-7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Kimitaka Tanaka
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, N-15, W-7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan.
| | - Yuma Ebihara
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, N-15, W-7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Yo Kurashima
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, N-15, W-7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Soichi Murakami
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, N-15, W-7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Toshiaki Shichinohe
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, N-15, W-7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, N-15, W-7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
| |
Collapse
|
|
26
|
Maajani K, Khodadost M, Fattahi A, Shahrestanaki E, Pirouzi A, Khalili F, Fattahi H. Survival Rate of Colorectal Cancer in Iran: A Systematic Review and Meta-Analysis. Asian Pac J Cancer Prev 2019; 20:13-21. [PMID: 30677864 PMCID: PMC6485573 DOI: 10.31557/apjcp.2019.20.1.13] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 01/05/2019] [Indexed: 12/16/2022] Open
Abstract
Background: Different studies have been conducted to estimate the survival rate of colorectal cancer in Iran but there is no overall estimate of the survival rate. The aim of this study was to calculate the pooled 1, 3, and 5-year survival rate of the patients with colorectal cancer in Iran. Methods: To retrieve relevant studies, we conducted a systematic search in Iranian databases, including Iran Medex, Magiran, SID, and international databases such as Medlin/PubMed, Scopus, and Google scholar using “Colorectal Neoplasms” and “Survival Rate” as keywords up to December 1st, 2017. We used random effect model to estimate pooled 1, 3, and 5-year survival rates of the patients with colorectal cancer in Iran. To assess the heterogeneity, we used Chi-squared test at the 5 % significance level (p <0.05) and I2 Index. We used meta-regression and subgroup analysis to find a potential source of heterogeneity. Results: After a systematic search, 196 articles were found, of the 38 studies met the eligibility criteria and are included in our meta-analysis. The pooled 1, 3, and 5-year survival rates in patient with colorectal cancer were 0.84 (95% CI: 0.81-0.87), 0.64 (95%CI: 0.59-0.70), and 0.54 (95%CI: 0.49-0.58) respectively. The 5-year survival rate in the subgroup of women was 0.5 (0.44-0.56) and in male subgroup was 0.44 (0.40-0.48). In a subgroup of the tumor site, the 5-year survival rate in colon cancer was 0.6 (0.49-0.75) and rectum cancer was 0.54 (0.36-0.69). In multivariable models, there was a significant association between years of study and 5-year survival rate as a source of heterogeneity (β = 18.9, P=0.01). Conclusion: According to the results of this study, women had a better survival rate than men, and according to the tumor site, the 5-year survival rate in colon cancer was better than the rectum cancer.
Collapse
Affiliation(s)
- Khadije Maajani
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences Tehran, Iran
| | | | | | | | | | | | | |
Collapse
|
|
27
|
Samawi HH, Yin Y, Speers CH, Cheung WY. Sex Disparities in Outcomes of Early Stage Colorectal Cancer: A Population-Based Study. Clin Colorectal Cancer 2018; 17:e711-e717. [DOI: 10.1016/j.clcc.2018.07.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 07/12/2018] [Accepted: 07/16/2018] [Indexed: 11/26/2022]
|
|
28
|
Byeon KH, Ha YS, Choi SH, Kim BS, Kim HT, Yoo ES, Kwon TG, Lee JN, Kim TH. Predictive factors for adrenal metastasis in extra-adrenal malignancy patients with solitary adrenal mass. J Surg Oncol 2018; 118:1271-1276. [PMID: 30367684 DOI: 10.1002/jso.25272] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 09/20/2018] [Indexed: 01/22/2023]
Abstract
BACKGROUND AND OBJECTIVES The adrenal gland is a frequent site for metastasis, and a solitary adrenal mass is often observed during staging workup or imaging follow-up in patients with extra-adrenal malignancy. To create an appropriate management plan, it is essential to distinguish between benign adrenal lesions and metastasis in patients with extra-adrenal cancer having solitary adrenal masses. Therefore, here we evaluated the predictive factors for adrenal metastasis in patients with extra-adrenal malignancy having solitary adrenal mass. MATERIALS AND METHODS From September 2003 to June 2016, we retrospectively reviewed patients with extra-adrenal malignancy having solitary adrenal mass on a cancer staging workup or follow-up study who subsequently underwent adrenalectomy at our institution. All patients underwent preoperative functional studies; those with positive results were excluded from this study. Characteristics of oncology patients with adrenal mass including age, sex, body mass index, smoking, mass location, mass size, hypertension, diabetes mellitus, precontrast Hounsfield unit (HU), and synchronous or metachronous adrenal mass based on the time of the extra-adrenal cancer diagnosis were analyzed. RESULTS Of the total 68 patients with extra-adrenal cancer having solitary adrenal mass, 22 had pathologically confirmed adrenal metastasis. Primary cancers consisted of hepatocellular cell carcinoma (n = 7), renal cell carcinoma (n = 7), lung cancer (n = 4), colon cancer (n = 3), and breast cancer (n = 1). On multivariate analysis, a higher precontrast HU (P = 0.001, odds ratio [OR] = 1.105, 95% confidence interval [CI] = 1.042-1.172), male sex ( P = 0.019, OR = 9.782, 95% CI = 1.462-65.461), and metachronous adrenal mass ( P = 0.007, OR = 11.090, 95% CI = 1.937-63.490) were observed as predictive factors for adrenal metastasis in patients with extra-adrenal cancer having solitary adrenal mass. The cut-off value of precontrast HU to distinguish between metastasis and benign lesions was 36.2 (sensitivity = 81.8%; specificity = 91.3%). CONCLUSION High precontrast HU (> 36), male sex, and metachronous adrenal mass are predictive factors for adrenal metastasis in patients with extra-adrenal malignancy having solitary adrenal mass.
