Kara A Michels

Physical Activity From Adolescence Through Midlife and Associations With Body Mass Index and Endometrial Cancer Risk

Abstract Background Physical activity is associated with lower risk for endometrial cancer, but the extent to which the association is mediated by body mass index (BMI) in midlife is unclear. This study describes the physical activity–endometrial cancer association and whether BMI mediates this relationship. Methods Participants were 67 705 women in the National Institutes of Health-AARP Diet and Health Study (50-71 years) who recalled their physical activity patterns starting at age 15-18 years. We identified 5 long-term physical activity patterns between adolescence and cohort entry (ie, inactive, maintained low, maintained high, increasers, decreasers). We used Cox regression to assess the relationship between these patterns and midlife BMI and endometrial cancer, adjusting for covariates. Mediation analysis was used to estimate the proportion of the physical activity–endometrial cancer association that was mediated by midlife BMI. Results During an average 12.4 years of follow-up 1468 endometrial cancers occurred. Compared with long-term inactive women, women who maintained high or increased activity levels had a 19% to 26% lower risk for endometrial cancer (maintained high activity: hazard ratio = 0.81, 95% confidence interval [CI] = 0.67 to 0.98; increasers: hazard ratio = 0.74, 95% CI = 0.61 to 0.91). They also had a 50% to 77% lower risk for obesity in midlife (eg, maintained high activity: odds ratio for a BMI of 30-39.9 kg/m2 = 0.50, 95% CI = 0.46 to 0.55; and maintained high activity, odds ratio for a BMI of ≥40 kg/m2 = 0.32, 95% CI = 0.26 to 0.39). BMI was a statistically significant mediator accounting for 55.5% to 62.7% of the physical activity–endometrial cancer associations observed. Conclusions Both maintaining physical activity throughout adulthood and adopting activity later in adulthood can play a role in preventing obesity and lowering the risk for endometrial cancer.

Association of Endogenous Pregnenolone, Progesterone, and Related Metabolites with Risk of Endometrial and Ovarian Cancers in Postmenopausal Women: The B∼FIT Cohort

AbstractBackground:Postmenopausal pregnenolone and/or progesterone levels in relation to endometrial and ovarian cancer risks have been infrequently evaluated. To address this, we utilized a sensitive and reliable assay to quantify prediagnostic levels of seven markers related to endogenous hormone metabolism.Methods:Hormones were quantified in baseline serum collected from postmenopausal women in a cohort study nested within the Breast and Bone Follow-up to the Fracture Intervention Trial (B∼FIT). Women using exogenous hormones at baseline (1992–1993) were excluded. Incident endometrial (n = 65) and ovarian (n = 67) cancers were diagnosed during 12 follow-up years and compared with a subcohort of 345 women (no hysterectomy) and 413 women (no oophorectomy), respectively. Cox models with robust variance were used to estimate cancer risk.Results:Circulating progesterone levels were not associated with endometrial [tertile (T)3 vs. T1 HR (95% confidence interval): 1.87 (0.85–4.11); Ptrend = 0.17] or ovarian cancer risk [1.16 (0.58–2.33); 0.73]. Increasing levels of the progesterone-to-estradiol ratio were inversely associated with endometrial cancer risk [T3 vs. T1: 0.29 (0.09–0.95); 0.03]. Increasing levels of 17-hydroxypregnenolone were inversely associated with endometrial cancer risk [0.40 (0.18–0.91); 0.03] and positively associated with ovarian cancer risk [3.11 (1.39–6.93); 0.01].Conclusions:Using sensitive and reliable assays, this study provides novel data that endogenous progesterone levels are not strongly associated with incident endometrial or ovarian cancer risks. 17-hydroxypregnenolone was positively associated with ovarian cancer and inversely associated with endometrial cancer.Impact:While our results require replication in large studies, they provide further support of the hormonal etiology of endometrial and ovarian cancers.

Circulating biomarkers of infection and endometrial cancer risk

Abstract Purpose Incidence and mortality rates for endometrial cancer are rising. We need to better understand the etiology of this disease and identify new risk factors. We examined whether common genital infections are associated with endometrial cancer. Methods Using serum samples from The Polish Endometrial Cancer Study (443 cases, 443 controls), we measured antibodies against microbial antigens with a multiplex fluorescent bead-based assay. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI), comparing women with positive versus negative serology. Results Most antibodies were not associated with endometrial cancer overall, but seropositivity for Herpes simplex virus 2 was associated with low-grade tumors (OR 1.43 CI 1.02, 2.00). While increased risks for type II, but not type I tumors, were consistently indicated for multiple Chlamydia trachomatis antigens, most estimates did not reach statistical significance (e.g., Pgp3 seropositivity and type I cancers: OR 0.97 CI 0.73, 1.31; and type II: OR 2.96 CI 0.85, 10.31; heterogeneity p -value = 0.03). The strongest associations for type II tumors were observed with seropositivity for Chlamydial stress response proteins. Conclusion Reproductive tract infections may increase risk for endometrial cancer, but the biologic mechanisms are likely both microbe- and histology-specific. Some C. trachomatis infections may be a risk factor for type II endometrial cancers. Given that so few risk factors for type II endometrial cancers are identified, infection-related mechanisms of carcinogenesis in the endometrium merit continued investigation.