Association Analysis of Genetic Variation of Estrogen Related Candidate Genes in Breast and Endometrial Cancers

Abstract

Given the established role of estrogen in the development of breast and endometrial cancers, I surmised that common genetic variation in the pathways of hormonal exposure and response may alter individual responses to endogenous estrogen and consequently modify hormonal related cancer risk. I used a candidate gene based approach in three independent studies to investigate DNA polymorphisms within 37 genes of the estrogen metabolism pathway and 60 genes encoding ER-cofactors in samples of European ancestry to ascertain whether these polymorphisms could modify the risk of breast and endometrial cancer. The combination of multi-variant analysis with biochemically and genomically informed candidate genes, through pathway-based studies, enhances the discovery of moderate disease susceptibility alleles and their interactions. The findings in the current studies may help to improve our understanding on the genetic basis of breast and endometrial cancers risk and facilitate the effort of identifying women with high risk for such cancers.