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McHale MT. New Insights in Endometriosis Subtypes and Ovarian Cancer Risk. JAMA 2024; 332:460-461. [PMID: 39018063 DOI: 10.1001/jama.2024.12357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/18/2024]
Affiliation(s)
- Michael T McHale
- Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, and Perioperative Services, Moores Cancer Center, UC San Diego Health, University of California, San Diego
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2
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Butler H, Saulat O, Guinn BA. Identification of biomarkers for the diagnosis and targets for therapy in patients with clear cell ovarian cancer: a systematic literature review. Carcinogenesis 2022; 43:183-189. [PMID: 35104328 PMCID: PMC9036986 DOI: 10.1093/carcin/bgac012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 01/26/2022] [Indexed: 02/03/2023] Open
Abstract
Clear cell ovarian cancer (CCOC) is a rare type of epithelial cancer often resistant to platinum-based chemotherapy. Biomarkers for the diagnosis of CCOC, and targets for immunotherapy, both have the potential to improve outcomes for patients. Our review aims to determine whether any antigens already identified in the literature could fulfil this remit. PubMed, Medline, Web of Science, Scopus, Cochrane, CINAHL and EMBASE were searched and included all reported studies up until August 2021. Primary research articles on human adult females including at least 10 CCOC patients were included. Quality assurance was carried out using a modified version of the QUADAS-2 tool. Sensitivity, specificity and area under the curve were extracted from each included study by two independent reviewers. Twenty-three articles were included which identified 19 gene transcripts/proteins and one antibody, with reported sensitivities between 21% and 100% and specificities between 0% and 100% for expression in CCOC and differentiation from other epithelial ovarian cancer subtypes, benign gynaecological disease or normal tissue. Twelve studies identified biomarkers with a sensitivity and specificity above 80%. A panel of biomarkers consisting of IMP3, napsin A and hepatocyte nuclear factor 1 beta achieved the highest area under the curve of 0.954. This review demonstrates that there are promising candidate biomarkers for the diagnosis of CCOC, some of which are highly specific, and have the potential to act as targets for therapy. However, larger cohort studies are needed to validate these biomarkers and their potential use in clinical practice.
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Affiliation(s)
- Holly Butler
- Hull York Medical School, University of Hull, Hull, UK
| | - Omar Saulat
- Hull York Medical School, University of Hull, Hull, UK
| | - Barbara-ann Guinn
- To whom correspondence should be addressed: Tel: +44 (0)1482 466543;
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Harman RM, Das SP, Bartlett AP, Rauner G, Donahue LR, Van de Walle GR. Beyond tradition and convention: benefits of non-traditional model organisms in cancer research. Cancer Metastasis Rev 2020; 40:47-69. [PMID: 33111160 DOI: 10.1007/s10555-020-09930-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 09/01/2020] [Indexed: 02/07/2023]
Abstract
Traditional laboratory model organisms are indispensable for cancer research and have provided insight into numerous mechanisms that contribute to cancer development and progression in humans. However, these models do have some limitations, most notably related to successful drug translation, because traditional model organisms are often short-lived, small-bodied, genetically homogeneous, often immunocompromised, are not exposed to natural environments shared with humans, and usually do not develop cancer spontaneously. We propose that assimilating information from a variety of long-lived, large, genetically diverse, and immunocompetent species that live in natural environments and do develop cancer spontaneously (or do not develop cancer at all) will lead to a more comprehensive understanding of human cancers. These non-traditional model organisms can also serve as sentinels for environmental risk factors that contribute to human cancers. Ultimately, expanding the range of animal models that can be used to study cancer will lead to improved insights into cancer development, progression and metastasis, tumor microenvironment, as well as improved therapies and diagnostics, and will consequently reduce the negative impacts of the wide variety of cancers afflicting humans overall.
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Affiliation(s)
- Rebecca M Harman
- Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA
| | - Sanjna P Das
- Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA
| | - Arianna P Bartlett
- Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA
| | - Gat Rauner
- Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA
| | - Leanne R Donahue
- Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA
| | - Gerlinde R Van de Walle
- Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
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Protective Effects of Epigallocatechin Gallate (EGCG) on Endometrial, Breast, and Ovarian Cancers. Biomolecules 2020; 10:biom10111481. [PMID: 33113766 PMCID: PMC7694163 DOI: 10.3390/biom10111481] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 10/22/2020] [Accepted: 10/23/2020] [Indexed: 02/07/2023] Open
Abstract
Green tea and its major bioactive component, (-)-epigallocatechin gallate (EGCG), possess diverse biological properties, particularly antiproliferation, antimetastasis, and apoptosis induction. Many studies have widely investigated the anticancer and synergistic effects of EGCG due to the side effects of conventional cytotoxic agents. This review summarizes recent knowledge of underlying mechanisms of EGCG on protective roles for endometrial, breast, and ovarian cancers based on both in vitro and in vivo animal studies. EGCG has the ability to regulate many pathways, including the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), inhibition of nuclear factor-κB (NF-κB), and protection against epithelial-mesenchymal transition (EMT). EGCG has also been found to interact with DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), which affect epigenetic modifications. Finally, the action of EGCG may exert a suppressive effect on gynecological cancers and have beneficial effects on auxiliary therapies for known drugs. Thus, future clinical intervention studies with EGCG will be necessary to more and clear evidence for the benefit to these cancers.
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Goodman JE, Kerper LE, Prueitt RL, Marsh CM. A critical review of talc and ovarian cancer. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART B, CRITICAL REVIEWS 2020; 23:183-213. [PMID: 32401187 DOI: 10.1080/10937404.2020.1755402] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
The association between perineal talc use and ovarian cancer has been evaluated in several epidemiology studies. Some case-control studies reported weak positive associations, while other case-control and three large prospective cohort investigations found this association to be null. A weight-of-evidence evaluation was conducted of the epidemiology, toxicity, exposure, transport, in vitro, and mechanistic evidence to determine whether, collectively, these data support a causal association. Our review of the literature indicated that, while both case-control and cohort studies may be impacted by bias, the possibility of recall and other biases from the low participation rates and retrospective self-reporting of talc exposure cannot be ruled out for any of the case-control studies. The hypothesis that talc exposure induces ovarian cancer is only supported if one discounts the null results of the cohort studies and the fact that significant bias and/or confounding are likely reasons for the associations reported in some case-control investigations. In addition, one would need to ignore the evidence from animal experiments that show no marked association with cancer, in vitro and genotoxicity studies that did not indicate a carcinogenic mechanism of action for talc, and mechanistic and transport investigations that did not support the retrograde transport of talc to the ovaries. An alternative hypothesis that talc does not produce ovarian cancer, and that bias and confounding contribute the reported positive associations in case-control studies, is better supported by the evidence across all scientific disciplines. It is concluded that the evidence does not support a causal association between perineal talc use and ovarian cancer.
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Briseño Campos AG, Cruz Rodríguez A, García Perales MO, Serna Vela FJ, Camarillo Elizalde DG, Robles Martínez MDC. Incidence of intraepithelial fallopian tube neoplasias in mexican women over 40 years of age that underwent elective hysterectomy. J Ovarian Res 2019; 12:54. [PMID: 31182132 PMCID: PMC6558869 DOI: 10.1186/s13048-019-0515-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Accepted: 04/18/2019] [Indexed: 11/10/2022] Open
Abstract
AIMS The incidence of intraepithelial neoplasia in the fallopian tubes of women over 40 years of age who had undergone elective hysterectomy was assessed at the Aguascalientes Women's Hospital. METHODS An observational, prospective, descriptive study was carried out at the Aguascalientes Women's Hospital on female patients over 40 years of age who underwent elective hysterectomy between July and October 2017. In these 4 months, 85 patients underwent elective hysterectomy. RESULTS In this study, 85 patients who received a hysterectomy for non-oncological reasons were analyzed. Salpinx alterations compatible with intraepithelial neoplasia in the Fallopian tubes were found in 2.4% of the patients studied. CONCLUSIONS The incidence of intraepithelial neoplasia in the fallopian tubes of high-risk patients at the Aguascalientes Women's Hospital is 2.4%. Prophylactic salpingectomy is a simple procedure and has the potential to decrease the risk of high-grade ovarian cancer. In premenopausal patients, total abdominal hysterectomy with bilateral salpingectomy should be the procedure most often performed.
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Affiliation(s)
| | - Antonio Cruz Rodríguez
- Gynecological Oncology Department, Aguascalientes Women's Hospital, Siglo XXI # 109; Morelos, 20298, Aguascalientes, Mexico.
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Nagle CM, Ibiebele T, Shivappa N, Hébert JR, DeFazio A, Webb PM. The association between the inflammatory potential of diet and risk of developing, and survival following, a diagnosis of ovarian cancer. Eur J Nutr 2018; 58:1747-1756. [PMID: 30027314 DOI: 10.1007/s00394-018-1779-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 07/11/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE Inflammation has been implicated in ovarian carcinogenesis. This study evaluated two dietary indices: the Dietary Inflammatory Index (DII®) and the Empirical Dietary Inflammatory Pattern (EDIP), in relation to risk of developing, and survival following, a diagnosis of ovarian cancer. METHODS Data came from the Australian Ovarian Cancer Study (1375 cases, 1415 population controls). DII and EDIP scores were computed from dietary information obtained using a semiquantitative food-frequency questionnaire. Logistic regression was used to assess the association between DII and EDIP scores and risk of ovarian cancer and proportional hazards models were used for survival analysis. RESULTS A high DII score, reflecting a more pro-inflammatory diet, was associated with a modest increased risk of ovarian cancer [odds ratio (OR) DII scoreQ4 vs.Q1 = 1.31, 95% CI 1.06-1.63, ptrend = 0.014]. Likewise a high EDIP score was associated with an increase in risk of ovarian cancer [OR EDIP scoreQ4 vs.Q1 = 1.39, 95% confidence interval (CI) 1.12-1.73, ptrend = 0.002]. We found no association between DII or EDIP score and overall or ovarian cancer-specific survival. CONCLUSION In conclusion, our results suggest that a pro-inflammatory diet modestly increases the risk of developing ovarian cancer.