Collapse
Affiliation(s)
- Kyeong-Hyeon Byeon
- Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Yun-Sok Ha
- Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Seock Hwan Choi
- Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Bum Soo Kim
- Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Hyun Tae Kim
- Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Eun Sang Yoo
- Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Tae Gyun Kwon
- Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jun Nyung Lee
- Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Tae-Hwan Kim
- Department of Urology, School of Medicine, Kyungpook National University, Daegu, Korea
| |
Collapse
|
|
29
|
Wen J, Chen J, Chen D, Liu D, Xu X, Huang L, Cao J, Zhang J, Gu Y, Fan M, Chen Y. Evaluation of the prognostic value of surgery and postoperative radiotherapy for patients with thymic neuroendocrine tumors: A propensity-matched study based on the SEER database. Thorac Cancer 2018; 9:1603-1613. [PMID: 30276969 PMCID: PMC6275836 DOI: 10.1111/1759-7714.12868] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Revised: 08/15/2018] [Accepted: 08/15/2018] [Indexed: 12/27/2022] Open
Abstract
Background The prognostic value of surgery and postoperative radiotherapy (PORT) for primary thymic neuroendocrine tumors (TNETs) was estimated using the SEER database. Methods This retrospective study used SEER data of TNET patients between 1998 and 2015. Propensity score matching (PSM) was performed according to whether surgery was performed. The prognostic effects on overall survival (OS) and cancer‐specific survival (CSS) were evaluated using multivariate Cox regression. Results A total of 3947 patients were included: 293 (7.4%) TNET, 2788 (70.6%) thymoma, and 866 (21.9%) thymic carcinoma. Compared to other subtypes, TNET patients were younger, included a larger proportion of men, had a well or moderately differentiated histological grade, higher disease stage at diagnosis, and were more likely to have regional lymph node metastasis. The median OS and CSS for TNET were 82.9 (95% confidence interval 74.3–91.4) and 101.9 (95% confidence interval 91.9–111.8) months, respectively, significantly shorter than for thymomas. In the matched cohort of TNET patients, multivariate analysis of OS and CSS revealed a significantly poorer prognosis in the non‐surgery group (P < 0.001). Compared to total/radical resection, TNET patients who underwent debulking resection had significantly inferior outcomes (P < 0.05). Postoperative radiotherapy favorably impacted OS and CSS in Masaoka–Koga stage III–IV TNET patients; this OS impact was also observed in stage IIB patients. Conclusion TNETs are extremely rare with relatively dismal outcomes. This analysis revealed the role of complete surgical resection and the favorable effect of postoperative radiotherapy in specific TNET subgroups.
Collapse
Affiliation(s)
- Junmiao Wen
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jiayan Chen
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Donglai Chen
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China
| | - Di Liu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xinyan Xu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lv Huang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jianzhao Cao
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Junhua Zhang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yu Gu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Min Fan
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yongbing Chen
- Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, China
| |
Collapse
|
|
30
|
Abstract
GOALS This study sought to clarify sex differences in KRAS mutations and clinical predictors of KRAS 13 codon mutations. BACKGROUND Sex differences in KRAS mutations and predictors for KRAS codon 13 mutations in colorectal cancer (CRC) are unclear. STUDY Between October 2007 and May 2016, 328 patients underwent surgery for CRCs that were analyzed for KRAS mutations at a referral university hospital. Sex differences in the rates and distributions of KRAS mutations, and factors predictive of overall KRAS and KRAS codon 13 mutations were analyzed. RESULTS KRAS mutations were significantly more common in women than men patients (46.0% vs. 34.4%, P<0.033). However, no sex differences were detected for KRAS mutations by codon subtypes (P=0.592). The Gly13Asp (GGC>GAC) point mutation was identified only within codon 13 in both sexes. For right-sided CRC, KRAS mutations were twice as frequent in men as in women (univariate analysis; P=0.016, multivariate analysis; P=0.019). High-plasma cholesterol level was an independent predictive factor of KRAS codon 13 mutations by univariate (odds ratio, 1.013; 95% confidence interval, 1.003-1.023) and multivariate analysis (odds ratio, 1.011; 95% confidence interval, 1.001-1.021). CONCLUSIONS Sex differences may affect the presentation of KRAS mutations, as they were more frequently detected in women and in right-sided CRC in men. KRAS codon 13 mutations were significantly associated with high-plasma cholesterol. Further studies are needed on the clinical implications of this finding.
Collapse
|
|
31
|
Gender-related prognostic significance of clinical and biological tumor features in rectal cancer patients receiving short-course preoperative radiotherapy. Rep Pract Oncol Radiother 2017; 22:368-377. [PMID: 28794690 DOI: 10.1016/j.rpor.2017.07.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Revised: 05/15/2017] [Accepted: 07/11/2017] [Indexed: 12/24/2022] Open
Abstract
AIM To study the prognostic value of clinical and biological features of rectal cancer and potential gender differences in patients' overall survival (OS), local recurrence-free survival (RFS) and metastasis-free survival (MFS) after short-course preoperative radiotherapy (SCRT) with short or long interval between RT and surgery (break). BACKGROUND The length of the interval between RT and surgery in SCRT is debatable and gender-related differences in patients survival are not established yet. MATERIALS AND METHODS 126 patients received SCRT with 5 Gy dose per fraction during 5 days, followed by radical surgery after short break ≤17 days, and a long break >17 days. Pretreatment tumor proliferation (bromodeoxyuridine labeling index, BrdUrdLI and S-phase fraction) was evaluated by flow cytometry and proteins: CD34, Ki-67, GLUT-1, Ku70, BCL-2, P53 expression was studied immunohistochemically. RESULTS The studied group included 84 men and 42 women. There were 33, 76, and 17 cTNM (AJCC) tumor stages I, II, III, respectively. The median follow-up time was 53.3 months (range 2-142 months). For the whole group Cox multivariate analysis revealed that tumor grade (G > 1), interval between RT and surgery >17 days, pTNM stage >1 and P53 positivity + BrdUrdLI > 7.9% were negative prognostic factors for OS. Tumor aneuploidy and MVD > 140.8 vessels/mm2 were important for RFS. pTNM stage > 1 and P53 positivity combined with BrdUrdLI > 7.9% were risk predictors for MFS. Based on tumor biological features, gender-related difference in OS, RFS, and MFS were observed. In multivariate analysis, male patients age > 62 years and break >17 days only appeared to be significant for OS. CONCLUSIONS In male rectal patients treated with SCRT, breaks between RT and surgery >17 days should be avoided because they negatively influence patients' survival.
Collapse
|
|
32
|
Topi G, Ehrnström R, Jirström K, Palmquist I, Lydrup ML, Sjölander A. Association of the oestrogen receptor beta with hormone status and prognosis in a cohort of female patients with colorectal cancer. Eur J Cancer 2017; 83:279-289. [PMID: 28763692 DOI: 10.1016/j.ejca.2017.06.013] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 06/09/2017] [Accepted: 06/11/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND The oestrogen receptor beta (ERβ) is the predominant oestrogen receptor in the normal colon mucosa and has been reported to exert anti-proliferative and pro-apoptotic effects. However, the role of ERβ in colorectal cancer (CRC) progression remains unclear. AIM To investigate the role of ERβ and its association with hormone status and lifestyle indicators in a female cohort of patients with CRC. METHODS Tissue microarrays of primary CRC tumour samples from 320 female patients were conducted with a monoclonal anti-ERβ antibody. The staining intensity was evaluated using immunohistochemistry. The association of ERβ expression with overall survival, disease-free survival, hormone status and lifestyle was evaluated, and effect estimators with 95% confidence intervals (CIs) were reported. RESULTS Among the 314 samples with successfully detected ERβ, 182 (58%) had low expression and 132 (42%) had high expression. The Cox multivariate analysis indicated that patients with high ERβ expression had a decreased risk of overall mortality by 50% (hazard ratio [HR], 0.50; CI, 0.30-0.83) and of cancer recurrence by 76% (HR, 0.24; CI, 0.11-0.52) after adjusting for age, tumour-node-metastasis stage and tumour intravascular invasion. Furthermore, high ERβ expression was significantly correlated with shorter breastfeeding time and longer use of hormone replacement therapy. No association was found between ERβ expression and lifestyle indicators. CONCLUSION Elevated ERβ expression is independently associated with a better prognosis and hormone status but not lifestyle indicators in female CRC patients.
