Determinants of serous ovarian, fallopian tube and peritoneal cancers: A new perspective on ovarian carcinogenesis.

PR-15

Background: Invasive serous cancers are diagnosed in the ovary, fallopian tube and peritoneum although peritoneal cancer, and particularly fallopian tube cancer, are diagnosed much less commonly than ovarian cancer. It is widely believed that these are variants of the same malignancy but little is known about fallopian tube and primary peritoneal cancers. A comparison of risk factors for these tumor types may shed light on the etiology of ovarian cancer. Methods: We investigated risk factors for the three cancers using data from a large Australian population-based case-control study. We included women with incident serous ovarian (n=627), primary peritoneal (n=129) and fallopian tube (n=45) cancer and 1508 control women. Participants completed a comprehensive reproductive and lifestyle questionnaire. Logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: Hormonal contraceptive use was inversely related to risk of all three cancers with OR for 5+ years vs never use of 0.5 (95%CI 0.4-0.6) for ovarian, 0.5 (0.2-1.1) for fallopian tube and 0.7 (0.4-1.1) for peritoneal cancer. Parity and breast-feeding were also significantly inversely related to risk of both serous ovarian and fallopian tube cancer. In contrast, parous women had an increased risk of peritoneal cancer (OR=1.8, 95%CI 0.8-3.9), and increasing parity did not lower risk. There was also no association between breast-feeding and peritoneal cancer. However, obesity was associated with a doubling of risk for peritoneal cancer alone (OR=2.3, 95%CI =1.4-3.7). Conclusion: The strikingly similar patterns of risk for serous ovarian and fallopian tube cancers and the distinctly different results for primary peritoneal cancer suggest that peritoneal cancers develop along a different pathway. These results also call into question the role of the physical effects of ovulation in the development of serous ovarian cancer, as they would not affect the fallopian tube epithelium, and suggest instead that the hormonal and/or chemical effects of ovulation may be more important.