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Ren J, Tang C, Wang J, Wang Y, Yang D, Sheng J, Zhu S, Liu Y, Li X, Liu W. Association of overweight/obesity and digestive system cancers: A meta-analysis and trial sequential analysis of prospective cohort studies. PLoS One 2025; 20:e0318256. [PMID: 40168281 PMCID: PMC11960891 DOI: 10.1371/journal.pone.0318256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 01/14/2025] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND Previous researches have reported correlations between overweight/obesity and common digestive system cancers (DSCs), including gastric, liver, esophageal, colorectal, and pancreatic cancers. However, the inconsistency in defining overweight/obesity and the risk of recall bias from case-control and retrospective cohort studies may influence existing results. Therefore, we aimed to validate the relationship between overweight/obesity and common DSCs by combining prospective cohort studies based on the World Health Organization (WHO) criteria for defining overweight/obesity. METHODS A comprehensive literature search was conducted across PubMed, Embase, Web of Science, and Cochrane databases, covering all publications up to February 7, 2024. The inclusion criteria focused on prospective cohort studies that examined the link between overweight/obesity and risks of DSCs. R software 4.1.3 and STATA 12 were utilised to calculate the relative risk (RR), with 95% confidence interval (CI) and prediction interval (PI). TSA v0.9.5.10 Beta software was used for trial sequential analysis (TSA). RESULTS The meta-analysis encompassed 39 articles. The overall analysis showed that compared with normal weight, overweight/obesity increased the risks of liver cancer (overweight: RR [95% CI] = 1.237 [1.112-1.377]; 95% PI: 0.888-1.725; obesity: RR [95% CI] = 1.642 [1.466-1.839]; 95% PI: 1.143-2.358) and colorectal cancer (overweight: RR [95% CI] = 1.124 [1.056-1.197]; 95% PI: 0.931-1.357; obesity: RR [95% CI] = 1.366 [1.242-1.503]; 95% PI: 0.959-1.945) in the total population. Subgroup analysis revealed that overweight (RR [95% CI] = 1.237 [1.165-1.314]; 95% PI: 1.154-1.327) and obesity (RR [95% CI] = 1.306 [1.152-1.480]; 95% PI: 1.108-1.539) were associated with an increased risk of pancreatic cancer only in women, and overweight also increased the gastric cancer risk of women (RR [95% CI] = 1.041 [1.013-1.070], 95% PI: 0.806-1.230). No significant association of overweight/obesity and esophageal cancer was observed in both male and female. CONCLUSION Our study suggested that overweight/obesity elevated the risks of liver and colorectal cancer in both men and women. No significant association was found between overweight/obesity and the risk of developing esophageal cancer. Clinicians are advised to consider weight control as an effective measure for preventing pancreatic, liver, and colorectal cancers.
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Affiliation(s)
- Ji Ren
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Chunyan Tang
- Department of Nursing, Dezhou Municipal Hospital (Dezhou University Affiliated Hospital), Dezhou, China
| | - Jinghe Wang
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Yanan Wang
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Dongying Yang
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Jianming Sheng
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Shili Zhu
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Yunli Liu
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Xiaoqi Li
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Wei Liu
- Department of Medicine and Health, Dezhou University, Dezhou, China
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Liu YQ, Chen F, Zhang F, Ye YM, Su YJ, Liu YT, Leng YF. New insights into tRNA-derived small RNAs in human digestive diseases. Mol Biol Rep 2025; 52:295. [PMID: 40063289 DOI: 10.1007/s11033-025-10393-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 02/25/2025] [Indexed: 05/13/2025]
Abstract
tRNA-derived small RNAs (tsRNAs) is a type of non-coding RNA that is present in large quantities in humans and exhibits high stability. It plays a crucial role in various physiological processes and diseases. In recent years, research on tsRNAs in tumors has expanded significantly, revealing its regulatory effects in non-neoplastic diseases as well. Additionally, tsRNAs has been extensively studied in the context of digestive system diseases, encompassing both digestive system tumors and non-tumor conditions. It is believed to influence the biological characteristics of diseases as well as clinical pathological features. Given its potential, tsRNAs is anticipated to have broad applications in disease diagnosis and prognosis prediction, and it is expected to emerge as a new class of biomarkers. Nevertheless, numerous issues remain that require in-depth discussion. This article presents an overview of the characteristics and roles of tsRNAs in digestive system diseases, aiming to provide a comprehensive perspective and to inspire new ideas for the diagnosis and treatment of these conditions.
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Affiliation(s)
- Yong-Qiang Liu
- The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, GanSu Province, China
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, 730000, GanSu Province, China
| | - Feng Chen
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, 730000, GanSu Province, China
| | - Fa Zhang
- Department of Urology, Gansu Provincial Hospital, Lanzhou, Gansu, China
| | - Yuan-Mei Ye
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, 730000, GanSu Province, China
| | - Yu-Jie Su
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, 730000, GanSu Province, China
| | - Ya-Tao Liu
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, 730000, GanSu Province, China
| | - Yu-Fang Leng
- The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, GanSu Province, China.
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, 730000, GanSu Province, China.
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Tanaka T, Wehby G, Vander Weg M, Mueller K, Axelrod D. US Population Size and Outcomes of Adults on Liver Transplant Waiting Lists. JAMA Netw Open 2025; 8:e251759. [PMID: 40131274 PMCID: PMC11937946 DOI: 10.1001/jamanetworkopen.2025.1759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 01/22/2025] [Indexed: 03/26/2025] Open
Abstract
Importance Disparities in organ supply and demand led to geographic inequities in the score-based liver transplant (LT) allocation system, prompting a change to allocation based on acuity circles (AC) defined by fixed distances. However, fixed distances do not ensure equivalent population size, potentially creating new sources of disparity. Objective To estimate the association between population size around LT centers and waiting list outcomes for critically ill patients with chronic end-stage liver disease and high Model for End-stage Liver Disease (MELD) scores or acute liver failure (ALF). Design, Setting, and Participants This US nationwide retrospective cohort study included adult (aged ≥18 years) candidates for deceased donor LT wait-listed between June 18, 2013, and May 31, 2023. Follow-up was completed June 30, 2023. Participants were divided into pre-AC and post-AC groups. Exposure Population size within defined radii around each LT center (150 nautical miles [nm] for participants with high MELD scores and 500 nm for those with ALF) based on AC allocation policy. Main Outcomes and Measures LT candidate waiting list mortality and dropout rate were analyzed using generalized linear mixed-effect models with random intercepts for center and listing date before and after AC implementation. Fine-Gray competing risk regression, accounting for clustering, was used as a secondary model. Results The study analyzed 6142 LT candidates (1581 with ALF and 4561 with high MELD scores) during the pre-AC era and 4344 candidates (749 with ALF and 3595 with high- MELD scores) in the post-AC era, for a total of 10 486 participants (6331 male [60.5%]; mean [SD] age, 48.5 [7.1] years). In the high-MELD cohort, being listed at a center in the lowest tertile of population size was associated with increased waiting list mortality in the AC era (adjusted odds ratio [AOR], 1.68; 95% CI, 1.14-2.46). Doubling of the population size was associated with a 34% reduction in the odds of mortality or dropout (AOR, 0.66; 95% CI, 0.49-0.90). These results were consistent with those of the extended Fine-Gray models and were also corroborated by multiple sensitivity analyses. However, there were no significant population density-associated disparities in the ALF cohort. Conclusions and Relevance In this retrospective nationwide cohort study, being wait-listed in less populated regions was associated with greater mortality among critically ill LT candidates with high MELD scores, underscoring the limitations of allocation systems based purely on fixed distances.
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Affiliation(s)
- Tomohiro Tanaka
- Division of Gastroenterology and Hepatology, University of Iowa Carver College of Medicine, Iowa City
- Department of Health Management and Policy, College of Public Health, University of Iowa, Iowa City
- Center for Access & Delivery Research and Evaluation, Iowa City Veterans Affairs Health Care System, Iowa City, Iowa
| | - George Wehby
- Department of Health Management and Policy, College of Public Health, University of Iowa, Iowa City
- Center for Access & Delivery Research and Evaluation, Iowa City Veterans Affairs Health Care System, Iowa City, Iowa
- Department of Economics, University of Iowa, Iowa City
- National Bureau of Economic Research, Cambridge, Massachusetts
| | - Mark Vander Weg
- Center for Access & Delivery Research and Evaluation, Iowa City Veterans Affairs Health Care System, Iowa City, Iowa
- Department of Community and Behavioral Health, College of Public Health, University of Iowa, Iowa City
| | - Keith Mueller
- Department of Health Management and Policy, College of Public Health, University of Iowa, Iowa City
| | - David Axelrod
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City
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Christakoudi S, Tsilidis KK, Gunter MJ, Riboli E. Prospective Associations of Body Composition and Body Shape With the Risk of Developing Pancreatic Cancer in the UK Biobank Cohort. Cancer Med 2025; 14:e70809. [PMID: 40129249 PMCID: PMC11933721 DOI: 10.1002/cam4.70809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 11/18/2024] [Accepted: 03/11/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Obesity and diabetes are positively associated with pancreatic cancer risk. It is unclear, however, whether fat or fat-free mass plays a role in these relationships, whether abdominal obesity is more important than general obesity or whether the associations with anthropometric indices and diabetes are independent of each other. METHODS We used multivariable Cox proportional hazards models to examine the prospective associations of body composition (allometric fat-mass index (AFI) and allometric lean-mass index (ALI), based on bioelectrical impedance, uncorrelated with each other and with height), waist size (allometric waist-to-hip index (WHI), uncorrelated with weight and height) and diabetes with pancreatic cancer risk in UK Biobank. We tested heterogeneity by sex, age and follow-up time with the augmentation method (p_het). RESULTS During a mean follow-up of 10.4 years, 999 pancreatic cancer cases were ascertained in 427,939 participants. AFI was positively associated with pancreatic cancer risk in participants overall, independent of ALI, WHI, diabetes and covariates (hazard ratio HR = 1.102; 95% confidence interval CI = 1.033-1.176 per 1 standard deviation (SD) increase), more strongly in women aged under 55 years at recruitment (HR = 1.457; 95% CI = 1.181-1.797; p_het = 0.007) and in men only for follow-up 6 years or longer (HR = 1.159; 95% CI = 1.037-1.295; p_het = 0.075). ALI was positively associated with pancreatic cancer risk in participants overall (HR = 1.072; 95% CI = 1.005-1.145), more specifically in men (HR = 1.132; 95% CI = 1.035-1.238; p_het = 0.091). A positive association of WHI with pancreatic cancer risk was observed only in unadjusted models but was lost after adjustment for smoking status and diabetes. Independent of anthropometric indices, diabetes was associated positively with pancreatic cancer risk in participants overall (HR = 1.688; 95% CI = 1.365-2.087), but in women only for follow-up under 6 years (HR = 2.467; 95% CI = 1.477-4.121; p_het = 0.042). CONCLUSIONS General obesity (reflected in AFI and ALI) and diabetes but not abdominal obesity were associated positively with pancreatic cancer risk, independent of each other and covariates.
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Affiliation(s)
- Sofia Christakoudi
- Department of Epidemiology and Biostatistics, School of Public HealthImperial College LondonLondonUK
| | - Konstantinos K. Tsilidis
- Department of Epidemiology and Biostatistics, School of Public HealthImperial College LondonLondonUK
- Department of Hygiene and EpidemiologyUniversity of Ioannina School of MedicineIoanninaGreece
| | - Marc J. Gunter
- Department of Epidemiology and Biostatistics, School of Public HealthImperial College LondonLondonUK
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public HealthImperial College LondonLondonUK
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Heller M, Mann DA, Katona BW. Current Approaches of Pancreatic Cancer Surveillance in High-Risk Individuals. J Gastrointest Cancer 2025; 56:61. [PMID: 39932614 PMCID: PMC11814005 DOI: 10.1007/s12029-025-01184-1] [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] [Accepted: 01/25/2025] [Indexed: 02/14/2025]
Abstract
Currently, those recommended to undergo pancreatic cancer (PC) surveillance include appropriately aged individuals at high risk of PC due to an identifiable genetic susceptibility or those without identifiable genetic susceptibility who nonetheless have a strong family history of PC. With increases in identification of individuals at high risk for PC and increased use of PC surveillance in clinical practice, there has been increasing debate about who should undergo surveillance as well as how surveillance should be performed including use of imaging and blood-based testing. Furthermore, there is increasing interest in the outcomes of PC surveillance in high-risk individuals with some studies demonstrating that surveillance leads to downstaging of PC and improvements in survival. In this review, we summarize the current state of PC surveillance in high-risk individuals, providing an overview of the risk factors associated with PC, selection of high-risk individuals for PC surveillance, and the current, but non-uniform, recommendations for performing PC surveillance. Additionally, we review approaches to apply various imaging and blood-based tests to surveillance and the outcomes of PC surveillance.
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Affiliation(s)
- Melissa Heller
- Division of Hematology and Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Derek A Mann
- Division of Hematology and Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Bryson W Katona
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Blvd., 751 South Pavilion, Philadelphia, PA, 19104, USA.
