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Genetic variants in cell death pathway genes and HBV-related hepatocellular carcinoma among a Chinese Han population

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Abstract

Cell death pathway plays an important role in apoptosis, and corruption of this signaling pathway has been shown to participate in carcinogenesis. We aimed at determining whether genetic variants in CASP8, CASP10 and CFLAR influence the development and clinical outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A hospital-based case-control study, including 600 HCC cases and 600 HBsAg positive controls without HCC, was conducted to assess the relationship between 11 tagging SNPs in CASP8, CASP10 and CFLAR and HBV-related HCC risk and prognosis in a Chinese Han population. Among the 11 polymorphisms, only CASP8 rs3834129 (−652 6N ins/del) modified HCC risk. Compared with CASP8 −652 insins genotype, the deldel (adjusted OR 0.717, 95% CI 0.553–0.930) and insdel (adjusted OR 0.731, 95% CI 0.554–0.964) genotypes had a significantly decreased HCC risk. Furthermore, this polymorphism was significantly associated with decreased portal vein tumor thrombosis (adjusted OR 0.554; P = 0.044) and reduced postoperative recurrence (adjusted OR 0.356; P < 0.001) of resected HCC. In addition, the multivariate analysis showed that the −652 6N ins/del polymorphism was significantly associated with improved overall survival and recurrence-free survival of resected HCC patients. The expression levels of CASP8 in HCC tumor tissues were significantly lower than those in paracancerous liver tissues, although no significant association between −652 6N ins/del genotypes and the expression levels of CASP8 were observed in these tissues. These results suggest that the CASP8 −652 6N ins/del polymorphism may play a protective role in the development, progression, and survival of HBV-related HCC among the Chinese Han population.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 81602910) and the Fundamental Research Fund for the Central Universities (No. 2017SCU11045).

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Author notes

  1. Fei Liu, Fuqiang Li and Limei Luo have contributed equally to this study.

Authors and Affiliations

  1. Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, 37 Guo Xue Road, Chengdu, 610041, Sichuan, China

    Fei Liu, Fuqiang Li, Hanteng Yang, Yonggang Wei, Wentao Wang, Lvnan Yan, Tianfu Wen, Jiayin Yang & Bo Li

  2. Department of General Surgery, First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, 310003, Zhejiang, China

    Fuqiang Li

  3. Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, 37 Guo Xue Road, Chengdu, 610041, Sichuan, China

    Limei Luo

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  1. Fei Liu
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Correspondence to Yonggang Wei or Bo Li.

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10495_2017_1385_MOESM1_ESM.jpg

Supporting Figure 1. Genotyping of CASP8 -652 6N ins/delpolymorphism by MALDI-TOF. The horizontal axis represents the mass and the vertical axis represents the signal intensity. Around the 5700 dalton in the horizontal axis, two lines (the 6N allele and the del allele) can be observed. If only a wave crest appeared at the 6N line, the genotype of this patient was 6N6N (insins,1A); if only a wave crest appeared at the del line, the genotype of this patient was deldel(1B); if two wave crest appeared at both the 6N line and the del line, the genotype of this patient was 6Ndel (insdel, 1C) (JPG 108 KB)

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Liu, F., Li, F., Luo, L. et al. Genetic variants in cell death pathway genes and HBV-related hepatocellular carcinoma among a Chinese Han population. Apoptosis 22, 1035–1047 (2017). https://doi.org/10.1007/s10495-017-1385-z

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