The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; <i>P</i> = 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR = 4.29; <i>P</i> = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68; <i>P</i> = 0.004), and c.8187G>T, p.Lys2729Asn (OR = 1.4; <i>P</i> = 0.004) were associated with moderate and low risks of breast cancer among Asians.
We found three missense variants with minor allele frequency (MAF) <0.05: rs80358978 (Gly2508Ser), rs80359065 (Lys2729Asn) and rs11571653 (Met784Val) in the BRCA2 gene, showing statistically significant associations with breast cancer risk, with P-values of 1.2 × 10-4, 1.0 × 10-3 and 5.0 × 10-3, respectively.
Remarkably, FA-AML1 cells appeared to lack the characteristic cellular FA phenotype, i.e., a hypersensitivity to growth inhibition and chromosomal breakage by the cross-linking agent mitomycin C. Genomic DNA from the patient showed biallelic mutations [8415G>T (K2729N)and 8732C>A (S2835STOP)] in the breast cancer susceptibility gene FANCD1/BRCA2 [N. Howlett et al., Science (Wash. DC), 297: 606-609, 2002].