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Affiliation(s)
- C M Nagle
- Gynaecological Cancers Group, QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Herston, QLD, 4029, Australia. .,Faculty of Medicine, School of Public Health, The University of Queensland, Brisbane, Australia.
| | - T Ibiebele
- Gynaecological Cancers Group, QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Herston, QLD, 4029, Australia
| | - N Shivappa
- Cancer Prevention and Control Program, University of South Carolina, 915 Greene Street, Suite 241-2, Columbia, SC, 29208, USA.,Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene Street, Suite 400, Columbia, SC, 29208, USA.,Connecting Health Innovations LLC (CHI), 1417 Gregg Street, Columbia, SC, 29201, USA
| | - J R Hébert
- Cancer Prevention and Control Program, University of South Carolina, 915 Greene Street, Suite 241-2, Columbia, SC, 29208, USA.,Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, 915 Greene Street, Suite 400, Columbia, SC, 29208, USA.,Connecting Health Innovations LLC (CHI), 1417 Gregg Street, Columbia, SC, 29201, USA
| | - A DeFazio
- Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia.,Department of Gynaecological Oncology, Westmead Hospital, Sydney, Australia
| | - P M Webb
- Gynaecological Cancers Group, QIMR Berghofer Medical Research Institute, Locked Bag 2000, Royal Brisbane Hospital, Herston, QLD, 4029, Australia.,Faculty of Medicine, School of Public Health, The University of Queensland, Brisbane, Australia
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Hoskins PJ, Gotlieb WH. Missed therapeutic and prevention opportunities in women with BRCA-mutated epithelial ovarian cancer and their families due to low referral rates for genetic counseling and BRCA testing: A review of the literature. CA Cancer J Clin 2017; 67:493-506. [PMID: 28881380 DOI: 10.3322/caac.21408] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 07/18/2017] [Accepted: 07/19/2017] [Indexed: 12/24/2022] Open
Abstract
Answer questions and earn CME/CNE Fifteen percent of women with epithelial ovarian cancer have inherited mutations in the BRCA breast cancer susceptibility genes. Knowledge of her BRCA status has value both for the woman and for her family. A therapeutic benefit exists for the woman with cancer, because a new family of oral drugs, the poly ADP-ribose polymerase (PARP) inhibitors, has recently been approved, and these drugs have the greatest efficacy in women who carry the mutation. For her family, there is the potential to prevent ovarian cancer in those carrying the mutation by using risk-reducing surgery. Such surgery significantly reduces the chance of developing this, for the most part, incurable cancer. Despite these potential benefits, referral rates for genetic counseling and subsequent BRCA testing are low, ranging from 10% to 30%, indicating that these therapeutic and prevention opportunities are being missed. The authors have reviewed the relevant available literature. Topics discussed are BRCA and its relation to ovarian cancer, the rates of referral for genetic counseling/BRCA testing, reasons for these low rates, potential strategies to improve on those rates, lack of effectiveness of current screening strategies, the pros and cons of risk-reducing surgery, other prevention options, and the role and value of PARP inhibitors. CA Cancer J Clin 2017;67:493-506. © 2017 American Cancer Society.
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Affiliation(s)
- Paul J Hoskins
- Medical Oncologist and Past President, Society of Gynecologic Oncology Canada, British Columbia Cancer Agency, Vancouver Center, BC, Canada
| | - Walter H Gotlieb
- Gynecologic Oncologist and President, Society of Gynecologic Oncology Canada, McGill University, Jewish General Hospital, Montreal, QC, Canada
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Caglayan A, Katlan DC, Selçuk Tuncer Z, Yüce K, Sayal HB, Coşkun Salman M, Kocer-Gumusel B. Impaired antioxidant enzyme functions with increased lipid peroxidation in epithelial ovarian cancer. IUBMB Life 2017; 69:802-813. [PMID: 28884887 DOI: 10.1002/iub.1675] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 07/12/2017] [Indexed: 02/06/2023]
Abstract
We aimed to identify the possible role of oxidant-antioxidant status in epithelial ovarian cancer (EOC) by measuring (a) antioxidant enzyme (AOE) activities [total superoxide dismutase (SODtotal ), manganese-SOD (Mn-SOD), copper,zinc-SOD (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GPx1)], (b) Mn-SOD protein expression, (c) lipid peroxidation markers [malondialdehyde (MDA), 8-epi-prostaglandin-F2α (8-epi-PGF2α)] and by evaluating the possible correlations between tumor biomarkers, reproductive hormone levels and all measured parameters, comprehensively. The data obtained from the patients with EOC (M, n = 26) evaluated according to the histopathological/clinical characteristics of tumors and compared with data of healthy controls [Ctissue (C1) and Cblood/urine (C2), n = 30, respectively). Significantly, low activities of tumor SODtotal (52%), Mn-SOD (42%), Cu,Zn-SOD (55%); high activities of tumor and erythrocyte CAT (66%, 33% respectively) and tumor GPx1 (60%); high levels of tumor Mn-SOD protein expression; tumor MDA (193%) and urinary 8-epi-PGF2α (179%) were observed in serous EOC tumors (M1, n = 18) compared with controls (P < 0.05). However, higher levels of tumor MDA, Mn-SOD protein expression and urinary 8-epi-PGF2α were observed along with lower tumor CAT activity in poorly differentiated or undifferentiated (grade 3, G 3) versus well or moderately well differentiated (grade 1-2, G 1-2) serous EOC tumors. Obtained data indicate the presence of a severe redox imbalance in EOC and draw attention to the criticial role of AOEs in the pathogenesis of the disease. © 2017 IUBMB Life, 69(10):802-813, 2017.
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Affiliation(s)
- Aydan Caglayan
- Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
| | - Doruk Cevdi Katlan
- Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.,Obstetrics and Gynecology, Suleymaniye Research and Education Hospital, ıstanbul, Turkey
| | - Zafer Selçuk Tuncer
- Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Kunter Yüce
- Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Hasan Berkan Sayal
- Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.,Republic of Turkey Ministry of Health, Malatya Research and Education Hospital, Malatya, Turkey
| | - Mehmet Coşkun Salman
- Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Belma Kocer-Gumusel
- Department of Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
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Burke AJ, Garrido P, Johnson C, Sullivan FJ, Glynn SA. Inflammation and Nitrosative Stress Effects in Ovarian and Prostate Pathology and Carcinogenesis. Antioxid Redox Signal 2017; 26:1078-1090. [PMID: 28326819 DOI: 10.1089/ars.2017.7004] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
SIGNIFICANCE Prostate and ovarian cancers are major contributors to cancer-related deaths worldwide. Recently, inflammation and nitrosative stress have been implicated in carcinogenesis, with the overexpression of NOS2 and concomitant release of nitric oxide (NO) associated with cancer initiation and progression. Recent Advances: An increasing body of evidence indicates an association between NOS2 expression and aggressive ovarian cancer. Research also indicates a role for NO in prostate disease pathology and prostate cancer. A therapeutic role for NOS2 inhibition and/or NO drugs exists for the treatment of both ovarian and prostate tumors. CRITICAL ISSUES Herein, we review the key molecular effects associated with NOS2 in ovarian and prostate cancer. NOS2 increases angiogenesis and tumor proliferation and correlates with aggressive type II ovarian tumors. NOS2 expressing tumors are sensitive to cisplatin chemotherapy, and NO may be used to sensitize cisplatin-resistant tumors to chemotherapy. NOS2 is highly expressed in prostate tumors compared to non-neoplastic prostate pathologies. NO may play a role in the development of androgen-independent prostate cancer via s-nitrosylation of the androgen receptor. Moreover, NOS2 inhibitors and NO donor drugs show therapeutic potential in ovarian and prostate cancer as single agents or dual drugs, by either inhibiting the effects of NOS2 or increasing NO levels to induce cytotoxic effects. FUTURE DIRECTIONS NOS2 and NO present new targets for the treatment of ovarian and prostate tumors. Furthermore, understanding NO-related tumor biology in these cancers presents a new means for improved patient stratification to the appropriate treatment regimen. Antioxid. Redox Signal. 26, 1078-1090.
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Affiliation(s)
- Amy J Burke
- 1 Prostate Cancer Institute, School of Medicine, National University of Ireland Galway , Galway, Ireland
| | - Pablo Garrido
- 1 Prostate Cancer Institute, School of Medicine, National University of Ireland Galway , Galway, Ireland .,2 Discipline of Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway , Galway, Ireland
| | - Carol Johnson
- 1 Prostate Cancer Institute, School of Medicine, National University of Ireland Galway , Galway, Ireland .,2 Discipline of Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway , Galway, Ireland
| | - Francis J Sullivan
- 1 Prostate Cancer Institute, School of Medicine, National University of Ireland Galway , Galway, Ireland
| | - Sharon A Glynn
- 1 Prostate Cancer Institute, School of Medicine, National University of Ireland Galway , Galway, Ireland .,2 Discipline of Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway , Galway, Ireland .,3 Apoptosis Research Centre, Biomedical Sciences, National University of Ireland Galway , Galway, Ireland
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Irons R, McIntosh E, Hageboutros A, Warshal D, McClane S. Bilateral ovarian micrometastatic adenocarcinoma upon prophylactic oophorectomy concurrent with low anterior resection for rectal cancer. World J Surg Oncol 2017; 15:40. [PMID: 28173877 PMCID: PMC5297189 DOI: 10.1186/s12957-017-1115-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Accepted: 02/01/2017] [Indexed: 11/17/2022] Open
Abstract
Background This case report draws attention to the debated role of prophylactic oophorectomy in women undergoing definitive surgical resection of colon and rectal cancers. It can be challenging to discern the indications and appropriate patient population for this procedure based on the current literature. Potential benefits include treatment and prevention of metastatic disease, preventing development of primary ovarian cancer, and prolonging survival. Negative effects include an increase in operative time and potential morbidity, development of osteoporosis, the risk of cardiac events, and decreasing sexual function. Multiple patient factors such as age, menopausal status, patient preference, presence of hereditary conditions, exposure to radiation, site, and stage of disease should be considered. Case presentation We present a case in which a premenopausal 49-year-old female underwent a prophylactic bilateral salpingo-oophorectomy concurrently with a low anterior resection following neoadjuvant chemoradiation for clinical stage III rectal cancer. On pathologic examination, resection margins and all 14 lymph nodes harvested were negative for malignancy. Interestingly, she was found to have micrometastatic adenocarcinoma in the bilateral ovaries which had appeared grossly normal at the time of surgery. Conclusions After consideration of the current literature, patient preference, and our clinical judgment, our patient ultimately had a therapeutic effect after undergoing prophylactic bilateral oophorectomy concurrently with a low anterior resection for rectal cancer. The addition of prophylactic oophorectomy in a select population, specifically women 50 years of age or younger and/or women who are in the premenopausal state, may carry a survival benefit in the setting of definitive surgical resection of colon and rectal cancers.
