Evaluation of variants in BRIP1, PALB2 and CHEK2 in a west of Ireland breast cancer cohort.

Abstract

Abstract Abstract #3092 Introduction
 Positive family history is the most important risk factor in breast cancer predisposition. Recent studies have identified variants in BRIP1, PALB2 and CHEK2, which have been proposed as breast cancer susceptibility genes conferring an increased relative risk of 2-4%.
 Aims
 To evaluate the role of the above variants in the West of Ireland population and to examine their potential clinical relevance.
 Methods
 Proposed candidate genetics variants in BRIP1, PALB2 and CHEK2 were interrogated in 192 patients with a high risk of familial breast cancer. Genescan analysis and direct sequencing were used to evaluate these variants. Where a variant was exhibited, it was then examined further in 990 sporadic breast cancer patients and 1016 matched non-cancer controls using KASPar genotyping technology.
 Results
 We demonstated mutations in BRIP1 and CHEK2 genes. 1 mutation was found in BRIP1 2392C→T in our 192 patients with a high risk of familial breast cancer. 5 breast cancer patients and 1 control exhibited a CHEK2110delC mutation within 990 breast cancer patients and 1016 matched non-cancer controls. Mutations previously demonstrated in PALB2 were not evident in 192 high risk patients.
 Conclusions
 We have confirmed the presence of variants in BRIP1 and CHEK2, candidate moderate penetrance genes, in breast cancer patients with a strong family history of breast cancer. This may have implications in clinical practice as our knowledge of these variants expands. The absense of PALB2 variants in patients at high genetic risk points to a low clinical significance. Our findings contribute to a better understanding of inherited breast cancer risk while helping to optimize future screening, therapeutic and prophylactic programs. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3092.