Journal article

Multigene testing of moderate-risk genes: be mindful of the missense

EL Young, BJ Feng, AW Stark, F Damiola, G Durand, N Forey, TC Francy, A Gammon, WK Kohlmann, KA Kaphingst, S McKay-Chopin, T Nguyen-Dumont, J Oliver, AM Paquette, M Pertesi, N Robinot, JS Rosenthal, M Vallee, C Voegele, JL Hopper Show all

JOURNAL OF MEDICAL GENETICS | BMJ PUBLISHING GROUP | Published : 2016

Abstract

BACKGROUND: Moderate-risk genes have not been extensively studied, and missense substitutions in them are generally returned to patients as variants of uncertain significance lacking clearly defined risk estimates. The fraction of early-onset breast cancer cases carrying moderate-risk genotypes and quantitative methods for flagging variants for further analysis have not been established. METHODS: We evaluated rare missense substitutions identified from a mutation screen of ATM, CHEK2, MRE11A, RAD50, NBN, RAD51, RINT1, XRCC2 and BARD1 in 1297 cases of early-onset breast cancer and 1121 controls via scores from Align-Grantham Variation Grantham Deviation (GVGD), combined annotation dependent d..

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Grants

Awarded by United States National Institutes of Health (NIH) National Cancer Institute (NCI)


Awarded by USA National Cancer Institute


Awarded by NATIONAL CANCER INSTITUTE


Awarded by National Breast Cancer Foundation


Funding Acknowledgements

This work was supported by the United States National Institutes of Health (NIH) National Cancer Institute (NCI) grants R01 CA121245 and R01 CA155767, by the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer programme, by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, and the Ministere de l'enseignement superieur, de la recherche, de la science, et de la technologie du Quebec through Genome Quebec. The BCFR is supported by grant UM1 CA164920 from the USA National Cancer Institute.