Collapse
Affiliation(s)
- Geriolda Topi
- Division of Cell Pathology, Department of Translational Medicine, Lund University, Skåne University Hospital, Malmö, Sweden
| | - Roy Ehrnström
- Division of Pathology, Department of Translational Medicine, Lund University, Skåne University Hospital, Malmö, Sweden
| | - Karin Jirström
- Division of Oncology and Pathology, Department of Clinical Sciences, Lund, Lund University, Skåne University Hospital, Lund, Sweden
| | - Ingrid Palmquist
- Division of Surgery, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden
| | - Marie-Louise Lydrup
- Division of Surgery, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden
| | - Anita Sjölander
- Division of Cell Pathology, Department of Translational Medicine, Lund University, Skåne University Hospital, Malmö, Sweden.
| |
Collapse
|
|
33
|
Park JW, Lee JH, Park YH, Park SJ, Cheon JH, Kim WH, Kim TI. Sex-dependent difference in the effect of metformin on colorectal cancer-specific mortality of diabetic colorectal cancer patients. World J Gastroenterol 2017; 23:5196-5205. [PMID: 28811714 PMCID: PMC5537186 DOI: 10.3748/wjg.v23.i28.5196] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2017] [Revised: 05/29/2017] [Accepted: 07/04/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To assess factors associated with the higher effect of metformin on mortality in diabetic colorectal cancer (CRC) patients, since the factors related to the effectiveness of metformin have not been identified yet.
METHODS Between January 2000 and December 2010, 413 patients diagnosed with both stage 3/4 CRC and diabetes mellitus were identified. Patients’ demographics and clinical characteristics were analyzed. The effect of metformin on CRC-specific mortality and the interactions between metformin and each adjusted factor were evaluated.
RESULTS Total follow-up duration was median 50 mo (range: 1-218 mo). There were 85 deaths (45.9%) and 72 CRC-specific deaths (38.9%) among 185 patients who used metformin, compared to 130 total deaths (57.0%) and 107 CRC-specific deaths (46.9%) among 228 patients who did not use metformin. In multivariate analysis, survival benefit associated with metformin administration was identified (HR = 0.985, 95%CI: 0.974-0.997, P = 0.012). Interaction test between metformin and sex after adjustment for relevant factors revealed that female CRC patients taking metformin exhibited a significantly lower CRC-specific mortality rate than male CRC patients taking metformin (HR = 0.369, 95%CI: 0.155-0.881, P = 0.025). Furthermore, subgroup analysis revealed significant differences in CRC-specific mortality between the metformin and non-metformin groups in female patients (HR = 0.501, 95%CI: 0.286-0.879, P = 0.013) but not male patients (HR = 0.848, 95%CI: 0.594-1.211, P = 0.365). There were no significant interactions between metformin and other adjusted factors on CRC-specific mortality.
CONCLUSION We showed a strong sex-dependent difference in the effect of metformin on CRC-specific mortality in advanced stage CRC patients with diabetes.
Collapse
|
|
34
|
Yang Y, Wang G, He J, Ren S, Wu F, Zhang J, Wang F. Gender differences in colorectal cancer survival: A meta-analysis. Int J Cancer 2017; 141:1942-1949. [PMID: 28599355 DOI: 10.1002/ijc.30827] [Citation(s) in RCA: 111] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Revised: 05/18/2017] [Accepted: 06/01/2017] [Indexed: 02/06/2023]
Abstract
A meta-analysis was conducted to determine the influence of gender on overall survival (OS) and cancer-specific survival (CSS) in colorectal cancer patients. Major databases were searched for clinical trials, which compare survival differences between male and female for colorectal cancer patients. A list of these studies and references, published in English and Chinese from 1960 to 2017, was obtained independently by two reviewers from databases such as PubMed, Medline, ScienceDirect, the China National Knowledge Infrastructure (CNKI) and Web of Science. Overall survival and cancer-specific survival were compared using Review Manager 5.3. Females had significantly better OS (hazard ratio [HR] = 0.87; 95% confidence interval [CI] = 0.85-0.89) and CSS (HR = 0.92; 95% CI = 0.89-0.95) than males after meta-analysis. These results suggest that gender seems to be a significant factor influencing survival results among colorectal cancer patients.
Collapse
Affiliation(s)
- Yafan Yang
- Department of General Surgery, Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Guiying Wang
- Department of General Surgery, Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jingli He
- Department of General Surgery, Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shuguang Ren
- Animal Center, Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Fengpeng Wu
- Department of Radiotherapy, Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, 050010, China
| | - Jianfeng Zhang
- Department of General Surgery, Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Feifei Wang
- Department of General Surgery, Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| |
Collapse
|
|
35
|
Karim S, Nanji S, Brennan K, Pramesh CS, Booth CM. Chemotherapy for resected colorectal cancer pulmonary metastases: Utilization and outcomes in routine clinical practice. Eur J Surg Oncol 2017. [PMID: 28634014 DOI: 10.1016/j.ejso.2017.05.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND The role of chemotherapy in the setting of resected colorectal cancer pulmonary metastases (CRCPM) is not well defined. Here we describe utilization of peri-operative chemotherapy and outcomes among patients with resected CRCPM in the general population. METHODS All cases of CRCPM who underwent resection from 2002 to 2009 were identified using the Ontario Cancer Registry (OCR). Electronic treatment records identified peri-operative chemotherapy delivered within 16 weeks before or after pulmonary metastasectomy (PM). Modified Poisson regression was used to evaluate factors associated with chemotherapy delivery. Cox proportional models were used to explore the association between post-operative chemotherapy and cancer-specific (CSS) and overall survival (OS). RESULTS The study population included 420 patients. Thirty-six percent of patients (151/420) received peri-operative chemotherapy. Among these patients, 75% (113/151) received post-operative chemotherapy. Factors that were independently associated with use of post-operative chemotherapy included higher socioeconomic status (SES) and no prior adjuvant chemotherapy (p < 0.01). In adjusted analyses post-operative chemotherapy was not associated with improved CSS (HR 0.99, 95% CI 0.67-1.47) or OS (HR 0.93 95% CI 0.66-1.31). In exploratory analyses, among those patients who did not receive previous adjuvant therapy for the primary colorectal cancer, post-operative chemotherapy following lung metastasectomy was associated with HR 0.50 (95% CI 0.27-0.95) for OS and HR 0.59 (95% CI 0.27-1.27) for CSS. CONCLUSION One third of patients with resected CRCPM in routine practice receive peri-operative chemotherapy. A randomized controlled trial is warranted to evaluate whether chemotherapy following resection of CRCPM is associated with improved survival.
