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

Abstract

Single-nucleotide polymorphisms (SNPs) of DNA repair genes have been reported to modify cancer risk. This study aimed to determine SNPs of the DNA repair genes X-ray repair cross-complementing group 3 (XRCC3) and X-ray cross-complementing group 4 (XRCC4) and their association with non-small-cell lung cancer (NSCLC) susceptibility in a Chinese population. A total of 507 NSCLC patients and 662 healthy controls were recruited for genotyping. Epidemiological and clinical data were also collected for association studies. The data showed that the rs1799794 G allele in the XRCC3 gene and minor allele carriers of XRCC4, including rs1056503 and rs9293337, were inversely associated with NSCLC risk (GG vs homozygote AA), whereas the rs861537 AG or AA genotype and XRCC4 rs6869366 had a significantly increased NSCLC risk. Furthermore, tobacco smoking over 26 pack-years, a family history of lung cancer, exposure to environmental tobacco smoke (ETS) and negative mental status were risk factors for developing NSCLC. This study suggests that SNPs of XRCC3 and XRCC4 and other environmental factors are risk factors for developing NSCLC in this Chinese Han population.

The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer

“…The XRCC4 SNP rs1805377 is also associated with poor survival in patients with metastatic prostate cancer [ 146 ]. Carriers of the XRCC4 G-1384T polymorphism (SNP rs6869366) are at a significantly higher risk of developing NSCLC, esophageal, bladder, prostate, gastric, colorectal, and urothelial cancer [ 147 , 148 , 149 , 150 , 151 , 152 ].…”

XRCC4 rs6869366 polymorphism is associated with susceptibility to both nicotine dependence and/or schizophrenia

“…Previously, it was shown that frequencies of XRCC4 rs6869366 TG+GG genotypes were higher in patients with autism spectrum disorder than the controls 33 . He et al reported that patients who smoked and carried the XRCC4 rs6869366 G allele had an increased risk for non small cell lung cancer (NSCLC) 34 . In a study conducted on the patients with lung cancer, Hsu et al demonstrated that people with rs 6869366 GT genotype and smoking habit present the highest risk of lung cancer than other groups 35 .…”

Association between single nucleotide polymorphisms of X-ray repair cross-complementing protein 4 gene and development of pancreatic cancer

“…Zhou et al (2013) conducted a meta-analysis that included five studies, and suggested that rs2075685 and rs6869366 polymorphisms increase the risk of breast cancer. He et al (2013) investigated the association between the XRCC4 gene polymorphisms and the risk of non-small-cell lung cancer and suggested that XRCC4 rs6869366 polymorphism had a significantly increased NSCLC risk. Zhao et al (2013) investigated the association between DSB gene polymorphisms and glioma risk in a Chinese population and found that the XRCC4 rs1805377 polymorphism was associated with an increased risk of gliomas.…”

“…Numerous epidemiologic studies have reported that XRCC4 gene polymorphisms are associated with the risk of several types of cancers, such as colorectal cancer, acute lymphoblastic leukemia, breast cancer, glioma, hepatocellular carcinoma, non-small-cell lung cancer, esophageal cancer and prostate cancer (Bau et al, 2010;Chokkalingam et al, 2011;Zhou et al, 2012;He et al, 2013;Long et al, 2013;Zhao et al, 2013;Fan et al, 2013;Shao et al, 2014). Bau et al (2010) investigated the association between XRCC4 gene polymorphisms and the susceptibility to colorectal cancer, and suggested that XRCC4 rs6869366 polymorphism may contribute to the development of esophageal cancer and may be useful for early detection of colorectal cancer.…”