Lung cancer is a major cause of cancer-related death in the developed countries and the overall survival rate has still an extremely poor. Although cigarette smoking is the main cause of lung cancer, not all smokers develop lung cancer, and a fraction of lifelong nonsmokers will die from lung cancer. Genetic host factors have recently been implicated to account for some of the observed differences in lung cancer susceptibility. Various DNA alterations can be caused by exposure to environmental and endogenous carcinogens. Most of these alterations, if not repaired, may result in genetic instability, mutagenesis and cell death. DNA repair mechanisms are important for maintaining DNA integrity and preventing carcinogenesis. Recent genetic association studies on lung cancer risk have focused on identifying effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. The authors identified a sufficient number of epidemiologic studies on lung cancer to conduct meta-analyses for genetic polymorphisms in DNA repair genes. They found increased risk of lung cancer among subjects carrying excision repair cross complementing group 2 (ERCC2/ xeroderma pigmentosum group D (XPD)) 751Gln/Gln genotype (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.14 - 1.49). They found a protective effect of XPA 23G/G genotype (OR = 0.75, 95% CI = 0.59 - 0.95). X-ray cross-complementing group 1 (XRCC1) 399Gln/Gln genotype was associated with an increased risk of lung cancer among Asians (OR = 1.34, 95% CI = 1.16 - 1.54). Little evidence of associations has been found between other DNA repair genes and lung cancer risk. Considering the data available, it can be conjectured that if there is any risk association between single SNP, such as the XRCC1 Arg399Gln, the XPA G23A or the ERCC2/XPD Lys751Gln, and lung cancer, this risk increase/decrease will probably be minimal. Advances in identification of new polymorphisms and in high-throughput genotyping techniques will facilitate analysis of multiple genes in multiple DNA repair pathways. Therefore, it is likely that the defining feature of future epidemiologic studies will be the simultaneous analysis of large samples of cases and controls.
|Title of host publication||New Research on DNA Repair|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||46|
|Publication status||Published - 2007|
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)