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Tan Z, Meng Y, Wu Y, Zhen J, He H, Pu Y, Zhang J, Dong W. The burden and temporal trend of early onset pancreatic cancer based on the GBD 2021. NPJ Precis Oncol 2025; 9:32. [PMID: 39880919 PMCID: PMC11779834 DOI: 10.1038/s41698-025-00820-0] [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: 10/03/2024] [Accepted: 01/20/2025] [Indexed: 01/31/2025] Open
Abstract
In the context of the global increase in early-onset tumours, investigating the global disease burden caused by early-onset pancreatic cancer (EOPC) is imperative. Data on the burden of EOPC were obtained from the Global Burden of Disease Study 2021. A joinpoint regression model was used to analyse the temporal trend of the EOPC burden, and an age‒period‒cohort (APC) model was used to analyse the influence of age, period, and birth cohort on burden trends. Globally, the number of EOPC cases increased from 24,480 to 42,254, and the number of deaths increased from 17,193 to 26,996 between 1990 and 2021. The results of the APC model showed that the burden of EOPC increases with increasing age, whereas the variations in period and cohort effects exhibited a complex pattern across different sociodemographic index regions. Consequently, the disease burden of EOPC is increasing worldwide, highlighting the need for effective interventions.
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Affiliation(s)
- Zongbiao Tan
- Department of Gastroenterology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China
| | - Yang Meng
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, 510060, China
| | - Yanrui Wu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China
| | - Junhai Zhen
- Department of General Practice, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, China
| | - Haodong He
- Department of Gastroenterology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China
| | - Yu Pu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China
| | - Jixiang Zhang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China.
| | - Weiguo Dong
- Department of Gastroenterology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, China.
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Zhan T, Betge J, Schulte N, Dreikhausen L, Hirth M, Li M, Weidner P, Leipertz A, Teufel A, Ebert MP. Digestive cancers: mechanisms, therapeutics and management. Signal Transduct Target Ther 2025; 10:24. [PMID: 39809756 PMCID: PMC11733248 DOI: 10.1038/s41392-024-02097-4] [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: 06/29/2024] [Revised: 10/20/2024] [Accepted: 11/29/2024] [Indexed: 01/16/2025] Open
Abstract
Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% of annual cases of cancer deaths. The etiologies, molecular features, and therapeutic management of these cancer entities are highly heterogeneous and complex. Over the last decade, genomic and functional studies have provided unprecedented insights into the biology of digestive cancers, identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system. This knowledge is continuously translated into novel treatment concepts and targets, which are dynamically reshaping the therapeutic landscape of these tumors. In this review, we provide a concise overview of the etiology and molecular pathology of the six most common cancers of the digestive system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, and colorectal cancers. We comprehensively describe the current stage-dependent pharmacological management of these malignancies, including chemo-, targeted, and immunotherapy. For each cancer entity, we provide an overview of recent therapeutic advancements and research progress. Finally, we describe how novel insights into tumor heterogeneity and immune evasion deepen our understanding of therapy resistance and provide an outlook on innovative therapeutic strategies that will shape the future management of digestive cancers, including CAR-T cell therapy, novel antibody-drug conjugates and targeted therapies.
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Affiliation(s)
- Tianzuo Zhan
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Johannes Betge
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and Preclinical Models, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Nadine Schulte
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Lena Dreikhausen
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Michael Hirth
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Moying Li
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Philip Weidner
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Antonia Leipertz
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Andreas Teufel
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Matthias P Ebert
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany.
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
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Paranal RM, Wood LD, Klein AP, Roberts NJ. Understanding familial risk of pancreatic ductal adenocarcinoma. Fam Cancer 2024; 23:419-428. [PMID: 38609521 PMCID: PMC11660179 DOI: 10.1007/s10689-024-00383-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Accepted: 03/24/2024] [Indexed: 04/14/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that is the result of an accumulation of sequential genetic alterations. These genetic alterations can either be inherited, such as pathogenic germline variants that are associated with an increased risk of cancer, or acquired, such as somatic mutations that occur during the lifetime of an individual. Understanding the genetic basis of inherited risk of PDAC is essential to advancing patient care and outcomes through improved clinical surveillance, early detection initiatives, and targeted therapies. In this review we discuss factors associated with an increased risk of PDAC, the prevalence of genetic variants associated with an increased risk in patients with PDAC, estimates of PDAC risk in carriers of pathogenic germline variants in genes associated with an increased risk of PDAC. The role of common variants in pancreatic cancer risk will also be discussed.
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Affiliation(s)
- Raymond M Paranal
- The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Human Genetics Predoctoral Training Program, the McKusick-Nathans Department of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Laura D Wood
- The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Alison P Klein
- The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, MD, USA.
| | - Nicholas J Roberts
- The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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9
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Cao F, Li F, Shi L, Zhang G, Zhang L, Ma T, Zhang K. Spatial and Temporal Trends in Pancreatic Cancer Burden Attributable to High Body Mass Index at the Global and National Levels. J Epidemiol Glob Health 2023; 13:831-841. [PMID: 37796406 PMCID: PMC10686914 DOI: 10.1007/s44197-023-00155-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 09/14/2023] [Indexed: 10/06/2023] Open
Abstract
OBJECTIVES To examine the spatiotemporal trends in pancreatic cancer (PC) disability-adjusted life years (DALYs) and mortality attributable to high body-mass index (BMI) by age, gender, and countries from 1990 to 2019. METHODS Data were extracted from the Global Burden of Disease Study 2019 results. We presented the annual number of PC DALYs and mortality, and corresponding age-standardized rates (ASDR and ASMR), which were further stratified by age, gender, and countries. The estimated annual percentage change (EAPC) was computed to assess the longitudinal trends in ASRs. RESULTS In 2019, 0.7 million DALYs and 31.9 thousand deaths worldwide were caused by PC attributable to high BMI, with the largest amount reported in high-income North America, Western Europe, and East Asia. The corresponding ASDR and ASMR were highest in females and in high SDI regions, while quite varied across countries. The global EAPC in ASDR and ASMR was 1.45 (95% uncertainty interval [UI]: 1.40, 1.50) and 1.44 (95% UI: 1.39, 1.49), respectively. Almost all involved countries demonstrated significant uptrends in ASRs from 1990 to 2019. CONCLUSIONS More productive efforts to reduce the impact of modifiable risk factors, such as overweight, should be undertaken, and thus effectively curb the rise of PC burden.
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Affiliation(s)
- Fei Cao
- Department of Oncology, Luohe Central Hospital, People's East Road 54, Luohe City, 462000, Henan Province, China
| | - Feng Li
- Department of General Surgery, Shaoling District People's Hospital of Luohe, Luohe City, 462000, Henan Province, China
| | - Lei Shi
- Department of Oncology, Luohe Central Hospital, People's East Road 54, Luohe City, 462000, Henan Province, China
| | - Guoyao Zhang
- Department of Oncology, Luohe Central Hospital, People's East Road 54, Luohe City, 462000, Henan Province, China
| | - Lei Zhang
- Department of Oncology, Luohe Central Hospital, People's East Road 54, Luohe City, 462000, Henan Province, China
| | - Tianjiang Ma
- Department of Oncology, Luohe Central Hospital, People's East Road 54, Luohe City, 462000, Henan Province, China
| | - Kexun Zhang
- Department of Infectious Disease Control, Kunshan Centers for Disease Control and Prevention, Tongcheng South Road 567, Kunshan, 215300, Jiangsu, China.
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Luo W, Wang J, Chen H, Ye L, Qiu J, Liu Y, Wang R, Weng G, Liu T, Su D, Tao J, Ding C, You L, Zhang T. Epidemiology of pancreatic cancer: New version, new vision. Chin J Cancer Res 2023; 35:438-450. [PMID: 37969957 PMCID: PMC10643340 DOI: 10.21147/j.issn.1000-9604.2023.05.03] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 10/16/2023] [Indexed: 11/17/2023] Open
Abstract
Pancreatic cancer (PC) is a devastating malignancy with an extremely high mortality rate and poses significant challenges to healthcare systems worldwide. The prevalence of PC risk factors spiked over the years, leading to a global increase in PC incidence rates. The contribution of different risk factors, however, varied from region to region due to genetic predisposition, environmental, social, and political factors underlying disease prevalence in addition to public health strategies. This comprehensive review aims to provide a thorough analysis of the epidemiology of PC, discussing its incidence, risk factors, screening strategies and socioeconomic burden. We compiled a wide range of seminal studies as well as epidemiological investigations to serve this review as a comprehensive guide for researchers, healthcare professionals, and policymakers keen for a more profound understanding of PC epidemiology. This review highlights the essentiality of persistent research efforts, interdisciplinary collaboration, and public health initiatives to address the expanding burden of this malignancy.
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Affiliation(s)
- Wenhao Luo
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jun Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Hao Chen
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Liyuan Ye
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jiangdong Qiu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Yueze Liu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Ruobing Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Guihu Weng
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Tao Liu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Dan Su
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jinxin Tao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Chen Ding
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Lei You
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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11
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Leowattana W, Leowattana P, Leowattana T. Systemic treatment for advanced pancreatic cancer. World J Gastrointest Oncol 2023; 15:1691-1705. [PMID: 37969416 PMCID: PMC10631439 DOI: 10.4251/wjgo.v15.i10.1691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/24/2023] [Accepted: 09/22/2023] [Indexed: 10/10/2023] Open
Abstract
Pancreatic cancer is a deadly disease with an extremely poor 5-year survival rate due to treatment resistance and late-stage detection. Despite numerous years of research and pharmaceutical development, these figures have not changed. Treatment options for advanced pancreatic cancer are still limited. This illness is typically detected at a late stage, making curative surgical resection impossible. Chemotherapy is the most commonly utilized technique for treating advanced pancreatic cancer but has poor efficacy. Targeted therapy and immunotherapy have made significant progress in many other cancer types and have been proven to have extremely promising possibilities; these therapies also hold promise for pancreatic cancer. There is an urgent need for research into targeted treatment, immunotherapy, and cancer vaccines. In this review, we emphasize the foundational findings that have fueled the therapeutic strategy for advanced pancreatic cancer. We also address current advancements in targeted therapy, immunotherapy, and cancer vaccines, all of which continue to improve the clinical outcome of advanced pancreatic cancer. We believe that clinical translation of these novel treatments will improve the low survival rate of this deadly disease.
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Affiliation(s)
- Wattana Leowattana
- Department of Clinical Tropical Medicine, Mahidol University, Rachatawee 10400, Bangkok, Thailand
| | - Pathomthep Leowattana
- Department of Clinical Tropical Medicine, Mahidol University, Rachatawee 10400, Bangkok, Thailand
| | - Tawithep Leowattana
- Department of Medicine, Srinakharinwirot University, Wattana 10110, Bangkok, Thailand
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12
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Tanaka T, Lynch CF, Yu KJ, Morawski BM, Hsieh MC, Alverson G, Austin AA, Zeng Y, Engels EA. Pancreatic cancer among solid organ transplant recipients in the United States. J Cancer Res Clin Oncol 2023; 149:3325-3333. [PMID: 35932302 DOI: 10.1007/s00432-022-04227-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/18/2022] [Indexed: 12/01/2022]
Abstract
INTRODUCTION Pancreatic cancer (PC) in solid organ transplant (SOT) recipients is not well studied. Some PC cases may be incidentally detected during hepatobiliary imaging. METHODS We evaluated PC among 374,106 SOT recipients during 1995-2017 in the United States using linked data from the national transplant registry and multiple state/regional cancer registries. Standardized incidence ratios (SIRs) were used to compare PC risk in recipients to the general population. We used multivariate Poisson regression to identify independent risk factors for PC. We assessed survival after PC diagnosis using Kaplan-Meier curves and log-rank tests. RESULTS SOT recipients had elevated incidence for PC compared with the general population (SIR 1.40, 95% CI 1.29-1.52), and this increase was strongest in liver recipients (1.65, 1.41-1.92). Among all recipients, PC incidence was especially increased for cases arising in the head of the pancreas (SIR 1.50, 95% CI 1.34-1.68) and for cases diagnosed at localized stage (1.85, 1.37-2.44). Among SOT recipients, factors independently associated with increased incidence were consistent with those in general population including male sex, older age, non-O blood type, and history of diabetes. Additionally, compared to other organ recipients, liver transplant recipients had higher PC incidence (adjusted incidence rate ratio 1.28; 95% CI 1.06-1.54). Overall survival after PC diagnosis was poor (median 4 months) and similar between liver and other organ transplant recipients (p = 0.08). CONCLUSIONS PC incidence is elevated among SOT recipients, and more commonly diagnosed in liver transplant recipients perhaps related to incidental detection. However, survival is poor even in liver recipients, arguing against routine PC screening.
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Affiliation(s)
- Tomohiro Tanaka
- Division of Gastroenterology and Hepatology, The University of Iowa, Iowa City, IA, USA.
| | - Charles F Lynch
- Department of Epidemiology, The University of Iowa, Iowa City, IA, USA
| | - Kelly J Yu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Bozena M Morawski
- Cancer Data Registry of Idaho, Idaho Hospital Association, Boise, ID, USA
| | - Mei-Chin Hsieh
- Louisiana Tumor Registry and Epidemiology Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Georgetta Alverson
- Michigan Cancer Surveillance Program, Michigan Department of Health and Human Services, Lansing, MI, USA
| | - April A Austin
- New York State Cancer Registry, New York State Department of Health, Albany, NY, USA
| | - Yun Zeng
- North Dakota Statewide Cancer Registry, Grand Forks, ND, USA
| | - Eric A Engels
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
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13
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Recalde M, Pistillo A, Davila-Batista V, Leitzmann M, Romieu I, Viallon V, Freisling H, Duarte-Salles T. Longitudinal body mass index and cancer risk: a cohort study of 2.6 million Catalan adults. Nat Commun 2023; 14:3816. [PMID: 37391446 PMCID: PMC10313757 DOI: 10.1038/s41467-023-39282-y] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 05/31/2023] [Indexed: 07/02/2023] Open
Abstract
Single body mass index (BMI) measurements have been associated with increased risk of 13 cancers. Whether life course adiposity-related exposures are more relevant cancer risk factors than baseline BMI (ie, at start of follow-up for disease outcome) remains unclear. We conducted a cohort study from 2009 until 2018 with population-based electronic health records in Catalonia, Spain. We included 2,645,885 individuals aged ≥40 years and free of cancer in 2009. After 9 years of follow-up, 225,396 participants were diagnosed with cancer. This study shows that longer duration, greater degree, and younger age of onset of overweight and obesity during early adulthood are positively associated with risk of 18 cancers, including leukemia, non-Hodgkin lymphoma, and among never-smokers, head and neck, and bladder cancers which are not yet considered as obesity-related cancers in the literature. Our findings support public health strategies for cancer prevention focussing on preventing and reducing early overweight and obesity.
