title: Polymorphisms in DNA damage binding protein 2 (DDB2) and susceptibility of primary lung cancer in the Chinese: a case-control study.
abstract: 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.
authors.affiliation: Department of Epidemiology and Biostatistics, Cancer Research Center of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Minhua
authors.initials: M
authors.lastname: Shao
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Wentao
authors.initials: W
authors.lastname: Yuan
authors.forename: Ji
authors.initials: J
authors.lastname: Qian
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.forename: Weihong
authors.initials: W
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Xiang
authors.initials: X
authors.lastname: Huo
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Daru
authors.initials: D
authors.lastname: Lu
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002681:China; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: C117669:DDB2 protein, human; D004268:DNA-Binding Proteins