Collapse
Affiliation(s)
- S Karim
- Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Canada; Department of Oncology, Queen's University, Kingston, Canada
| | - S Nanji
- Department of Oncology, Queen's University, Kingston, Canada; Department of Surgery, Queen's University, Kingston, Canada
| | - K Brennan
- Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Canada
| | - C S Pramesh
- Department of Surgical Oncology, Tata Memorial Centre, Mumbai, India
| | - C M Booth
- Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute, Canada; Department of Oncology, Queen's University, Kingston, Canada; Department of Public Health Sciences, Queen's University, Kingston, Canada.
| |
Collapse
|
|
36
|
Quirt JS, Nanji S, Wei X, Flemming JA, Booth CM. Is there a sex effect in colon cancer? Disease characteristics, management, and outcomes in routine clinical practice. ACTA ACUST UNITED AC 2017; 24:e15-e23. [PMID: 28270728 DOI: 10.3747/co.24.3410] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION The incidence of colon cancer varies by sex. Whether women and men show differences in extent of disease, treatment, and outcomes is not well described. We used a large population-based cohort to evaluate sex differences in colon cancer. METHODS Using the Ontario Cancer Registry, all cases of colon cancer treated with surgery in Ontario during 2002-2008 were identified. Electronic records of treatment identified use of surgery and adjuvant chemotherapy. Pathology reports for a random 25% sample of all cases were obtained, and disease characteristics, treatment, and outcomes in women and men were compared. A Cox proportional hazards model was used to identify factors associated with overall (os) and cancer-specific survival (css). RESULTS The study population included 7249 patients who underwent resection of colon cancer; 49% (n = 3556) were women. Stage of disease and histologic grade did not vary by sex. Compared with men, women were more likely to have right-sided disease (55% vs. 44%, p ≤ 0.001). Surgical procedure and lymph node yield did not differ by sex. Adjuvant chemotherapy was delivered to 18% of patients with stage ii and 64% of patients with stage iii disease; when adjusted for patient- and disease-related factors, use of adjuvant chemotherapy was similar for women and men [relative risk: 0.99; 95% confidence interval (ci): 0.94 to 1.03]. Adjusted analyses demonstrated that os [hazard ratio (hr): 0.80; 95% ci: 0.75 to 0.86] and css (hr: 0.82; 95% ci: 0.76 to 0.90) were superior for women compared with men. CONCLUSIONS Long-term survival after colon cancer is significantly better for women than for men, which is not explained by any substantial differences in extent of disease or treatment delivered.
Collapse
Affiliation(s)
- J S Quirt
- Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute
| | - S Nanji
- The departments of Oncology, Queen's University, Kingston, ON.; Surgery, Queen's University, Kingston, ON
| | - X Wei
- Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute
| | - J A Flemming
- Medicine, Queen's University, Kingston, ON.; Public Health Sciences, Queen's University, Kingston, ON
| | - C M Booth
- Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute; The departments of Oncology, Queen's University, Kingston, ON.; Medicine, Queen's University, Kingston, ON.; Public Health Sciences, Queen's University, Kingston, ON
| |
Collapse
|
|
37
|
Gender-related significance of time interval between radiotherapy and surgery in hypofractionated preoperative radiotherapy for rectal cancer patients' survival. Rep Pract Oncol Radiother 2016; 21:174-80. [PMID: 27601947 DOI: 10.1016/j.rpor.2016.01.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 10/30/2015] [Accepted: 01/21/2016] [Indexed: 11/24/2022] Open
Abstract
AIM AND BACKGROUND An optimal break between radiotherapy (RT) and surgery in short-course of RT (SCRT) for locally advanced rectal cancer is not clearly established. The aim of the study was to investigate the influence of the break in the preoperative SCRT and overall treatment time (OTT) for locally advanced rectal cancer patients (whole group and male/female subgroups) on patients overall survival (OS), recurrence-free survival (RFS), metastasis-free survival (MFS). MATERIALS AND METHODS 131 patients were treated with SCRT (5 Gy/5 days), followed by surgery 3-53 days later. Break was calculated as the time interval between the end of irradiation to surgery and OTT as time interval from the beginning of RT to surgery. RESULTS Mean break was 21.5 (range 3-53.0) days and mean OTT was 26.5 (range 7-58.0) days. In univariate analysis, a break longer than 15 days and OTT >23 days were negative prognostic factors for OS for all patients, and particularly for the male patients' subgroup. RFS was non-significantly higher (P = 0.066) for patients treated with a break ≤15 days and OTT ≤23 days (P = 0.099), irrespectively of patients' sex. Patients treated with a break longer than 15 days and OTT >23 days had non-significantly lower level of MFS than those treated with a shorter break (P = 0.269) and OTT ≤23 days (P = 0.498). CONCLUSION In SCRT, a break in the treatment longer than 15 days, especially in the male patients subgroup, should be avoided, because it negatively affects patients' survival.
Collapse
|
|
38
|
Oberoi DV, Jiwa M, McManus A, Parsons R. Do Men Know Which Lower Bowel Symptoms Warrant Medical Attention? A Web-Based Video Vignette Survey of Men in Western Australia. Am J Mens Health 2016; 10:474-486. [DOI: 10.1177/1557988315574739] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
The current study aims to explor how men would advise other men about seeking help for lower bowel symptoms and also to determine the factors that may influence help seeking. A purposive sample of Western Australian men aged 18 years and older was recruited for the study. Participants completed 8 of the 28 randomly assigned video vignettes (video clips) displaying men (older or younger) with various combinations of one or more lower bowel symptoms. Participants were asked if the person in the vignette should seek health advice. Subsequently, the participants answered a set of questions based on the Health Belief Model. A total of 408 participants (response rate = 51%) answered 3,264 vignettes. Participants younger than 50 years, participants who were not tertiary educated and those who had lower incomes, or those living in regional or remote areas were less likely to advise help seeking from general practitioner (GP). Participants who visited their general practitioner less frequently were also less likely to advisehelp seeking. There was a trend to consider unintentional weight loss and diarrhea as minor symptoms not necessitating medical attention compared with rectal bleeding. The findings suggest for a need to improve public awareness among men about the need to seek timely medical advice for lower bowel symptoms in primary care. The importance of early presentation of persistent lower bowel symptoms must be specifically targeted at men younger than 50 years, those with lower incomes, or residing in regional or remote areas.
