Polymorphisms in DNA repair genes of XRCC1, XPA, XPC, XPD and associations with lung cancer risk in Chinese people

Abstract

Background: The carcinogenic chemicals and reactive oxygen species in tobacco can result in DNA damage. DNA repair genes play an important role in maintaining genome integrity. Genetic polymorphisms of DNA repair genes and smoking may contribute to susceptibility of lung cancer. Methods: In this hospital-based case-control study, we investigated the relationship between 13 tagging single nucleotide polymorphisms (SNPs) in base excision repair pathway and nucleotide excision repair pathway genes, smoking, and lung cancer susceptibility. Thirteen tag SNPs were genotyped in 265 lung cancer patients and 301 healthy controls. Logistic regression and multifactor dimensionality reduction method were applied to explore the association and high-order gene-gene and genesmoking interaction. Results: In single tag SNP analysis, XPA rs2808668, XPC rs2733533, and XPD rs1799787 were significantly associated with lung cancer susceptibility. Joint effects analysis of XPA rs2808668, XPC rs2733533 and XPD rs1799787 showed that there was an increased risk of lung cancer with increasing numbers of risk alleles. Haplotype analysis showed that XRCC1 (rs25487, rs1799782, rs3213334) GCC had a positive association with lung cancer.Analysis of gene-gene and gene-smoking interaction by multifactor dimensionality reduction showed that a positive interaction existed between the four genes and smoking. The two-factor model, including XPC rs2755333 and smoking, had the best prediction ability for lung cancer. Compared with the C/C genotype of XPC rs2733533 and no smoking, the combination of genotype A carriers with XPC rs2733533 and heavy smokers (≥30 pack-year) had a 13.32-fold risk of lung cancer. Conclusion: Our results suggest multiple genetic variants in multiple DNA repair genes may jointly contribute to lung cancer risk through gene-gene and genesmoking interactions.

Polymorphisms in DNA repair pathway genes and&nbsp;<em>ABCG2</em>&nbsp;gene in advanced colorectal cancer: correlation with tumor characteristics and clinical outcome in oxaliplatin-based chemotherapy

“…Although reports on the SNP in the XPA gene have been published previously, these did not share a relation with the significant XPA SNPs that was identified in our current study. Most of those previous studies mainly focused on identifying the relationships between the SNPs and cancer risk in different populations 17,38,40–49. Only Gao et al50 found a prognostic importance related to the XPA rs10817938 C allele, which indicated that it is a potential functional SNP and a biomarker for prognosis in oral squamous cell carcinoma patients, similarly with our results, no significant association of rs2808668 polymorphism with OSCC prognosis observed.…”

A Functional Polymorphism (rs10817938) in the XPA Promoter Region Is Associated with Poor Prognosis of Oral Squamous Cell Carcinoma in a Chinese Han Population

“…It remains controversial on the association of rs2808668 with different type of cancers risk. In lung cancer and breast cancer, previous studies reported that rs2808668 polymorphism was significantly associated with cancer susceptibility[ 17 , 20 ]. However, no significant association between rs2808668 polymorphism with pancreatic cancer, larynx cancer could be observed[ 33 , 34 ].…”

“…rs2808668 is also a T to C substitution located -514bp from the transcriptional start site. Previous studies have found the positive association between rs2808668 polymorphism and lung cancer, breast cancer risk[ 17 , 20 ]. However, no report has been provided to show the association of these two polymorphisms with OSCC.…”

XPA gene polymorphisms and risk of neuroblastoma in Chinese children: a two-center case-control study

“…Owing to the important role of XPA protein in NER pathway, the association between XPA polymorphisms and cancer risk remains a hot spot of research. By now, several epidemiological studies have been performed to determine of the association with the risk of cancer, including colorectal cancer 36 , laryngeal cancer 37 , lung cancer 38 , and B-cell lymphoma 39 .…”