BioScientifica, Endocrine-Related Cancer, 5(22), p. 851-861, 2015
DOI: 10.1530/erc-15-0319
Full text: Unavailable
Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded byESR1. Consequently, several studies have investigated whether variation at theESR1locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of theESR1gene (lead SNP rs79575945,P=1.86×10−5), which was stronger for cancers of endometrioid subtype (P=3.76×10−6). Bioinformatic analysis suggests that this risk signal is in a functionally important region targetingESR1, and eQTL analysis found that rs79575945 was associated with expression ofSYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located atESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types.