Collapse
Affiliation(s)
| | - Moyez Jiwa
- Curtin University, Bentley, Western Australia, Australia
| | | | | |
Collapse
|
|
39
|
Body mass index and colorectal cancer prognosis: a systematic review and meta-analysis. Tech Coloproctol 2016; 20:517-35. [PMID: 27343117 DOI: 10.1007/s10151-016-1498-3] [Citation(s) in RCA: 96] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2016] [Accepted: 05/18/2016] [Indexed: 02/07/2023]
Abstract
Colorectal cancer is one of the most common cancers worldwide. However, it is unclear what influence body mass index (BMI) has on colorectal cancer prognosis. We conducted a systematic review and meta-analysis of observational studies to examine the association of BMI with colorectal cancer outcomes. We searched MEDLINE and EMBASE databases from inception to February 2015 and references of identified articles. We selected observational studies that reported all-cause mortality, colorectal cancer-specific mortality, recurrence and disease-free survival according to BMI category. Random-effects meta-analyses were conducted to combine estimates. We included 18 observational studies. Obese patients had an increased risk of all-cause mortality [relative risk (RR) 1.14; 95 % confidence interval (CI) 1.07-1.21], cancer-specific mortality (RR 1.14; 95 % CI 1.05-1.24), recurrence (RR 1.07; 95 % CI 1.02-1.13) and worse disease-free survival (RR 1.07; 95 % CI 1.01-1.13). Underweight patients also had an increased risk of all-cause mortality (RR 1.43; 95 % CI 1.26-1.62), cancer-specific mortality (RR 1.50; 95 % CI 1.20-1.87), recurrence (RR 1.13; 95 % CI 1.05-1.21) and worse disease-free survival (RR 1.27; 95 % CI 1.13-1.43). Overweight patients had no increased risk for any of the outcomes studied. Both obese and underweight patients with colorectal cancer have an increased risk of all-cause mortality, cancer-specific mortality, disease recurrence and worse disease-free survival compared to normal weight patients.
Collapse
|
|
40
|
Kleemann M, Benecke C, Helfrich D, Bruch HP, Keck T, Laubert T. Prospective Analysis of More than 1,000 Patients with Rectal Carcinoma: Are There Gender-Related Differences? VISZERALMEDIZIN 2015; 30:118-24. [PMID: 26288586 PMCID: PMC4513819 DOI: 10.1159/000362680] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Background Since the beginning of the new millennium gender medicine has become more and more relevant. The goal has been to unveil differences in presentation, treatment response, and prognosis of men and women with regard to various diseases. Methods This study encompassed 1,061 patients who underwent surgery for rectal cancer at the Department of Surgery, University Medical Center Schleswig-Holstein Campus Lübeck, Germany, between January 1990 and December 2011. Prospectively documented demographic, clinical, pathological, and follow-up data were obtained. Analysis encompassed the comparison of clinical, histopathological, and oncological parameters with regard to the subcohorts of male and female patients. Results No statistically significant differences could be found for clinical and histopathological parameters, location of tumor, resection with or without anastomosis, palliative or curative treatment, conversion rates, duration of surgery, and long-term survival. For the entire cohort, gender-related statistically significant differences in complications encompassed anastomotic leakage, burst abdomen, pneumonia, and urinary tract complications all of which occurred more often in men. Conclusion Data obtained in this study suggest that there are no gender-related differences in the oncologic surgical treatment of patients with rectal carcinoma. However, male sex seems to be a risk factor for increased early postoperative morbidity.
Collapse
Affiliation(s)
- Markus Kleemann
- Department of Surgery, University Hospital Schleswig-Holstein, Campus Lübeck, Berlin, Germany
| | - Claudia Benecke
- Department of Surgery, University Hospital Schleswig-Holstein, Campus Lübeck, Berlin, Germany
| | - Diana Helfrich
- Lübeck Medical School, University of Lübeck, Berlin, Germany
| | - Hans-Peter Bruch
- Berufsverband der Deutschen Chirurgen e.V. (BDC), Berlin, Germany
| | - Tobias Keck
- Department of Surgery, University Hospital Schleswig-Holstein, Campus Lübeck, Berlin, Germany
| | - Tilman Laubert
- Department of Surgery, University Hospital Schleswig-Holstein, Campus Lübeck, Berlin, Germany
| |
Collapse
|
|
41
|
Gender differences in colorectal cancer survival in Japan. Int J Clin Oncol 2015; 21:194-203. [PMID: 26150258 DOI: 10.1007/s10147-015-0868-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Accepted: 06/22/2015] [Indexed: 01/05/2023]
Abstract
BACKGROUND A gender difference in survival has been documented in colorectal cancer (CRC) patients, although the underlying mechanism remains undefined. This study aimed to gain improved insight into this difference, with a special focus on improved cancer-specific survival. METHODS The study population consisted of 82,402 patients with invasive CRC who had undergone surgery in Japan between 1985 and 2004. To estimate improved survival, multivariate adjustment using patient demographics and tumor characteristics was performed. RESULTS Patient characteristics changed over time. The 5-year survival rates increased from 66.5 to 76.3 % during the study period. Higher survival rates persisted in women over time (multivariate-adjustment model-hazard ratio [HR] 0.87, 95 % confidence interval [CI] 0.85-0.90). Patients who received surgery during the period 2000-2004 had significantly longer survival than those during the period 1985-1989 (men: HR 0.70, 95 % CI 0.67-0.74; women: HR 0.72, 95 % CI 0.67-0.76). However, there was no gender difference regarding improved survival. CONCLUSIONS A reduced risk of cancer-specific death for women relative to men persisted over time; however, enhancement of survival was equally observed in both genders. Identification of factors associated with gender differences and changes over time in CRC survival may serve as targets for further improvement.
Collapse
|
|
42
|
Yuan J, Wang L, Lin Y, Chen J, Hu J. Differences of plasma IL-1 and TNF-α in healthy Chinese Population. Open Med (Wars) 2015; 10:306-310. [PMID: 28352710 PMCID: PMC5152990 DOI: 10.1515/med-2015-0044] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2014] [Accepted: 05/13/2015] [Indexed: 11/15/2022] Open
Abstract
Pleiotropic proinflammatory cytokines, interleukin- 1 (IL-1) and tumor necrosis factor-α (TNF-α), involved in the regulations of various immune responses, inflammatory processes and hematopoiesis. In the present study, the expression levels of IL-1 and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA). Following the cytokine blockade as a successful clinical therapy for autoimmune diseases such as rheumatoid arthritis, the patients are more susceptible to a variety of opportunistic infections. IL-1 and TNF-α may be useful predictive biomarkers of diseases and offer potential targets for therapeutic intervention of inflammatory diseases. However, our results showed that the plasma IL-1 level was significantly higher in women compared to men (69.5 ± 19.8 pg/ml in men and 80.1 ± 19.5 pg/ml in women, respectively); the plasma levels of TNF-α were higher in men than women (20.8 ± 4.9 pg/ml and 18.7 ± 7.1 pg/ml, respectively). The significant gender difference of plasma interleukin-1 (IL-1) and TNF-α levels present in healthy adults in Jiangsu Province, China (P=0.002 and P=0.015, respectively), and may be as a hint for sex differences of susceptibility to many diseases and elementary immune response.
