Format

Send to

Choose Destination
Carcinogenesis. 2008 Apr;29(4):762-5. doi: 10.1093/carcin/bgn044. Epub 2008 Feb 14.

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

Author information

1
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, ul. Połabska 4, 70-115 Szczecin, Poland. cezarycy@sci.pam.szczecin.pl

Abstract

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 x 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.

PMID:
18281249
DOI:
10.1093/carcin/bgn044
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center