CHEK2 variant I157T may be associated with increased breast cancer risk

Outi Kilpivaara, Pia Vahteristo, Jacob Falck, Kirsi Syrjäkoski, Hannaleena Eerola, Douglas Easton, Jirina Bartkova, Jiri Lukas, Päivi Heikkilä, Kristiina Aittomäki, Kaija Holli, Carl Blomqvist, Olli Kallioniemi, Jiri Bartek, Heli Nevanlinna (Corresponding Author)

    Research output: Contribution to journalArticleScientificpeer-review

    137 Citations (Scopus)


    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.
    Original languageEnglish
    Pages (from-to)543 - 547
    Number of pages5
    JournalInternational Journal of Cancer
    Issue number4
    Publication statusPublished - 2004
    MoE publication typeA1 Journal article-refereed


    • CHEK2
    • germ line
    • mutation
    • susceptibility
    • population


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