Novel Shared Heritable Candidate Risk Loci of Breast and Endometrial Cancer-A Swedish Haplotype Genome-Wide Association Study

Abstract

Breast and endometrial cancer are prevalent and share both hormonal and environmental risk factors. This study aimed to identify shared germline genetic risk loci for these cancers. In total, 1116 endometrial cancer cases, 3200 breast cancer cases, and 5021 healthy controls were included in a merged sliding window haplotype genome-wide association study (GWAS). This analysis employed a logistic regression model in PLINK v1.07. The results from this merged analysis were compared with previous individual analyses of the same samples. The analysis identified three loci that influenced both the risk of breast and endometrial cancer: 8p21.1 (OR 2.1; p 1.6 × 10^-8), 16q24.3 (OR 2.4; p 3.8 × 10^-8) and 17q11.2 (OR 1.3; p 4.3 × 10^-8). This combined haplotype GWAS of endometrial and breast cancers identified three loci associated with shared genetic risk, two of which were novel: 16q24.3 and 17q11.2. Further studies are warranted to replicate these findings and to determine its pathophysiological role and future clinical implications.

Keywords: GWAS; breast cancer; endometrial cancer; genetic risk loci; haplotype.

Figure 1

Three loci associated with combined endometrial and breast cancer risk. The first and last SNP of the haplotypes listed in Table 1 are here indicated by dashed lines and variant rs-name along with gene(s) within the locus.

Figure 2

Flowchart of included individuals and variants. n = individuals; Geno 0.02 = excluded variants with a genotyping rate < 2%; MAF 0.01 = excluded variants with a minor allele frequency < 0.01; HWE 0.001 = excluded variants that failed the Hardy–Weinberg equilibrium test at p < 0.001; mind 0.1 = excluded individuals with missing genotypes > 10%.