Person:

Tworoger, Shelley

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.

Several recent studies have evaluated the association between dietary flavonoid intake and ovarian cancer risk, and all reported significant or suggestive inverse associations with certain flavonoids or flavonoid subclasses; however, most of these studies were small to moderate in size. We therefore examined this association in a large, population-based case-control study. We calculated intake of five common dietary flavonoids (myricetin, kaempferol, quercetin, luteolin, and apigenin), as well as total intake of these flavonoids, for 1,141 cases and 1,183 frequency-matched controls. We used unconditional logistic regression to estimate the relative risk (RR) of ovarian cancer for each quintile of flavonoid intake, compared to the lowest quintile. We did not observe an association between total flavonoid intake and ovarian cancer risk. The multivariable-adjusted RR for the highest versus lowest quintile of total flavonoid intake was 1.06 (95% confidence interval [CI]=0.78–1.45). In analyses of each individual flavonoid, only intake of apigenin was associated with a borderline significant decrease in risk (RR, highest versus lowest quintile=0.79, 95% CI=0.59–1.06; p-trend=0.26), and this association was significant after adjustment for intake of the other four individual flavonoids (comparable RR=0.72, 95% CI=0.53–0.98; p-trend=0.09). These results provide limited support for an association between flavonoid intake and ovarian cancer risk. However, given the findings of previous studies and the biologic plausibility of this association, additional studies are warranted.