Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Cancer Epidemiol Biomarkers Prev. 2013 Jul;22(7):1325-31. doi: 10.1158/1055-9965.EPI-13-0105. Epub 2013 May 15.
Hormonal and reproductive factors modulate bioavailable estrogen to influence endometrial cancer risk. Estrogen affects the microsatellite status of tumors, but the relation between these estrogen-related factors and microsatellite instability (MSI) status of endometrial tumors is not known. We evaluated associations between hormonal and reproductive factors and risks of microsatellite stable (MSS) and MSI endometrial cancer among postmenopausal women (MSS cases = 258, MSI cases = 103, and controls = 742) in a population-based case-control study in Alberta, Canada (2002-2006). Polytomous logistic regression was used to estimate ORs and 95% confidence intervals (95% CI). We observed a significant trend in risk reduction for MSI (Ptrend = 0.005) but not MSS (Ptrend = 0.23) cancer with oral contraceptive use; with 5-year use or more, the risk reduction was stronger for MSI (OR = 0.42; 95% CI, 0.23-0.77) than for MSS cancer (OR = 0.80; 95% CI, 0.54-1.17; Pheterogeneity = 0.05). For more recent use (<30 years), the risk reduction was stronger for MSI (OR = 0.36; 95% CI, 0.19-0.69) than for MSS cancer (OR = 0.77; 95% CI, 0.51-1.15; Pheterogeneity = 0.032). No differential risk associations were observed for menopausal hormone use, parity and age at menarche, menopause or first pregnancy. We found limited evidence for statistical heterogeneity of associations of endometrial cancer risk with hormonal and reproductive factors by MSI status, except with oral contraceptive use. This finding suggests a potential role for the MMR system in the reduction of endometrial cancer risk associated with oral contraceptive use, although the exact mechanism is unclear. This study shows for the first time that oral contraceptive use is associated with a reduced risk for MSI but not for MSS endometrial cancer.
激素和生殖因素调节生物可利用的雌激素，从而影响子宫内膜癌的风险。雌激素影响肿瘤的微卫星状态，但这些与雌激素相关的因素与子宫内膜肿瘤的微卫星不稳定性（MSI）状态之间的关系尚不清楚。我们评估了激素和生殖因素与绝经后妇女中微卫星稳定（MSS）和 MSI 子宫内膜癌风险之间的关联（MSS 病例=258 例，MSI 病例=103 例，对照=742 例），这是一项基于人群的病例对照研究，在加拿大艾伯塔省进行（2002-2006 年）。多分类逻辑回归用于估计 OR 和 95%置信区间（95%CI）。我们观察到使用口服避孕药与 MSI（Ptrend=0.005）而非 MSS（Ptrend=0.23）癌症的风险呈显著降低趋势；使用 5 年或更长时间，MSI（OR=0.42；95%CI，0.23-0.77）的风险降低强于 MSS 癌症（OR=0.80；95%CI，0.54-1.17；P 异质性=0.05）。对于最近的使用（<30 年），MSI（OR=0.36；95%CI，0.19-0.69）的风险降低强于 MSS 癌症（OR=0.77；95%CI，0.51-1.15；P 异质性=0.032）。绝经激素使用、产次和初潮年龄、绝经或首次妊娠与子宫内膜癌风险的关联无差异。我们发现，除了口服避孕药的使用外，MSI 状态对激素和生殖因素与子宫内膜癌风险关联的异质性的关联存在有限的证据。这一发现表明，错配修复系统在降低与口服避孕药使用相关的子宫内膜癌风险方面可能发挥作用，尽管确切机制尚不清楚。本研究首次表明，口服避孕药的使用与 MSI 但不是 MSS 子宫内膜癌的风险降低相关。