Collapse
Affiliation(s)
- Jintao Yuan
- Danyang People's Hospital of Jiangsu Province, 2 Xinmin West Road, Danyang, 212300, China, Tel.: +86 511 86523551; Danyang affiliated Hospital with Nantong University, Danyang, Jiangsu 212300, China
| | - Lan Wang
- Danyang Blood Center of Jiangsu Province, Danyang, Jiangsu 212300, China
| | - Yijin Lin
- Danyang People's Hospital of Jiangsu Province, Danyang, Jiangsu 212300, China. Danyang affiliated Hospital with Nantong University, Danyang, Jiangsu 212300, China
| | - Jianhong Chen
- Danyang People's Hospital of Jiangsu Province, Danyang, Jiangsu 212300, China. Danyang affiliated Hospital with Nantong University, Danyang, Jiangsu 212300, China
| | - Jianghong Hu
- Danyang People's Hospital of Jiangsu Province, Danyang, Jiangsu 212300, China. Danyang affiliated Hospital with Nantong University, Danyang, Jiangsu 212300, China
| |
Collapse
|
|
43
|
Lydrup ML, Höglund P. Gender aspects of survival after surgical treatment for rectal cancer. Colorectal Dis 2015; 17:390-6. [PMID: 25510408 DOI: 10.1111/codi.12871] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Accepted: 10/02/2014] [Indexed: 02/08/2023]
Abstract
AIM Longer survival in women than men after rectal cancer surgery has been reported. Our hypothesis was that after correction for their longer life expectancy a survival benefit for women would still remain. METHOD We studied 2792 patients diagnosed with rectal cancer in the southern part of Sweden between 1996 and 2006. The following parameters were included in a prespecified multivariable Cox regression analysis: age at diagnosis, gender, preoperative radiotherapy, stage, year and type of surgery. In addition to overall survival, relative survival was calculated using the Hakulinen approach utilizing an age-, gender- and calendar year-matched Swedish control cohort. RESULTS Female patients were significantly older, received neoadjuvant treatment less often and were more often operated on by local excision. Overall survival was significantly longer in women. In the multivariable analysis of relative survival, controlling for neoadjuvant treatment, Dukes stage and year and type of surgery, no significant effect of gender [hazard ratio (HR) 1.10 for men, P = 0.114] was found, whereas an improved relative survival with increased age (HR 0.96 per year, P < 0.001) was seen. In contrast, using the same multivariable model with no correction for underlying mortality in the population, male gender (HR 1.38, P < 0.001) and greater age (HR 1.05 per year, P < 0.001) increased the risk of death. CONCLUSION The results show that after correction for the underlying longer survival in women and some known confounders, survival after surgical treatment for rectal cancer appears to be gender neutral.
Collapse
Affiliation(s)
- M-L Lydrup
- Division of Surgery, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden
| | | |
Collapse
|
|
44
|
Abstract
PURPOSE Research suggests that recurrence and survival from colorectal cancer are worse in men than in women but the causes for this are unclear. Our aims were to (1) assess for sex differences in colorectal cancer screening (CRCS) within a large, contemporary population-based sample in California; and (2) examine the impact of income, education, and insurance status on sex differences in CRCS. METHODS Screening-eligible patients were identified from the 2007 US California Health Interview Survey. Up-to-date, CRCS was defined as fecal occult blood test within 1 year, flexible sigmoidoscopy within 5 years, or colonoscopy within 10 years. Logistic regression models were constructed to evaluate the relationship between sex and CRCS. Stratified analyses on the basis of self-reported income (low vs. high), education (≤ high school vs. > high school), and health insurance status (insured vs. uninsured) were performed to determine if sex differences in screening were modified by these parameters. RESULTS In total, 11,260 men and 17,705 women were identified: mean ages were 65 and 66 years, respectively, and 63% were white in both the sexes. In the entire cohort, only two thirds of men and women reported undergoing up-to-date CRCS. Women had decreased odds of CRCS than men, after adjusting for potential confounders. Stratified analyses indicated that sex disparities in CRCS persisted among the insured, educated, and high-income earners. CONCLUSIONS Women are less likely to undergo CRCS than men, but poor health care access is associated with low CRCS in both the sexes. Conventional strategies aimed at improving health care access should also include sex-specific interventions that raise awareness about preventive care to most effectively optimize CRCS.
Collapse
|
|
45
|
Oberoi DV, Jiwa M, McManus A, Hodder R, de Nooijer J. Help-seeking experiences of men diagnosed with colorectal cancer: a qualitative study. Eur J Cancer Care (Engl) 2014; 25:27-37. [PMID: 25521505 DOI: 10.1111/ecc.12271] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/27/2014] [Indexed: 01/12/2023]
Abstract
Advanced-stage diagnosis of colorectal cancer (CRC) leads to poor prognosis and reduced survival rates. The current study seeks to explore the reasons for diagnostic delays in a sample of Australian men with CRC. Semi-structured interviews were conducted in a purposive sample of 20 male CRC patients. Data collection ceased when no new data emerged. Interviews were audiotaped, transcribed and thematically analysed using Andersen's Model of Total Patient Delay as the theoretical framework. Most participants (18/20) had experienced lower bowel symptoms prior to diagnosis. Patient-related delays were more common than delays attributable to the health-care system. Data regarding patient delays fit within the first four stages of Andersen's model. The barriers to seeking timely medical advice were mainly attributed to misinterpretation of symptoms, fear of cancer diagnosis, reticence to discuss the symptoms or consulting a general practitioner. Treatment delays were a minor cause for delayed diagnosis. Delay in referral and scheduling for colonoscopy were among the system-delay factors. In many instances, delays resulted from men's failure to attribute their symptoms to cancer and, subsequently, delay in diagnosis.
