Ovarian cancer risk factors by tumor dominance, a surrogate for cell of origin

Abstract

Differentiating ovarian tumors based on developmental pathway may further our understanding of the disease. Traditionally, ovarian cancers were thought to arise from the ovarian surface epithelium; however, recent evidence suggests some tumors originate in the fallopian tube. We classified cases in a population-based case-control study (NECC) and two cohort studies (NHS/NHSII) by tumor dominance, a proxy for tissue of origin. Dominant tumors (likely ovarian origin) are restricted to one ovary or are at least twice as large on one ovary compared to the other. Ovarian cancer risk factors were evaluated in relation to dominant and non-dominant tumors (likely tubal origin) using polytomous logistic regression (NECC) or competing risks Cox models (NHS/NHSII). Results were combined using random-effects meta-analyses. Among 1,771 invasive epithelial ovarian cancer cases, we observed 1,089 tumors with a dominant mass and 682 with no dominant mass. Dominant tumors were more likely to be mucinous, endometrioid, or clear cell, whereas non-dominant tumors were more likely to be serous. Tubal ligation, two or more births, endometriosis, and age were more strongly associated with dominant (RRs = 0.60, 0.83, 1.58, 1.37, respectively) than non-dominant tumors (RRs = 1.03, 0.93, 0.84, 1.14 p-difference = 0.0001, 0.01, 0.0003, 0.01, respectively). These data suggest that risk factors for tumors putatively arising from ovarian versus fallopian tube sites may differ; in particular, reproductive factors may be more important for ovarian-derived tumors. As this is the first study to evaluate ovarian cancer risk factors by tumor dominance, these results need to be validated by other studies.