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CHEK2 variant I157T may be associated with increased breast cancer risk
Author(s) -
Kilpivaara Outi,
Vahteristo Pia,
Falck Jacob,
Syrjäkoski Kirsi,
Eerola Hannaleena,
Easton Douglas,
Bartkova Jirina,
Lukas Jiri,
Heikkilä Päivi,
Aittomäki Kristiina,
Holli Kaija,
Blomqvist Carl,
Kallioniemi OlliPekka,
Bartek Jiri,
Nevanlinna Heli
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20299
Subject(s) - chek2 , breast cancer , population , cancer , cancer research , medicine , biology , heterozygote advantage , odds ratio , oncology , allele , genetics , mutation , gene , germline mutation , environmental health
Cell cycle checkpoint kinase 2 (CHEK2) is a transducer of cellular responses to DNA damage. The CHEK2 1100delC has previously been shown to be a low‐penetrance breast cancer susceptibility allele. We have evaluated the role of another CHEK2 variant, I157T in the FHA domain of the gene, for association with breast cancer. I157T was found at a significantly higher frequency in the population‐based series of breast cancer patients (77/1035, 7.4%, odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.06–1.95, p = 0.021) than among population controls (100/1885, 5.3%). The frequency in the familial breast cancer patients was not elevated (28/507, 5.5%, OR = 1.04, 95% CI = 0.68–1.61). The I157T protein, that undermines cellular responses to ionizing radiation and shows deficiency in substrate recognition in vivo , was expressed at normal level in tumor tissues as well as in cultured cells. The I157T protein was stable and it dimerized with the wild‐type CHEK2 co‐expressed in human cells. These functional properties of the I157T protein suggest that this variant may have negative effect on the pool of normal CHEK2 protein in heterozygous carrier cells by formation of heterodimers with wild‐type CHEK2. The I157T variant may be associated with breast cancer risk, but the risk is lower than for 1100delC. © 2004 Wiley‐Liss, Inc.