Abstract 1829: Measures of body size and the risk of microsatellite stable and unstable molecular subtypes of sporadic endometrial cancer

Abstract

Abstract Introduction: Obesity is an established risk factor for endometrial cancer, but its association with microsatellite stable (MSS) and microsatellite instable (MSI) endometrial cancer is not well understood. Therefore, we evaluated the risk for sporadic MSI and MSS endometrial cancers associated with various measures of body size in a population-based case control study. Methods: The study included 126 MSI and 311 MSS incident invasive endometrial cancer cases and 1030 frequency age-matched controls in Alberta, Canada (2002-2006). Risk factor information was ascertained with an in-person interview and microsatellite status of cases was determined using five microsatellite markers (Bat25, Bat26, D5S346, D2S123 and D17S250). Tumors that exhibited instability in ≥2 markers were classified as MSI and tumors that exhibited instability in <2 markers were classified as MSS. Associations were estimated with odds ratios (OR) and 95% confidence intervals (95% CI) using multivariable polytomous logistic regression, which estimated ORs for MSS or MSI cases versus controls as well as for MSI cases versus MSS cases. Results: There was a consistent pattern of increasing risks for both MSS and MSI cancer with increasing waist circumference (WC), waist-to-hip ratio and body mass index (BMI) (all Ptrend < 0.005). Nonetheless, the magnitude of risk with the increasing measures of body size was generally greater for MSI cancer than for MSS cancer. Overweight women (BMI=25-30 kg/m2) had an increased risk for MSI cancer (OR=1.8, 95%CI=1.0-3.4), but not for MSS cancer (OR=1.0, 95%CI=0.7-1.4), with a suggested elevation in risk for MSI compared to MSS cancer (OR=1.9 95%CI=1.0-3.8). Obese women (≥30 kg/m2) had an increased risk for both MSS (OR=2.3, 95%CI=1.6-3.2) and MSI (OR=4.5, 95%CI=2.5-8.0) cancer, but again, there was a suggested elevation in risk for MSI cancer compared to MSS cancer (OR=1.9 95%CI=1.0-3.7). After adjusting for waist circumference, the risk for MSS cancer among obese women was completely attenuated (OR=1.1, 95%CI=0.6-1.9), while the risk for MSI cancer (OR=3.2, 95%CI=1.4-7.2) was only slightly attenuated. Further, in the case-case comparisons the risks for MSI compared to MSS cancer for overweight (OR=2.5, 95%CI=1.1-5) and obese women (OR=2.9, 95%CI=1.2-7.3) were strengthened after adjusting for WC. Conclusion: Our findings indicate that greater body size increases the risk for both MSS and MSI cancer and imply that maintaining a healthy body weight will reduce endometrial cancer risk. Since bioavailable estrogen is elevated in overweight and obese women, the relatively greater risks for MSI compared to MSS cancer observed for these women suggest that the proliferative effects of estrogen in the endometrium are more pronounced when DNA mismatch repair has been compromised as occurs in MSI cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1829.