DNA repair gene XPC genotypes/haplotypes and risk of lung cancer in a Chinese population

Authors

  • Zhibin Hu,

    1. Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, Nanjing, China
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  • Yonggang Wang,

    1. Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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  • Xinru Wang,

    1. Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, Nanjing, China
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  • Gang Liang,

    1. Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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  • Xiaoping Miao,

    1. Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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  • Yaochu Xu,

    1. Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, Nanjing, China
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  • Wen Tan,

    1. Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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  • Qingyi Wei,

    1. Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
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  • Dongxin Lin,

    Corresponding author
    1. Department of Etiology and Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    • Co-corresponding author
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  • Hongbing Shen

    Corresponding author
    1. Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, Nanjing, China
    • Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, 140 Hanzhong Road, Nanjing 210029, China
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    • Fax: +86-25-865-27613.


Abstract

DNA repair is central to normal cellular functions, and polymorphisms of DNA repair genes may cause variation in DNA repair capacity in the general population. Newly identified polymorphisms of xeroderma pigmentosum group C (XPC), one of the nucleotide excision repair genes, were shown to contribute to genetic susceptibility to cancer. In this study, we hypothesized that 2 exonic variants C499T and A939C and their haplotypes in XPC are associated with lung cancer risk. To test this hypothesis, we performed a case-control study of 320 histologically confirmed lung cancer patients and 322 age and sex frequency-matched cancer-free controls in a Chinese population. Multivariate logistic regression analyses revealed that the risks [adjusted odds ratios (ORs) and 95% confidence intervals (CIs)] associated with the XPC variant genotypes were 1.57 (95% CI = 1.13–2.19) for 499CT/TT and 1.21 (95% CI = 0.87–1.69) for 939AC/CC compared with the 499CC and 939AA wild-type homozygotes, respectively. Individuals with both putative risk genotypes (499CT/TT and 939AC/CC) had a greater risk of lung cancer (adjusted OR = 2.37; 95% CI = 1.33–4.21) compared with individuals with both wild-type genotypes (499CC and 939AA). When we performed the haplotype analysis and assumed the XPC 499T and 939C as risk alleles, the adjusted ORs increased as the number of variants in the haplotype genotypes increased (ptrend < 0.001). In the stratified analysis, the greatest risk was found in smokers having the combined variant genotypes (adjusted OR = 7.36; 95% CI = 3.19–17.00) compared with nonsmokers having both wild-type genotypes and in smokers with 2 or 3 haplotype variants (adjusted OR = 7.27; 95% CI = 3.37–15.68) compared with nonsmokers having 0 haplotype variant. These findings indicate that XPC exonic variants may contribute to the risk of lung cancer in the Chinese population, and these variant genotypes may modulate the risk of lung cancer associated with smoking. © 2005 Wiley-Liss, Inc.

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