Rare mutations in XRCC2 increase the risk of breast cancer

DJ Park; F Lesueur; T Nguyen-Dumont; M Pertesi; F Odefrey; F Hammet; SL Neuhausen; EM John; IL Andrulis; MB Terry; M Daly; S Buys; F Le Calvez-Kelm; A Lonie; BJ Pope; H Tsimiklis; C Voegele; FM Hilbers; N Hoogerbrugge; A Barroso; A Osorio; GG Giles; P Devilee; J Benitez; JL Hopper; SV Tavtigian; DE Goldgar; MC Southey

Journal article

Rare mutations in XRCC2 increase the risk of breast cancer

DJ Park, F Lesueur, T Nguyen-Dumont, M Pertesi, F Odefrey, F Hammet, SL Neuhausen, EM John, IL Andrulis, MB Terry, M Daly, S Buys, F Le Calvez-Kelm, A Lonie, BJ Pope, H Tsimiklis, C Voegele, FM Hilbers, N Hoogerbrugge, A Barroso Show all

American Journal of Human Genetics | Published : 2012

DOI: 10.1016/j.ajhg.2012.02.027

Abstract

An exome-sequencing study of families with multiple breast-cancer-affected individuals identified two families with XRCC2 mutations, one with a protein-truncating mutation and one with a probably deleterious missense mutation. We performed a population-based case-control mutation-screening study that identified six probably pathogenic coding variants in 1,308 cases with early-onset breast cancer and no variants in 1,120 controls (the severity grading was p < 0.02). We also performed additional mutation screening in 689 multiple-case families. We identified ten breast-cancer-affected families with protein-truncating or probably deleterious rare missense variants in XRCC2. Our identification o..

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University of Melbourne Researchers

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NIH AUSTRALIAN BREAST CANCER FAMILY REGISTRY SOUTHEY-HOPPER

DESCRIPTION (provided by applicant): The broad objective of the Breast Cancer Family Registry (Breast CFR) is to establish and maintain a hy..

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Grants

Awarded by National Institutes of Health

Funding Acknowledgements

This work was supported by Cancer Council Victoria (grant 628774), the National Institutes of Health (R01CA155767 and R01CA121245), the Australian National Health and Medical Research Council (grant 466668), The University of Melbourne (infrastructure award to J.L.H.), a Victorian Life Sciences Computation Initiative grant (VR00353) on its Peak Computing Facility at the University of Melbourne, and an initiative of the Victorian Government and Dutch Cancer Society (grant UL 2009-4388). The research resources, including the Melbourne Collaborative Cohort Study, the Australian Breast Cancer Family Study, the Breast Cancer Family Registry, and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, are further acknowledged in the supplementary information. We wish to thank Nivonirina Robinot and Geoffroy Durand for their technical help during the case-control mutation screening at the International Agency for Research on Cancer, Georgia Chenevix-Trench for her support of and contribution to the establishment of the case-control mutation-screening study, and Greg Wilhoite for sequencing the male breast cancer cases at the Beckman Research Institute of City of Hope. This work and partial support for S.L.N. was provided by the Morris and Horowitz Families Endowment. Work at the Spanish National Cancer Center was partially funded by the Spanish Association Against Cancer and Health Ministry (FIS08/1120). M.C.S. is a National Health and Medical Research Council (NHMRC) Senior Research Fellow and a Victorian Breast Cancer Research Consortium (VBCRC) Group Leader. J.L.H. is a NHMRC Australia Fellow and a VBCRC Group Leader. T.N.-D. is a Susan G. Komen for the Cure Postdoctoral Fellow.