We carried out a genome-wide association study of breast cancer predisposition with replication and refinement studies involving 6,145 cases and 33,016 controls and identified two SNPs (rs4415084 and rs10941679) on 5p12 that confer risk, preferentially for estrogen receptor (ER)-positive tumors (OR = 1.27, P = 2.5 x 10(-12) for rs10941679).
We confirmed the reported association of rs4415084 SNP with overall risk of breast cancer (P = 0.06), and, as in the original study, observed a stronger association with estrogen receptor positive tumors (P = 0.03).
In subtype specific analysis, rs13387042 (per-allele adjusted OR = 1.36, 95% CI = 1.00-1.87) and rs4415084 (per-allele adjusted OR = 0.82, 95% CI = 0.66-1.00) showed slightly significant association with Luminal-A subtype; however, only rs13387042 was associated with ER-&PR-&HER2+ tumors (per-allele adjusted OR = 1.55, 95% CI = 1.00-2.40), and none of them were linked to Luminal-B and triple negative subtype.
Furthermore, statistically significant multiplicative interactions were found between rs4415084 and age at diagnosis and between rs3803662 and tumor grade.