Estrogen receptor alpha gene polymorphism and endometrial cancer risk – a case-control study

In 702 cases with invasive endometrial cancer and 1563 controls, we genotyped five markers in ESR1 and used logistic regression models to estimate odds ratios (OR) and 95 percent confidence intervals (CI).We found an association between rs2234670, rs2234693, as well as rs9340799, markers in strong linkage disequilibrium (LD), and endometrial cancer risk. The association with rs9340799 was the strongest, OR 0.75 (CI 0.60–0.93) for heterozygous and OR 0.53 (CI 0.37–0.77) for homozygous rare compared to those homozygous for the most common allele. Haplotype models did not fit better to the data than single marker models.We found that intronic variation in ESR1 was associated with endometrial cancer risk.Estrogens, whether from endogenous or exogenous sources, are potent mitogens in the endometrium and thus constitute a major carcinogen in this tissue [1]. Endometrial cancer is therefore a good model for investigating clinical effects of estrogen signaling. Estrogen receptor alpha is the principal estrogen receptor expressed in the endometrium [2,3] and it is considered to be crucial in the development of endometroid endometrial carcinoma, the most common histological subtype among endometrial neoplasms [1]. Since altered ER function could have impact on the risk of endometrial cancer, the estrogen receptor alpha gene (ESR1) is a plausible endometrial cancer candidate gene which has been investigated in a few studies [4-6]. We have investigated whether polymorphic variation in the ESR1 is associated with invasive endometrial cancer risk, overall and in subgroups defined by other hormonally related factors.This nation-wide population-based case-control study encompassed all cases of incident, primary histopathologically confirmed invasive endometrial cancer among women 50 to 74 years of age resident in Sweden between January 1, 1994 and December 31, 1995 as previously described in detail [7]. Endometrial cancer patients were identified at diagnosis through a notification