Fertility treatments and invasive epithelial ovarian cancer risk in Jewish Israeli BRCA1 or BRCA2 mutation carriers

In Europe ovarian cancer represents the third most common cancer of the female genital tract, with 30,000 newly diagnosed patients per year. Family history is the most significant risk factor. Lifetime risk for ovarian cancer increases from 1.4% for women with a negative family history to 14.6-32.2% in women from affected families. About 5-10% of ovarian cancers are hereditary and supposed to occur in three different forms: hereditary breast and ovarian cancer syndrome (HBOC), site-specific hereditary ovarian cancer (HOC) and hereditary nonpolyposis colorectal cancer syndrome (HNPCC). HBOC and HOC account for 80-90% of the cases and are associated with inactivating germline mutations of the BRCA1 and BRCA2 genes. For BRCA1 and BRCA2 mutation carriers the cumulative risk by age 70 of developing ovarian cancer is 45-60% and 25-30%, respectively. Approximately 10-15% of familial ovarian cancers are related to the HNPCC syndrome with a cumulative ovarian cancer risk of 9% by age 70. Germline polymorphisms may further modify ovarian cancer risk. Bilateral prophylactic oophorectomy reduces the risk of developing ovarian cancer in HBOC and HOC families by 50%. Tubal ligation also significantly reduces the risk in BRCA1 mutation carriers (odds ratio 0.39). Knowledge of the genetic background provides an objective basis for individual risk assessment and prevention.

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Oral Contraceptives and Risk of Ovarian Cancer and Breast Cancer Among High-Risk Women: A Systematic Review and Meta-Analysis

Journal of Clinical Oncology ◽

10.1200/jco.2013.48.9021 ◽

2013 ◽

Vol 31 (33) ◽

pp. 4188-4198 ◽

Cited By ~ 138

Author(s):

Patricia G. Moorman ◽

Laura J. Havrilesky ◽

Jennifer M. Gierisch ◽

Remy R. Coeytaux ◽

William J. Lowery ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Family History ◽

Cancer Risk ◽

Meta Analysis ◽

Brca2 Mutation ◽

Ovarian Cancer Risk ◽

Mutation Carriers ◽

History Of ◽

Meta Analyses

Purpose To estimate the risks of ovarian cancer and breast cancer associated with oral contraceptive (OC) use among women at elevated risk owing to mutations in BRCA1/2 or a strong family history. Methods We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published 2000 to 2012 that evaluated associations between OC use and breast or ovarian cancer among women who are carriers of a BRCA1/2 mutation or have a family history of breast or ovarian cancer. Results From 6,476 unique citations, we identified six studies examining ovarian cancer risk in BRCA1/2 mutation carriers and eight studies examining breast cancer risk in BRCA1/2 mutation carriers. For BRCA1/2 mutation carriers combined, meta-analysis showed an inverse association between OC use and ovarian cancer (odds ratio [OR], 0.58; 95% CI, 0.46 to 0.73) and a nonstatistically significant association with breast cancer (OR, 1.21; 95% CI, 0.93 to 1.58). Findings were similar when examining BRCA1 and BRCA2 mutation carriers separately. Data were inadequate to perform meta-analyses examining duration or timing of use. For women with a family history of ovarian or breast cancer, we identified four studies examining risk for ovarian cancer and three for breast cancer, but differences between studies precluded combining the data for meta-analyses, and no overall pattern could be discerned. Conclusion Our analyses suggest that associations between ever use of OCs and ovarian and breast cancer among women who are BRCA1 or BRCA2 mutation carriers are similar to those reported for the general population.

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Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djaa099 ◽

2020 ◽

Author(s):

Alice W Lee ◽

Stacey Rosenzweig ◽

Ashley Wiensch ◽

Susan J Ramus ◽

Usha Menon ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Risk ◽

Epithelial Ovarian Cancer ◽

Race And Ethnicity ◽

Clear Cell ◽

Ovarian Cancer Risk ◽

Inverse Association ◽

Case Control Studies ◽

Invasive Epithelial Ovarian Cancer ◽

Reduced Risk

Abstract Background Parity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated. Methods A pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses. Results Ever having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend < .001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer. Conclusions Incomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.

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