Relationship between XPG codon 1104 polymorphism and risk of primary lung cancer.

DNA repair plays a critical role in protecting the genome from insults of cancer-causing agents, such as those found in tobacco smoke. Therefore, reduced DNA repair capacity can increase the susceptibility to smoking-related cancers. Recently, several polymorphisms have been identified in the xeroderma pigmentosum group G (XPG) gene, and it is possible that these polymorphisms may affect the DNA repair capacity, thereby modulating cancer susceptibility. We investigated the relationship between the His1104Asp polymorphism in the XPG gene and the risk of lung cancer. The study population consisted of 310 lung cancer patients and 311 healthy controls who were frequency (1:1) matched based on age and sex. The Asp/Asp genotype was more frequent in the controls (28.9%) than in the cases (18.7%) and associated with a significantly decreased risk of lung cancer [adjusted odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.37-0.80] when the combined His/His and His/Asp genotype was used as the reference. The protective effect of the Asp/Asp genotype against lung cancer was statistically significant in the older subjects (adjusted OR = 0.51, 95% CI = 0.37-0.80), males (adjusted OR = 0.54, 95% CI = 0.35-0.83), and lighter smokers (adjusted OR = 0.48, 95% CI = 0.25-0.94) in a stratification analysis. When the lung cancers were analyzed by histologic type, the Asp/Asp genotype was associated with a significantly decreased risk of squamous cell carcinoma (adjusted OR = 0.55, 95% CI = 0.34-0.88) and small cell lung cancer (adjusted OR = 0.44, 95% CI = 0.20-0.97), but non-significant decreased risk of adenocarcinoma (adjusted OR = 0.64, 95% CI = 0.36-1.12). These results suggest that the XPG codon 1104 polymorphism contributes to genetic susceptibility to lung cancer.

[1]  H. Bernstein,et al.  DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. , 2002, Mutation research.

[2]  J. Park,et al.  Lys751Gln polymorphism in the DNA repair gene XPD and risk of primary lung cancer. , 2002, Lung cancer.

[3]  K. Schulz,et al.  Bias and causal associations in observational research , 2002, The Lancet.

[4]  J. Hoeijmakers.  Genome maintenance mechanisms for preventing cancer , 2001, Nature.

[5]  T. D. Schneider,et al.  The human XPG gene: gene architecture, alternative splicing and single nucleotide polymorphisms. , 2001, Nucleic acids research.

[6]  D. Christiani,et al.  The NAD(P)H:quinone oxidoreductase 1 gene polymorphism and lung cancer: differential susceptibility based on smoking behavior. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[7]  Richard D. Wood,et al.  Human DNA Repair Genes , 2001, Science.

[8]  Y. Koh,et al.  Characteristics of lung cancer in Korea, 1997. , 2000, Lung cancer.

[9]  C. Harris,et al.  Cancer risk and low-penetrance susceptibility genes in gene-environment interactions. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  M. West,et al.  XRCC1 keeps DNA from getting stranded. , 2000, Mutation research.

[11]  R. Wood,et al.  Damage recognition in nucleotide excision repair of DNA. , 2000, Gene.

[12]  M. García-Closas,et al.  Misclassification in case-control studies of gene-environment interactions: assessment of bias and sample size. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[13]  S. Hecht,et al.  Tobacco smoke carcinogens and lung cancer. , 1999, Journal of the National Cancer Institute.

[14]  A. Sancar,et al.  Order of Assembly of Human DNA Repair Excision Nuclease* , 1999, The Journal of Biological Chemistry.

[15]  M. Spitz,et al.  Reduced DNA repair capacity in head and neck cancer patients. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[16]  I. M. Jones,et al.  Variation in DNA repair is a factor in cancer susceptibility: a paradigm for the promises and perils of individual and population risk estimation? , 1998, Mutation research.

[17]  J. T. Reardon,et al.  The Non-catalytic Function of XPG Protein during Dual Incision in Human Nucleotide Excision Repair* , 1997, The Journal of Biological Chemistry.

[18]  M. Spitz,et al.  Reduced DNA repair capacity in lung cancer patients. , 1996, Cancer research.

[19]  N. Iyer,et al.  Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein. , 1996, Biochemistry.

[20]  S. West,et al.  XPG endonuclease makes the 3′ incision in human DNA nucleotide excision repair , 1994, Nature.

[21]  S. Clarkson,et al.  Mutations that disable the DNA repair gene XPG in a xeroderma pigmentosum group G patient. , 1994, Human molecular genetics.

[22]  T. Saito,et al.  An ERCC5 gene with homology to yeast RAD2 is involved in group G xeroderma pigmentosum. , 1994, Mutation research.

[23]  J. Mudgett,et al.  Human ERCC5 cDNA-cosmid complementation for excision repair and bipartite amino acid domains conserved with RAD proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe , 1993, Molecular and cellular biology.

[24]  A. Bairoch,et al.  Complementation of the DNA repair defect in xeroderma pigmentosum group G cells by a human cDNA related to yeast RAD2 , 1993, Nature.

[25]  K. Nakachi,et al.  Genetic susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose. , 1991, Cancer research.

[26]  J. Mudgett,et al.  Isolation of the functional human excision repair gene ERCC5 by intercosmid recombination. , 1990, Genomics.

[27]  T. Sellers,et al.  Evidence for mendelian inheritance in the pathogenesis of lung cancer. , 1990, Journal of the National Cancer Institute.

[28]  S. Prakash,et al.  Nucleotide sequence, transcript mapping, and regulation of the RAD2 gene of Saccharomyces cerevisiae , 1986, Journal of bacteriology.

[29]  G. Grimmer,et al.  Experimental studies in rat lungs on the carcinogenicity and dose-response relationships of eight frequently occurring environmental polycyclic aromatic hydrocarbons. , 1983, Journal of the National Cancer Institute.

[30]  C. H. Kim,et al.  Polymorphism of the DNA repair gene XRCC1 and risk of primary lung cancer. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[31]  B. Glickman,et al.  Human DNA repair systems: An overview , 1999, Environmental and molecular mutagenesis.

[32]  S. Amin,et al.  Cigarette smoking and adenocarcinoma of the lung: The relevance of nicotine-derived N-nitrosamines , 1993 .