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Affiliation(s)
- Robin Irons
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Three Cooper Plaza, Suite 403, Camden, NJ, 08103, USA.
| | - Erin McIntosh
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Three Cooper Plaza, Suite 403, Camden, NJ, 08103, USA
| | - Alexandre Hageboutros
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Three Cooper Plaza, Suite 403, Camden, NJ, 08103, USA
| | - David Warshal
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Three Cooper Plaza, Suite 403, Camden, NJ, 08103, USA
| | - Steven McClane
- Department of Surgery, Cooper University Hospital and Cooper Medical School of Rowan University, Three Cooper Plaza, Suite 403, Camden, NJ, 08103, USA
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Anand L, Padmavathi V, Dhivya V, Mahalaxmi I, Balachandar V. De novo germ-line mutation of APC gene in periampullary carcinoma with familial adenomatous polyps – A novel familial case report in South India. KARBALA INTERNATIONAL JOURNAL OF MODERN SCIENCE 2016. [DOI: 10.1016/j.kijoms.2016.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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13
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Pan C, Wang D, Zhang Y, Yu W. MicroRNA-1284 Inhibits Cell Viability and Induces Apoptosis of Ovarian Cancer Cell Line OVCAR3. Oncol Res 2016; 24:429-435. [PMID: 28281963 PMCID: PMC7838609 DOI: 10.3727/096504016x14685034103518] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Ovarian cancer is a malignancy with high mortality among women. Multiple reports show that microRNAs (miRs) act as regulators in ovarian cancer inhibition, while the role of miR-1284 in ovarian cancer is still unknown. This study aimed to investigate the effects of miR-1284 on ovarian cancer cells. Human ovarian cancer cell line OVCAR3 was cultured and transfected with miR-1284 mimics, inhibitors, or control. Viability and apoptosis of transfected cells were then determined by MTT assay, BrdU assay, and flow cytometry. Expression changes of p27, p21, and PI3K/Akt pathway-related proteins were measured by Western blot. Results showed that miR-1284 overexpression suppressed cell viability while increasing the apoptosis in OVCAR3 cells. Moreover, the expression level of p27 was upregulated by miR-1284 overexpression. Furthermore, miR-1284 overexpression and Akt inhibitor GSK690693 downregulated the levels of p-Akt and Bcl-2 while upregulating the levels of Bax and caspase 3. However, miR-1284 suppression attenuated the regulatory effects of GSK690693 on these proteins. In conclusion, miR-1284 could inhibit cell viability via regulating the expression of p27 and induce apoptosis via regulating the PI3K/Akt pathway in OVCAR3 cells.
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Affiliation(s)
- Changqing Pan
- Department of Obstetrics and Gynecology, Mianyang Central Hospital, Mianyang, Sichuan, P.R. China
| | - Dan Wang
- Department of Obstetrics and Gynecology, Mianyang Central Hospital, Mianyang, Sichuan, P.R. China
| | - Yao Zhang
- Department of Obstetrics and Gynecology, Mianyang Central Hospital, Mianyang, Sichuan, P.R. China
| | - Wenliang Yu
- Department of Obstetrics and Gynecology, Mianyang Central Hospital, Mianyang, Sichuan, P.R. China
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Thomson CA, Crane TE, Miller A, Garcia DO, Basen-Engquist K, Alberts DS. A randomized trial of diet and physical activity in women treated for stage II-IV ovarian cancer: Rationale and design of the Lifestyle Intervention for Ovarian Cancer Enhanced Survival (LIVES): An NRG Oncology/Gynecologic Oncology Group (GOG-225) Study. Contemp Clin Trials 2016; 49:181-9. [PMID: 27394382 PMCID: PMC5108358 DOI: 10.1016/j.cct.2016.07.005] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 06/30/2016] [Accepted: 07/05/2016] [Indexed: 11/21/2022]
Abstract
Ovarian cancer is the most common cause of gynecological cancer death in United States women. Efforts to improve progression free survival (PFS) and quality of life (QoL) after treatment for ovarian cancer are necessary. Observational studies suggest that lifestyle behaviors, including diet and physical activity, are associated with lower mortality in this population. The Lifestyle Intervention for Ovarian Cancer Enhanced Survival (LIVES) NRG 0225 study is a randomized, controlled trial designed to test the hypothesis that a 24month lifestyle intervention will significantly increase PFS after oncological therapy for stage II-IV ovarian cancer. Women are randomized 1:1 to a high vegetable and fiber, low-fat diet with daily physical activity goals or an attention control group. Secondary outcomes to be evaluated include QoL and gastrointestinal health. Moreover an a priori lifestyle adherence score will be used to evaluate relationships between adoption of the diet and activity goals and PFS. Blood specimens are collected at baseline, 6, 12 and 24months for analysis of dietary adherence (carotenoids) in addition to mechanistic biomarkers (lipids, insulin, telomere length). Women are enrolled at NRG clinic sites nationally and the telephone based lifestyle intervention is delivered from The University of Arizona call center by trained health coaches. A study specific multi-modal telephone, email, and SMS behavior change software platform is utilized for information delivery, coaching and data capture. When completed, LIVES will be the largest behavior-based lifestyle intervention trial conducted among ovarian cancer survivors.
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Affiliation(s)
- Cynthia A Thomson
- Mel & Enid Zuckerman College of Public Health, Department of Health Promotion Sciences, University of Arizona, 1295 N. Martin Ave., PO Box 245209, Tucson, AZ 85724-5209, United States.
| | - Tracy E Crane
- Mel & Enid Zuckerman College of Public Health, Department of Health Promotion Sciences, University of Arizona, 1295 N. Martin Ave., PO Box 245209, Tucson, AZ 85724-5209, United States.
| | - Austin Miller
- NRG Oncology/Gynecologic Oncology Group, Statistics and Data Management Center, Elm & Carlton Streets, Buffalo, NY 14263, United States.
| | - David O Garcia
- Mel & Enid Zuckerman College of Public Health, Department of Health Promotion Sciences, University of Arizona, 1295 N. Martin Ave., PO Box 245209, Tucson, AZ 85724-5209, United States.
| | - Karen Basen-Engquist
- Department of Behavioral Science, Cancer Prevention and Population Sciences, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, United States.
| | - David S Alberts
- University of Arizona Cancer Center, 1515 N. Campbell Ave., Tucson, AZ 85721, United States.
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Mostowska A, Sajdak S, Pawlik P, Lianeri M, Jagodzinski PP. Polymorphic variants in the vitamin D pathway genes and the risk of ovarian cancer among non-carriers of BRCA1/BRCA2 mutations. Oncol Lett 2015; 11:1181-1188. [PMID: 26893716 DOI: 10.3892/ol.2015.4033] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2014] [Accepted: 10/26/2015] [Indexed: 12/26/2022] Open
Abstract
Previous studies have produced inconsistent results regarding the contribution of single-nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene to ovarian cancer (OC) in various ethnicities. Additionally, little has been established with regard to the role of SNPs located in the retinoid X receptor α (RXRA), vitamin D-binding protein [also know as group-specific component (GC)] and VDR genes in non-carriers of the breast cancer 1/2 early onset (BRCA1/BRCA2) gene mutations. All participating individuals in the present study were evaluated for BRCA1 mutations (5382incC, C61G and 4153delA) with HybProbe assays, and for BRCA2 mutation (5946delT) using high-resolution melting (HRM) analysis. The associations of 8 SNPs located in RXRA, GC and VDR were investigated in OC patients without the BRCA1/BRCA2 mutations (n=245) and healthy controls (n=465). Genotyping of RXRA rs10881578 and rs10776909, and GC rs1155563 and rs2298849 SNPs was conducted by HRM analysis, while RXRA rs749759, GC rs7041, VDR BsmI rs1544410 and FokI rs2228570 genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. In addition, the gene-gene interactions among all tested SNPs were studied using the epistasis option in PLINK software. The lowest P-values of the trend test were identified for VDR rs1544410 and GC rs2298849 as Ptrend=0.012 and Ptrend=0.029, respectively. It was also found that, in the dominant inheritance model, VDR BsmI contributed to an increased risk of OC [odds ratio (OR), 1.570; 95% confidence interval (CI), 1.136-2.171; P=0.006; Pcorr=0.048]. The gene-gene interaction analysis indicated a significant interaction between RXRA rs749759 and VDR FokI rs2228570 (OR for interaction, 1.687; χ2=8.278; asymptotic P-value=0.004; Pcorr=0.032). In conclusion, this study demonstrated that certain VDR and RXRA SNPs may be risk factors for OC in non-carriers of BRCA1/BRCA2 mutations in the Polish population.
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Affiliation(s)
- Adrianna Mostowska
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań 60-781, Poland
| | - Stefan Sajdak
- Clinic of Gynecological Surgery, Poznań University of Medical Sciences, Poznań 60-781, Poland
| | - Piotr Pawlik
- Clinic of Gynecological Surgery, Poznań University of Medical Sciences, Poznań 60-781, Poland
| | - Margarita Lianeri
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań 60-781, Poland
| | - Paweł P Jagodzinski
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań 60-781, Poland
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Chowdhury R, Sinha B, Sankar MJ, Taneja S, Bhandari N, Rollins N, Bahl R, Martines J. Breastfeeding and maternal health outcomes: a systematic review and meta-analysis. Acta Paediatr 2015; 104:96-113. [PMID: 26172878 PMCID: PMC4670483 DOI: 10.1111/apa.13102] [Citation(s) in RCA: 626] [Impact Index Per Article: 62.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 06/16/2015] [Accepted: 06/18/2015] [Indexed: 12/12/2022]
Abstract
AIM To evaluate the effect of breastfeeding on long-term (breast carcinoma, ovarian carcinoma, osteoporosis and type 2 diabetes mellitus) and short-term (lactational amenorrhoea, postpartum depression, postpartum weight change) maternal health outcomes. METHODS A systematic literature search was conducted in PubMed, Cochrane Library and CABI databases. Outcome estimates of odds ratios or relative risks or standardised mean differences were pooled. In cases of heterogeneity, subgroup analysis and meta-regression were explored. RESULTS Breastfeeding >12 months was associated with reduced risk of breast and ovarian carcinoma by 26% and 37%, respectively. No conclusive evidence of an association between breastfeeding and bone mineral density was found. Breastfeeding was associated with 32% lower risk of type 2 diabetes. Exclusive breastfeeding and predominant breastfeeding were associated with longer duration of amenorrhoea. Shorter duration of breastfeeding was associated with higher risk of postpartum depression. Evidence suggesting an association of breastfeeding with postpartum weight change was lacking. CONCLUSION This review supports the hypothesis that breastfeeding is protective against breast and ovarian carcinoma, and exclusive breastfeeding and predominant breastfeeding increase the duration of lactational amenorrhoea. There is evidence that breastfeeding reduces the risk of type 2 diabetes. However, an association between breastfeeding and bone mineral density or maternal depression or postpartum weight change was not evident.
