Citations 2
Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies
Lee, Alice W. , Rosenzweig, Stacey, Wiensch, Ashley , Group, the Australian Ovarian Cancer Study, Ramus, Susan J. , Menon, Usha , Ziogas, Argyrios , Anton‐Culver, Hoda , Whittemore, Alice S. , Sieh, Weiva , Rothstein, Joseph H. , McGuire, Valerie, Wentzensen, Nicolas , Qin, Bo , Terry, Kathryn L. , Titus, Linda , Schildkraut, Joellen M. , Goode, Ellen L. , Jordan, Susan J. , Ness, Roberta B., Moysich, Kirsten B. , Thompson, Pamela J., Goodman, Marc T. , Carney, Michael E. , Chang‐Claude, Jenny , Rossing, Mary Anne, Khoja, Lilah , Alimujiang, Aliya , Phung, Minh Tung , Brieger, Katharine K. , Wu, Anna H. , Pike, Malcolm C. , Webb, Penelope M. , Pearce, Celeste Leigh , Ramus, Susan J , Webb, Penelope M , Menon, Usha , Anton-Culver, Hoda , Moysich, Kirsten , Sieh, Weiva , Ziogas, Argyrios , Qin, Bo , Khoja, Lilah , Goodman, Marc T , Group, the Australian Ovarian Cancer Study, Gentry‐Maharaj, Aleksandra , Bandera, Elisa V. , Cramer, Daniel W. , Berchuck, Andrew , Kjær, Susanne K. , Jensen, Allan , Modugno, Francesmary , Harris, Holly R. , Doherty, Jennifer A. , Risch, Harvey A. , Mukherjee, Bhramar , Pharoah, Paul D.P. , Phung, Minh Tung
JNCI: Journal of the National Cancer Institute | August 4, 2020 | Volume: 113 | Issue: 3 | Pages: 301-308
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.
A comprehensive gene–environment interaction analysis in Ovarian Cancer using genome‐wide significant common variants
Jensen, Allan , Wiensch, Ashley , Lee, Alice W. , Ness, Roberta B., Salvatore, Maxwell , Tworoger, Shelley S. , Whittemore, Alice S. , Sieh, Weiva , Goode, Ellen L. , Goodman, Marc T. , Chenevix‐Trench, Georgia , Rossing, Mary Anne, Webb, Penelope M. , Terry, Kathryn L. , Fortner, Renée T. , Menon, Usha , Gayther, Simon A. , Wu, Anna H. , Song, Honglin , Brooks‐Wilson, Angela , Thompson, Pamela J., Chang‐Claude, Jenny , Schildkraut, Joellen M. , Le, Nhu D. , Wentzensen, Nico, Trabert, Britton , Høgdall, Estrid , Huntsman, David G. , Pike, Malcolm C. , Pearce, Celeste Leigh , Salvatore, Maxwell , Anton-Culver, Hoda , Goode, Ellen L , Fortner, Renée T , Wu, Anna H. , Cramer, Daniel W , Modugno, Francesmary , Trabert, B , Pike, Malcolm C , Pearce, Celeste Leigh , Tworoger, Shelley S , Webb, Penelope M , Jensen, Allan , Menon, Usha , Brooks-Wilson, Angela R , Sieh, Weiva , Chenevix-Trench, Georgia , Høgdall, Estrid , Goodman, Marc T , Kim, Sehee , Wang, Miao , Tyrer, Jonathan P. , Liu, Gang , Anton‐Culver, Hoda , Olson, Sara H. , Berchuck, Andrew , Doherty, Jennifer A. , Giles, Graham G. , Ziogas, Argyrios , Bandera, Elisa V. , Cook, Linda S. , Cramer, Daniel W. , Milne, Roger L. , Winham, Stacey J. , Kjær, Susanne K. , Modugno, Francesmary , Harris, Holly R. , Pharoah, Paul D.P. , Mukherjee, Bhramar
International Journal of Cancer | November 30, 2018 | Volume: 144 | Issue: 9 | Pages: 2192-2205
As a follow‐up to genome‐wide association analysis of common variants associated with ovarian carcinoma (cancer), our study considers seven well‐known ovarian cancer risk factors and their interactions with 28 genome‐wide significant common genetic variants. The interaction analyses were based on data from 9971 ovarian cancer cases and 15,566 controls from 17 case–control studies. Likelihood ratio and Wald tests for multiplicative interaction and for relative excess risk due to additive interaction were used. The top multiplicative interaction was noted between oral contraceptive pill (OCP) use (ever vs. never) and rs13255292 (p value = 3.48 × 10−4). Among women with the TT genotype for this variant, the odds ratio for OCP use was 0.53 (95% CI = 0.46–0.60) compared to 0.71 (95%CI = 0.66–0.77) for women with the CC genotype. When stratified by duration of OCP use, women with 1–5 years of OCP use exhibited differential protective benefit across genotypes. However, no interaction on either the multiplicative or additive scale was found to be statistically significant after multiple testing correction. The results suggest that OCP use may offer increased benefit for women who are carriers of the T allele in rs13255292. On the other hand, for women carrying the C allele in this variant, longer (5+ years) use of OCP may reduce the impact of carrying the risk allele of this SNP. Replication of this finding is needed. The study presents a comprehensive analytic framework for conducting gene–environment analysis in ovarian cancer.