Carcinogenesis Advance Access originally published online on March 7, 2006
Carcinogenesis 2006 27(7):1475-1480; doi: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
Department of Epidemiology and Biostatistics, Cancer Research Center of Nanjing Medical University, Nanjing 210029, China 1 State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China 2 Institute of Occupational Medicine, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 3 Department of Genetics, Chinese National Human Genome Center at Shanghai, Shanghai 201203, China and 4 Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
* To whom correspondence and reprints should be addressed Email: hbshen{at}njmu.edu.cn
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Guerrero-Santoro, M. G. Kapetanaki, C. L. Hsieh, I. Gorbachinsky, A. S. Levine, and V. Rapic-Otrin The Cullin 4B-Based UV-Damaged DNA-Binding Protein Ligase Binds to UV-Damaged Chromatin and Ubiquitinates Histone H2A Cancer Res., July 1, 2008; 68(13): 5014 - 5022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Itoh, S. Iwashita, M. B. Cohen, D. K. Meyerholz, and S. Linn Ddb2 is a haploinsufficient tumor suppressor and controls spontaneous germ cell apoptosis Hum. Mol. Genet., July 1, 2007; 16(13): 1578 - 1586. [Abstract] [Full Text] [PDF]
|
|