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Affiliation(s)
- Ranadip Chowdhury
- Centre for Health Research and Development, Society for Applied StudiesNew Delhi, India
| | - Bireshwar Sinha
- Centre for Health Research and Development, Society for Applied StudiesNew Delhi, India
| | - Mari Jeeva Sankar
- Newborn Health Knowledge Centre, ICMR Centre for Advanced Research in Newborn Health, Department of Paediatrics, All India Institute of Medical SciencesNew Delhi, India
| | - Sunita Taneja
- Centre for Health Research and Development, Society for Applied StudiesNew Delhi, India
| | - Nita Bhandari
- Centre for Health Research and Development, Society for Applied StudiesNew Delhi, India
| | - Nigel Rollins
- Department of Maternal, Newborn, Child and Adolescent Health, World Health OrganizationGeneva, Switzerland
| | - Rajiv Bahl
- Department of Maternal, Newborn, Child and Adolescent Health, World Health OrganizationGeneva, Switzerland
| | - Jose Martines
- Centre for Intervention Science in Maternal and Child Health, Centre for International Health, University of BergenBergen, Norway
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BRCA1 185delAG Mutation Enhances Interleukin-1β Expression in Ovarian Surface Epithelial Cells. BIOMED RESEARCH INTERNATIONAL 2015; 2015:652017. [PMID: 26357657 PMCID: PMC4556869 DOI: 10.1155/2015/652017] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Accepted: 06/17/2015] [Indexed: 12/19/2022]
Abstract
Familial history remains the strongest risk factor for developing ovarian cancer (OC) and is associated with germline BRCA1 mutations, such as the 185delAG founder mutation. We sought to determine whether normal human ovarian surface epithelial (OSE) cells expressing the BRCA1 185delAG mutant, BRAT, could promote an inflammatory phenotype by investigating its impact on expression of the proinflammatory cytokine, Interleukin-1β (IL-1β). Cultured OSE cells with and without BRAT were analyzed for differential target gene expression by real-time PCR, western blot, ELISA, luciferase reporter, and siRNA assays. We found that BRAT cells expressed increased cellular and secreted levels of active IL-1β. BRAT-expressing OSE cells exhibited 3-fold enhanced IL-1β mRNA expression, transcriptionally regulated, in part, through CREB sites within the (−1800) to (−900) region of its promoter. In addition to transcriptional regulation, BRAT-mediated IL-1β expression appears dualistic through enhanced inflammasome-mediated caspase-1 cleavage and activation of IL-1β. Further investigation is warranted to elucidate the molecular mechanism(s) of BRAT-mediated IL-1β expression since increased IL-1β expression may represent an early step contributing to OC.
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YAN SHI, YUAN CUNZHONG, YANG QIFENG, LI XIAOYAN, YANG NING, LIU XIAOYAN, DONG RUIHUA, ZHANG XI, YUAN ZENG, ZHANG NING, KONG BEIHUA. A genetic polymorphism (rs17251221) in the calcium-sensing receptor is associated with ovarian cancer susceptibility. Oncol Rep 2015; 34:2151-5. [DOI: 10.3892/or.2015.4179] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2015] [Accepted: 07/17/2015] [Indexed: 11/05/2022] Open
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Abstract
OBJECTIVE The aim of this study was to determine whether pelvic inflammation contributes to the pathogenesis of ovarian cancer or other malignancies. DESIGN This article is a cohort study. SETTING The study was conducted in a tertiary university and provincial cancer referral institutions. POPULATION SAMPLE The population sample was composed of women referred for fertility surgery and women diagnosed with ovarian cancer in British Columbia. METHODS We conducted a cohort study using prospectively collected data on fertility surgery patients. Eight hundred eighty-eight women with past pelvic inflammation, as diagnosed by characteristic findings at fertility surgery, and 552 women without were compared for the subsequent development of malignancy, during the period of 1981 to 2012. Logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. Standardized incidence ratios were also calculated using age-specific cancer incidence rates among all women in British Columbia. RESULTS The adjusted odds ratio for ovarian cancer, after past inflammation, was 5.56 (95% confidence interval, 0.52-59.40). Age-adjusted ovarian cancer incidence was significantly elevated among women with previous pelvic inflammation (standardized incidence ratio, 3.99; 95% confidence interval, 1.46-8.68). The rates of other malignancies were similar in both cohorts. CONCLUSION The rate of ovarian cancer was not significantly elevated in women with past pelvic inflammation compared with the controls. However, a significantly increased risk for ovarian cancer was apparent among women with pelvic inflammation when compared with the general population. Pelvic inflammation may be a contributory factor in the pathogenesis of ovarian cancer.
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20
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Feng LP, Chen HL, Shen MY. Breastfeeding and the risk of ovarian cancer: a meta-analysis. J Midwifery Womens Health 2015; 59:428-37. [PMID: 25066743 DOI: 10.1111/jmwh.12085] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
INTRODUCTION The aim of this meta-analysis was to assess the association between breastfeeding and risk of ovarian cancer. METHODS Relevant observational studies were identified by a search of the MEDLINE and EMBASE databases through December 2012. Summary odds ratios (ORs) for ovarian cancer, comparing women who had breastfed with women who had not, were calculated using a random-effects model. A dose-response meta-analysis assessed the risk of ovarian cancer by breastfeeding duration. RESULTS A total of 19 studies were included in the meta-analysis. Compared with women who had not breastfed, women who had breastfed had a significantly decreased risk of ovarian cancer, with an OR of 0.66 (95% CI, 0.57-0.76; P < .001). We observed an inverse linear relationship with breastfeeding duration: for every one-month increase in breastfeeding, the OR was 0.98 (95% CI, 0.97-0.99; P < .001). A nonlinear association was also apparent, with a sharp decrease in the OR when breastfeeding duration was 8 to 10 months. There was evidence of heterogeneity (I(2) = 83.9%). No publication bias was found (Begg test, P = 0.89; Egger test, P = 0.89). DISCUSSION Breastfeeding reduces the risk of ovarian cancer proportional to duration. Breastfeeding for 8 to 10 months may be most effective for reducing the risk of ovarian cancer.
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Perri T, Lifshitz D, Sadetzki S, Oberman B, Meirow D, Ben-Baruch G, Friedman E, Korach J. Fertility treatments and invasive epithelial ovarian cancer risk in Jewish Israeli BRCA1 or BRCA2 mutation carriers. Fertil Steril 2015; 103:1305-12. [PMID: 25792249 DOI: 10.1016/j.fertnstert.2015.02.011] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2014] [Revised: 02/07/2015] [Accepted: 02/09/2015] [Indexed: 10/23/2022]
Abstract
OBJECTIVE To determine whether BRCA mutation carriers who undergo fertility treatments are at increased risk of developing invasive epithelial ovarian cancer (IEOC). DESIGN Historical cohort study. SETTING Tertiary university-affiliated medical center and the National Cancer Registry. PATIENT(S) A total of 1,073 Jewish Israeli BRCA mutation carriers diagnosed in a single institution between 1995 and 2013, including 164 carriers (15.2%) who had fertility treatments that included clomiphene citrate (n = 82), gonadotropin (n = 69), in vitro fertilization (IVF) (n = 66), or a combination (n = 50), and 909 carriers not treated for infertility. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Odds ratios (OR) and 95% confidence intervals (CI) for IEOC association with fertility treatments and other hormone and reproductive variables. RESULT(S) In 175 (16.3%) mutation carriers, IEOC was diagnosed; 139 women carried BRCA1, 33 carried BRCA2, and 3 had unknown mutations. Fertility treatments were not associated with IEOC risk (age-adjusted OR 0.63; 95% CI, 0.38-1.05) regardless of treatment type (with clomiphene citrate, OR 0.87; 95% CI, 0.46-1.63; with gonadotropin, OR 0.59; 95% CI, 0.26-1.31; with IVF, OR 1.08, 95% CI, 0.57-2.06). Multivariate analysis indicated an increased risk of IEOC with hormone-replacement therapy (OR 2.22; 95% CI, 1.33-3.69) and a reduced risk with oral contraceptives (OR 0.19; 95% CI, 0.13-0.28) in both BRCA1 and BRCA2 mutation carriers. Parity was a risk factor for IEOC by univariate but not multivariate analysis. CONCLUSION(S) According to our results, treatments for infertile BRCA mutation carriers should not be contraindicated or viewed as risk modifiers for IEOC. Parity as a risk factor in BRCA mutation carriers warrants further investigation.