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Affiliation(s)
- Martina Recalde
- International Agency for Research on Cancer (IARC-WHO), 25 avenue Tony Garnier, CS 90627, 69366 Lyon Cedex 07, Lyon, France
- Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Andrea Pistillo
- Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
| | - Veronica Davila-Batista
- International Agency for Research on Cancer (IARC-WHO), 25 avenue Tony Garnier, CS 90627, 69366 Lyon Cedex 07, Lyon, France.
- Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, 28029, Madrid, Spain.
| | - Michael Leitzmann
- Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
| | - Isabelle Romieu
- Center for Research on Population Health, National Institute of Public Health, Mexico City, Mexico
| | - Vivian Viallon
- International Agency for Research on Cancer (IARC-WHO), 25 avenue Tony Garnier, CS 90627, 69366 Lyon Cedex 07, Lyon, France
| | - Heinz Freisling
- International Agency for Research on Cancer (IARC-WHO), 25 avenue Tony Garnier, CS 90627, 69366 Lyon Cedex 07, Lyon, France.
| | - Talita Duarte-Salles
- Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.
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14
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Yuen MMA. Health Complications of Obesity: 224 Obesity-Associated Comorbidities from a Mechanistic Perspective. Gastroenterol Clin North Am 2023; 52:363-380. [PMID: 37197879 DOI: 10.1016/j.gtc.2023.03.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2023]
Abstract
Obesity is associated with a wide range of comorbidities that transverse multiple specialties in clinical medicine. The development of these comorbidities is driven by various mechanistic changes including chronic inflammation and oxidative stress, increased growth-promoting adipokines, insulin resistance, endothelial dysfunction, direct loading and infiltrative effect of adiposity, heightened activities of the renin-angiotensin-aldosterone system and sympathetic nervous system, impaired immunity, altered sex hormones, altered brain structure, elevated cortisol levels, and increased uric acid production, among others. Some of the comorbidities might develop secondary to one or more other comorbidities. Considering the obesity-associated comorbidities in the context of the mechanistic changes is helpful in understanding these conditions and in guiding treatment and future research.
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Affiliation(s)
- Michele M A Yuen
- Department of Medicine, Obesity, Metabolism and Nutrition Institute, Massachusetts General Hospital; University of Hong Kong, 102 Pokfulam Road, Pok Fu Lam, Hong Kong.
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15
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Al-Hetty HRAK, Abdulameer SJ, Alkubaisy SA, Zaid SA, Jalil AT, Jasim IK. STAT3 signaling in pancreatic ductal adenocarcinoma: a candidate therapeutic target. Pathol Res Pract 2023; 245:154425. [PMID: 37019018 DOI: 10.1016/j.prp.2023.154425] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 03/19/2023] [Accepted: 03/21/2023] [Indexed: 04/05/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a poor prognosis which is lethal in over 90% of cases despite the standard therapies. Mainly activated by Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) is a key transcription factor, capable of exerting the expression of multitude of genes involved in survival. Moreover, STAT3 activity is regulated by the interleukin 28 receptor α (IL28RA) and glutathione s-transferase mu-3 (GSTM3), up-regulation of both contributes to the invasiveness of pancreatic cancer cells. In this regard, STAT3 overactivity has an important pathogenic role in the development of PDAC as it is associated with enhanced cell proliferation, survival, angiogenesis, and metastasis. STAT3-associated expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 3 and 9 are implicated in the angiogenic and metastatic behavior of the PDAC. Multitude of evidence underline the protective role of STAT3 inhibition against PDAC both in cell cultures and in tumor grafts. However, specific inhibition of STAT3 was not feasible until recently, when a selective potent chemical STAT3 inhibitor, termed N4, were developed and it turned out to be highly effective against PDAC in vitro, as well as in vivo. This review aims to discuss the most recent advances in our understanding of STAT3 role in the pathogenesis of PDAC and its therapeutic applications.
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16
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Ruze R, Chen Y, Xu R, Song J, Yin X, Wang C, Xu Q. Obesity, diabetes mellitus, and pancreatic carcinogenesis: Correlations, prevention, and diagnostic implications. Biochim Biophys Acta Rev Cancer 2023; 1878:188844. [PMID: 36464199 DOI: 10.1016/j.bbcan.2022.188844] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/13/2022] [Accepted: 11/26/2022] [Indexed: 12/03/2022]
Abstract
The prevalence of obesity, diabetes mellitus (DM), and pancreatic cancer (PC) has been consistently increasing in the last two decades worldwide. Sharing various influential risk factors in genetics and environmental inducers in pathogenesis, the close correlations of these three diseases have been demonstrated in plenty of clinical studies using multiple parameters among different populations. On the contrary, most measures aimed to manage and treat obesity and DM effectively reduce the risk and prevent PC occurrence, yet certain drugs can inversely promote pancreatic carcinogenesis instead. Most importantly, an elevation of blood glucose with or without a reduction in body weight, along with other potential tools, may provide valuable clues for detecting PC at an early stage in patients with obesity and DM, favoring a timely intervention and prolonging survival. Herein, the epidemiological and etiological correlations among these three diseases and the supporting clinical evidence of their connections are first summarized to favor a better and more thorough understanding of obesity- and DM-related pancreatic carcinogenesis. After comparing the distinct impacts of different weight-lowering and anti-diabetic treatments on the risk of PC, the possible diagnostic implications of hyperglycemia and weight loss in PC screening are also addressed in detail.
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Affiliation(s)
- Rexiati Ruze
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China; Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Yuan Chen
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China; Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Ruiyuan Xu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China; Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Jianlu Song
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China; Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Xinpeng Yin
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China; Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dongdan Santiao, Beijing, China
| | - Chengcheng Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China.
| | - Qiang Xu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, China.
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17
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Effects of Berberine against Pancreatitis and Pancreatic Cancer. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27238630. [PMID: 36500723 PMCID: PMC9738201 DOI: 10.3390/molecules27238630] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 11/28/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022]
Abstract
The pancreas is a glandular organ with endocrine and exocrine functions necessary for the maintenance of blood glucose homeostasis and secretion of digestive enzymes. Pancreatitis is characterized by inflammation of the pancreas leading to temporary or permanent pancreatic dysfunction. Inflammation and fibrosis caused by chronic pancreatitis exacerbate malignant transformation and significantly increase the risk of developing pancreatic cancer, the world's most aggressive cancer with a 5-year survival rate less than 10%. Berberine (BBR) is a naturally occurring plant-derived polyphenol present in a variety of herbal remedies used in traditional medicine to treat ulcers, infections, jaundice, and inflammation. The current review summarizes the existing in vitro and in vivo evidence on the effects of BBR against pancreatitis and pancreatic cancer with a focus on the signalling mechanisms underlying the effects of BBR.
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18
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Burra P, Arvanitakis M, Dias JA, Bretthauer M, Dugic A, Hartmann D, Michl P, Seufferlein T, Torres J, Törnblom H, van Leerdam ME, Zelber‐Sagi S, Botos A. UEG position paper: Obesity and digestive health. United European Gastroenterol J 2022; 10:1199-1201. [PMID: 36457185 PMCID: PMC9752259 DOI: 10.1002/ueg2.12334] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant UnitDepartment of Surgery, Oncology and GastroenterologyPadua University HospitalPaduaItaly
| | - Marianna Arvanitakis
- Department of Gastroenterology, Hepatopancreatology and GI OncologyErasme University HospitalUniversité Libre de BruxellesBrusselsBelgium,Nutrition TeamErasme University HospitalUniversité Libre de BruxellesBrusselsBelgium
| | | | - Michael Bretthauer
- Department of Transplantation MedicineClinical Effectiveness Research GroupOslo University HospitalOsloNorway,Clinical Effectiveness Research GroupInstitute of Health and SocietyUniversity of OsloOsloNorway
| | - Ana Dugic
- Department of GastroenterologyFriedrich‐Alexander‐Universität Erlangen‐Nürnberg (FAU)Medizincampus OberfrankenBayreuthGermany,Department of MedicineKarolinska InstitutetStockholmSweden
| | - Daniel Hartmann
- Department of SurgeryKlinikum rechts der Isar Technische Universität MunichMunichGermany
| | - Patrick Michl
- Department of Internal Medicine IMartin‐Luther University Halle‐WittenbergHalleGermany
| | | | - Joana Torres
- Division of GastroenterologyHospital Beatriz ÂngeloLouresPortugal,Faculdade de MedicinaUniversidade de LisboaLisboaPortugal
| | - Hans Törnblom
- Department of Molecular and Clinical MedicineInstitute of MedicineSahlgrenska AcademyUniversity of GothenburgGothenburgSweden
| | | | - Shira Zelber‐Sagi
- School of Public HealthFaculty of Social Welfare and Health SciencesUniversity of HaifaHaifaIsrael,Department of GastroenterologyTel Aviv Medical CenterTel AvivIsrael
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19
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Hoyt M, Song Y, Gao S, O'Palka J, Zhang J. Prediagnostic BMI trajectories in relation to pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Obesity (Silver Spring) 2022; 30:2275-2285. [PMID: 36156459 PMCID: PMC9826088 DOI: 10.1002/oby.23550] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 06/26/2022] [Accepted: 06/28/2022] [Indexed: 01/11/2023]
Abstract
OBJECTIVE It remains elusive whether prediagnostic BMI trajectory is associated with pancreatic cancer. METHODS This study investigated this question among 145,489 participants who gave rise to 696 incident cases of pancreatic cancer over a median follow-up of 12 years in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. At baseline, participants were asked to recall their weight at ages 20, 50, and 55 to 74 years (at enrollment), as well as their height. RESULTS At age 50 years, people with obesity had a significantly increased risk of pancreatic cancer compared with those with a normal weight after adjustment for confounders (hazard ratio [95% CI]: 1.27 [1.01-1.60]). Individuals who had overweight at age 20 years experienced a marginally significant elevated risk of pancreatic cancer (hazard ratio [95% CI]: 1.22 [0.99-1.50]). Compared with individuals who maintained a steady normal weight during follow-up, no significantly altered risk of pancreatic cancer was observed for those whose weight status changed from normal weight to overweight, from normal weight to obesity, and from overweight to obesity. CONCLUSIONS The present study revealed that prediagnostic adulthood BMI trajectory was not associated with pancreatic cancer risk, but overweight at young adulthood and obesity at middle adulthood may confer an elevated risk of this malignancy.
