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The ATM missense mutation p.Ser49Cys (c.146C>G) and the risk of breast cancer
Author(s) -
Stredrick Denise L.,
GarciaClosas Montserrat,
Pineda Marbin A.,
Bhatti Parveen,
Alexander Bruce H.,
Doody Michele M.,
Lissowska Jolanta,
Peplonska Beata,
Brinton Louise A.,
Chanock Stephen J.,
Struewing Jeffery P.,
Sigurdson Alice J.
Publication year - 2006
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20323
Subject(s) - missense mutation , breast cancer , genetics , biology , hum , ataxia telangiectasia , mutation , allele , odds ratio , population , medicine , oncology , cancer , gene , dna , environmental health , dna damage , art , performance art , art history
Abstract Homozygous mutation in the ATM gene causes ataxia telangiectasia and heterozygous mutation carriers may be at increased risk of breast cancer. We studied a total of 22 ATM variants; 18 variants were analyzed in one of two large population‐based studies from the U.S. and Poland, and four variants were analyzed in all 2,856 breast cancer cases and 3,344 controls from the two studies. The missense mutation Ser49Cys (c.146C>G, p.S49C), carried by approximately 2% of subjects, was more common in cases than controls in both study populations, combined odds ratio (OR) 1.69 (95% CI, 1.19–2.40; P=0.004). Another missense mutation at approximately 2% frequency, Phe858Leu (c.2572T>C, p.F858L), was associated with a significant increased risk in the U.S. study but not in Poland, and had a combined OR of 1.44 (95% CI, 0.98–2.11; P=0.06). These analyses provide the most convincing evidence thus far that missense mutations in ATM , particularly p.S49C, may be breast cancer susceptibility alleles. Because of their low frequency, even larger sample sizes are required to more firmly establish these associations. Hum Mutat 27(6), 538–544, 2006. Published 2006 Wiley‐Liss, Inc.