1. Independent and additive interaction between polymorphisms of tumor necrosis factor α −308 and lymphotoxin α +252 on risk of hepatocellular carcinoma related to hepatitis B
- Author
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M.-L. Yu, Jung-Fa Tsai, Chia-Yen Dai, Wan-Long Chuang, Jee-Fu Huang, Shinn-Chern Chen, and Zu-Yau Lin
- Subjects
Liver Cirrhosis ,Male ,0301 basic medicine ,Cirrhosis ,Hepatitis B related hepatocellular carcinoma ,Gene Expression ,medicine.disease_cause ,Gastroenterology ,0302 clinical medicine ,Gene Frequency ,Risk Factors ,Odds Ratio ,Promoter Regions, Genetic ,Lymphotoxin-alpha ,lcsh:R5-920 ,Lymphotoxin α ,Liver Neoplasms ,General Medicine ,Middle Aged ,Hepatitis B ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Synergy index ,Female ,Tumor necrosis factor alpha ,lcsh:Medicine (General) ,Adult ,Hepatitis B virus ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Internal medicine ,medicine ,Tumor necrosis factor α ,Humans ,Genetic Predisposition to Disease ,Alleles ,Aged ,Tumor Necrosis Factor-alpha ,business.industry ,Epistasis, Genetic ,Odds ratio ,medicine.disease ,digestive system diseases ,Single nucleotide polymorphism ,030104 developmental biology ,Lymphotoxin ,Haplotypes ,Case-Control Studies ,Immunology ,5' Untranslated Regions ,business - Abstract
This case–control study was aimed to assess the effect of genetic variants of tumor necrosis factor (TNF) α−308 and lymphotoxin (LT) α+252 on development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Their gene–gene interaction was also investigated. We enrolled 200 pairs of age- and sex-matched patients with cirrhotic HBV-HCC and unrelated patients with HBV-cirrhosis alone. Polymorphisms of TNFα −308 and LTα +252 were genotyped. Synergy index was used to calculate interaction between the variant genotypes. The results indicated that the frequency distribution of the variant genotypes ( TNFα −308 G/A and LTα +252 G/G) in patients with HCC were significantly higher than those in patients with cirrhosis alone. Multivariate analysis indicated that TNFα −308 G/A (odds ratio [OR], 2.34) and LTα +252 G/G (OR, 2.04) were independent risk factors for HCC. By the clinical characteristics of study population, multivariate analysis demonstrated that independent factors associated with harboring the variant genotypes included cirrhosis with Child-Pugh C (OR = 6.47 in cases and OR = 11.56 in controls) and thrombocytopenia (OR = 8.86 in cases and OR = 7.74 in controls). Calculation of synergy index (SI) indicated that there are additive interaction between TNFα −308 G/A and LTα +252 G/G on risk of HCC (SI = 1.29). In conclusion: There are independent and additive interactions between TNFα −308 G/A and LTα +252 G/G on risk for HBV-HCC. They correlated with advanced hepatic fibrosis and severe liver damage, which might contribute to a higher risk for HCC.
- Published
- 2017
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