Journal article

Rare, Evolutionarily Unlikely Missense Substitutions in ATM Confer Increased Risk of Breast Cancer

Sean V Tavtigian, Peter J Oefner, Davit Babikyan, Anne Hartmann, Sue Healey, Florence Le Calvez-Kelm, Fabienne Lesueur, Graham B Byrnes, Shu-Chun Chuang, Nathalie Forey, Corinna Feuchtinger, Lydie Gioia, Janet Hall, Mia Hashibe, Barbara Herte, Sandrine McKay-Chopin, Alun Thomas, Maxime P Vallee, Catherine Voegele, Penelope M Webb Show all

AMERICAN JOURNAL OF HUMAN GENETICS | CELL PRESS | Published : 2009

Abstract

The susceptibility gene for ataxia telangiectasia, ATM, is also an intermediate-risk breast-cancer-susceptibility gene. However, the spectrum and frequency distribution of ATM mutations that confer increased risk of breast cancer have been controversial. To assess the contribution of rare variants in this gene to risk of breast cancer, we pooled data from seven published ATM case-control mutation-screening studies, including a total of 1544 breast cancer cases and 1224 controls, with data from our own mutation screening of an additional 987 breast cancer cases and 1021 controls. Using an in silico missense-substitution analysis that provides a ranking of missense substitutions from evolution..

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