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Affiliation(s)
- Tamar Perri
- Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Dror Lifshitz
- Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Siegal Sadetzki
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Cancer and Radiation Epidemiology Unit, Gertner Institute, Sheba Medical Center, Tel Hashomer, Israel
| | - Bernice Oberman
- Cancer and Radiation Epidemiology Unit, Gertner Institute, Sheba Medical Center, Tel Hashomer, Israel
| | - Dror Meirow
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Fertility Preservation Center and IVF Unit, Sheba Medical Center, Tel Hashomer, Israel
| | - Gilad Ben-Baruch
- Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Eitan Friedman
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Susanne Levy-Gertner Oncogenetics Unit, Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel
| | - Jacob Korach
- Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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22
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Johnson PA, Stephens CS, Giles JR. The domestic chicken: Causes and consequences of an egg a day. Poult Sci 2015; 94:816-20. [PMID: 25667424 DOI: 10.3382/ps/peu083] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
The domestic laying chicken has been intensely selected to be a persistent ovulator. That is, the tendency for broodiness has been nearly eliminated and, given the appropriate lighting and nutrition, many strains of laying hens produce an egg on almost every day. The regulatory mechanisms involved in coordination of neuroendocrine and ovarian events have been well studied and described. In spite of this, there has been little attention focused on the oocyte itself. Recent findings in mammals have indicated that the oocyte produces several oocyte-specific factors, including growth differentiation factor 9 (GDF9) and bone morphogenetic factor 15 (BMP15), which influence the surrounding cells and follicular development. Our studies indicate that GDF9 is present in the hen oocyte and influences granulosa cell proliferation. Additionally, Bmp15 mRNA is most abundant in oocytes of small follicles and stimulates an increase in follicle stimulating hormone (FSH) receptor mRNA in granulosa cells. BMP15 also enhances yolk uptake in growing follicles by decreasing tight junctions between granulosa cells. These studies indicate that the oocyte likely contributes to follicle development. Commercial laying hens also spontaneously develop ovarian cancer at a high rate, and susceptibility to this disease has been associated with ovulatory events in women. Studies have shown that ovulation, or events associated with ovulation, increase the prevalence of ovarian cancer in hens. Inhibition of ovulation in hens through a hormonal strategy mimicking oral contraceptives results in a decrease of ovarian cancer incidence. Recent studies in women have suggested that some ovarian tumors may arise from the distal oviduct. Gene expression profiles in very early stage tumors from hens show a high expression of oviduct-related genes, supporting the possibility of oviduct origin for some ovarian tumors. Genetic selection for high productivity in commercial laying hens has generated an efficient and valuable food source as well as an important animal model for human ovarian cancer.
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Affiliation(s)
- P A Johnson
- Department of Animal Science, Cornell University, Ithaca, NY 14853
| | - C S Stephens
- Department of Animal Science, Cornell University, Ithaca, NY 14853
| | - J R Giles
- Department of Animal Science, Cornell University, Ithaca, NY 14853
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Langhe R. microRNA and Ovarian Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2015; 889:119-51. [DOI: 10.1007/978-3-319-23730-5_8] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Yavuzcan A, Çağlar M, Özgü E, Üstün Y, Dilbaz S, Ozdemir I, Güngör T, Kumru S. Addition of parity to the risk of malignancy index score in evaluating adnexal masses. Taiwan J Obstet Gynecol 2014; 53:518-22. [PMID: 25510694 DOI: 10.1016/j.tjog.2014.08.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/12/2014] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE The aim of our study was to evaluate the individual contribution of parity when incorporated as another parameter into the four risk of malignancy indices (RMI 1-4) to differentiate noninvasive benign lesions from invasive malignant ovarian lesions. MATERIALS AND METHODS After calculating RMI 1-4 for each patient included in this study, the resulting RMI scores were further multiplied by the parity score (P) of each patient to calculate the RMI parity (RMIP) score. RESULTS A cutoff value of 300 for RMIP 1 yielded 95.0% specificity, 97.4% negative predictive value (NPV), 88.5% sensitivity, and 79.3% positive predictive value (PPV) and performed better than RMI 1 in the preoperative diagnosis of invasive malignant lesions. RMIP 2 with a cutoff value of 400 yielded 95.0% specificity, 97.4% NPV, 88.5% sensitivity, and 79.3% PPV, and it also performed better than RMI 2. A cutoff value of 400 for RMIP 3 provided 97.5% specificity, 97.5% NPV, 88.5% sensitivity, and 88.5% PPV and performed better than RMI 3. However, a cutoff value of 400 for RMIP 4 provided 90.0% specificity, 97.3% NPV, 88.5% sensitivity, and 65.7% PPV but did not perform better than RMI 4 in the preoperative diagnosis of invasive malignant lesions. CONCLUSION RMIP 1-3 scales were more reliable tools for the preoperative diagnosis of invasive adnexal masses compared with the traditional RMI 1-3 scales.
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Affiliation(s)
- Ali Yavuzcan
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Düzce University, Düzce, Turkey.
| | - Mete Çağlar
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Düzce University, Düzce, Turkey
| | - Emre Özgü
- Department of Obstetrics and Gynaecology, Zekai Tahir Burak Women's Health Education and Research Hospital, Ankara, Turkey
| | - Yusuf Üstün
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Düzce University, Düzce, Turkey
| | - Serdar Dilbaz
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Düzce University, Düzce, Turkey
| | - Ismail Ozdemir
- Department of Obstetrics and Gynaecology, Medicana International Istanbul Hospital, Istanbul, Turkey
| | - Tayfun Güngör
- Department of Obstetrics and Gynaecology, Zekai Tahir Burak Women's Health Education and Research Hospital, Ankara, Turkey
| | - Selahattin Kumru
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Düzce University, Düzce, Turkey
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Eddie SL, Quartuccio SM, Zhu J, Shepherd JA, Kothari R, Kim JJ, Woodruff TK, Burdette JE. Three-dimensional modeling of the human fallopian tube fimbriae. Gynecol Oncol 2014; 136:348-54. [PMID: 25527363 DOI: 10.1016/j.ygyno.2014.12.015] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2014] [Revised: 12/05/2014] [Accepted: 12/10/2014] [Indexed: 11/28/2022]
Abstract
OBJECTIVE Ovarian cancer is the most lethal gynecological malignancy that affects women. Recent data suggests that the disease may originate in the fallopian fimbriae; however, the anatomical origin of ovarian carcinogenesis remains unclear. This is largely driven by our lack of knowledge regarding the structure and function of normal fimbriae and the relative paucity of models that accurately recapitulate the in vivo fallopian tube. Therefore, a human three-dimensional (3D) culture system was developed to examine the role of the fallopian fimbriae in serous tumorigenesis. METHODS Alginate matrix was utilized to support human fallopian fimbriae ex vivo. Fimbriae were cultured with factors hypothesized to contribute to carcinogenesis, namely; H2O2 (1mM) a mimetic of oxidative stress, insulin (5μg/ml) to stimulate glycolysis, and estradiol (E2, 10nM) which peaks before ovulation. Cultures were evaluated for changes in proliferation and p53 expression, criteria utilized to identify potential precursor lesions. Further, secretory factors were assessed after treatment with E2 to identify if steroid signaling induces a pro-tumorigenic microenvironment. RESULTS 3D fimbriae cultures maintained normal tissue architecture up to 7days, retaining both epithelial subtypes. Treatment of cultures with H2O2 or insulin significantly induced proliferation. However, p53 stabilization was unaffected by any particular treatment, although it was induced by ex vivo culturing. Moreover, E2-alone treatment significantly induced its canonical target PR and expression of IL8, a factor linked to poor outcome. CONCLUSIONS 3D alginate cultures of human fallopian fimbriae provide an important microphysiological model, which can be further utilized to investigate serous tumorigenesis originating from the fallopian tube.
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Affiliation(s)
- Sharon L Eddie
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60607, USA
| | - Suzanne M Quartuccio
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60607, USA
| | - Jie Zhu
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Jessica A Shepherd
- Department of Obstetrics and Gynecology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60607, USA
| | - Rajul Kothari
- Division of Gynecological Oncology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60607, USA
| | - J Julie Kim
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Teresa K Woodruff
- Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Joanna E Burdette
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60607, USA.
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Mostowska A, Pawlik P, Sajdak S, Markowska J, Pawałowska M, Lianeri M, Jagodzinski PP. An analysis of polymorphisms within the Wnt signaling pathway in relation to ovarian cancer risk in a Polish population. Mol Diagn Ther 2014; 18:85-91. [PMID: 24078348 PMCID: PMC3899496 DOI: 10.1007/s40291-013-0059-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Background and Objective The Wnt/β-catenin signaling pathway has been considered to be a factor in the development and progression of ovarian cancer. Methods All patients with ovarian cancer and controls were tested for BRCA1 mutations (5382incC, C61G, 4153delA) with HybProbe assays and for BRCA2 mutation (5946delT) using high-resolution melting curve analysis (HRM). Mutation carriers were excluded from the association analysis. We studied nine single nucleotide polymorphisms (SNPs) located in CTNNB1 (β-catenin) [rs4533622, rs2953], APC (rs11954856, rs351771, rs459552), and AXIN2 (rs4074947, rs7224837, rs3923087, rs2240308) in women with ovarian cancer without BRCA1/BRCA2 mutations (n = 228) and controls (n = 282). Genotyping of CTNNB1 rs4533622, rs2953, APC rs351771, AXIN2 rs4074947, rs3923087, and rs2240308 was performed by HRM, while that of APC rs11954856, rs459552 and AXIN2 rs7224837 was conducted by PCR followed by the appropriate restriction enzyme digestion [PCR–restriction fragment length polymorphism (PCR-RFLP)]. Results The most common BRCA1/BRCA2 mutations were identified in 30 patients with ovarian cancer. These mutations were not found in controls. The lowest p values of the trend test (ptrend) were observed for the APC rs351771 and rs11954856 SNPs in patients with ovarian cancer (ptrend = 0.006 and ptrend = 0.007, respectively). Using a dominant inheritance model, we found that the APC rs11954856 SNP is associated with an increased risk of ovarian cancer development [odds ratio = 2.034 (95 % CI 1.302–3.178); p = 0.002]. We also observed significant allelic differences for the APC rs351771 SNP between patients and controls (p = 0.006). Conclusion Our study demonstrated significantly increased APC rs11954856 and rs351771 SNP frequencies in Polish women with ovarian cancer. Electronic supplementary material The online version of this article (doi:10.1007/s40291-013-0059-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Adrianna Mostowska
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St., 60-781 Poznan, Poland
| | - Piotr Pawlik
- Clinic of Gynecological Surgery, Poznań University of Medical Sciences, Poznan, Poland
| | - Stefan Sajdak
- Clinic of Gynecological Surgery, Poznań University of Medical Sciences, Poznan, Poland
| | - Janina Markowska
- Chair of Gynecologic Oncology, Poznań University of Medical Sciences, Poznan, Poland
| | - Monika Pawałowska
- Chair of Gynecologic Oncology, Poznań University of Medical Sciences, Poznan, Poland
| | - Margarita Lianeri
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St., 60-781 Poznan, Poland
| | - Paweł P. Jagodzinski
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St., 60-781 Poznan, Poland
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Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women. Nat Commun 2014; 5:4682. [PMID: 25134534 DOI: 10.1038/ncomms5682] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Accepted: 07/14/2014] [Indexed: 12/25/2022] Open
Abstract
Ovarian cancer is the leading cause of death from gynaecological malignancies worldwide. Here we perform a three-stage genome-wide association study (GWAS) in Han Chinese women to identify risk genetic variants for epithelial ovarian cancer (EOC). We scan 900,015 single-nucleotide polymorphisms (SNPs) in 1,057 EOC cases and 1,191 controls in stage I, and replicate 41 SNPs (P(meta)<10(-4)) in 960 EOC cases and 1,799 controls (stage II), and an additional 492 EOC cases and 1,004 controls (stage III). Finally, we identify two EOC susceptibility loci at 9q22.33 (rs1413299 in COL15A1, P(meta) = 1.88 × 10(-8)) and 10p11.21 (rs1192691 near ANKRD30A, P(meta) = 2.62 × 10(-8)), and two consistently replicated loci at 12q14.2 (rs11175194 in SRGAP1, P(meta) = 1.14 × 10(-7)) and 9q34.2 (rs633862 near ABO and SURF6, P(meta) = 8.57 × 10(-7)) (P<0.05 in all three stages). These results may advance our understanding of genetic susceptibility to EOC.
