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

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 confir...

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Bibliographic Details
Published in:Carcinogenesis (New York) 2008-04, Vol.29 (4), p.762-765
Main Authors: Cybulski, Cezary, Masojć, Bartłomiej, Oszutowska, Dorota, Jaworowska, Ewa, Grodzki, Tomasz, Waloszczyk, Piotr, Serwatowski, Piotr, Pankowski, Juliusz, Huzarski, Tomasz, Byrski, Tomasz, Górski, Bohdan, Jakubowska, Anna, Dębniak, Tadeusz, Wokołorczyk, Dominika, Gronwald, Jacek, Tarnowska, Czesława, Serrano-Fernández, Pablo, Lubiński, Jan, Narod, Steven A.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Carcinoma, Squamous Cell - epidemiology
Carcinoma, Squamous Cell - genetics
Checkpoint Kinase 2
Child
Confidence Intervals
DNA, Neoplasm - blood
DNA, Neoplasm - genetics
DNA, Neoplasm - isolation & purification
Female
Founder Effect
Humans
Laryngeal Neoplasms - epidemiology
Laryngeal Neoplasms - genetics
Laryngeal Neoplasms - pathology
Lung Neoplasms - epidemiology
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Male
Medical sciences
Middle Aged
Mutation
Otorhinolaryngology. Stomatology
Pneumology
Protein-Serine-Threonine Kinases - genetics
Reference Values
Risk Reduction Behavior
Tumors
Tumors of the respiratory system and mediastinum
Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
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Summary: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.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/bgn044