Many cancers, including ovarian, overexpress epithelial mucin (MUC1) and promote anti-MUC1 antibodies that may correlate with more favorable prognosis. By extension, risk for ovarian cancer might be reduced by preexisting MUC1-specific immunity. We measured anti-MUC1 antibodies in 705 control women, identified events predicting antibodies, and estimated ovarian cancer risk by comparing profiles of events generating antibodies in controls with those in 668 ovarian cancer cases. Factors predicting antibodies included oral contraceptive use, breast mastitis, bone fracture or osteoporosis, pelvic surgeries, nonuse of talc in genital hygiene, and to a lesser extent intrauterine device use and current smoking. There was a significant increase in the likelihood of having anti-MUC1 antibodies from 24.2% in women with 0 or 1 condition, to 51.4% in those with five or more conditions. By the same index of events, the risk for ovarian cancer was inversely associated with number of conditions predisposing to anti-MUC1 antibodies. Compared with having experienced 0 or 1 event, the adjusted risk for ovarian cancer decreased progressively with relative risks (and 95% confidence limits) of 0.69 (0.52-0.92), 0.64 (0.47-0.88), 0.49 (0.34-0.72), and 0.31 (0.16-0.61), respectively for women with two, three, four, and five or more events related to the presence of antibodies (P_trend < 0.0001.) We conclude that several traditional and new risk factors for ovarian cancer may be explained by their ability to induce MUC1 immunity through exposure of MUC1 to immune recognition in the context of inflammatory or hormonal processes in various MUC1-positive tissues.

An inverse association between adult body mass index (BMI) and risk of endometriosis has frequently been reported. However, the association between body size during childhood and early adulthood and endometriosis is not as well documented. Using data collected from the Nurses' Health Study II, a prospective cohort study of premenopausal US nurses, that began in 1989, we have attempted to clarify this relationship. Data are updated every 2 years with follow-up for these analyses through 2001. In 1989 women recalled their body size at ages 5, 10 and 20 years using a validated 9-level figure drawing. During 831 910 person-years of follow-up, 1817 cases of self-reported laparoscopically-confirmed endometriosis were observed among women with no past infertility. After adjusting for age, birthweight, age at menarche, parity, oral contraceptive use and adult BMI, we observed a significant reduction in the incidence of endometriosis with increasing body size for all time periods. The relative risks (RRs) comparing the smallest and largest figure sizes to the middle category during childhood (ages 5–10) were 1.18 (95% confidence interval 1.02–1.36) and 0.82 (0.66–1.02), P-trend = 0.0002. At age 20, the RRs for the same comparisons were 1.32 (1.06–1.65) and 0.87 (0.74–1.03), P-trend = 0.04. Additional adjustment by menstrual cycle length and regularity yielded similar associations. The associations were stronger among nulliparous women than among parous women, although not all differences were statistically significant. In this large cohort of premenopausal women, there was evidence of a persistent inverse association between childhood and early adulthood body size and incidence of laparoscopically confirmed endometriosis, independent of adult BMI and menstrual cycle characteristics.

Exposure to persistent organic pollutants, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, is widespread among the general population. There is evidence of adverse effects on reproduction and early pregnancy in relation to organochlorine exposure but human studies remain limited. The increased use of assisted reproductive technologies (ART) presents unique opportunities for the assessment of environmental influences on early pregnancy outcomes not otherwise observable in humans, but studies need to be designed to maximize the efficiency of the exposure data collected while minimizing exposure measurement error.

Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Herein, we characterize variation in DNA methylation (DNAm) and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genotype data and methylation in endometrial samples from 984 deeply-phenotyped participants. We estimate that 15.4% of the variation in endometriosis is captured by DNAm and identify significant differences in DNAm profiles associated with stage III/IV endometriosis, endometriosis sub-phenotypes and menstrual cycle phase, including opening of the window for embryo implantation. Menstrual cycle phase was a major source of DNAm variation suggesting cellular and hormonally-driven changes across the cycle can regulate genes and pathways responsible for endometrial physiology and function. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTLs including 51 associated with risk of endometriosis, highlighting candidate genes contributing to disease risk. Our work provides functional evidence for epigenetic targets contributing to endometriosis risk and pathogenesis. Data generated serve as a valuable resource for understanding tissue-specific effects of methylation on endometrial biology in health and disease.

Background: Regular exercise has been associated with a 40%–80% reduction in risk for endometriosis in several case-control studies. However, women experiencing symptoms prior to their diagnosis may be less likely to exercise than healthy controls, thus biasing the observed association. Methods: Using data collected from the Nurses' Health Study II, a prospective cohort study of premenopausal US nurses that began in 1989, we have attempted to clarify this relation. Data are updated every 2 years with follow-up for these analyses through 2001. In 1989, 1991, and 1997 women reported average amount of time per week engaging in various physical activities. A metabolic equivalent (MET) score was assigned to each activity, and these were summed to estimate total activity. Results: A total of 102,197 premenopausal women contributed 996,422 person-years of follow-up with 2703 cases of laparoscopically confirmed endometriosis. After adjusting for BMI at age 18, current BMI, smoking, parity, infertility status, oral contraceptive use, age at menarche, and menstrual cycle length and pattern in college, we observed only a slight reduction in the incidence of endometriosis, comparing the highest level of activity (≥42 MET hours/week) to the lowest (<3 MET hours/week) (rate ratio = 0.89 [95% confidence interval = 0.77–1.03]). The association was limited to participants with no past or concurrent infertility (P = 0.002, test for heterogeneity). No associations were seen with inactivity. Conclusions: In this first prospective assessment, we did not find evidence of the strong inverse association previously reported, although we cannot rule out a modest inverse association.