Collapse
Affiliation(s)
- D V Oberoi
- Faculty of Health Sciences, Curtin University, Bentley, Western Australia, Australia
| | - M Jiwa
- Faculty of Health Sciences, Curtin University, Bentley, Western Australia, Australia
| | - A McManus
- Faculty of Health Sciences, Curtin University, Bentley, Western Australia, Australia
| | - R Hodder
- Department of General Surgery, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - J de Nooijer
- Faculty of Health Sciences, Maastricht University, Maastricht, the Netherlands
| |
Collapse
|
|
46
|
Wang Y, Freemantle N, Nazareth I, Hunt K. Gender differences in survival and the use of primary care prior to diagnosis of three cancers: an analysis of routinely collected UK general practice data. PLoS One 2014; 9:e101562. [PMID: 25014510 PMCID: PMC4094390 DOI: 10.1371/journal.pone.0101562] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 06/06/2014] [Indexed: 01/13/2023] Open
Abstract
Objective To explore whether there are gender differences in the number of GP recorded cases, the probability of survival and consulting pattern prior to diagnosis amongst patients with three non-sex-specific cancers. Design Cross sectional study. Setting UK primary care. Subjects 12,189 patients aged 16 years or over diagnosed with colorectal cancer (CRC), 11,081 patients with lung cancer and 4,352 patients with malignant melanoma, with first record of cancer diagnosis during 1997–2006. Main outcome measures Cancer cases recorded in primary care; probability of survival following diagnosis; and number of GP contacts within the 24 months preceding diagnosis. Results From 1997–2006, overall rates of GP recorded CRC and lung cancer cases recorded were higher in men than in women, but rates of malignant melanoma were higher in women than in men. Gender differences in survival were small; 49% of men and 53% of women survived at least 5 years following CRC diagnosis; 9% of men and 12% of women with lung cancer, and 77% of men and 86% of women with malignant melanoma. The adjusted male to female relative hazard ratio of death in all patients was 1.20 (95%CI 1.13–1.30), 1.24 (95%CI 1.16–1.33) and 1.73 (95%CI 1.51–2.00) for CRC, lung cancer and malignant melanoma respectively. However, gender differences in the relative risk were much smaller amongst those who died during follow-up. For each cancer, there was little evidence of gender difference in the percentage who consulted and the number of GP contacts made within 24 months prior to diagnosis. Conclusions This study found that patterns of consulting prior to cancer diagnosis differed little between two genders, providing no support for the hypothesis that gender differences in survival are explained by gender differences in consultation for more serious illness, and suggests the need for a more critical view of gender and consultation.
Collapse
Affiliation(s)
- Yingying Wang
- MRC|CSO Social & Public Health Science Unit, University of Glasgow, Glasgow, United Kingdom
- * E-mail:
| | - Nick Freemantle
- Department of Primary Care and Population Health, University College London, London, United Kingdom
| | - Irwin Nazareth
- Department of Primary Care and Population Health, University College London, London, United Kingdom
| | - Kate Hunt
- MRC|CSO Social & Public Health Science Unit, University of Glasgow, Glasgow, United Kingdom
| |
Collapse
|
|
47
|
Liang Y, Tang W, Huang T, Gao Y, Tan A, Yang X, Zhang H, Hu Y, Qin X, Li S, Zhang S, Mo L, Liang Z, Shi D, Huang Z, Guan Y, Zhou J, Winkler C, O'Brien SJ, Xu J, Mo Z, Peng T. Genetic variations affecting serum carcinoembryonic antigen levels and status of regional lymph nodes in patients with sporadic colorectal cancer from Southern China. PLoS One 2014; 9:e97923. [PMID: 24941225 PMCID: PMC4062418 DOI: 10.1371/journal.pone.0097923] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2013] [Accepted: 04/27/2014] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications. METHODS AND FINDINGS Genome-wide association study (GWAS) was conducted in a cohort study with 4,346 healthy male adults using the Illumina Omni 1 M chip. Candidate SNPs associated with elevated sCEA levels were validated in 194 CRC patients on ABI Taqman platform. Eight candidate SNPs were validated in CRC patients. The rs1047781 (chr19- FUT2) (A/T) was associated with elevated sCEA levels, and rs8176746 (chr9- ABO) was associated with the regional lymph metastasis in the CRC patients. The preoperative sCEA level was a risk factor for tumor recurrence in 5 years after operation (OR = 1.427, 95% CI: 1.005∼1.843, P = 0.006). It was also one of the risk factors for regional lymph node metastasis (OR = 2.266, 95% CI: 1.196∼4.293, P = 0.012). The sCEA level in rs1047781-T carriers was higher than that in the A carriers in CRC patients without lymph node metastasis (P = 0.006). The regional lymph node metastasis in patients with homozygote AA of rs8176746 was more common than that in the heterozygote AG carriers (P = 0.022). In addition, rs1047781-AT and TT CRC patients exhibited a worse disease-free survival than AA genotype carriers (P = 0.023). CONCLUSIONS We found candidate SNPs associated with elevated sCEA levels in both healthy males and CRC population. Rs1047781 (chr19- FUT2) may be the susceptible locus for recurrence of CRC in a population from Southern China.
Collapse
Affiliation(s)
- Yu Liang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Weizhong Tang
- Department of Anal and colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Tiqiang Huang
- Department of Anal and colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Yong Gao
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Aihua Tan
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Xiaobo Yang
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Haiying Zhang
- Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Yanling Hu
- Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Xue Qin
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Shan Li
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Shijun Zhang
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Linjian Mo
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
- Institute of Urology and Nephrology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Zhenjia Liang
- Medical Examination Center, Fangchenggang First People's Hospital, Fangchenggang, Guangxi, People's Republic of China
| | - Deyi Shi
- Medical Examination Center, Fangchenggang First People's Hospital, Fangchenggang, Guangxi, People's Republic of China
| | - Zhang Huang
- Medical Examination Center, Guigang First People's Hospital, Guigang, Guangxi, People's Republic of China
| | - Yingyong Guan
- Medical Examination Center, Yulin First People's Hospital, Yulin, Guangxi, People's Republic of China
| | - Jicheng Zhou
- Department of Hematology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Cheryl Winkler
- Molecular Genetics Epidemiology Sec., Frederick Nat. Lab for Cancer Research, National Cancer Institute, NIH, Frederick, Maryland, United States of America
| | - Stephen J. O'Brien
- Laboratory of Genomic Diversity, National Cancer Institute, NIH, Frederick, Maryland, United States of America
- Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg, Russia
- Oceanographic Center, Nova Southeastern University, Ft. Lauderdale, Florida, United States of America
| | - Jianfeng Xu
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
- Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America
| | - Zengnan Mo
- Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
- Institute of Urology and Nephrology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
- * E-mail: (TP); (ZM)
| | - Tao Peng
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
- Laboratory of Genomic Diversity, National Cancer Institute, NIH, Frederick, Maryland, United States of America
- * E-mail: (TP); (ZM)
| |
Collapse
|
|
48
|
Ung L, Chua TC, Morris DL. The importance of gender in patients with peritoneal metastases of appendiceal origin treated by cytoreduction and intraperitoneal chemotherapy: an analysis of 257 consecutive patients from an Australian centre. J Cancer Res Clin Oncol 2014; 140:1037-45. [PMID: 24652408 DOI: 10.1007/s00432-014-1633-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Accepted: 02/28/2014] [Indexed: 10/25/2022]
Abstract
BACKGROUND AND OBJECTIVES In the setting of colorectal cancer, female gender has been associated with superior long-term outcomes. Our aim is to investigate the gender differences for metastatic epithelial neoplasms of the appendix treated by cytoreductive surgery (CS) and intraperitoneal chemotherapy (IPC). METHODS The survival outcomes of patients treated with CS/IPC from 1996 to 2013 at St. George Hospital, Sydney, Australia, for peritoneal metastases of appendiceal origin were retrospectively analysed. RESULTS Two hundred and fifty-seven consecutive patients were followed for a median of 35.3 months. Baseline characteristics between genders were comparable, including age (p = 0.13) and peritoneal cancer index (p = 0.94). Median overall survival (OS) and progression-free survival (PFS) was not reached (NR) and 44.4 months, with a 3-, 5- and 10-year survival of 82, 74 and 64 %. OS and PFS for females was NR and 50.7 months, compared to NR (p = 0.007) and 31.5 months for males (p = 0.07). Three-, 5- and 10-year survival rates for females were 88, 84 and 72 % compared to 74, 61 and 53 % for males. CONCLUSION Observed gender differences for neoplasms of the appendix may direct future research in gender-specific tumour markers and the development of adjuvant therapies to improve patient outcomes.
