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TY - JOUR AU - Healey, Catherine S. AU - Dunning, Alison M. AU - Dawn Teare, M. AU - Chase, Diana AU - Parker, Louise AU - Burn, John AU - Chang-Claude, Jenny AU - Mannermaa, Arto AU - Kataja, Vesa AU - Huntsman, David G. AU - Pharoah, Paul D.P. AU - Luben, Robert N. AU - Easton, Douglas F. AU - Ponder, Bruce A.J. PY - 2000 DA - 2000/11/01 TI - A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability JO - Nature Genetics SP - 362 EP - 364 VL - 26 IS - 3 AB - Inherited mutations in the gene BRCA2 predispose carriers to early onset breast cancer, but such mutations account for fewer than 2% of all cases in East Anglia. It is likely that low penetrance alleles explain the greater part of inherited susceptibility to breast cancer; polymorphic variants in strongly predisposing genes, such as BRCA2, are candidates for this role. BRCA2 is thought to be involved in DNA double strand break-repair1,2. Few mice in which Brca2 is truncated survive to birth; of those that do, most are male, smaller than their normal littermates and have high cancer incidence3,4. Here we show that a common human polymorphism (N372H) in exon 10 of BRCA2 confers an increased risk of breast cancer: the HH homozygotes have a 1.31-fold (95% CI, 1.07–1.61) greater risk than the NN group. Moreover, in normal female controls of all ages there is a significant deficiency of homozygotes compared with that expected from Hardy-Weinberg equilibrium, whereas in males there is an excess of homozygotes: the HH group has an estimated fitness of 0.82 in females and 1.38 in males. Therefore, this variant of BRCA2 appears also to affect fetal survival in a sex-dependent manner. SN - 1546-1718 UR - https://doi.org/10.1038/81691 DO - 10.1038/81691 ID - Healey2000 ER -