Reproductive and hormonal factors and risk of ovarian cancer by tumor dominance: results from the Ovarian Cancer Cohort Consortium (OC3).

Background: Laterality of epithelial ovarian tumors may reflect the underlying carcinogenic pathways and origins of tumor cells. Methods: We pooled data from 9 prospective studies participating in the Ovarian Cancer Cohort Consortium. Information on measures of tumor size or tumor dominance was extracted from surgical pathology reports or obtained through cancer registries. We defined dominant tumors as those restricted to one ovary or where the dimension of one ovary was at least twice as large as the other, and nondominant tumors as those with similar dimensions across the two ovaries or peritoneal tumors. Competing risks Cox models were used to examine whether associations with reproductive and hormonal risk factors differed by ovarian tumor dominance. Results: Of 1,058 ovarian cancer cases with tumor dominance information, 401 were left-dominant, 363 were right-dominant, and 294 were nondominant. Parity was more strongly inversely associated with risk of dominant than nondominant ovarian cancer (P-heterogeneity = 0.004). Ever use of oral contraceptives (OC) was associated with lower risk of dominant tumors, but was not associated with nondominant tumors (Pheterogeneity = 0.01). Higher body mass index was associated with higher risk of left-dominant tumors, but not significantly associated with risk of right-dominant or nondominant tumors (P-heterogeneity = 0.08). Conclusions: These data suggest that reproductive and hormonal risk factors appear to have a stronger impact on dominant tumors, which may have an ovarian or endometriosis origin. Impact: Examining the associations of ovarian cancer risk factors by tumor dominance may help elucidate the mechanisms through which these factors influence ovarian cancer risk.