Collapse
Affiliation(s)
- Lawson Ung
- Hepatobiliary and Surgical Oncology Unit, UNSW Department of Surgery, St George Hospital, Kogarah, Sydney, NSW, 2217, Australia
| | | | | |
Collapse
|
|
49
|
Warren RS, Atreya CE, Niedzwiecki D, Weinberg VK, Donner DB, Mayer RJ, Goldberg RM, Compton CC, Zuraek MB, Ye C, Saltz LB, Bertagnolli MM. Association of TP53 mutational status and gender with survival after adjuvant treatment for stage III colon cancer: results of CALGB 89803. Clin Cancer Res 2013; 19:5777-87. [PMID: 23983256 DOI: 10.1158/1078-0432.ccr-13-0351] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE The TP53 tumor suppressor is frequently mutated in colon cancer, but the influence of such mutations on survival remains controversial. We investigated whether mutations in the DNA-binding domain of TP53 are associated with survival in stage III colon cancer. EXPERIMENTAL DESIGN The impact of TP53 genotype was prospectively evaluated in Cancer and Leukemia Group B 89803, a trial that randomized stage III colon cancer patients to receive adjuvant 5-fluorouracil/leucovorin (5FU/LV) or 5FU/LV with irinotecan (IFL). RESULTS TP53 mutations were identified in 274 of 607 cases. The presence of any TP53 mutation did not predict disease-free survival (DFS) or overall survival with either adjuvant regimen when men and women were considered together or as separate groups. However, outcome differences among women became apparent when tumor TP53 genotype was stratified as wild-type versus zinc- or non-zinc-binding mutations in the TP53 DNA-binding domain. DFS at 5 years was 0.59, 0.52, and 0.78 for women with TP53 wild-type tumors, and tumors with zinc- or non-zinc-binding mutations, respectively. Survival at 5 years for these same women was 0.72, 0.59, and 0.90, respectively. No differences in survival by TP53 genotype were observed in men. CONCLUSIONS The presence of any TP53 mutation within the DNA-binding domain did not predict survival in stage III colon cancer. However, TP53 genotype was predictive of survival in women following adjuvant therapy. Future colon cancer therapeutic trials, with inclusion of correlative molecular markers, should be designed to permit evaluation of survival and/or response to treatment in women separately from men.
Collapse
Affiliation(s)
- Robert S Warren
- Authors' Affiliations: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California; Department of Biostatistics and Bioinformatics, Alliance Statistics and Data Center, Duke University Medical Center, Durham, North Carolina; Dana-Farber Cancer Institute; Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts; The Ohio State University, Columbus, Ohio; National Cancer Institute, Bethesda, Maryland; and Memorial Sloan-Kettering Cancer Center, New York, New York
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Majek O, Gondos A, Jansen L, Emrich K, Holleczek B, Katalinic A, Nennecke A, Eberle A, Brenner H, the GEKID Cancer Survival Working Group. Sex differences in colorectal cancer survival: population-based analysis of 164,996 colorectal cancer patients in Germany. PLoS One 2013; 8:e68077. [PMID: 23861851 PMCID: PMC3702575 DOI: 10.1371/journal.pone.0068077] [Citation(s) in RCA: 116] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Accepted: 05/26/2013] [Indexed: 12/15/2022] Open
Abstract
Risk of colorectal cancer (CRC) is considerably higher in men compared to women; however, there is inconclusive evidence of sex differences in CRC prognosis. We aimed to assess and explain sex differences in 5-year relative survival using standard and model-based period analysis among 164,996 patients diagnosed with CRC from 1997 to 2006 and reported to 11 German cancer registries covering a population of 33 million inhabitants. Age-adjusted 5-year relative survival was higher in women (64.5% vs. 61.9%, P<0.0001). A substantial survival advantage of women was confirmed in multivariate analysis after adjusting for CRC stage and subsite in subjects under 65 years of age (relative excess risk, RER 0.86, 95% CI 0.82-0.90), but not in older subjects (RER 1.01, 95% CI 0.98-1.04); this pattern was similar in the 1st and in the 2nd to 5th year after diagnosis. The survival advantage of women varied by CRC stage and age and was most pronounced for localized disease (RERs 0.59-0.88 in various age subgroups) and in patients under 45 years of age (RERs 0.59, 0.72 and 0.76 in patients with localized, regional or advanced disease, respectively). On the contrary, sex differences in survival did not vary by location of CRC. In conclusion, our large population-based study confirmed a survival advantage of female compared to male CRC patients, most notably in young and middle aged patients and patients with localized disease. The effect of sex hormones, either endogenous or through hormonal replacement therapy, might be the most plausible explanation for the observed patterns.
Collapse
Affiliation(s)
- Ondrej Majek
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
- Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic
| | - Adam Gondos
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Lina Jansen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | - Katharina Emrich
- Cancer Registry of Rhineland-Palatinate, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
| | | | - Alexander Katalinic
- Cancer Registry of Schleswig-Holstein, Institute of Cancer Epidemiology, University of Lübeck, Lübeck, Germany
| | - Alice Nennecke
- Hamburg Cancer Registry, Ministry for Health and Consumer Protection, Hamburg, Germany
| | - Andrea Eberle
- Cancer Registry of Bremen, Leibniz-Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
| | | |
Collapse
|