Abstract 3712: Ovarian cancer risk factors by histologic subtypes in the NIH-AARP Diet and Health Study
Authors: Yang Hannah P. , Trabert Britton , Murphy Megan A. , Sherman Mark E. , Sampson Joshua N. , Brinton Louise A. , Hartge Patricia , Hollenbeck Albert , Schatzkin Arthur , Wentzensen Nicolas 
Published: June 2012

Abstract
Background: Epithelial ovarian cancer is highly heterogeneous, but it is currently not well understood whether variation in histology reflects etiologic heterogeneity. To date, only a limited number of studies have assessed these relationships, with inconsistent results.
Methods: We prospectively evaluated the association between risk factors by histological subtypes of incident ovarian cancer (n = 850) in a cohort of 169,491 US women enrolled in the NIH-AARP Diet and Health Study, a cohort established in 1995-1996 with last follow-up to 2006. We constructed Cox models of individual exposures by comparing case subtypes to the entire non-case group. For each exposure, differences in risk estimates across histologic type were assessed using p-values from unconditional logistic regression models that treated serous as the reference category and excluded controls. In addition, we used the likelihood ratio test to determine the significance of heterogeneity across subtypes and the risk factors.
Results: Substantial risk differences between histologic subtypes were observed for menopausal hormone therapy (MHT) use, oral contraceptive (OC) use, parity, and body mass index (BMI) (p -heterogeneity=0.01, 0.03, 0.05, 0.03, respectively). MHT users were at increased risk for all histologic subtypes except for mucinous carcinomas, where risk was reduced (OR=0.37; 95% CI: 0.18-0.80). OC users were at significantly decreased risk for serous cancers (OR=0.69; 95% CI: 0.55-0.85), but at slightly increased risk for mucinous (OR=1.72; 95% CI: 0.86-3.42) and clear cell (OR=1.47; 95% CI: 0.64-3.40) tumors. Although parity was inversely associated with risk of all subtypes, the ORs ranged from 0.28 (clear cell) to 0.82 (serous). Obesity was a significant risk factor only for endometrioid cancers (OR=1.64; 95% CI: 1.00-2.70). We also observed differences in the risks associated with smoking by histologic type, albeit the heterogeneity was not statistically significant.
Conclusion: We observed significant heterogeneity of risk factor associations across ovarian histologies, with several associations similar to those observed for the same tissue-type of other cancers. For example, BMI was associated with an increased risk of endometrioid ovarian tumors similar to endometrioid endometrial cancers, OC use with decreased risk of serous subtypes as reported for fallopian tube cancers, and OC use with increased risk for mucinous cancers as for colorectal cancers. Although some of these findings were based on small numbers and we cannot exclude occasional misclassification of metastases from other cancer sites (endometrium, colon), our data suggest that phenotypic heterogeneity of ovarian cancers reflects etiologic heterogeneity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3712. doi:10.1158/1538-7445.AM2011-3712