The HER2/neu (erbB2) polymorphism, body mass index, and the risk of endometrial cancer

Abstract

22199 Background: Obesity has been identified as a risk factor for endometrial cancer in epidemiologic studies. The transmembrane receptor with a tyrosine kinase encoded by the HER-2 proto-oncogene is amplified in several types of human carcinomas and provides an attractive therapeutic target. HER-2 genes could be disease susceptibility candidate for endometrial cancer. We evaluated the association between HER-2 genotypes and body mass index (BMI) in a case-control study of endometrial cancer. Methods: Cases and controls for this study were recruited between 2001 and 2005. DNA sample and medical histories were obtained from incident cases of endometrial cancer (n= 126) and population controls (n=302). Genotypes evaluated included HER-2 gene single nucleotide polymorphisms (SNP) in coding region at position -423, -655, -776, -857, -1170, -1177, -1253; and two SNP in intron by SNP-IT assay using SNPstream UHT system. Four of 9 SNPs were polymorphic and had greater than 10% of minor allele frequencies. Statistical adjustment was made for age. Results: We observed a statistically significant association between women who were overweight (BMI >25 kg/m2) and carried at least one variant allele with endometrial cancer risk. Compared with wild-type lean women, the odds ratio (OR) for overweight women variant carriers was about 2–4 fold stronger than that for overweight women who did not carry the variants in each SNPs. Conclusions: In summary, although there is no potential association between HER-2 polymorphisms and endometrial cancer risk, our finding suggest that the HER-2 minor variant alleles is reinforced the risk of endometrial cancer among women with higher BMI than low BMI. Future large studies of the HER-2 polymorphism might clarify this putative gene-epidemiologic interaction. No significant financial relationships to disclose.