Background: Recently, rare germline variants in XRCC2 were detected in non-BRCA1/2 familial breast cancer cases, and a significant association with breast cancer was reported. However, the breast cancer risk associated with these variants needs further evaluation. Methods: The coding regions and exon-intron boundaries of XRCC2 were scanned for mutations in an international cohort of 3548 non-BRCA1/2 familial breast cancer cases and 1435 healthy controls using various mutation scanning methods. Predictions on functional relevance of detected missense variants were obtained from three different prediction algorithms. Results: The only protein-truncating variant detected was found in a control. Rare non-protein-truncating variants were detected in 20 familial cases (0.6%) and nine healthy controls (0.6%). Although the number of variants predicted to be damaging or neutral differed between prediction algorithms, in all instances these categories were evenly represented among cases and controls. Conclusions: Our data do not confirm an association between XRCC2 variants and breast cancer risk, although a relative risk smaller than two could not be excluded. Variants in XRCC2 are unlikely to explain a substantial proportion of familial breast cancer.

dx.doi.org/10.1136/jmedgenet-2012-101191, hdl.handle.net/1765/67144
Journal of Medical Genetics
Department of Clinical Genetics

Hilbers, F.S, Wijnen, J.T, Hoogerbrugge, N, Oosterwijk, J.C, Collée, J.M, Peterlongo, P, … Devilee, P. (2012). Rare variants in XRCC2 as breast cancer susceptibility alleles. Journal of Medical Genetics, 49(10), 618–620. doi:10.1136/jmedgenet-2012-101191