Direct evidence for the polygenic basis of the residual familial clustering not due to BRCA1 and BRCA2 mutations has more recently been provided by the identification of further loci that confer moderate risks, including mutations in CHEK2, ATM, PALB2, BRIP1 (The CHEK2 Breast Cancer Case–Control Consortium, 2004; Renwick et al, 2006; Seal et al, 2006; Rahman et al, 2007) and the low-risk variants identified through genome-wide or candidate gene association studies (Cox et al, 2007; Easton et al, 2007; Hunter et al, 2007; Stacey et al, 2007). The gene discussed is BRCA1; the disease is breast carcinoma.