Two associated loci lie within or close to known breast cancer susceptibility genes. rs11571833 is a polymorphic variant in BRCA2 that introduces a premature stop codon (p.Lys3326*), previously reported to have no association with breast cancer risk27. The results from the current study, however, indicate that this variant is associated with a modestly higher risk of breast cancer. Further work will be required to determine whether this association is due to a higher risk variant or variants in linkage disequilibrium (LD). SNP rs132390 at 22q12 lies within an intron of EMID1 but is ~500 kb upstream of CHEK2, raising the possibility that this association is mediated through the latter. CHEK2 c.1100delC, the major deleterious CHEK2 variant in European populations28, occurs more frequently in association with the risk allele at rs132390 (r2 = 0.06); however, the association between r132390 and breast cancer risk persisted after adjustment for CHEK2 c.1100delC, although attenuated (unadjusted OR in iCOGS = 1.12, P = 5.9 × 10−6; adjusted OR = 1.09, P = 0.04).
