%0 Journal Article
%T A common missense variant in BRCA2 predisposes to early onset breast cancer
%A Bohdan G¨®rski
%A Steven A Narod
%A Jan Lubi¨˝ski
%J Breast Cancer Research
%D 2005
%I BioMed Central
%R 10.1186/bcr1338
%X We genotyped 3,241 cases of breast cancer diagnosed at under 51 years of age, unselected for family history, from 18 hospitals throughout Poland and 2,791 ethnic-matched controls for a single BRCA2 C5972T variant.The variant was present in approximately 6% of the Polish population. In the study, 13 women (11 cases and two controls (OR = 4.7; p = 0.02)) were homozygous for the variant allele. The overall odds ratio for breast cancer in women with a single copy of the BRCA2 C5972T variant was 1.1 (p = 0.7); however, the effect was significant for patients diagnosed at or before age 40 (OR = 1.4; p = 0.04). We reviewed the association between the BRCA2 variant in different histologic subgroups and found the effect most pronounced in women who had ductal carcinoma in situ (DCIS) with micro-invasion (OR = 2.8; p < 0.0001).The BRCA2 C5972T allele is a common variant in Poland that increases the risk of DCIS with micro-invasion. The homozygous state is rare but increases the risk of breast cancer five-fold.There are several approaches to identifying low-penetrance candidate genes for breast cancer. In one approach, it is assumed that missense variants of genes for which truncating mutations are clearly pathogenic might also be deleterious. If the missense allele demonstrates high penetrance (i.e. like truncating mutations), then it will be relatively straightforward to establish the association when allele frequency is high. If the penetrance of the missense variant is low, however, then the association may be missed if only a small number of cancers is studied and the variant may falsely be classified as a neutral polymorphism. We are in the process of establishing a large database of breast cancer cases and ethnic-matched controls in order to evaluate the pathogenicity of the common founder alleles of the most important cancer susceptibility genes. Several deleterious founder alleles have been identified in BRCA1, but to date, no founder mutation in BRCA2 has been identi
%U http://breast-cancer-research.com/content/7/6/R1023