The polymorphisms and haplotypes of WWOX gene are associated with the risk of lung cancer in southern and eastern chinese populations

Authors

  • Dongsheng Huang,

    1. The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, P.R. China
    2. Guangzhou Chest Hospital, Guangzhou, P.R. China
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  • Fuman Qiu,

    1. The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, P.R. China
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  • Lei Yang,

    1. The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, P.R. China
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  • Yinyan Li,

    1. The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, P.R. China
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  • Mei Cheng,

    1. The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, P.R. China
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  • Hui Wang,

    1. The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, P.R. China
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  • Guanpei Ma,

    1. The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, P.R. China
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  • Yunnan Wang,

    1. Guangzhou Chest Hospital, Guangzhou, P.R. China
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  • Min Hu,

    1. Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, P.R. China
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  • Weidong Ji,

    1. The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, P.R. China
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  • Yifeng Zhou,

    1. Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, P.R. China
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  • Jiachun Lu

    Corresponding author
    1. The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, P.R. China
    • The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, P.R. China.

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  • D. Huang, F. Qiu, and L. Yang contributed equally to this work.
  • The authors declare no competing interests.

Abstract

The WW domain-containing oxidoreductase (WWOX) gene is an identified tumor suppressor gene, of which several single nucleotide polymorphisms have been reported to contribute to cancer susceptibility. We hypothesized that genetic variations in WWOX are associated with lung cancer risk. In two independent case–control studies conducted in southern and eastern Chinese, we genotyped five tagSNPs of WWOX gene (rs10220974C > T, rs3764340C > G, rs12918952G > A, rs383362G > T, and rs12828G > A) in 1,559 lung cancer cases and 1,679 controls. Logistic regression analysis showed that two tagSNPs (rs3764340C > G; rs383362G > T) were significantly associated with lung cancer risk in dominant model (rs3764340C > G, GC/GG vs. CC: adjust OR = 1.35, 95% CI = 1.11–1.65; rs383362G > T, TG + TT vs. GG: adjust OR = 1.33, 95% CI = 1.14–1.55). The haplotype analysis further shown that the haplotype “G-T” was associated with the highest increased risk of lung cancer (OR = 2.20; 95% CI = 1.43–3.37). After combined these two loci, the number of the risk genotypes was associated with increased cancer risk in a dose–response manner (Ptrend = 3.16 × 10−6). In addition, a gene-based association analysis by using VEGAS software suggested the WWOX as a susceptible gene for lung cancer (P = 0.009). However, for rs10220974C > T, rs12918952G > A, and rs12828G > A, no significant association was observed for lung cancer risk. Taken together, our data suggested that genetic variants in WWOX may be genetic biomarkers for susceptibility to lung cancer. Copyright © 2012 Wiley Periodicals, Inc.

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