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Affiliation(s)
- Margaret Hoyt
- Department of EpidemiologyRichard M. Fairbanks School of Public Health, Indiana University–Purdue UniversityIndianapolisIndianaUSA
| | - Yiqing Song
- Department of EpidemiologyRichard M. Fairbanks School of Public Health, Indiana University–Purdue UniversityIndianapolisIndianaUSA
| | - Sujuan Gao
- Department of Biostatistics and Health Data ScienceRichard M. Fairbanks School of Public Health and School of Medicine, Indiana University–Purdue UniversityIndianapolisIndianaUSA
| | - Jacquelynn O'Palka
- Department of Nutrition and DieteticsSchool of Health and Human Sciences, Indiana University–Purdue UniversityIndianapolisIndianaUSA
| | - Jianjun Zhang
- Department of EpidemiologyRichard M. Fairbanks School of Public Health, Indiana University–Purdue UniversityIndianapolisIndianaUSA
- Melvin and Bren Simon Comprehensive Cancer CenterIndiana University–Purdue UniversityIndianapolisIndianaUSA
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20
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Kim JT, Lim MA, Lee SE, Kim HJ, Koh HY, Lee JH, Jun SM, Kim JM, Kim KH, Shin HS, Cho SW, Kim KS, Shong M, Koo BS, Kang YE. Adrenomedullin2 stimulates progression of thyroid cancer in mice and humans under nutrient excess conditions. J Pathol 2022; 258:264-277. [PMID: 36098211 PMCID: PMC9826144 DOI: 10.1002/path.5997] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 07/28/2022] [Accepted: 08/02/2022] [Indexed: 01/11/2023]
Abstract
Thyroid cancer is associated with genetic alterations, e.g. BRAFV600E , which may cause carcinomatous changes in hormone-secreting epithelial cells. Epidemiological studies have shown that overnutrition is related to the development and progression of cancer. In this study, we attempted to identify the cell nonautonomous factor responsible for the progression of BRAFV600E thyroid cancer under overnutrition conditions. We developed a mouse model for inducible thyrocyte-specific activation of BRAFV600E , which showed features similar to those of human papillary thyroid cancer. LSL-BrafV600E ;TgCreERT2 showed thyroid tumour development in the entire thyroid, and the tumour showed more abnormal cellular features with mitochondrial abnormalities in mice fed a high-fat diet (HFD). Transcriptomics revealed that adrenomedullin2 (Adm2) was increased in LSL-BrafV600E ;TgCreERT2 mice fed HFD. ADM2 was upregulated on the addition of a mitochondrial complex I inhibitor or palmitic acid with integrated stress response (ISR) in cancer cells. ADM2 stimulated protein kinase A and extracellular signal-regulated kinase in vitro. The knockdown of ADM2 suppressed the proliferation and migration of thyroid cancer cells. We searched The Cancer Genome Atlas and Genotype-Tissue Expression databases and found that increased ADM2 expression was associated with ISR and poor overall survival. Consistently, upregulated ADM2 expression in tumour cells and circulating ADM2 molecules were associated with aggressive clinicopathological parameters, including body mass index, in thyroid cancer patients. Collectively, we identified that ADM2 is released from cancer cells under mitochondrial stress resulting from overnutrition and acts as a secretory factor determining the progressive properties of thyroid cancer. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Jung Tae Kim
- Research Center for Endocrine and Metabolic DiseasesChungnam National University School of MedicineDaejeonRepublic of Korea,Department of Medical ScienceChungnam National University School of MedicineDaejeonRepublic of Korea
| | - Mi Ae Lim
- Department of Otolaryngology‐Head and Neck SurgeryChungnam National University School of MedicineDaejeonRepublic of Korea
| | - Seong Eun Lee
- Research Center for Endocrine and Metabolic DiseasesChungnam National University School of MedicineDaejeonRepublic of Korea
| | - Hyun Jung Kim
- Graduate School of Medical Science and EngineeringKorea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
| | - Hyun Yong Koh
- Graduate School of Medical Science and EngineeringKorea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
| | - Jeong Ho Lee
- Graduate School of Medical Science and EngineeringKorea Advanced Institute of Science and Technology (KAIST)DaejeonRepublic of Korea
| | - Sang Mi Jun
- Center for Research EquipmentKorea Basic Science InstituteCheongjuRepublic of Korea,Convergent Research Center for Emerging Virus InfectionKorea Research Institute of Chemical TechnologyDaejeonRepublic of Korea
| | - Jin Man Kim
- Department of PathologyChungnam National University School of MedicineDaejeonRepublic of Korea
| | - Kun Ho Kim
- Department of Nuclear MedicineChungnam National University School of MedicineDaejeonRepublic of Korea
| | - Hyo Shik Shin
- Department of Internal MedicineSeoul National University College of MedicineSeoulRepublic of Korea
| | - Sun Wook Cho
- Department of Internal MedicineSeoul National University College of MedicineSeoulRepublic of Korea,Department of Internal MedicineSeoul National University HospitalSeoulRepublic of Korea,Cellus Inc.SeoulRepublic of Korea
| | - Koon Soon Kim
- Research Center for Endocrine and Metabolic DiseasesChungnam National University School of MedicineDaejeonRepublic of Korea,Division of Endocrinology and Metabolism, Department of Internal MedicineChungnam National University School of MedicineDaejeonRepublic of Korea
| | - Minho Shong
- Research Center for Endocrine and Metabolic DiseasesChungnam National University School of MedicineDaejeonRepublic of Korea,Department of Medical ScienceChungnam National University School of MedicineDaejeonRepublic of Korea,Division of Endocrinology and Metabolism, Department of Internal MedicineChungnam National University School of MedicineDaejeonRepublic of Korea
| | - Bon Seok Koo
- Department of Medical ScienceChungnam National University School of MedicineDaejeonRepublic of Korea,Department of Otolaryngology‐Head and Neck SurgeryChungnam National University School of MedicineDaejeonRepublic of Korea
| | - Yea Eun Kang
- Research Center for Endocrine and Metabolic DiseasesChungnam National University School of MedicineDaejeonRepublic of Korea,Division of Endocrinology and Metabolism, Department of Internal MedicineChungnam National University School of MedicineDaejeonRepublic of Korea
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21
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Arjani S, Saint-Maurice PF, Julián-Serrano S, Eibl G, Stolzenberg-Solomon R. Body Mass Index Trajectories Across the Adult Life Course and Pancreatic Cancer Risk. JNCI Cancer Spectr 2022; 6:6762867. [PMID: 36255251 PMCID: PMC9651977 DOI: 10.1093/jncics/pkac066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 09/09/2022] [Accepted: 09/16/2022] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Body mass index (BMI) during adulthood has been associated with pancreatic ductal adenocarcinoma (PDAC), however, patterns of body size across the adult life course have not been studied extensively. We comprehensively evaluated the association between adiposity across adulthood and PDAC. METHODS We conducted a prospective analysis of 269 480 (162 735 males, 106 745 females) National Institutes of Health-AARP Diet and Health Study participants, aged 50-71 years (1995-1996) who self-reported height and weight history. Participants were followed through December 31, 2011. We examined associations between BMI (kg/m2) at ages 18, 35, 50, and 50-71 (baseline) years, their trajectories determined from latent-class trajectory modeling, and incident PDAC. Cox proportional hazard models were used to calculate multivariable adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). RESULTS During up to 15.2 years of follow-up, 3092 (2020 males, 1072 females) patients with incident PDAC were identified. BMI at all 4 ages were statistically significantly associated with increased PDAC (per 5-unit increase, HR = 1.09-1.13) with higher magnitude associations in males than females at ages 35 years and older (Pinteraction < .05). Four BMI trajectories were created. Compared with normal-weight maintainers, normal-to-overweight, normal-to-obese class I, and overweight-to-obese class III trajectories had hazard ratios of 1.15 (95% CI = 1.06 to 1.25), 1.39 (95% CI = 1.25 to 1.54), and 1.48 (95% CI = 1.18 to 1.87), respectively (Pinteraction by sex = .07). CONCLUSIONS High BMI and BMI trajectories that result in overweight or obesity during adulthood were positively associated with PDAC, with stronger associations among those with early onset adiposity and those with male sex. Avoidance of excess body weight throughout the adult life course may prevent PDAC.
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Affiliation(s)
- Simran Arjani
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA,Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Pedro F Saint-Maurice
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA
| | - Sachelly Julián-Serrano
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA,Department of Public Health, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, Lowell, MA, USA
| | - Guido Eibl
- Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA
| | - Rachael Stolzenberg-Solomon
- Correspondence to: Rachael Stolzenberg-Solomon, RD, MPH, PhD, Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, 9609 Medical Center Drive, NCI Shady Grove, Room 6E420, Rockville, MD 20850, USA (e-mail: )
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22
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Dunne RF, Roeland EJ. The Interplay Among Pancreatic Cancer, Cachexia, Body Composition, and Diabetes. Hematol Oncol Clin North Am 2022; 36:897-910. [PMID: 36154783 DOI: 10.1016/j.hoc.2022.07.001] [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] [Indexed: 11/18/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is associated with complex changes in body composition. Visceral obesity and type 2 diabetes mellitus are established risk factors for developing PDAC; however, clinical and metabolic features of PDAC commonly lead to cancer cachexia, a hypermetabolic syndrome characterized by weight loss secondary to muscle and adipose tissue wasting. Reduction in muscle mass in patients with PDAC is associated with poorer survival in patients undergoing surgical resection and increased chemotherapy toxicity. Although no standardized treatment exists, a multidisciplinary, tailored, symptom-based approach is recommended to improve outcomes and quality of life for patients with PDAC and cachexia.
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Affiliation(s)
- Richard F Dunne
- Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, 601 Elmwood Avenue, Box 704, Rochester, NY 14642, USA.
| | - Eric J Roeland
- Division of Hematology/Oncology, Oregon Health and Science University, Knight Cancer Institute, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
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23
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Tao S, Tian L, Wang X, Shou Y. A pyroptosis-related gene signature for prognosis and immune microenvironment of pancreatic cancer. Front Genet 2022; 13:817919. [PMID: 36118860 PMCID: PMC9476319 DOI: 10.3389/fgene.2022.817919] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 07/20/2022] [Indexed: 11/13/2022] Open
Abstract
Pancreatic cancer is one of the most lethal tumors owing to its unspecific symptoms during the early stage and multiple treatment resistances. Pyroptosis, a newly discovered gasdermin-mediated cell death, facilitates anti- or pro-tumor effects in a variety of cancers, whereas the impact of pyroptosis in pancreatic cancer remains unclear. Therefore, we downloaded RNA expression and clinic data from the TCGA-PAAD cohort and were surprised to find that most pyroptosis-related genes (PRGs) are not only overexpressed in tumor tissue but also strongly associated with overall survival. For their remarkable prognostic value, cox regression analysis and lasso regression were used to establish a five-gene signature. All patients were divided into low- and high-risk groups based on the media value of the risk score, and we discovered that low-risk patients had better outcomes in both the testing and validation cohorts using time receiver operating characteristic (ROC), nomograms, survival, and decision analysis. More importantly, a higher somatic mutation burden and less immune cell infiltration were found in the high-risk group. Following that, we predicted tumor response to chemotherapy and immunotherapy in both low- and high-risk groups, which suggests patients with low risk were more likely to respond to both immunotherapy and chemotherapy. To summarize, our study established an effective model that can help clinicians better predict patients’ drug responses and outcomes, and we also present basic evidence for future pyroptosis related studies in pancreatic cancer.
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Affiliation(s)
- Sifan Tao
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Li Tian
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xiaoyan Wang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- *Correspondence: Xiaoyan Wang, ; Yajun Shou,
| | - Yajun Shou
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
- *Correspondence: Xiaoyan Wang, ; Yajun Shou,
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24
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Gili Ortiz E. Factors influencing mortality trends of pancreatic cancer in Spain, 1955-2020. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2022; 114:474-480. [PMID: 35548865 DOI: 10.17235/reed.2022.8559/2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2023]
Abstract
OBJECTIVES The aim of this study was to analyze the trends of pancreatic cancer mortality in Spain from 1955-2020 in both genders and every age group, in order to describe the changes in the prevalence of some risk factors and their possible influence on mortality. METHODS Direct standardized mortality rates were calculated using the World Standard Population 2000-2025 and Joinpoint analysis was performed for age-specific and age-standardized mortality trends for the period from 1955-2020. RESULTS Mortality rates increased with age in both genders, with a marked increase in older groups. During 2020, 71.5% of male deaths and 81.5% of female deaths from pancreatic cancer occurred among those aged 65 years or more. Spanish National Health Surveys since 1987 show decreasing trends in daily smoking, but striking increases in obesity and diabetes mellitus rates in both genders, and rates of daily smoking and obesity are remarkably higher among disadvantaged social classes. CONCLUSIONS Pancreatic cancer mortality rates have increased uninterruptedly in Spain during the last decades. Increasing trends in obesity and diabetes mellitus, particularly among males, and the different prevalence of obesity and smoking according to social class are public health problems of great concern. Smoking and obesity are potentially avoidable risk factors. Thus, educational programs and legislative measures should be implemented more widely, such as programs for smoking prevention, healthy nutrition and physical exercise, and would be applied more intensively in the most disadvantaged social classes.
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25
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The timing of adiposity and changes in the life course on the risk of cancer. Cancer Metastasis Rev 2022; 41:471-489. [PMID: 35908000 DOI: 10.1007/s10555-022-10054-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 07/23/2022] [Indexed: 11/02/2022]
Abstract
Excess body weight has been established as a risk factor for at least twelve cancer sites, though questions remain as to the timing of associations for adiposity and cancer risk throughout the life course. We conducted a narrative review summarizing existing evidence to provide insights into the complex timing relationship between adiposity and risk of seven common obesity-related cancers. We considered five types of studies, including traditional epidemiologic studies examining adiposity at different time points, studies examining weight gain in specific life phases, studies examining weight loss over a period including from bariatric surgery, life course trajectory analysis, and Mendelian randomization studies. The results showed that lifetime excess body weight is associated with increased risk of cancers of endometrium, colorectum, liver, kidney, and pancreas. Early life obesity is one of the strongest risk factors for pancreatic cancer but less directly important than adult obesity for endometrial and kidney cancer. Interestingly, heavy weight during childhood, adolescence, and early adulthood is protective against pre- and postmenopausal breast cancer and possibly advanced prostate cancer. It is apparent that preventing weight gain later in adulthood would likely reduce risk of many cancers, including postmenopausal breast cancer, endometrial cancer, colorectal cancer (especially in men), liver cancer, kidney cancer, and probably advanced prostate cancer. Furthermore, weight loss even late in life may confer benefits for cancers of breast, endometrium, colorectum, and liver among patients with obesity, as mostly demonstrated by studies of bariatric surgery. Overall, maintaining a healthy weight throughout the life course will help prevent a large number of cancers.
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26
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Poman DS, Motwani L, Asif N, Patel A, Vedantam D. Pancreatic Cancer and the Obesity Epidemic: A Narrative Review. Cureus 2022; 14:e26654. [PMID: 35959181 PMCID: PMC9360631 DOI: 10.7759/cureus.26654] [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] [Accepted: 07/07/2022] [Indexed: 11/05/2022] Open
Abstract
Pancreatic cancer (PC) is one of the most frequent causes of death. It usually affects older individuals with incidence closely approaching mortality due to its early asymptomatic feature and highly metastatic nature. Multiple risk factors such as family history, smoking, and germline mutations are associated with PC development, with obesity being one of the controllable factors. This review article focuses on the compilation of various studies to help establish a correlation between obesity or an increased body mass index and PC development. Hence, in this review, we have summarised multiple biological mechanisms of PC development induced by obesity, including insulin resistance, inflammation, beta-cell dysfunction, and oxidative stress, to prove that their correlation when combined with other factors, such as smoking, alcohol and chronic pancreatitis, may increase its risk. We have also reviewed potential diagnostic and screening techniques, such as evaluating precancerous lesions in high-risk patients and management plans discussing upcoming advances in treatment tactics such as neoadjuvant therapy, to reduce post-operative complications.
