Risk factors for invasive endometrioid and clear cell ovarian cancers Free

B113

PURPOSE: Epidemiological evidence suggests that endometriosis and other endometrial pathologies increase risk of ovarian cancer but that this increased risk is related almost exclusively to the clear cell and endometrioid subtypes of ovarian cancer. Despite the histologic and genetic heterogeneity of these two subtypes, these associations suggest a shared etiological pathway and, if this were the case, we would anticipate a similar set of risk factors for the two tumor types.
 >METHODS: To investigate this we have evaluated an array of risk factors including personal, lifestyle, reproductive and hormonal exposures in an Australia-wide case control study including among others, 90 women with invasive clear cell and 142 with endometrioid ovarian cancers and 1,508 population based controls. We also compared the frequency of other hormonally-related gynaecological conditions (as documented on diagnostic pathology reports) among women with clear cell and endometrioid cancers. As a benchmark, we compared these results to occurrence rates among 847 women with the commonest subtype, invasive serous cancer recruited for the same study.
 >RESULTS: Consistent with most studies we found inverse associations between oral contraceptive use, parity, breastfeeding and tubal ligation and risk of endometrioid and clear cell ovarian cancers, though the latter two exposures were significant for the endometrioid subtype only. Recent obesity was associated with increased risk of clear cell cancer (adjusted OR 2.2, 95% CI 1.2-4.1) and higher levels of education were associated with decreased risk (adjusted OR 0.4, 95% CI 0.1-0.9). Although there was no clear association between smoking history and risk of the endometrioid subtype, there was a significant inverse trend associated with increasing pack-years for clear cell cancers (p=0.03). We also found a statistically significant increased risk of both subtypes with self-reported history of endometriosis, with this effect stronger for the clear cell group (adjusted OR 3.0, 95% CI 1.5-5.9 for clear cell and adjusted OR 2.1, 95% CI 1.2-3.8 for endometrioid). Histologically-confirmed endometriosis was significantly more common in the endometrioid (34%) and clear cell subtypes (41%) compared to invasive serous ovarian cancers (7%) (p <0.001). Endometrial hyperplasia and endometrial dysplasia/atypia were also more frequent in the endometrioid and clear cell subtypes. Other factors potentially associated with hormonal milieu (menstrual characteristics, adenomyosis, polyps, fibroids) were not associated with risk.
 >CONCLUSION: The results of this study suggest that reproductive risk factors commonly associated with epithelial ovarian cancer do not differ between the endometrioid and clear cell subtypes. Both subtypes also showed a strong association with abnormal proliferation of the endometrium. On the other hand, the associations with BMI, smoking, education observed solely for the clear cell subtype, and its stronger association with endometriosis, support the conjecture that endometrioid and clear cell ovarian cancers have some distinct as well as shared etiological factors.