Endometrial Cancer, BRCA1, and BRCA2 in the UK Biobank Cohort

Objectives: Endometrial cancer (EC) risk in BRCA1/2 mutation carriers has been uncertain. EC risk in women with germline BRCA1 or BRCA2 mutations was recently assessed in a multicenter cohort study. BRCA1/2 mutation carriers had a 2- to 3-fold increased risk for EC, with highest risk observed for the rare subgroups of serous-like and p53-abnormal EC in BRCA1 mutation carriers. To further evaluate risk, we looked at EC and BRCA1/2 in the UK Biobank cohort.

Methods: EC diagnosis was ascertained using the 10th Revision of the International Classification of Diseases. We analyzed the single nucleotide polymorphisms (SNPs) rs799917 (BRCA1) and rs144848 (BRCA2). A case-control study found a possible association of rs799917 but not rs144848 with EC. Data processing was performed on Minerva, a Linux mainframe with Centos 7.6, at the Icahn School of Medicine at Mount Sinai.

Results: Percentage ECs within genotypes for SNPs rs799917 and rs144848 was 0.6%. The variability within SNP genotypes was insignificant (P=0.288 for rs799917, 2-tailed Fisher exact test; P=0.931 for rs144848). In comparison, an estimated 70,200 women who had been diagnosed with uterine cancer between 1991 and 2010 were alive in the UK at the end of 2010. A total of 21,892,000 UK residents were ages 50 to 92; approximately half were women. Therefore, prevalence of EC in these UK women was 0.6%, identical to percentage EC within 6 genotypes for SNPs rs799917 and rs144848.

Conclusion: Although we cannot rule out an increase in several rare types of EC, our analysis suggests that the overall incidence or risk of EC does not appear to be increased by the presence of BRCA1 or BRCA2 mutations.