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.

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