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Affiliation(s)
| | - Lakshya Motwani
- Research and Development, Smt. Nathiba Hargovandas Lakhmichand (NHL) Municipal Medical College, Ahmedabad, IND
| | - Nailah Asif
- Research, Ras Al Khaimah (RAK) College of Medical Sciences, Ras Al Khaimah, ARE
| | - Apurva Patel
- Research, Gujarat Medical Education & Research Society (GMERS) Medical College, Gotri, Vadodara, IND
| | - Deepanjali Vedantam
- Internal Medicine, Kamineni Academy of Medical Sciences and Research Center, Hyderabad, IND
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27
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Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an intractable cancer and a leading cause of cancer deaths worldwide. Over 90% of patients die within 1 year of diagnosis. Deaths from PDAC are increasing and it remains a cancer of substantial unmet need. A number of factors contribute to its poor prognosis: namely, late presentation, early metastases and limited systemic therapy options because of chemoresistance. A variety of research approaches underway are aimed at improving patient survival. Here, we review high-risk groups and efforts for early detection. We examine recent developments in the understanding of complex molecular and metabolic alterations which accompany PDAC. We explore artificial intelligence and biological targets for therapy and examine the role of tumour stroma and the immune microenvironment. We also review recent developments with respect to the PDAC microbiome. It is hoped that current research efforts will translate into earlier diagnosis, improvements in treatment and better outcomes for patients.
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Affiliation(s)
- Martyn C Stott
- Department of Molecular & Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Sherrington Building, Liverpool, UK
| | - Lucy Oldfield
- Department of Molecular & Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Sherrington Building, Liverpool, UK
| | - Jessica Hale
- Department of Molecular & Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Sherrington Building, Liverpool, UK
| | - Eithne Costello
- Department of Molecular & Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Sherrington Building, Liverpool, UK
| | - Christopher M Halloran
- Department of Molecular & Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Sherrington Building, Liverpool, UK
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28
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Schwalb ME, Smith-Warner SA, Hou J, Rohan TE, Snetselaar L, Luo J, Genkinger JM. Sustained Weight Loss, Weight Cycling, and Weight Gain During Adulthood and Pancreatic Cancer Incidence in the Women's Health Initiative. Am J Epidemiol 2022; 191:1009-1020. [PMID: 35102370 PMCID: PMC9393067 DOI: 10.1093/aje/kwac016] [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: 06/23/2021] [Revised: 01/11/2022] [Accepted: 01/25/2022] [Indexed: 02/03/2023] Open
Abstract
Pancreatic cancer (PC) is the fourth leading cause of cancer mortality among women in the United States. Obesity is positively associated with PC risk. Current health recommendations focus on weight maintenance for healthy-weight individuals and weight loss for overweight/obese individuals; however, little research has assessed associations between PC risk and changes in weight throughout the life course. Using prospective cohort study data, we examined the relationship between baseline adulthood weight patterns self-reported between 1993 and 1998 and PC risk in 136,834 postmenopausal women with 873 incident PC cases through September 30, 2015, in the Women's Health Initiative. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models, adjusting for age, smoking habits, heavy alcohol consumption, and body mass index. Compared with women with stable weight, no significant associations were found between steady weight gain (HR = 1.01, 95% CI: 0.83, 1.22), sustained weight loss (HR = 1.26, 95% CI: 0.85, 1.87), or weight cycling patterns (HR = 1.08, 95% CI: 0.89, 1.30) and PC. Results were similar when the outcome definition was restricted to pancreatic adenocarcinoma cases. Overall, we did not find evidence to suggest that weight changes in adulthood significantly impact PC risk among postmenopausal women.
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Affiliation(s)
| | | | | | | | | | | | - Jeanine M Genkinger
- Correspondence to Dr. Jeanine Genkinger, Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 West 168th Street, Room 712, New York, NY 10032 (e-mail: )
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29
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Vanek P, Eid M, Psar R, Zoundjiekpon V, Urban O, Kunovský L. Current trends in the diagnosis of pancreatic cancer. VNITRNI LEKARSTVI 2022; 68:363-370. [PMID: 36316197 DOI: 10.36290/vnl.2022.076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a dreaded malignancy with a dismal 5-year survival rate despite maximal efforts on optimizing treatment strategies. Currently, early detection is considered to be the most effective way to improve survival as radical resection is the only potential cure. PDAC is often divided into four categories based on the extent of disease: resectable, borderline resectable, locally advanced, and metastatic. Unfortunately, the majority of patients are diagnosed with locally advanced or metastatic disease, which renders them ineligible for curative resection. This is mainly due to the lack of or vague symptoms while the disease is still localized, although appropriate utilization and prompt availability of adequate diagnostic tools is also critical given the aggressive nature of the disease. A cost-effective biomarker with high specificity and sensitivity allowing early detection of PDAC without the need for advanced or invasive methods is still not available. This leaves the diagnosis dependent on radiodiagnostic methods or endoscopic ultrasound. Here we summarize the latest epidemiological data, risk factors, clinical manifestation, and current diagnostic trends and implications of PDAC focusing on serum biomarkers and imaging modalities. Additionally, up-to-date management and therapeutic algorithms are outlined.
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30
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Qiu G, Zhang L, Gu Z, Ren H, Du Y, Li Z, Wang C. Preoperative Alkaline Phosphatase-to-Cholesterol Ratio as a Predictor of Overall Survival in Pancreatic Ductal Adenocarcinoma Patients Undergoing Radical Pancreaticoduodenectomy. Med Sci Monit 2021; 27:e931868. [PMID: 34599137 PMCID: PMC8493854 DOI: 10.12659/msm.931868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background The value of alkaline phosphatase and cholesterol for predicting overall survival (OS) in cancer patients has been previously studied. However, the predictive value of these variables in patients with pancreatic ductal adenocarcinoma (PDAC) was limited. Hence, we conducted this study to investigate the prognostic value of the alkaline phosphatase-to-cholesterol ratio (ACR) in patients undergoing radical pancreaticoduodenectomy (PD) for PDAC. Material/Methods A total of 102 PDAC patients undergoing radical PD at the Cancer Hospital Chinese Academy of Medical Sciences were retrospectively enrolled based on medical records from June 2009 to June 2019. R programming language was used for the optimal cutoff value of biological markers such as preoperative ACR. Kaplan-Meier method and log-rank test were used for univariate survival analysis, and a Cox regression model was used for multivariate survival analysis. Results The optimal cutoff value of preoperative ACR was 32.988. Patients with higher preoperative ACR values had worse OS (P<0.001). Higher preoperative ACR was significantly correlated with the degree of tumor differentiation (P<0.018); levels of alanine aminotransferase (P<0.001), aspartate aminotransferase (P<0.001), total bilirubin (P<0.001), and carbohydrate antigen 19-9 (P=0.016); and clinical symptoms (P=0.001). Multivariate analysis showed that tumor differentiation (P<0.001), ACR value (hazard ratio [HR]: 2.225, 95% confidence interval [CI]: 1.33–3.724, P=0.002), and sex (HR, 1.725, 95% CI: 1.1–2.704, P=0.018) were independent factors associated with the prognosis of PDAC patients undergoing radical PD. Conclusions The preoperative ACR was correlated with OS in pancreatic cancer patients undergoing radical pancreaticoduodenectomy. Elevated ACR was correlated with poor OS.
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Affiliation(s)
- Guotong Qiu
- State Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (mainland)
| | - Lipeng Zhang
- State Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (mainland)
| | - Zongting Gu
- State Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (mainland)
| | - Hu Ren
- State Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (mainland)
| | - Yongxing Du
- State Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (mainland)
| | - Zongze Li
- State Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (mainland)
| | - Chengfeng Wang
- State Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (mainland)
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31
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Stolzenberg-Solomon R. Are Prediagnostic Biomarkers of Inflammation and an Empirically Based Proinflammatory Dietary Pattern Associated With Poorer Pancreatic Cancer Survival? J Natl Cancer Inst 2021; 113:1123-1124. [PMID: 33739407 PMCID: PMC8418422 DOI: 10.1093/jnci/djab043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 03/10/2021] [Indexed: 12/17/2022] Open
Affiliation(s)
- Rachael Stolzenberg-Solomon
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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32
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Michl P, Löhr M, Neoptolemos JP, Capurso G, Rebours V, Malats N, Ollivier M, Ricciardiello L. UEG position paper on pancreatic cancer. Bringing pancreatic cancer to the 21st century: Prevent, detect, and treat the disease earlier and better. United European Gastroenterol J 2021; 9:860-871. [PMID: 34431604 PMCID: PMC8435257 DOI: 10.1002/ueg2.12123] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 05/24/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma is the deadliest cancer worldwide with a 98% loss-of-life expectancy and a 30% increase in the disability-adjusted life years during the last decade in Europe. The disease cannot be effectively prevented nor being early detected. When diagnosed, 80% of patients have tumors that are in incurable stages, while for those who undergo surgery, 80% of patients will present with local or distant metastasis. Importantly, chemotherapies are far from being effective. OBJECTIVE Pancreatic cancer represents a great challenge and, at the same time, a huge opportunity for advancing our understanding on the basis of the disease, the molecular profiles, that would lead to develop tools for early detection and effective treatments, thus, boosting patient survival. RESULTS Research on pancreatic cancer has being receiving little or minimal funds from European funding bodies. UEG is calling for public-private partnerships that would effectively fund research on pancreatic cancer. CONCLUSION This would increase our understanding of this disease and better treatment, through pan-European efforts that take advantage of the strong academic European research landscape on pancreatic cancer, and the contribution by the industry of all sizes.
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Affiliation(s)
- Patrick Michl
- Department of Internal Medicine IUniversity Medicine Halle (Saale)HalleGermany
| | - Matthias Löhr
- Department of CancerKarolinska University Hospital and Karolinska InstitutetStockholmSweden
| | | | - Gabriele Capurso
- Pancreato‐Biliary Endoscopy and Endosonography DivisionPancreas Translational and Clinical Research CenterIRCCS San Raffaele Scientific InstituteMilanItaly
| | - Vinciane Rebours
- Pancreatology UnitBeaujon HospitalAPHPUniversité de ParisParisFrance
| | - Nuria Malats
- Genetic and Molecular Epidemiology GroupSpanish National Cancer Research Centre (CNIO)CIBERONCPancreatic Cancer Europe (PCE)MadridSpain
| | | | - Luigi Ricciardiello
- IRCCS Azienda Ospedaliero Universitaria di BolognaBolognaItaly
- Department of Medical and Surgical SciencesUniversity of BolognaBolognaItaly
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33
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Diaconescu S, Gîlcă-Blanariu GE, Poamaneagra S, Marginean O, Paduraru G, Stefanescu G. Could the burden of pancreatic cancer originate in childhood? World J Gastroenterol 2021; 27:5322-5340. [PMID: 34539135 PMCID: PMC8409163 DOI: 10.3748/wjg.v27.i32.5322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 06/08/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
The presence of pancreatic cancer during childhood is extremely rare, and physicians may be tempted to overlook this diagnosis based on age criteria. However, there are primary malignant pancreatic tumors encountered in pediatric patients, such as pancreatoblastoma, and tumors considered benign in general but may present a malignant potential, such as the solid pseudo-papillary tumor, insulinoma, gastrinoma, and vasoactive intestinal peptide secreting tumor. Their early diagnosis and management are of paramount importance since the survival rates tend to differ for various types of these conditions. Many pediatric cancers may present pancreatic metastases, such as renal cell carcinoma, which may evolve with pancreatic metastatic disease even after two or more decades. Several childhood diseases may create a predisposition for the development of pancreatic cancer during adulthood; hence, there is a need for extensive screening strategies and complex programs to facilitate the transition from pediatric to adult healthcare. Nevertheless, genetic studies highlight the fact the specific gene mutations and family aggregations may be correlated with a special predisposition towards pancreatic cancer. This review aims to report the main pancreatic cancers diagnosed during childhood, the most important childhood diseases predisposing to the development of pancreatic malignancies, and the gene mutations associates with pancreatic malignant tumors.
