Genetic variants of p21 and p27 and hepatocellular cancer risk in a Chinese Han population: A case-control study

Authors

  • Fei Liu,

    1. Division of Liver Transplantation, Department of liver and vascular surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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  • Yong-Gang Wei,

    Corresponding author
    1. Division of Liver Transplantation, Department of liver and vascular surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
    • Division of Liver Transplantation, Department of liver and vascular surgery, West China Hospital, Sichuan University, 37 Guo Xue Road, Chengdu, 610041, Sichuan Province, China
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    • Tel.: +86 28 85422476, Fax: +86 28 85423724

  • Li-Mei Luo,

    1. Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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  • Wen-Tao Wang,

    1. Division of Liver Transplantation, Department of liver and vascular surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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  • Lv-Nan Yan,

    1. Division of Liver Transplantation, Department of liver and vascular surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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  • Tian-Fu Wen,

    1. Division of Liver Transplantation, Department of liver and vascular surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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  • Ming-Qing Xu,

    1. Division of Liver Transplantation, Department of liver and vascular surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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  • Jia-Yin Yang,

    1. Division of Liver Transplantation, Department of liver and vascular surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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  • Bo Li

    Corresponding author
    1. Division of Liver Transplantation, Department of liver and vascular surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
    • Division of Liver Transplantation, Department of liver and vascular surgery, West China Hospital, Sichuan University, 37 Guo Xue Road, Chengdu, 610041, Sichuan Province, China
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    • Tel.: +86 28 85422476, Fax: +86 28 85423724


Abstract

The p21 (Cip1/CDKN1A) and p27 (Kip1/CDKN1B) are members of the Cip/Kip family of cyclin-dependent kinase inhibitors, which can arrest cell proliferation and serve as tumour suppressors. We hypothesized that genetic variants in p21 and p27 may modify individual susceptibility to hepatocellular carcinoma (HCC). To test this hypothesis, we evaluated the associations of the polymorphisms of Ser31Arg and C+20T in p21 and C-79T and Gly109Val in p27, as well as their combinations, with HCC risk in a case-control study of 476 HCC cases and 526 cancer-free controls in a Chinese population. The matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry method was performed to detect these polymorphisms. We found that the variant genotypes of p21 Ser31Arg and p27 C-79T were individually associated with a significantly increased risk of HCC, but no associations were observed for other variant genotypes. Moreover, the combined variant genotypes of the four loci were associated with a significantly increased HCC risk (adjusted OR = 2.24, 95% CI = 1.72, 2.91 among subjects carrying 3 or more variant alleles), especially among HbsAg-positive individuals (adjusted OR = 3.09, 95% CI = 1.86, 5.14). Furthermore, the combined variant genotypes of the four loci (carrying three or more variant alleles) increased a 1.93-fold (95% CI = 1.20, 3.09) and 1.76-fold (95% CI = 1.17, 2.64) risk of HCC among smokers and nonsmokers. The variant genotypes of the two genes in this study have negative correlation with the clinicopathologicals observed. These results suggest that p21 polymorphisms individually or in combination with p27 polymorphisms increases risk of HCC, particularly among HbsAg-positive individuals.

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