Genome-wide association study of endometrial cancer in E2C2

Abstract

Endometrial cancer (EC), a neoplasm of the uterine epithelial lining, is the most common gynecological malignancy in developed countries and the fourth most common cancer among US women. Women with a family history of EC have an increased risk for the disease, suggesting that inherited genetic factors play a role. We conducted a two-stage genome-wide association study of Type I EC. Stage 1 included 5,472 women (2,695 cases and 2,777 controls) of European ancestry from seven studies. We selected independent single-nucleotide polymorphisms (SNPs) that displayed the most significant associations with EC in Stage 1 for replication among 17,948 women (4,382 cases and 13,566 controls) in a multiethnic population (African America, Asian, Latina, Hawaiian and European ancestry), from nine studies. Although no novel variants reached genome-wide significance, we replicated previously identified associations with genetic markers near the HNF1B locus. Our findings suggest that larger studies with specific tumor classification are necessary to identify novel genetic polymorphisms associated with EC susceptibility.

Fig. 1

Log quantile–quantile (Q–Q) plot. The observed –log10 P values (Y-axis) of 873,935 SNPs from a meta-analysis of seven studies included in the discovery phase of the endometrial cancer GWAS adjusted for the principal components of genetic variation plotted against the expected –log10 quantile (X-axis). The genomic control lambda is 1.008. Imputed P values are represented by the dashed line

Fig. 2

Manhattan plot of the association results. The –log10 P values from the meta-analysis of seven studies in the discovery phase of the endometrial cancer GWAS adjusted for principal components of genetic variation plotted against chromosomal base pair position. Chromosomes are color coded