Genetic susceptibility loci for subtypes of breast cancer in an African American population
Couplée à la cohorte "Black Women's Health Study", cette étude (1 199 cas et 1 948 témoins) analyse l'association entre des polymorphismes à simple nucléotide de 21 loci et le risque de cancer du sein par sous-type, dans une population afro-américaine
Background:Most genome-wide association scans (GWAS) have been carried out in European ancestry populations; no risk variants for breast cancer have been identified solely from African ancestry GWAS data. Few GWAS hits have replicated in African ancestry populations. Methods:In a nested case-control study of breast cancer in the Black Women's Health Study (1,199 cases/1,948 controls), we evaluated index SNPs in 21 loci from GWAS of European or Asian ancestry populations, overall, in subtypes defined by estrogen (ER) and progesterone (PR) receptor status (ER+/PR+, n=336; ER-/PR-, n=229), and in triple-negative breast cancer (TNBC, N=81). To evaluate the contribution of genetic factors to population differences in breast cancer subtype, we also examined global percent African ancestry. Results:Index SNPs in five loci were replicated, including three associated with ER-/PR- breast cancer (TERT rs10069690 in 5p15.33, rs704010 in 10q22.3, and rs8170 in 19p13.11): per allele odds ratios were 1.29 (95% confidence interval (CI) 1.04-1.59), p=0.02, 1.52 (95% CI 1.12-2.08), p=0.01, and 1.30 (95% CI 1.01-1.68), p=0.04, respectively. Stronger associations were observed for TNBC. Furthermore, cases in the highest quintile of percent African ancestry were three times more likely to have TNBC than ER+/PR+ cancer. Conclusions:These findings provide the first confirmation of the TNBC SNP rs8170 in an African ancestry population, and independent confirmation of the TERT ER- SNP. Further, the risk of developing ER- breast cancer, particularly TNBC, increased with increasing proportion of global African ancestry. Impact:The findings demonstrate the importance of genetic factors in the disproportionately high occurrence of TNBC in African American women.