Journal Article

Polymorphisms in DNA damage binding protein 2 (DDB2) and susceptibility of primary lung cancer in the Chinese: a case–control study

Zhibin Hu, Minhua Shao, Jing Yuan, Liang Xu, Feng Wang, Yi Wang, Wentao Yuan, Ji Qian, Hongxia Ma, Ying Wang, Hongliang Liu, Weihong Chen, Lin Yang, Guangfu Jin, Xiang Huo, Feng Chen, Li Jin, Qingyi Wei, Wei Huang, Daru Lu, Tangchun Wu and Hongbing Shen

in Carcinogenesis

Volume 27, issue 7, pages 1475-1480
Published in print July 2006 | ISSN: 0143-3334
Published online March 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi350
Polymorphisms in DNA damage binding protein 2 (DDB2) and susceptibility of primary lung cancer in the Chinese: a case–control study

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DNA damage binding protein 2 (DDB2) is one of the major DNA repair proteins involved in the nucleotide excision repair (NER) pathway. Mutations in the DDB2 gene can cause a repair-deficiency syndrome xeroderma pigmentosum group E. Because tobacco carcinogens can cause DNA damage that is repaired by NER and suboptimal NER capacity is reported to be associated with lung cancer risk, we hypothesized that common variants in the DDB2 gene are associated with lung cancer risk. To test this hypothesis, we conducted a case–control study of 1010 patients with incident lung cancer and 1011 cancer-free controls and genotyped two DDB2 single nucleotide polymorphisms (SNPs) (rs830083 and rs3781620) that are in linkage disequilibrium with other untyped SNPs. We found that compared with the rs830083CC, subjects carrying the heterozygous rs830083CG genotype had a significantly 1.31-fold increased risk of lung cancer [95% confidence interval (CI) 1.08–1.60] and those carrying the homozygous rs830083GG genotype had a non-significantly 1.22-fold elevated risk (95% CI 0.89–1.67). In addition, effects of the combined rs830083CG/GG variant genotypes were more evident in young subjects, heavy smokers and subjects with a positive family history of cancer. These findings indicate, for the first time, that the DDB2 rs830083 polymorphism may contribute to the etiology of lung cancer. Further functional studies on this SNP and/or related variants are warranted to elucidate the underlying molecular mechanisms of the association.

Keywords: CI, confidence interval; DDB2, DNA damage binding protein 2; LD, linkage disequilibrium; MAF, minor allele frequency; NER, nucleotide excision repair; OR, odds ratio; SNP, single nucleotide polymorphism; XPE, xeroderma pigmentosum group E

Journal Article.  4668 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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