XRCC3 Thr241Met polymorphism with lung cancer and bladder cancer: A meta‐analysis

Abstract

Several studies have investigated the associations between X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and the susceptibility to lung cancer and bladder cancer, but results have been inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 22 case control studies, including 2976 cases and 4495 controls for lung cancer, and 3445 cases and 4599 controls for bladder cancer, met the inclusion criteria and were selected. Overall, there was no evidence showing a significant association between XRCC3 Thr241Met polymorphism and lung cancer risk. Furthermore, the results for bladder cancer showed that significant decreased risk was found for the additive model (odds ratio [OR] = 0.959, 95% confidence interval [CI], 0.924-0.996) and dominant model (OR = 0.982, 95% CI, 0.963-1.000) but not for the recessive model (OR = 0.958, 95% CI, 0.905-1.014). In summary, our meta-analysis indicates that XRCC3 Thr241Met polymorphism may be weakly associated with the risk of bladder cancer. (Cancer Sci 2010; 101: 1777-1782 L ung cancer is one of the most common cancers worldwide, and it is the leading cause of cancer-related deaths in the world.(1) The role of genetic susceptibility in lung cancer has shown that the relatives of patients with lung cancer had an increased risk of the disease.(1,2) Only a fraction of smokers and a low number of non-smokers develop lung cancer, which implies influence of host factors in individual susceptibility. This inter-individual difference in susceptibility may be attributed to genetic polymorphisms in critical genes, including those involved in DNA repair. (3,4) Bladder cancer is among the most frequent diagnosed cancer in the developed world.(5) Although development of bladder cancer is associated with exposure to tobacco and occupational exposure, (6) only a small proportion of exposed individuals will develop cancer, suggesting the involvement of genetic factors.DNA repair systems play an critical role in maintaining genomic integrity.(3) If DNA damage is unrepaired, mutations are propagated during subsequent cellular replication and ultimately result in activation of oncogenes or inactivation of tumor suppressor genes. So mutations on these genes which alter the function of these proteins may predispose an individual to cancer. Increasing molecular epidemiologic evidence has shown that polymorphisms in various DNA repair genes are associated with an increased risk of cancer. (7,8) The X-ray repair cross-complementing group 3 (XRCC3) belongs to a family of genes responsible for repairing DNA double strand breaks caused by normal metabolic processes and ⁄ or exposure to ionizing radiation. The XRCC3 is involved in homologous recombination repair (HRR) and chromosomal double-strand breaks repair processes, and it is necessary to maintain genomic integrity. It was demonstrated that cell lines defective in XRCC3 had a 25-fold decrease in homology directed repair of DNA double-strand breaks.(9) Shen et al.ide...

DNA Repair Capacity-Related to Genetic Polymorphisms of DNA Repair Genes and Aflatoxin B1-Related Hepatocellular Carcinoma Among Chinese Population

“…This protein correlates directly with DNA breaks and facilitates of the formation of the RAD51 nucleoprotein filament, which is crucial both for homologous recombination and HRR (136)(137)(138). Previous studies have shown that a common polymorphism at codon 241 of XRCC3 gene (Thr to Met) modifies the function of this gene ad increases cancers risk (139)(140)(141)(142)(143). Two reports from high AFB1-exposure areas of China supported above-mentioned conclusions (58,60).…”

Association of XRCC3 and XRCC4 gene polymorphisms, family history of cancer and tobacco smoking with non-small-cell lung cancer in a Chinese population: a case–control study

“…29 However, the same group 4 years later failed to repeat their previous data on the association between rs861539 and cancer risk or G(2) chromosomal radiosensitivity. 30 Meta-analysis 19,31 studies concluded that this SNP might have not been associated with lung cancer risk. However, our current study demonstrated that XRCC3 rs861537 was associated with an increased risk of NSCLC, whereas the minor allele carriers of XRCC3 rs1799794 were inversely associated with NSCLC risk.…”

Single nucleotide polymorphisms of RAD51 G135C, XRCC2 Arg188His and XRCC3 Thr241Met homologous recombination repair genes and the risk of sporadic endometrial cancer in Polish women

“…[14][15][16][17][18][19] Earlier studies showed that XRCC3 Thr241Met gene polymorphism had been studied as a risk factor for various cancers. The Thr241Met genotype has been associated with an increased risk of breast, 20 colorectal, 21 bladder, 22 head and neck cancer. 23 However, no association was detected between the risk for endometrial carcinoma and XRCC3 Thr241Met polymorphism.…”