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Affiliation(s)
- Smaranda Diaconescu
- Department of Pediatrics, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Department of Pediatric Gastroenterology, St Mary Emergency Children's Hospital, Iasi 700309, Romania
| | - Georgiana Emmanuela Gîlcă-Blanariu
- Department of Gastroenterology and Hepatology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi 700115, Romania
- Department of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
| | - Silvia Poamaneagra
- Department of Pediatric Gastroenterology, St Mary Emergency Children's Hospital, Iasi 700309, Romania
- Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science and Technology, Targu Mures 540142, Romania
| | - Otilia Marginean
- Department of Pediatrics, Research Center of Disturbance of Growth and Development on Children-Belive, University of Medicine and Pharmacy “Victor Babes” Timisoara, Timisoara 300041, Romania
- First Clinic of Pediatrics, "Louis Turcanu" Emergency Childen's Hospital, Timisoara 300011, Romania
| | - Gabriela Paduraru
- Department of Pediatrics, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Department of Pediatric Gastroenterology, St Mary Emergency Children's Hospital, Iasi 700309, Romania
| | - Gabriela Stefanescu
- Department of Gastroenterology and Hepatology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi 700115, Romania
- Department of Gastroenterology and Hepatology, “St. Spiridon” Emergency Hospital, Iasi 700111, Romania
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Li J, Tong H, Li D, Jiang Q, Zhang Y, Tang W, Jin D, Chen S, Qin X, Zhang S, Xue R. The long non-coding RNA DKFZp434J0226 regulates the alternative splicing process through phosphorylation of SF3B6 in PDAC. Mol Med 2021; 27:95. [PMID: 34470609 PMCID: PMC8411526 DOI: 10.1186/s10020-021-00347-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 07/29/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Long noncoding RNAs (lncRNAs), a type of pervasive genes that regulates various biological processes, are differentially expressed in different types of malignant tumors. The role of lncRNAs in the carcinogenesis of pancreatic ductal adenocarcinoma (PDAC) remains unclear. Here, we investigated the role of the lncRNA DKFZp434J0226 in PDAC. METHODS Aberrantly expressed mRNAs and lncRNAs among six PDAC and paired non-tumorous tissues were profiled using microarray analysis. Quantitative real-time polymerase chain reaction was used to evaluate DKFZp434J0226 expression in PDAC tissues. CCK-8 assay, wound-healing assay, soft agar colony formation assay, and transwell assay were performed to assess the invasiveness and proliferation of PDAC cells. Furthermore, RNA pull-down, immunofluorescence, RNA immunoprecipitation, and western blotting assays were performed to investigate the association between DKFZp434J0226 and SF3B6. Tumor xenografts in mice were used to test for tumor formation in vivo. RESULTS In our study, 222 mRNAs and 128 lncRNAs were aberrantly expressed (≥ twofold change). Of these, 66 mRNAs and 53 lncRNAs were upregulated, while 75 lncRNAs and 156 mRNAs were downregulated. KEGG pathway analysis and the Gene ontology category indicated that these genes were associated with the regulation of mRNA alternative splicing and metabolic balance. Clinical analyses revealed that overexpression of DKFZp434J0226 was associated with worse tumor grading, frequent perineural invasion, advanced tumor-node-metastasis stage, and decreased overall survival and time to progression. Functional assays demonstrated that DKFZp434J0226 promoted PDAC cell migration, invasion, and growth in vitro and accelerated tumor proliferation in vivo. Mechanistically, DKFZp434J0226 interacted with the splicing factor SF3B6 and promoted its phosphorylation, which further regulated the alternative splicing of pre-mRNA. CONCLUSIONS This study indicates that DKFZp434J0226 regulates alternative splicing through phosphorylation of SF3B6 in PDAC and leads to an oncogenic phenotype in PDAC.
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Affiliation(s)
- Jinglei Li
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China
| | - Hanxing Tong
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China
| | - Dongping Li
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Shanghai Institute of Liver Disease, Fudan University, 180 FengLin Road, Shanghai, 200032, China
| | - Qiuyu Jiang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Shanghai Institute of Liver Disease, Fudan University, 180 FengLin Road, Shanghai, 200032, China
| | - Yong Zhang
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China
| | - Wenqing Tang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Shanghai Institute of Liver Disease, Fudan University, 180 FengLin Road, Shanghai, 200032, China
| | - Dayong Jin
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China
| | - She Chen
- NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, 130 DongAn Road, Shanghai, 200032, China
| | - Xinyu Qin
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, 200032, China.
| | - Si Zhang
- NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, 130 DongAn Road, Shanghai, 200032, China.
| | - Ruyi Xue
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Shanghai Institute of Liver Disease, Fudan University, 180 FengLin Road, Shanghai, 200032, China.
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Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors. Nat Rev Gastroenterol Hepatol 2021; 18:493-502. [PMID: 34002083 PMCID: PMC9265847 DOI: 10.1038/s41575-021-00457-x] [Citation(s) in RCA: 650] [Impact Index Per Article: 162.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/20/2021] [Indexed: 12/24/2022]
Abstract
Pancreatic cancer is a leading cause of cancer death worldwide and its global burden has more than doubled over the past 25 years. The highest incidence regions for pancreatic cancer include North America, Europe and Australia, and although much of this increase is due to ageing worldwide populations, there are key modifiable risk factors for pancreatic cancer such as cigarette smoking, obesity, diabetes and alcohol intake. The prevalence of these risk factors is increasing in many global regions, resulting in increasing age-adjusted incidence rates for pancreatic cancer, but the relative contribution from these risk factors varies globally due to variation in the underlying prevalence and prevention strategies. Inherited genetic factors, although not directly modifiable, are an important component of pancreatic cancer risk, and include pathogenic variants in hereditary cancer genes, genes associated with hereditary pancreatitis, as well as common variants identified in genome-wide association studies. Identification of the genetic changes that underlie pancreatic cancer not only provides insight into the aetiology of this cancer but also provides an opportunity to guide early detection strategies. The goal of this Review is to provide an up-to-date overview of the established modifiable and inherited risk factors for pancreatic cancer.
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Farias AJ, Streicher SA, Stram DO, Wang S, Pandol SJ, Le Marchand L, Setiawan VW. Racial/ethnic disparities in weight or BMI change in adulthood and pancreatic cancer incidence: The multiethnic cohort. Cancer Med 2021; 10:4097-4106. [PMID: 33998145 PMCID: PMC8209605 DOI: 10.1002/cam4.3958] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 04/16/2021] [Accepted: 04/17/2021] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Compared to non-Hispanic Whites, Japanese Americans, Native Hawaiians, and African Americans have higher incidences of pancreatic cancer (PCa) that are not entirely explained by rates of obesity but may be explained by weight changes throughout adulthood. METHODS The multiethnic cohort is a population-based prospective cohort study that has followed 155,308 participants since its establishment between 1993 and 1996. A total of 1,328 incident cases with invasive PCa were identified through 2015. We conducted separate multivariable Cox proportional hazards models for self-reported weight-change and BMI-change (age 21 to cohort entry) to determine the association with PCa risk, adjusting for potential confounders including weight or BMI at age 21. RESULTS The mean age at cohort entry was 59.3 years (SD 8.9). An increased risk of PCa was associated with: 1) weight (HR per10 lbs = 1.06; 95% CI = 1.03-1.09) or BMI (HR per kg/m2 = 1.04; 95% CI = 1.02-1.05) at age 21; and 2) weight (HR per 10 lbs = 1.03; 95% CI = 1.01-1.05) or BMI (HR = 1.02; 95% CI = 1.00-1.03) at cohort entry. We found increased risk of PCa between weight (HR per 10 lbs = 1.03; 95% CI = 1.01-1.05) and BMI (HR per 5 kg/m2 = 1.08; 95% CI = 1.01-1.15) change from age 21 to baseline. There were significant interactions between race/ethnicity and weight (p = 0.008) or BMI (p = 0.03) at baseline, and weight (p = 0.02) or BMI (p = 0.02) change. Weight and BMI change through adulthood significantly increased the risk of PCa for Japanese Americans and Latinos, but not for African American, White, or Hawaiian participants. CONCLUSION Our findings indicate that weight or BMI gain has a significant and independent impact on PCa risk, specifically among Latinos and Japanese Americans.
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Affiliation(s)
- Albert J. Farias
- Department of Preventive MedicineKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA
- Norris Comprehensive Cancer CenterLos AngelesCAUSA
| | | | - Daniel O. Stram
- Department of Preventive MedicineKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA
| | - Songren Wang
- Department of Preventive MedicineKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA
| | - Stephen J. Pandol
- Division of GastroenterologyDepartments of MedicineCedars‐Sinai Medical Center and Department of Veterans AffairsLos AngelesCAUSA
| | - Loïic Le Marchand
- Epidemiology ProgramUniversity of Hawaii Cancer CenterHonoluluHawaiiUSA
| | - Veronica W. Setiawan
- Department of Preventive MedicineKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA
- Norris Comprehensive Cancer CenterLos AngelesCAUSA
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Monroy-Iglesias MJ, Dolly S, Sarker D, Thillai K, Van Hemelrijck M, Santaolalla A. Pancreatic Cancer Exposome Profile to Aid Early Detection and Inform Prevention Strategies. J Clin Med 2021; 10:1665. [PMID: 33924591 PMCID: PMC8069449 DOI: 10.3390/jcm10081665] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/19/2021] [Accepted: 04/08/2021] [Indexed: 12/12/2022] Open
Abstract
Pancreatic cancer (PCa) is associated with a poor prognosis and high mortality rate. The causes of PCa are not fully elucidated yet, although certain exposome factors have been identified. The exposome is defined as the sum of all environmental factors influencing the occurrence of a disease during a life span. The development of an exposome approach for PCa has the potential to discover new disease-associated factors to better understand the carcinogenesis of PCa and help with early detection strategies. Our systematic review of the literature identified several exposome factors that have been associated with PCa alone and in combination with other exposures. A potential inflammatory signature has been observed among the interaction of several exposures (i.e., smoking, alcohol consumption, diabetes mellitus, obesity, and inflammatory markers) that further increases the incidence and progression of PCa. A large number of exposures have been identified such as genetic, hormonal, microorganism infections and immune responses that warrant further investigation. Future early detection strategies should utilize this information to assess individuals' risk for PCa.
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Affiliation(s)
- Maria J. Monroy-Iglesias
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK; (M.J.M.-I.); (M.V.H.)
| | - Saoirse Dolly
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK; (S.D.); (D.S.); (K.T.)
| | - Debashis Sarker
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK; (S.D.); (D.S.); (K.T.)
- School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK
| | - Kiruthikah Thillai
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK; (S.D.); (D.S.); (K.T.)
| | - Mieke Van Hemelrijck
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK; (M.J.M.-I.); (M.V.H.)
| | - Aida Santaolalla
- Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King’s College London, London SE1 9RT, UK; (M.J.M.-I.); (M.V.H.)
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Xiao Q, Jones RR, James P, Stolzenberg-Solomon RZ. Light at Night and Risk of Pancreatic Cancer in the NIH-AARP Diet and Health Study. Cancer Res 2021; 81:1616-1622. [PMID: 33514513 PMCID: PMC8693799 DOI: 10.1158/0008-5472.can-20-2256] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 12/07/2020] [Accepted: 01/27/2021] [Indexed: 11/16/2022]
Abstract
Circadian disruption may play a role in carcinogenesis. Recent research suggests that light at night (LAN), a circadian disruptor, may be a risk factor for cancer. Moreover, LAN has been linked to obesity and diabetes, two risk factors for pancreatic ductal adenocarcinoma (PDAC). Here we examine the relationship between LAN and PDAC in an epidemiologic study of 464,371 participants from the NIH-AARP Diet and Health Study. LAN was estimated from satellite imagery at baseline (1996), and incident primary PDAC cases were ascertained from state cancer registries. Cox proportional hazards models were used to estimate HRs and two-sided 95% confidence intervals (CI) for the association between quintiles of LAN and PDAC in the overall population stratified by sex. Over up to 16.2 years of follow-up, a total of 2,502 incident PDAC were identified in the cohort. Higher estimated LAN exposure was associated with an elevated PDAC risk. Compared with those living in areas in the lowest LAN quintile, those in areas in the highest quintile had a 27% increase PDAC risk [HR (95% CI), 1.24 (1.03-1.49)], with similar risk for men [1.21 (0.96-1.53)] and women [1.28 (0.94-1.75)]. In addition, stronger associations were observed in normal and overweight groups compared with the obese group (P interaction = 0.03). Our results support the hypothesis that LAN and circadian disruption may be risk factors for PDAC. SIGNIFICANCE: Our study suggests that higher LAN is a risk factor for pancreatic cancer, contributing to the growing literature that demonstrates the potentially adverse health effects of light pollution.
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Affiliation(s)
- Qian Xiao
- Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas.
| | - Rena R Jones
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, Rockville, Maryland
| | - Peter James
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts
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Luo Y, Li X, Ma J, Abbruzzese JL, Lu W. Pancreatic Tumorigenesis: Oncogenic KRAS and the Vulnerability of the Pancreas to Obesity. Cancers (Basel) 2021; 13:cancers13040778. [PMID: 33668583 PMCID: PMC7918840 DOI: 10.3390/cancers13040778] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 02/08/2021] [Accepted: 02/10/2021] [Indexed: 12/17/2022] Open
Abstract
Simple Summary Pancreatic cancer is a devastating disease with a poor survival rate, and oncogenic mutant KRAS is a major driver of its initiation and progression; however, effective strategies/drugs targeting major forms of mutant KRAS have not been forthcoming. Of note, obesity is known to worsen mutant KRAS-mediated pathologies, leading to PDAC with high penetrance; however, the mechanistic link between obesity and pancreatic cancer remains elusive. The recent discovery of FGF21 as an anti-obesity and anti-inflammation factor and as a downstream target of KRAS has shed new light on the problem. Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies and KRAS (Kirsten rat sarcoma 2 viral oncogene homolog) mutations have been considered a critical driver of PDAC initiation and progression. However, the effects of mutant KRAS alone do not recapitulate the full spectrum of pancreatic pathologies associated with PDAC development in adults. Historically, mutant KRAS was regarded as constitutively active; however, recent studies have shown that endogenous levels of mutant KRAS are not constitutively fully active and its activity is still subject to up-regulation by upstream stimuli. Obesity is a metabolic disease that induces a chronic, low-grade inflammation called meta-inflammation and has long been recognized clinically as a major modifiable risk factor for pancreatic cancer. It has been shown in different animal models that obesogenic high-fat diet (HFD) and pancreatic inflammation promote the rapid development of mutant KRAS-mediated PDAC with high penetrance. However, it is not clear why the pancreas with endogenous levels of mutant KRAS is vulnerable to chronic HFD and inflammatory challenges. Recently, the discovery of fibroblast growth factor 21 (FGF21) as a novel anti-obesity and anti-inflammatory factor and as a downstream target of mutant KRAS has shed new light on this problem. This review is intended to provide an update on our knowledge of the vulnerability of the pancreas to KRAS-mediated invasive PDAC in the context of challenges engendered by obesity and associated inflammation.
