Journal Article

Constitutional CHEK2 mutations are associated with a decreased risk of lung and laryngeal cancers

Cezary Cybulski, Bartłomiej Masojć, Dorota Oszutowska, Ewa Jaworowska, Tomasz Grodzki, Piotr Waloszczyk, Piotr Serwatowski, Juliusz Pankowski, Tomasz Huzarski, Tomasz Byrski, Bohdan Górski, Anna Jakubowska, Tadeusz Dębniak, Dominika Wokołorczyk, Jacek Gronwald, Czesława Tarnowska, Pablo Serrano-Fernández, Jan Lubiński and Steven A. Narod

in Carcinogenesis

Volume 29, issue 4, pages 762-765
Published in print April 2008 | ISSN: 0143-3334
Published online February 2008 | e-ISSN: 1460-2180 | DOI:
Constitutional CHEK2 mutations are associated with a decreased risk of lung and laryngeal cancers

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Mutations in the CHEK2 gene have been associated with increased risks of breast, prostate and colon cancer. In contrast, a previous report suggests that individuals with the I157T missense variant of the CHEK2 gene might be at decreased risk of lung cancer and upper aero-digestive cancers. To confirm this hypothesis, we genotyped 895 cases of lung cancer, 430 cases of laryngeal cancer and 6391 controls from Poland for four founder alleles in the CHEK2 gene, each of which has been associated with an increased risk of cancer at several sites. The presence of a CHEK2 mutation was protective against both lung cancer [odds ratio (OR) = 0.3; 95% confidence interval (CI) 0.2–0.5; P = 3 × 10−8] and laryngeal cancer (OR = 0.6; 95% CI 0.3–0.99; P = 0.05). The basis of the protective effect is unknown, but may relate to the reduced viability of lung cancer cells with a CHEK2 mutation. Lung cancers frequently possess other defects in genes in the DNA damage response pathway (e.g. p53 mutations) and have a high level of genotoxic DNA damage induced by tobacco smoke. We speculate that lung cancer cells with impaired CHEK2 function undergo increased rates of cell death.

Journal Article.  3149 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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