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

Thoracic Cancer

Chaorong Mei¹  Mei Hou²  Shanxian Guo¹  Feng Hua¹  Dejie Zheng¹  Feng Xu²  Yong Jiang³  Lu Li²  Youlin Qiao³  Yaguang Fan¹ 

[1] Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China;Cancer Center, West China Hospital, Sichuan University, Chengdu, China;Department of Cancer Epidemiology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

关键词: DNA repair gene;    haplotype;    lung cancer susceptibility;    multifactor dimensionality reduction;    tagging SNP;   

DOI  :  10.1111/1759-7714.12073

来源: Wiley

【 摘 要 】

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 gene-smoking 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 gene-smoking interactions.

【 授权许可】

Unknown   
© 2013 Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty Ltd