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Affiliation(s)
- Yongde Luo
- The First Affiliated Hospital & School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China;
- Department of Medicine, Stony Brook University, Stony Brook, NY 11794, USA;
- Correspondence: (Y.L.); (W.L.)
| | - Xiaokun Li
- The First Affiliated Hospital & School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China;
| | - Jianjia Ma
- Department of Medicine, Stony Brook University, Stony Brook, NY 11794, USA;
| | - James L. Abbruzzese
- Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University, Durham, NC 27710, USA;
| | - Weiqin Lu
- Department of Medicine, Stony Brook University, Stony Brook, NY 11794, USA;
- Correspondence: (Y.L.); (W.L.)
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Soltani S, Abdollahi S, Aune D, Jayedi A. Body mass index and cancer risk in patients with type 2 diabetes: a dose-response meta-analysis of cohort studies. Sci Rep 2021; 11:2479. [PMID: 33510262 PMCID: PMC7844243 DOI: 10.1038/s41598-021-81671-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Accepted: 01/11/2021] [Indexed: 01/10/2023] Open
Abstract
Although obesity has been associated with an increased cancer risk in the general population, the association in patients with type 2 diabetes (T2D) remains controversial. We conducted a dose-response meta-analysis of cohort studies of body mass index (BMI) and the risk of total and site-specific cancers in patients with T2D. A systematic literature search was conducted in PubMed, Scopus, and Medline until September 2020 for cohort studies on the association between BMI and cancer risk in patients with T2D. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects models. Ten prospective and three retrospective cohort studies (3,345,031 participants and 37,412 cases) were included in the meta-analysis. Each 5-unit increase in BMI (kg/m2) was associated with a 6% higher risk of total cancer (RR: 1.06, 95% CI 1.01, 1.10; I2 = 55.4%, n = 6), and with a 12% increased risk in the analysis of breast cancer (RR: 1.12, 95% CI 1.05, 1.20; I2 = 0%, n = 3). The pooled RRs showed no association with prostate cancer (RR: 1.02, 95% CI 0.92, 1.13; I2 = 64.6%, n = 4), pancreatic cancer (RR: 0.97, 95% CI 0.84, 1.11; I2 = 71%, n = 3), and colorectal cancer (RR: 1.05, 95% CI 0.98, 1.13; I2 = 65.9%, n = 2). There was no indication of nonlinearity for total cancer (Pnon-linearity = 0.99), however, there was evidence of a nonlinear association between BMI and breast cancer (Pnon-linearity = 0.004) with steeper increases in risk from a BMI around 35 and above respectively. Higher BMI was associated with a higher risk of total, and breast cancer but not with risk of other cancers, in patients with T2D, however, further studies are needed before firm conclusions can be drawn.
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Affiliation(s)
- Sepideh Soltani
- Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Shima Abdollahi
- Department of Nutrition and Public Health, School of Public Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Dagfinn Aune
- Department of Epidemiology and Biostatistics, Imperial College London, London, UK
- Department of Nutrition, Bjørknes University College, Oslo, Norway
- Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Ullevål, Oslo, Norway
| | - Ahmad Jayedi
- Food Safety Research Center (Salt), Semnan University of Medical Sciences, Semnan, Iran.
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Parra-Soto S, Cowley ES, Rezende LFM, Ferreccio C, Mathers JC, Pell JP, Ho FK, Celis-Morales C. Associations of six adiposity-related markers with incidence and mortality from 24 cancers-findings from the UK Biobank prospective cohort study. BMC Med 2021; 19:7. [PMID: 33423670 PMCID: PMC7798245 DOI: 10.1186/s12916-020-01848-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 11/09/2020] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Adiposity is a strong risk factor for cancer incidence and mortality. However, most of the evidence available has focused on body mass index (BMI) as a marker of adiposity. There is limited evidence on relationships of cancer with other adiposity markers, and if these associations are linear or not. The aim of this study was to investigate the associations of six adiposity markers with incidence and mortality from 24 cancers by accounting for potential non-linear associations. METHODS A total of 437,393 participants (53.8% women; mean age 56.3 years) from the UK Biobank prospective cohort study were included in this study. The median follow-up was 8.8 years (interquartile range 7.9 to 9.6) for mortality and 9.3 years (IQR 8.6 to 9.9) for cancer incidence. Adiposity-related exposures were BMI, body fat percentage, waist-hip ratio, waist-height ratio, and waist and hip circumference. Incidence and mortality of 24 cancers sites were the outcomes. Cox proportional hazard models were used with each of the exposure variables fitted separately on penalised cubic splines. RESULTS During follow-up, 47,882 individuals developed cancer and 11,265 died due to cancer during the follow-up period. All adiposity markers had similar associations with overall cancer incidence. BMI was associated with a higher incidence of 10 cancers (stomach cardia (hazard ratio per 1 SD increment 1.35, (95% CI 1.23; 1.47)), gallbladder (1.33 (1.12; 1.58)), liver (1.27 (1.19; 1.36)), kidney (1.26 (1.20; 1.33)), pancreas (1.12 (1.06; 1.19)), bladder (1.09 (1.04; 1.14)), colorectal (1.10 (1.06; 1.13)), endometrial (1.73 (1.65; 1.82)), uterine (1.68 (1.60; 1.75)), and breast cancer (1.08 (1.05; 1.11))) and overall cancer (1.03 (1.02; 1.04)). All these associations were linear except for breast cancer in postmenopausal women. Similar results were observed when other markers of central and overall adiposity were used. For mortality, nine cancer sites were linearly associated with BMI and eight with waist circumference and body fat percentage. CONCLUSION Adiposity, regardless of the marker used, was associated with an increased risk in 10 cancer sites.
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Affiliation(s)
- Solange Parra-Soto
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, G12 8RZ, UK.,Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK
| | - Emma S Cowley
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK
| | - Leandro F M Rezende
- Departamento de Medicina Preventiva, Universidade Federal de São Paulo, Escola Paulista de Medicina, Sao Paulo, Brazil
| | - Catterina Ferreccio
- Advanced Center for Chronic Diseases, Universidad de Chile and Pontificia Universidad Católica de Chile, Santiago, Chile.,Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - John C Mathers
- Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
| | - Jill P Pell
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, G12 8RZ, UK
| | - Frederick K Ho
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, G12 8RZ, UK
| | - Carlos Celis-Morales
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, G12 8RZ, UK. .,Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, G12 8TA, UK. .,Centro de Investigación en Fisiología del Ejercicio (CIFE), Universidad Mayor, 7510041, Santiago, Chile. .,Laboratorio de Rendimiento Humano, Grupo de Estudio en Educación, Actividad Física y Salud (GEEAFyS), Universidad Católica del Maule, 3480112, Talca, Chile.
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Stolzenberg-Solomon RZ, Derkach A, Moore S, Weinstein S, Albanes D, Sampson J. Associations between metabolites and pancreatic cancer risk in a large prospective epidemiological study. Gut 2020; 69:2008-2015. [PMID: 32060129 PMCID: PMC7980697 DOI: 10.1136/gutjnl-2019-319811] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 01/17/2020] [Accepted: 01/20/2020] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To assess whether prediagnostic metabolites were associated with incident pancreatic ductal adenocarcinoma (PDAC) in a prospective cohort study. DESIGN We conducted an untargeted analysis of 554 known metabolites measured in prediagnostic serum (up to 24 years) to determine their association with incident PDAC in a nested case-control study of male smokers (372 matched case-control sets) and an independent nested case-control study that included women and non-smokers (107 matched sets). Metabolites were measured using Orbitrap Elite or Q-Exactive high-resolution/accurate mass spectrometers. Controls were matched to cases by age, sex, race, date of blood draw, and follow-up time. We used conditional logistic regression adjusted for age to calculate ORs and 95% CIs for a 1 SD increase in log-metabolite level separately in each cohort and combined the two ORs using a fixed-effects meta-analysis. RESULTS Thirty-one metabolites were significantly associated with PDAC at a false discovery rate <0.05 with 12 metabolites below the Bonferroni-corrected threshold (p<9.04×10-5). Similar associations were observed in both cohorts. The dipeptides glycylvaline, aspartylphenylalanine, pyroglutamylglycine, phenylalanylphenylalanine, phenylalanylleucine and tryptophylglutamate and amino acids aspartate and glutamate were positively while the dipeptides tyrosylglutamine and α-glutamyltyrosine, fibrinogen cleavage peptide DSGEGDFXAEGGGVR and glutathione-related amino acid cysteine-glutathione disulfide were inversely associated with PDAC after Bonferroni correction. Five top metabolites demonstrated significant time-varying associations (p<0.023) with the strongest associations observed 10-15 years after participants' blood collection and attenuated thereafter. CONCLUSION Our results suggest that prediagnostic metabolites related to subclinical disease, γ-glutamyl cycle metabolism and adiposity/insulin resistance are associated with PDAC.
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Affiliation(s)
- Rachael Z. Stolzenberg-Solomon
- Metabolic Epidemiology Branch, Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States
| | - Andriy Derkach
- Biostatistics Branch, Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States
| | - Steven Moore
- Metabolic Epidemiology Branch, Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States
| | - Stephanie Weinstein
- Metabolic Epidemiology Branch, Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States
| | - Demetrius Albanes
- Metabolic Epidemiology Branch, Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States
| | - Joshua Sampson
- Biostatistics Branch, Division Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, United States
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Jacobs EJ, Newton CC, Stevens VL, Patel AV, Flanders WD, Gapstur SM. A Large Cohort Study of Body Mass Index and Pancreatic Cancer by Smoking Status. Cancer Epidemiol Biomarkers Prev 2020; 29:2680-2685. [PMID: 32962978 DOI: 10.1158/1055-9965.epi-20-0591] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 07/31/2020] [Accepted: 09/17/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Some evidence suggests the association between body mass index (BMI) and pancreatic cancer risk is weaker among current smokers than among never smokers. METHODS We examined the association between BMI and pancreatic cancer mortality among adults who reported smoking status at enrollment into Cancer Prevention Study-II in 1982, including 420,543 never smokers, 282,244 former cigarette smokers, and 219,885 current cigarette smokers. After excluding the first 3 years of follow-up to reduce reverse causation, we calculated multivariable-adjusted hazard ratios (HR). RESULTS During the full follow-up period from 1985 to 2014, 7,904 participants died of pancreatic cancer. The HR per 5 BMI units was lower among current smokers [HR = 1.14; 95% confidence interval (CI), 1.07-1.20] than never smokers (HR = 1.22; 95% CI, 1.17-1.27), although this difference was not statistically significant (P = 0.06). BMI was significantly less strongly associated with pancreatic cancer mortality among current smokers reporting ≥20 cigarettes/day (HR = 1.10; 95% CI, 1.03-1.18) than among never smokers. During follow-up within 10 years of enrollment, when current smokers at enrollment were the most likely to have still been smoking, BMI was not associated with pancreatic cancer mortality among current smokers (HR = 1.02; 95% CI, 0.90-1.16, P = 0.03 for difference between current and never smokers). BMI HRs were similar among former and never smokers. CONCLUSIONS These results support a weaker association between BMI and pancreatic cancer among current smokers than among never smokers. IMPACT In populations with low smoking prevalence, the pancreatic cancer burden due to BMI is likely to be higher than that predicted by risk estimates from studies including substantial numbers of smokers.
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Affiliation(s)
- Eric J Jacobs
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
| | - Christina C Newton
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
| | - Victoria L Stevens
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
| | - Alpa V Patel
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
| | - W Dana Flanders
- Rollins School of Public Health, Department of Epidemiology, Emory University, Atlanta, Georgia
| | - Susan M Gapstur
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
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Mizrahi JD, Surana R, Valle JW, Shroff RT. Pancreatic cancer. Lancet 2020; 395:2008-2020. [PMID: 32593337 DOI: 10.1016/s0140-6736(20)30974-0] [Citation(s) in RCA: 1626] [Impact Index Per Article: 325.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 04/06/2020] [Accepted: 04/17/2020] [Indexed: 02/07/2023]
Abstract
Pancreatic cancer is a highly fatal disease with a 5-year survival rate of approximately 10% in the USA, and it is becoming an increasingly common cause of cancer mortality. Risk factors for developing pancreatic cancer include family history, obesity, type 2 diabetes, and tobacco use. Patients typically present with advanced disease due to lack of or vague symptoms when the cancer is still localised. High quality computed tomography with intravenous contrast using a dual phase pancreatic protocol is typically the best method to detect a pancreatic tumour and to determine surgical resectability. Endoscopic ultrasound is an increasingly used complementary staging modality which also allows for diagnostic confirmation when combined with fine needle aspiration. Patients with pancreatic cancer are often divided into one of four categories based on extent of disease: resectable, borderline resectable, locally advanced, and metastatic; patient condition is also an important consideration. Surgical resection represents the only chance for cure, and advancements in adjuvant chemotherapy have improved long-term outcomes in these patients. Systemic chemotherapy combinations including FOLFIRINOX (5-fluorouracil, folinic acid [leucovorin], irinotecan, and oxaliplatin) and gemcitabine plus nab-paclitaxel remain the mainstay of treatment for patients with advanced disease. Data on the benefit of PARP inhibition as maintenance therapy in patients with germline BRCA1 or BRACA2 mutations might prove to be a harbinger of advancement in targeted therapy. Additional research efforts are focusing on modulating the pancreatic tumour microenvironment to enhance the efficacy of the immunotherapeutic strategies.