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Zhong S, Chen L, Lv M, Ma T, Zhang X, Zhao J. Nonoccupational physical activity and risk of ovarian cancer: a meta-analysis. Tumour Biol 2014; 35:11065-73. [DOI: 10.1007/s13277-014-2385-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2014] [Accepted: 07/23/2014] [Indexed: 01/24/2023] Open
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Sabaa BME. Pathological conditions predisposing to infertility and gynaecological neoplasia. World J Obstet Gynecol 2014; 3:28-34. [DOI: 10.5317/wjog.v3.i2.28] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2013] [Revised: 03/04/2013] [Accepted: 04/11/2013] [Indexed: 02/05/2023] Open
Abstract
Some of the conditions long blamed for female factor infertility are now acknowledged as well established risk factors of gynecological neoplasia. This realization has lead to the proposition that infertility might be a risk factor for the development of several types of gynecological neoplasms. This review addresses different conditions that play a role in both infertility and gynaecological neoplasia. An intricate interplay between growth factors and hormonal factors (estrogens and progestins, androgens and gonadotropins) is said to link the state of infertility to some gynecological tumors. The relation between endometriosis -as one of the well established causes of female infertility - and ovarian cancer is well known. Endometriosis has been particularly related to endometrioid and clear-cell ovarian carcinomas. Another evidence for this association is embodied in finding endometriotic lesions adjacent to ovarian cancers. The polycystic ovary syndrome (PCOS), one of the most prevalent endocrine disorders and a long studied cause of female infertility increases the risk of endometrial carcinoma. The link between PCOS and endometrial carcinoma seems to be endometrial hyperplasia. PCOS-associated endometrial carcinoma tends to present at a younger age and early stage, with lower grade and lower risk of metastasis. Turner’s syndrome and other types of ovarian dysgenesis constitute a rare cause of infertility and are known to confer a definite risk of germ cell tumors. There seems to be a link between infertility and an increased risk of gynecological neoplasia. Hence, it is important to assess the risk of malignancy in each category of infertile patients so as to provide optimal and timely intervention.
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Abstract
Ovarian cancer is the fifth most common cancer affecting women in the UK today, with associated statistics illustrating a steadily increasing rate, particularly in women aged 65 and over (Cancer Research UK, 2013). There are no recognised preventative measures and no effective screening tool. Although evidence suggests that the majority of women experience a variety of non-specific symptoms in the year before diagnosis, the disease it is not commonly recognised until an advanced stage, leading to increased mortality and morbidity. This highlights the need to raise awareness among health professionals and women as a whole, as early recognition undoubtedly improves ovarian cancer survival. Best clinical practice in the UK for the recognition and initial management of ovarian cancer is provided by the National Institute for Health and Care Excellence (NICE). Clinical guideline CG 122 (NICE, 2011) and quality standard QS 18 (NICE, 2012) use relevant clinical evidence to define high-quality care standards for ovarian cancer management. Accurate staging of ovarian cancer is essential to the provision of individualised care and management. However, there is currently no single test that provides a reliable indicator of ovarian malignancy. At present, risk-of-malignancy scores are calculated by serum cancer antigen 125 (CA 125) levels, ultrasound score and menopausal status. These are widely used to identify women who are at high risk and require referral to a specialised gynaecological oncology service. Women diagnosed with ovarian cancer require information and support. The clinical nurse specialist acts as a key worker, providing communication, support and holistic care throughout a woman's cancer journey. The value of this role cannot be underestimated. Surgery followed by platinum-based chemotherapy is the usual standard treatment pathway, although individualised assessment and management may deviate from it. Early disease may be successfully treated with surgery alone; advanced disease may require complex management and treatment. New treatments such as bevacizumab show promise of improving ovarian cancer outcomes.
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Hong MK, Chu TY, Ding DC. The fallopian tube is the culprit and an accomplice in type II ovarian cancer: A review. Tzu Chi Med J 2013. [DOI: 10.1016/j.tcmj.2013.04.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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Mostowska A, Sajdak S, Pawlik P, Lianeri M, Jagodzinski PP. DNMT1, DNMT3A and DNMT3B gene variants in relation to ovarian cancer risk in the Polish population. Mol Biol Rep 2013; 40:4893-9. [PMID: 23666104 PMCID: PMC3723978 DOI: 10.1007/s11033-013-2589-0] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2012] [Accepted: 04/29/2013] [Indexed: 12/24/2022]
Abstract
Studies have demonstrated that changes in DNA methylation of cancer related genes can be an elementary process accounting for ovarian tumorigenesis. Therefore, we evaluated the possible association of single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) genes, including DNMT1, DNMT3B, and DNMT3A, with ovarian cancer development in the Polish population. Using PCR-RFLP and HRM analyses, we studied the prevalence of the DNMT1 rs8101626, rs2228611 and rs759920, DNMT3A rs2289195, 7590760, rs13401241, rs749131 and rs1550117, and DNMT3B rs1569686, rs2424913 and rs2424932 SNPs in patients with ovarian cancer (n=159) and controls (n=180). The lowest p values of the trend test were observed for the DNMT1 rs2228611 and rs759920 SNPs in patients with ovarian cancer (p trend=0.0118 and p trend=0.0173, respectively). Moreover, we observed, in the recessive inheritance model, that the DNMT1 rs2228611 and rs759920 SNPs are associated with an increased risk of ovarian cancer development [OR 1.836 (1.143-2.949), p=0.0114, p corr=0.0342, and OR 1.932 (1.185-3.152), p=0.0078, p cor=0.0234, respectively]. However, none of other nine studied SNPs displayed significant contribution to the development of ovarian cancer. Furthermore, haplotype and multifactor dimensionality reduction analysis of the studied DNMT1, DNMT3B, and DNMT3A polymorphisms did not reveal either SNP combinations or gene interactions to be associated with the risk of ovarian cancer development. Our results may suggest that DNMT1 variants may be risk factors of ovarian cancer.
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Affiliation(s)
- Adrianna Mostowska
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego Street, 60-781 Poznan, Poland
| | - Stefan Sajdak
- Clinic of Gynecological Surgery, Poznań University of Medical Sciences, Poznan, Poland
| | - Piotr Pawlik
- Clinic of Gynecological Surgery, Poznań University of Medical Sciences, Poznan, Poland
| | - Margarita Lianeri
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego Street, 60-781 Poznan, Poland
| | - Paweł P. Jagodzinski
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego Street, 60-781 Poznan, Poland
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Khan MMH, Khan A, Nojima M, Suzuki S, Fujino Y, Tokudome S, Tamakoshi K, Mori M, Tamakoshi A. Ovarian cancer mortality among women aged 40-79 years in relation to reproductive factors and body mass index: latest evidence from the Japan Collaborative Cohort study. J Gynecol Oncol 2013; 24:249-57. [PMID: 23875075 PMCID: PMC3714463 DOI: 10.3802/jgo.2013.24.3.249] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Revised: 05/01/2013] [Accepted: 05/19/2013] [Indexed: 01/08/2023] Open
Abstract
Objective This study mainly aimed to investigate the association of ovarian cancer mortality with reproductive factors and body mass index among Japanese women aged 40-79 years. Methods The source of the data was the Japan Collaborative Cohort (JACC) study which covered the period of 1988 to 2009. A representative sample of 64,185 women was used. Cox model was used to estimate the relative risk (RR) and 95% confidence interval (CI). Results The total number of ovarian cancer deaths was 98, with a mortality rate of 9.30 per 100,000 person-years. Women with single marital status revealed significantly higher age-adjusted RR (RR, 4.11; 95% CI, 1.66 to 10.23; p=0.005) as compared to married women. The effect of single marital status was stronger among older women aged 50+ years (RR, 4.58; 95% CI, 1.65 to 12.72; p=0.003) than younger women. An elevated risk was found for both nulliparous and nullipregnant women. Similarly, an increased risk of ovarian cancer mortality was estimated among overweight among aged 50 years or less. Conclusion Out of many factors only single marital status indicated a higher risk for ovarian cancer mortality. All other factors provided inconclusive results, which imply further epidemiological investigations.
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Affiliation(s)
- Md Mobarak Hossain Khan
- Department of Public Health Medicine, Bielefeld University School of Public Health, Bielefeld, Germany
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Kirkeleit J, Riise T, Bjørge T, Christiani DC. The healthy worker effect in cancer incidence studies. Am J Epidemiol 2013; 177:1218-24. [PMID: 23595008 DOI: 10.1093/aje/kws373] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Use of the general population as a reference might cause serious underestimation of the risk of cancer in working populations because of the healthy worker effect. Using incidence rates, we studied how this underestimation varied according to subtypes of cancer by comparing a large cohort of randomly selected Norwegian workers hired between 1981 and 2003 (n = 366,114) with the general Norwegian population. The cohort was linked to the Cancer Registry of Norway, including all new cancer cases (n = 11,271) reported up to 2003. We found marked potential for the healthy worker effect for overall cancer incidence in male workers (standardized incidence ratio (SIR) = 0.91, 95% confidence interval: 0.89, 0.93) but not in female workers (SIR = 0.99, 95% confidence interval: 0.95, 1.03). A statistically significantly lower incidence was found among men for cancers of the head and neck (SIR = 0.78), lung (SIR = 0.81), prostate (SIR = 0.93), kidney (SIR = 0.83), and bladder (SIR = 0.77) and for leukemia (SIR = 0.80), whereas an increased incidence was found for malignant melanoma among both men (SIR = 1.09) and women (SIR = 1.29) and for ovarian cancer in women (SIR = 1.32). Depending on the type of cancer being studied, marked potential exists for both underestimation and overestimation of cancer risk when the general population is used as the reference for studies of worker populations.
