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Open Access Research article

Sequence variations in DNA repair gene XPC is associated with lung cancer risk in a Chinese population: a case-control study

Yun Bai1, Liang Xu2, Xiaobo Yang1, Zhibin Hu3, Jing Yuan1, Feng Wang1, Minhua Shao4, Wentao Yuan2, Ji Qian4, Hongxia Ma3, Ying Wang2, Hongliang Liu4, Weihong Chen1, Lin Yang2, Guangfu Jing3, Xiang Huo3, Feng Chen3, Yanhong Liu4, Li Jin4, Qingyi Wei5, Wei Huang2, Hongbing Shen3, Daru Lu4* and Tangchun Wu1*

Author Affiliations

1 Institute of Occupational Medicine and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China

2 Department of Genetics, Chinese National Human Genome Center at Shanghai, Shanghai 201203, PR China

3 Department of Epidemiology and Biostatistics, Cancer Research Center of Nanjing Medical University, Nanjing 210029, PR China

4 State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, PR China

5 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA

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BMC Cancer 2007, 7:81  doi:10.1186/1471-2407-7-81

Published: 13 May 2007

Abstract

Background

The nucleotide excision repair (NER) protein, xeroderma pigmentosum C (XPC), participates in recognizing DNA lesions and initiating DNA repair in response to DNA damage. Because mutations in XPC cause a high risk of cancer in XP patients, we hypothesized that inherited sequence variations in XPC may alter DNA repair and thus susceptibility to cancer.

Methods

In this hospital-based case-control study, we investigated five XPC tagging, common single nucleotide polymorphisms (tagging SNPs) in 1,010 patients with newly diagnosed lung cancer and 1,011 matched cancer free controls in a Chinese population.

Results

In individual tagging SNP analysis, we found that rs3731055AG+AA variant genotypes were associated with a significantly decreased risk of lung adenocarcinoma [adjusted odds ratio (OR), 0.71; 95% confidence interval (CI), 0.56–0.90] but an increased risk of small cell carcinomas [adjusted OR, 1.79; 95% CI, 1.05–3.07]. Furthermore, we found that haplotype ACCCA was associated with a decreased risk of lung adenocarcinoma [OR, 0.78; 95% CI, 0.62–0.97] but an increased risk of small cell carcinomas [OR, 1.68; 95% CI, 1.04–2.71], which reflected the presence of rs3731055A allele in this haplotype. Further stratified analysis revealed that the protective effect of rs3731055AG+AA on risk of lung adenocarcinoma was more evident among young subjects (age ≤ 60) and never smokers.

Conclusion

These results suggest that inherited sequence variations in XPC may modulate risk of lung cancer, especially lung adenocarcinoma, in Chinese populations. However, these findings need to be verified in larger confirmatory studies with more comprehensively selected tagging SNPs.