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Affiliation(s)
- Jonathan D Mizrahi
- Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rishi Surana
- Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Juan W Valle
- Division of Cancer Sciences, University of Manchester, Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, UK
| | - Rachna T Shroff
- Division of Hematology and Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson, AZ, USA.
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Jacobs EJ, Newton CC, Patel AV, Stevens VL, Islami F, Flanders WD, Gapstur SM. The Association Between Body Mass Index and Pancreatic Cancer: Variation by Age at Body Mass Index Assessment. Am J Epidemiol 2020; 189:108-115. [PMID: 31602476 DOI: 10.1093/aje/kwz230] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 09/26/2019] [Indexed: 01/02/2023] Open
Abstract
Higher body mass index (BMI; weight (kg)/height (m)2) is associated with increased risk of pancreatic cancer in epidemiologic studies. However, BMI has usually been assessed at older ages, potentially underestimating the full impact of excess weight. We examined the association between BMI and pancreatic cancer mortality among 963,317 adults who were aged 30-89 years at their enrollment in Cancer Prevention Study II in 1982. During follow-up through 2014, a total of 8,354 participants died of pancreatic cancer. Hazard ratios per 5 BMI units, calculated using proportional hazards regression, declined steadily with age at BMI assessment, from 1.25 (95% confidence interval: 1.18, 1.33) in persons aged 30-49 years at enrollment to 1.13 (95% confidence interval: 1.02, 1.26) in those aged 70-89 years at enrollment (P for trend = 0.005). On the basis of a hazard ratio of 1.25 per 5 BMI units at age 45 years, we estimated that 28% of US pancreatic cancer deaths among persons born in 1970-1974 will be attributable to BMI ≥25.0-nearly twice the equivalent proportion of those born in the 1930s, a birth cohort with much lower BMI in middle age. These results suggest that BMI before age 50 years is more strongly associated with pancreatic cancer risk than BMI at older ages, and they underscore the importance of avoiding excess weight gain before middle age for preventing this highly fatal cancer.
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Affiliation(s)
- Eric J Jacobs
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
| | - Christina C Newton
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
| | - Alpa V Patel
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
| | - Victoria L Stevens
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
| | - Farhad Islami
- Surveillance and Health Service Research, American Cancer Society, Atlanta, Georgia
| | - W Dana Flanders
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Susan M Gapstur
- Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
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De Rubeis V, Cotterchio M, Smith BT, Griffith LE, Borgida A, Gallinger S, Cleary S, Anderson LN. Trajectories of body mass index, from adolescence to older adulthood, and pancreatic cancer risk; a population-based case-control study in Ontario, Canada. Cancer Causes Control 2019; 30:955-966. [PMID: 31230151 PMCID: PMC6685923 DOI: 10.1007/s10552-019-01197-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 06/15/2019] [Indexed: 01/28/2023]
Abstract
PURPOSE Pancreatic cancer has the highest fatality rate of all cancers. Adulthood obesity is an established risk factor for pancreatic cancer; however, life-course obesity is not well understood. The aim of this study was to evaluate the association between body mass index (BMI) trajectories throughout the life-course and pancreatic cancer risk. METHODS A population-based case-control study was conducted (2011-2013) in Ontario, Canada. Cases were recruited from the Ontario pancreas cancer study (n = 310) and controls from the Ontario cancer risk factor study (n = 1258). Questionnaires captured self-reported height and weight at four timepoints (adolescence, 20 s, 30-40 s, 50-60 s). BMI trajectories were identified using latent class growth mixture modeling. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression. RESULTS Five BMI trajectories were identified: stable-normal weight (38.9%), progressively overweight (42.2%), persistent overweight (12.6%), progressive obesity (4.2%), and persistent obesity (2.1%). The persistent overweight (OR = 1.55; 95% CI 1.02, 2.39) and progressive obesity trajectories (OR = 1.49; 95% CI 0.77, 2.87) compared to stable-normal weight were associated with increased odds of pancreatic cancer. When BMI was evaluated separately the strongest associations with pancreatic cancer emerged in young and mid-adulthood. CONCLUSION BMI trajectories characterized by overweight in early adulthood were associated with increased pancreatic cancer risk suggesting a life-course approach to disease risk.
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Affiliation(s)
- Vanessa De Rubeis
- Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Hamilton, ON, L8S4L8, Canada
| | - Michelle Cotterchio
- Prevention and Cancer Control, Cancer Care Ontario, Toronto, ON, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Brendan T Smith
- Public Health Ontario, Toronto, ON, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Lauren E Griffith
- Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Hamilton, ON, L8S4L8, Canada
| | - Ayelet Borgida
- Division of General Surgery, Toronto General Hospital, Toronto, ON, Canada
| | - Steven Gallinger
- Division of General Surgery, Toronto General Hospital, Toronto, ON, Canada
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
| | - Sean Cleary
- Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Laura N Anderson
- Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Hamilton, ON, L8S4L8, Canada.
- Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, ON, Canada.
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Fukui H, Hori M, Fukuda Y, Onishi H, Nakamoto A, Ota T, Ogawa K, Ninomiya K, Tatsumi M, Osuga K, Yamada D, Eguchi H, Miyoshi E, Tomiyama N. Evaluation of fatty pancreas by proton density fat fraction using 3-T magnetic resonance imaging and its association with pancreatic cancer. Eur J Radiol 2019; 118:25-31. [PMID: 31439250 DOI: 10.1016/j.ejrad.2019.06.024] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 05/20/2019] [Accepted: 06/26/2019] [Indexed: 01/03/2023]
Abstract
PURPOSE To evaluate whether pancreatic magnetic resonance imaging-proton density fat fraction (MRI-PDFF) correlates with histological pancreatic fat fraction and its possible usefulness as a biomarker of pancreatic cancer compared with pancreatic index (PI) using computed tomography (CT number of the pancreas divided by that of the spleen). METHOD We included 55 consecutive patients (24 with pancreatic cancer and 31 controls; median age, 72 years) who preoperatively underwent MRI-PDFF using IDEAL-IQ and unenhanced CT and did not receive preoperative therapy. Histologic pancreatic fat fraction was measured in non-tumorous pancreatic tissues at the resection stump. A board-certified radiologist evaluated MRI-PDFF and PI. Correlations were evaluated among MRI-PDFF, PI, and histologic pancreatic fat fraction; the usefulness of MRI-PDFF as a predictor of pancreatic cancer was assessed. RESULTS Histologic pancreatic fat fraction significantly correlated with MRI-PDFF and PI (r = 0.802 and -0.534, respectively; P < 0.01). The absolute correlation coefficient was significantly higher for MRI-PDFF than for PI (P < 0.01). Compared with the control group, the pancreatic cancer group had higher MRI-PDFF and histologic pancreatic fat fraction (P < 0.01) but lower PI (P < 0.01). In multivariate analysis, MRI-PDFF was found to be the sole independent risk factor for pancreatic cancer (odds ratio: 1.19; P < 0.01). CONCLUSIONS Pancreatic fat, which was associated with pancreatic cancer, could be quantified by MRI-PDFF measurement; therefore, MRI-PDFF should be considered as a promising and superior imaging biomarker for estimating the probability of pancreatic cancer than PI.
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Affiliation(s)
- Hideyuki Fukui
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan.
| | - Masatoshi Hori
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
| | - Yasunari Fukuda
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan
| | - Hiromitsu Onishi
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
| | - Atsushi Nakamoto
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
| | - Takashi Ota
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
| | - Kazuya Ogawa
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
| | - Keisuke Ninomiya
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
| | - Mitsuaki Tatsumi
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
| | - Keigo Osuga
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Japan
| | - Eiji Miyoshi
- Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Japan
| | - Noriyuki Tomiyama
- Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
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Gordon-Dseagu VL, Devesa SS, Goggins M, Stolzenberg-Solomon R. Pancreatic cancer incidence trends: evidence from the Surveillance, Epidemiology and End Results (SEER) population-based data. Int J Epidemiol 2019; 47:427-439. [PMID: 29149259 DOI: 10.1093/ije/dyx232] [Citation(s) in RCA: 141] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/25/2017] [Indexed: 12/14/2022] Open
Abstract
Background Annual pancreatic cancer incidence rates have been increasing. We examine pancreatic cancer incidence trends by demographics and histologic type. Methods Data from the Surveillance, Epidemiology and End Results (SEER) registries were available to assess temporal trends and pancreatic cancer rates from 1974 to 2013. Results Pancreatic cancer incidence rates declined between the 1970s and 1990s but increased from 1994 to 2013 among White males. Among non-Hispanic White and Hispanic males, the annual percent change (APC) in incidence between 1992 and 2013 was 0.84% and 0.73%, respectively. Rates also rose among White non-Hispanic, Hispanic and Asian females (APC = 0.81%, 0.56% and 1.23%, respectively) and even more rapidly among females aged 25-34 years (APC > 2.5%). Rates among Black males and females remained unchanged, but higher compared with the other racial/ethnic groups. By histologic type, the increases were greatest for non-secretory endocrine cancers ( > 6%), followed by ductal adenocarcinomas (∼5%) and adenocarcinoma, NOS (∼1.4%)-the largest histologic subgroup of pancreatic cancer. Rates for mucinous adenocarcinomas and poorly specified pancreatic cancer decreased. Overall, incidence rates during 2000-13 were higher among males than females [MF incidence rate ratio (IRR) = 1.28]. The IRR was >1.00 at all ages ≥ 35, but rates among females were higher at younger ages (IRRs 15-24: 0.66, 25-34: 0.81). The MF IRRs for most of the histologic types were elevated among males apart from solid pseudopapillary adenocarcinoma and cystic carcinomas (IRR = 0.22, confidence interval: 0.14-0.34 and 0.52, 0.41-0.65, respectively). Conclusion Pancreatic cancer has been increasing overall, but patterns differ by demographic group and histologic type. Many of the trends parallel changing prevalence of lifestyle risk factors such as smoking, overweight and obesity, and diabetes in the USA, particularly for pancreatic adenocarcinoma, and improved diagnosis methods during the past 40 years.
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Affiliation(s)
- Vanessa L Gordon-Dseagu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20850, USA
| | - Susan S Devesa
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20850, USA
| | | | - Rachael Stolzenberg-Solomon
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20850, USA
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Arriaga ME, Vajdic CM, MacInnis RJ, Canfell K, Magliano DJ, Shaw JE, Byles JE, Giles GG, Taylor AW, Gill TK, Hirani V, Cumming RG, Mitchell RP, Banks E, Marker J, Adelstein BA, Laaksonen MA. The burden of pancreatic cancer in Australia attributable to smoking. Med J Aust 2019; 210:213-220. [PMID: 30656698 DOI: 10.5694/mja2.12108] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Accepted: 10/26/2018] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To estimate the burden of pancreatic cancer in Australia attributable to modifiable exposures, particularly smoking. DESIGN Prospective pooled cohort study. SETTING, PARTICIPANTS Seven prospective Australian study cohorts (total sample size, 365 084 adults); participant data linked to national registries to identify cases of pancreatic cancer and deaths. MAIN OUTCOME MEASURES Associations between exposures and incidence of pancreatic cancer, estimated in a proportional hazards model, adjusted for age, sex, study, and other exposures; future burden of pancreatic cancer avoidable by changes in exposure estimated as population attributable fractions (PAFs) for whole population and for specific population subgroups with a method accounting for competing risk of death. RESULTS There were 604 incident cases of pancreatic cancer during the first 10 years of follow-up. Current and recent smoking explained 21.7% (95% CI, 13.8-28.9%) and current smoking alone explained 15.3% (95% CI, 8.6-22.6%) of future pancreatic cancer burden. This proportion of the burden would be avoidable over 25 years were current smokers to quit and there were no new smokers. The burden attributable to current smoking is greater for men (23.9%; 95% CI, 13.3-33.3%) than for women (7.2%; 95% CI, -0.4% to 14.2%; P = 0.007) and for those under 65 (19.0%; 95% CI, 8.1-28.6%) than for older people (6.6%; 95% CI, 1.9-11.1%; P = 0.030). There were no independent relationships between body mass index or alcohol consumption and pancreatic cancer. CONCLUSIONS Strategies that reduce the uptake of smoking and encourage current smokers to quit could substantially reduce the future incidence of pancreatic cancer in Australia, particularly among men.
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Affiliation(s)
- Maria E Arriaga
- Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW
| | - Claire M Vajdic
- Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW
| | - Robert J MacInnis
- Cancer Council Victoria, Melbourne, VIC.,Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC
| | - Karen Canfell
- Cancer Council NSW, Sydney, NSW.,University of Sydney, Sydney, NSW.,Prince of Wales Clinical School, University of New South Wales, Sydney, NSW
| | | | | | - Julie E Byles
- Research Centre for Gender, Health and Ageing, University of Newcastle, Newcastle, NSW
| | - Graham G Giles
- Cancer Council Victoria, Melbourne, VIC.,Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC
| | - Anne W Taylor
- Adelaide Medical School, University of Adelaide, Adelaide, SA
| | - Tiffany K Gill
- Adelaide Medical School, University of Adelaide, Adelaide, SA
| | - Vasant Hirani
- University of Sydney, Sydney, NSW.,Charles Perkins Centre, University of Sydney, Sydney, NSW
| | - Robert G Cumming
- University of Sydney, Sydney, NSW.,ANZAC Research Institute, University of Sydney and Concord Hospital, Sydney, NSW
| | - R Paul Mitchell
- Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, NSW
| | - Emily Banks
- Australian National University, Canberra, ACT
| | | | | | - Maarit A Laaksonen
- Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW
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