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Affiliation(s)
- Jorunn Kirkeleit
- Department of Global Public Health and Primary Care, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway
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Stewart LM, Holman CDJ, Finn JC, Preen DB, Hart R. In vitro fertilization is associated with an increased risk of borderline ovarian tumours. Gynecol Oncol 2013; 129:372-6. [DOI: 10.1016/j.ygyno.2013.01.027] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2012] [Revised: 01/11/2013] [Accepted: 01/26/2013] [Indexed: 11/30/2022]
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Kovacs P. Fertility medications and the risk of cancer. Expert Rev Endocrinol Metab 2013; 8:159-171. [PMID: 30736176 DOI: 10.1586/eem.13.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Cancer is among the leading causes of death, and malignant diseases of the female genital tract are among the most common sites. Reproductive factors that are also associated with infertility have been identified as risk factors. Hormones are thought to play a role in the induction and promotion of some type of cancers. Hormonal preparations affect the endocrine milieu and, by acting on the reproductive organs themselves, could even have a direct effect on carcinogenesis. Numerous case-control and cohort studies have tried to determine whether fertility medication use increases cancer risk. Overall, the current data is reassuring but most research groups drew conclusions based on a small number of cases and after a relatively short follow-up. Proper counseling prior to fertility medication use is important and further studies on even larger patient groups with more cancer cases are needed to support widespread use of fertility medications.
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Affiliation(s)
- Peter Kovacs
- a Kaali Institute IVF Center, Budapest, Hungary.
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37
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Mostowska A, Sajdak S, Pawlik P, Lianeri M, Jagodzinski PP. Vitamin D receptor gene BsmI and FokI polymorphisms in relation to ovarian cancer risk in the Polish population. Genet Test Mol Biomarkers 2013; 17:183-7. [PMID: 23320576 PMCID: PMC3582284 DOI: 10.1089/gtmb.2012.0332] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The role of vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) in ovarian cancer has been studied in various populations; however, these results are discordant between different ethnicities. METHOD Using the polymerase chain reaction-restriction fragment length polymorphism method, we studied the prevalence of the VDR FokI (rs2228570) and BsmI (rs1544410) SNPs in women with ovarian cancer (n=168) and controls (n=182) in a Polish population. RESULTS We found a significant contribution of the BsmI SNP Bb+BB-versus-bb dominant inheritance model to ovarian cancer development (p=0.0221, p(corr)=0.0442, odds ratio [OR]=1.648 [95% confidence intervals, CI=1.073-2.532]). However, we did not observe an association of the BsmI SNP BB versus Bb+bb recessive inheritance model in patients (p=0.8059, OR=1.093 [95% CI=0.538-2.218]). Moreover, there was no association of FokI SNPs either in Ff+ff versus FF dominant or ff versus Ff+FF recessive inheritance models with ovarian cancer development (p=0.9924, OR=1.002 [95% CI=0.628-1.599] and p=0.1123, OR=1.542 [95% CI=0.901-2.638], respectively). The p-values of the trend test observed for the VDR BsmI and FokI SNPs in patients with ovarian cancer were p(trend)=0.0613 and p(trend)=0.3655, respectively. CONCLUSION Our study indicates that the VDR B gene variant might be a moderate risk factor of ovarian cancer development in the Polish population.
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Affiliation(s)
- Adrianna Mostowska
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland
| | - Stefan Sajdak
- Clinic of Gynecological Surgery, Poznań University of Medical Sciences, Poznań, Poland
| | - Piotr Pawlik
- Clinic of Gynecological Surgery, Poznań University of Medical Sciences, Poznań, Poland
| | - Margarita Lianeri
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland
| | - Pawel P. Jagodzinski
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland
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Epigenetics makes its mark on women-specific cancers—an opportunity to redefine oncological approaches? Gynecol Oncol 2013; 128:134-143. [DOI: 10.1016/j.ygyno.2012.09.027] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2012] [Revised: 09/21/2012] [Accepted: 09/22/2012] [Indexed: 01/21/2023]
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39
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Lee AH, Su D, Pasalich M, Wong YL, Binns CW. Habitual physical activity reduces risk of ovarian cancer: a case-control study in southern China. Prev Med 2013. [PMID: 23200876 DOI: 10.1016/j.ypmed.2012.11.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE To ascertain the relationship between habitual physical activity and the risk of ovarian cancer among southern Chinese women. METHOD A case-control study was conducted in Guangzhou, Guangdong Province, during 2006-2008. Information on physical activity exposure and lifestyle characteristics was obtained from 500 incident ovarian cancer patients and 500 hospital-based controls (mean age 59 years) using a validated and reliable questionnaire. Logistic regression analyses were performed to assess the association between physical activity levels and the ovarian cancer risk. RESULTS The control subjects reported significantly longer duration of strenuous sports and moderate activity in daily life than the ovarian cancer patients. Increased engagements in such leisure time activities were associated with reduced cancer risks after adjustment for confounding factors. A significant inverse dose-response relationship was also found for total physical activity exposure, with adjusted odds ratio 0.49 (95% confidence interval 0.35-0.68) for women engaged in 23 or more metabolic equivalent tasks (MET)-hours per week relative to those less than 12 MET-hours per week. CONCLUSION The study provided evidence of an inverse association between habitual physical activity and the risk of ovarian cancer, which is important for the promotion and encouragement of leisure time exercise activities to prevent the disease.
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Affiliation(s)
- Andy H Lee
- School of Public Health, Curtin University, Perth, WA, Australia.
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Siristatidis C, Sergentanis TN, Kanavidis P, Trivella M, Sotiraki M, Mavromatis I, Psaltopoulou T, Skalkidou A, Petridou ET. Controlled ovarian hyperstimulation for IVF: impact on ovarian, endometrial and cervical cancer—a systematic review and meta-analysis. Hum Reprod Update 2012; 19:105-23. [DOI: 10.1093/humupd/dms051] [Citation(s) in RCA: 108] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
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Braem MGM, Onland-Moret NC, Schouten LJ, Kruitwagen RFPM, Lukanova A, Allen NE, Wark PA, Tjønneland A, Hansen L, Braüner CM, Overvad K, Clavel-Chapelon F, Chabbert-Buffet N, Teucher B, Floegel A, Boeing H, Trichopoulou A, Adarakis G, Plada M, Rinaldi S, Fedirko V, Romieu I, Pala V, Galasso R, Sacerdote C, Palli D, Tumino R, Bueno-de-Mesquita HB, Gram IT, Gavrilyuk O, Lund E, Sánchez MJ, Bonet C, Chirlaque MD, Larrañaga N, Gurrea AB, Quirós JR, Idahl A, Ohlson N, Lundin E, Jirström K, Butt S, Tsilidis KK, Khaw KT, Wareham N, Riboli E, Kaaks R, Peeters PHM. Multiple miscarriages are associated with the risk of ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition. PLoS One 2012; 7:e37141. [PMID: 22623987 PMCID: PMC3356371 DOI: 10.1371/journal.pone.0037141] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2012] [Accepted: 04/15/2012] [Indexed: 01/10/2023] Open
Abstract
While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR≥4vs.0: 1.74, 95% CI: 1.20–2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR≥4vs.0: 1.99, 95% CI: 1.06–3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR≥4vs.0: 1.46, 95% CI: 0.68–3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.
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Affiliation(s)
- Marieke G M Braem
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
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Yli-Kuha AN, Gissler M, Klemetti R, Luoto R, Hemminki E. Cancer morbidity in a cohort of 9175 Finnish women treated for infertility. Hum Reprod 2012; 27:1149-55. [DOI: 10.1093/humrep/des031] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
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Hung LJ, Chan TF, Wu CH, Chiu HF, Yang CY. Traffic air pollution and risk of death from ovarian cancer in Taiwan: fine particulate matter (PM2.5) as a proxy marker. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2012; 75:174-182. [PMID: 22251265 DOI: 10.1080/15287394.2012.641200] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
The relationship between mortality attributed to ovarian cancer and exposure to ambient air pollutants was examined using an ecological design. The study areas consisted of 61 municipalities in Taiwan. Air quality data for recorded concentrations of fine particulate matter (PM2.5) from study municipalities for 2006-2009 were obtained as a marker of traffic emissions. These were used as a proxy for polycyclic aromatic hydrocarbons (PAH) exposure. Age-standardized mortality rates for ovarian cancer were calculated for the study municipalities for the years 1999-2008. A weighted multiple regression model was employed to calculate the adjusted risk ratio (RR) in relation to PM2.5 levels. After adjusting for urbanization level and fertility rate, the adjusted RR values (95% confidence interval [CI]) for ovarian cancer were 1.2 (1.02-1.41) for the municipalities with PM2.5 levels between 30.48 μg/m3 and 39.41 μg/m3 and 1.2 (1.03-1.39) for the municipalities with PM2.5 levels between 39.48 μg/m3 and 51.1 μg/m3, compared to the municipalities with PM2.5 levels less than 30.39 μg/m3. Results showed that individuals who resided in municipalities with higher levels of PM2.5, a proxy measure of PAH, were at an increased risk of death from ovarian cancer compared to those subjects living in municipalities with the lowest PM2.5. The findings of this study warrant further investigation into the role of exposure to air pollutants in the etiology of ovarian cancer development.
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Affiliation(s)
- Li-Ju Hung
- Institute of Occupational Safety and Health, College of Health Sciences, Kaohsiung Medical University, and Department of Family Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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Folate and choline metabolism gene variants in relation to ovarian cancer risk in the Polish population. Mol Biol Rep 2011; 39:5553-60. [PMID: 22183302 DOI: 10.1007/s11033-011-1359-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2011] [Accepted: 12/12/2011] [Indexed: 01/25/2023]
Abstract
Data indicates that genetic factors alone do not account for ovarian tumorigenesis, suggesting that epigenetic status additionally affects this process. Therefore, we assessed the possible contribution of polymorphic variants of genes that may affect DNA methylation to the risk of ovarian cancer incidence in the Polish population. Using PCR-RFLP and HRM analyses, we studied the distribution of BHMT (rs3733890), MTHFD1 (rs2236225), MTHFR (rs1801133), MTR (rs1805087), MTRR (rs1801394) and TCN2 (rs1801198) genotypes and alleles in patients with ovarian cancer (n = 136) and controls (n = 160). Moreover, using DNA and methylation-specific PCR (MSP) we also determined the methylation of the Cadherin 13 (CDH13) promoter in cancerous tissue from these patients. We did not observe a significant association between all studied gene variants and the incidence of ovarian cancer. The lowest P (trend) = 0.1226 was observed for the MTHFR Ala222Val polymorphism. Moreover, the lowest P = 0.0772 was found in the comparison of MTHFR Ala/Ala versus Val/Val and Val/Ala genotypes in patients and control groups. The multifactor dimensionality reduction analysis also did not indicate a significant interactive genetic effect on ovarian cancer incidence for all analyzed SNPs. However, we observed frequent methylation of the CDH13 promoter in approximately 21% (29/136) patients with ovarian carcinomas. Our results might suggest that the selected polymorphic gene variants may not contribute to ovarian cancer incidence.
