Ovarian cancer is a commonly fatal disease for which prevention strategies have been limited, in part because of a lack of understanding of the underlying biology. This paper reviews the epidemiologic literature in the English language on risk factors and protective factors for ovarian cancer and proposes a novel hypothesis that a common mechanism underlying this disease is inflammation. Previous hypotheses about the causes of ovarian cancer have attributed risk to an excess number of lifetime ovulations or to elevations in steroid hormones. Inflammation may underlie ovulatory events because an inflammatory reaction is induced during the process of ovulation. Additional risk factors for ovarian cancer, including asbestos and talc exposure, endometriosis (i.e., ectopic implantation of uterine lining tissue), and pelvic inflammatory disease, cannot be directly linked to ovulation or to hormones but do cause local pelvic inflammation. On the other hand, tubal ligation and hysterectomy act as protective factors, perhaps by diminishing the likelihood that the ovarian epithelium will be exposed to environmental initiators of inflammation. Inflammation entails cell damage, oxidative stress, and elevations of cytokines and prostaglandins, all of which may be mutagenic. The possibility that inflammation is a pathophysiologic contributor to the development of ovarian cancer suggests a directed approach to future research

Previous epidemiologic observations consistently suggest that suppression of ovulation, tubal ligation, and hysterectomy reduce the risk of ovarian cancer and that perineal talc use increases the risk. We examined these and other risk factors in the context of a new hypothesis: that inflammation may play a role in ovarian cancer risk. Ovulation entails ovarian epithelial inflammation; talc, endometriosis, cysts, and hyperthyroidism may be associated with inflammatory responses of the ovarian epithelium; gynecologic surgery may preclude irritants from reaching the ovaries via ascension from the lower genital tract. We evaluated these risk factors in a population-based case-control study. Cases 20-69 years of age with a recent diagnosis of epithelial ovarian cancer (767) were compared with community controls (1,367). We found that a number of reproductive and contraceptive factors that suppress ovulation, including gravidity, breast feeding, and oral contraception, reduced the risk of ovarian cancer. Environmental factors and medical conditions that increased risk included talc use, endometriosis, ovarian cysts, and hyperthyroidism. Gynecologic surgery including hysterectomy and tubal ligation were protective. Tubal ligation afforded a risk reduction even 20 or more years after the surgery. The spectrum of associations provides support for the hypothesis that inflammation may mediate ovarian cancer risk.

Background: The incidence of pregnancy-associated cancer (PAC) is expected to increase as more women delay childbearing until later ages. However, information on frequency and incidence of PAC is scarce in the United States. Methods: We identified pregnancies among women aged 10-54 years during 2001-2013 from five U.S. health plans participating in the Cancer Research Network (CRN) and the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP). We extracted information from the health plans' administrative claims and electronic health record databases, tumor registries, and infants' birth certificate files to estimate the frequency and incidence of PAC, defined as cancer diagnosed during pregnancy and up to 1 year postpartum. Results: We identified 846 PAC events among 775,709 pregnancies from 2001 to 2013. The overall incidence estimate was 109.1 (95% confidence interval [CI] = 101.8-116.7) per 100,000 pregnancies. There was an increase in the incidence between 2002 and 2012 (the period during which complete data were available), from 75.0 (95% CI = 54.9-100.0) per 100,000 pregnancies in 2002 to 138.5 (95% CI = 109.1-173.3) per 100,000 pregnancies in 2012. The most common invasive cancers diagnosed were breast (n = 208, 24.6%), thyroid (n = 168, 19.9%), melanoma (n = 93, 11.0%), hematologic (n = 87, 10.3%), and cervix/uterus (n = 74, 8.7%). Conclusions: Our study provides contemporary incidence estimates of PAC from a population-based cohort of U.S. women. These estimates provide the data needed to help develop clinical and public health policies aimed at diagnosing PAC at an early stage and initiating appropriate therapeutic interventions in a timely manner.

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