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Braem M, Schouten L, Peeters P, den Brandt PV, Onland-Moret N. Genetic susceptibility to sporadic ovarian cancer: A systematic review. Biochim Biophys Acta Rev Cancer 2011; 1816:132-46. [DOI: 10.1016/j.bbcan.2011.05.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2011] [Revised: 05/18/2011] [Accepted: 05/18/2011] [Indexed: 11/29/2022]
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Treviño LS, Buckles EL, Johnson PA. Oral contraceptives decrease the prevalence of ovarian cancer in the hen. Cancer Prev Res (Phila) 2011; 5:343-9. [PMID: 22135044 DOI: 10.1158/1940-6207.capr-11-0344] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Ovarian cancer is the leading cause of reproductive cancer death in U.S. women. This high mortality rate is due to the lack of early detection methods and ineffectiveness of therapy for advanced disease. Until more effective screening methods and therapies are developed, chemoprevention strategies are warranted. The hen has a high spontaneous prevalence of ovarian cancer and has been used as a model for studying ovarian cancer chemoprevention. In this study, we used the hen to determine the effect of progestin alone, estrogen alone, or progestin and estrogen in combination (as found in oral contraceptives) on ovarian cancer prevalence. We found that treatment with progestin alone and in combination with estrogen decreased the prevalence of ovarian cancer. A significant risk reduction of 91% was observed in the group treated with progestin alone (risk ratio = 0.0909; 95% CI: 0.0117-0.704) and an 81% reduction was observed in the group treated with progestin plus estrogen (risk ratio = 0.1916; 95% CI = 0.043-0.864). Egg production was also significantly reduced in these treatment groups compared with control. We found no effect of progestin, either alone or in combination with estrogen, on apoptosis or proliferation in the ovary, indicating that this is not the likely mechanism responsible for the protective effect of progestin in the hen. Our results support the use of oral contraceptives to prevent ovarian cancer and suggest that ovulation is related to the risk of ovarian cancer in hens and that other factors, such as hormones, more than likely modify this risk.
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Affiliation(s)
- Lindsey S Treviño
- Department of Animal Science, Cornell University, Ithaca, New York 14853, USA
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Royal CR, Ma H, Walker R, White RE. Estrogen signaling in microvascular arteries: parturition reduces vasodilation by reducing 17β-estradiol and nNOS. Steroids 2011; 76:991-7. [PMID: 21458475 PMCID: PMC3139781 DOI: 10.1016/j.steroids.2011.03.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2011] [Revised: 03/18/2011] [Accepted: 03/24/2011] [Indexed: 12/28/2022]
Abstract
Few studies have examined the potential effects of childbirth on the responses of the female vasculature--especially the resistance microvasculature of non-reproductive tissues. In the present study we have investigated the response of mesenteric microvascular resistance vessels to estrogen (E2), an important vasoactive hormone. Vessels were obtained from either nulliparous or postpartum female Sprague-Dawley rats, and isometric tension studies were performed. We found that E2 induced a concentration-dependent, endothelium-independent relaxation of microvessels precontracted with 10(-5) M phenylephrine; however, E2-induced relaxation was reduced by nearly half in vessels from postpartum animals compared to nulliparous controls. Inhibiting nitric oxide synthase activity with 10(-4) M L-NMMA or L-NPA (which exhibits selectivity for type 1 or nNOS) attenuated the relaxation effect of E2 on arteries from nulliparous animals. In contrast, L-NPA had little effect on arteries from postpartum animals, suggesting a reduced influence of nNOS after parturition. Moreover, expression of nNOS protein in microvessels was decreased 39% in the postpartum state compared to arteries from nulliparous animals. We propose that the impaired E2-induced relaxation response of microvessels from postpartum animals reflects a downregulation of NO production due to lower nNOS expressed in vascular smooth muscle cells. We measured a 73% decrease in serum E2 levels in the postpartum state compared to nulliparous animals. Because E2 has been shown to increase nNOS protein expression, we propose that lower E2 levels after parturition decrease expression of nNOS, leading to a reduced vasodilatory capacity of resistance microvessels.
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Affiliation(s)
- Crista R. Royal
- Department of Pharmacology & Toxicology, Medical College of Georgia, Georgia Health Sciences University, Augusta, GA 30912
| | - Handong Ma
- Department of Pharmacology & Toxicology, Medical College of Georgia, Georgia Health Sciences University, Augusta, GA 30912
| | - Richard Walker
- Department of Biostatistics, Georgia Health Sciences University, Augusta, GA 30912
| | - Richard E. White
- Department of Pharmacology & Toxicology, Medical College of Georgia, Georgia Health Sciences University, Augusta, GA 30912
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Camargo MC, Stayner LT, Straif K, Reina M, Al-Alem U, Demers PA, Landrigan PJ. Occupational exposure to asbestos and ovarian cancer: a meta-analysis. ENVIRONMENTAL HEALTH PERSPECTIVES 2011; 119:1211-7. [PMID: 21642044 PMCID: PMC3230399 DOI: 10.1289/ehp.1003283] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2010] [Accepted: 06/03/2011] [Indexed: 05/24/2023]
Abstract
OBJECTIVE A recent Monographs Working Group of the International Agency for Research on Cancer (IARC) concluded that there is sufficient evidence for a causal association between exposure to asbestos and ovarian cancer. We performed a meta-analysis to quantitatively evaluate this association. DATA SOURCES Searches of PubMed and unpublished data yielded a total of 18 cohort studies of women occupationally exposed to asbestos. DATA EXTRACTION Two authors independently abstracted data; any disagreement was resolved by consulting a third reviewer. DATA SYNTHESIS All but one study reported standardized mortality ratios (SMRs) comparing observed numbers of deaths with expected numbers for the general population; the exception was a study that reported standardized incidence ratios. For simplicity, we refer to all effect estimates as SMRs. The overall pooled SMR estimate for ovarian cancer was 1.77 (95% confidence interval, 1.37-2.28), with a moderate degree of heterogeneity among the studies (I2 = 35.3%, p = 0.061). Effect estimates were stronger for cohorts compensated for asbestosis, cohorts with estimated lung cancer SMRs > 2.0, and studies conducted in Europe compared with other geographic regions. Effect estimates were similar for studies with and without pathologic confirmation, and we found no evidence of publication bias (Egger's test p-value = 0.162). CONCLUSIONS Our study supports the IARC conclusion that exposure to asbestos is associated with increased risk of ovarian cancer.
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Affiliation(s)
- M Constanza Camargo
- Division of Epidemiology and Biostatistics, University of Illinois, Chicago, Illinois 60612-4392, USA
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Ovarian epithelial-stromal interactions: role of interleukins 1 and 6. Obstet Gynecol Int 2011; 2011:358493. [PMID: 21765834 PMCID: PMC3135012 DOI: 10.1155/2011/358493] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2011] [Revised: 04/12/2011] [Accepted: 04/27/2011] [Indexed: 01/03/2023] Open
Abstract
Ovarian epithelial cancer is the most lethal gynecologic malignancy. The high mortality is attributed to the fact that most cases typically present in late stage when ovarian cancer (OC) has already spread beyond the ovary. Ovarian epithelial cancer cells are shed into intraperitoneal ascites and easily disseminate throughout the peritoneal cavity with preferential metastasis to the omentum, peritoneum, and local organs. Understanding how ovarian epithelial cells interact with and modulate their microenvironment can provide insight into the molecular mechanism(s) involved with malignant transformation and progression which may eventually identify novel diagnostic, prognostic, and therapeutic targets. The objective of this paper is to provide a brief consideration of ovarian surface epithelial-stromal interactions in regard to normal physiological function and tumor progression as influenced by two potentially key interleukins, interleukins-1 (IL-1) and -6 (IL-6), present in the microenvironment. Lastly, we will consider the clinical implications of IL-1 and IL-6 for OC patients.
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Wright JW, Jurevic L, Stouffer RL. Dynamics of the primate ovarian surface epithelium during the ovulatory menstrual cycle. Hum Reprod 2011; 26:1408-21. [PMID: 21421660 DOI: 10.1093/humrep/der057] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Epithelial ovarian cancer (EOC) risk correlates strongly with the number of ovulations that a woman experiences. The primary source of EOC in women is the ovarian surface epithelium (OSE). Mechanistic studies on the etiology of OSE transformation to EOC cannot be realistically performed in women. Selecting a suitable animal model to investigate the normal OSE in the context of ovulation should be guided by the model's reproductive similarities to women in natural features that are thought to contribute to EOC risk. METHODS We selected the non-human primate, rhesus macaque, as a surrogate to study the normal OSE during the natural menstrual cycle. We investigated OSE morphology and marker expression, plus cell proliferation and death in relation to menstrual cycle stage and ovulation. RESULTS OSE cells displayed a morphological range from squamous to columnar. Cycle-independent parameters and cycle-dependent changes were observed for OSE histology, steroid receptor expression, cell death, DNA repair and cell adhesion. Contrary to findings in non-primates, primate OSE cells were not manifestly cleared from the site of ovulation, nor were proliferation rates affected by ovulation or stage of the menstrual cycle. DNA repair proteins were more highly expressed in OSE than in other ovarian cells. CONCLUSIONS This study identifies significant differences between primate and non-primate OSE. In contrast to established views, ovulation-induced death and proliferation are not indicated as prominent contributors to EOC risk, but disruption of OSE cadherin-mediated adhesion may be, as could the loss of ovary-mediated chronic suppression of proliferation and elevation of DNA repair potential.
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Affiliation(s)
- Jay W Wright
- Division of Reproductive Sciences, Oregon National Primate Research Center, Beaverton, OR 97006, USA.
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