Open AccessIndependent 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(s) -
Tsai JungFa,
Chen ShinnChern,
Lin ZuYau,
Dai ChiaYen,
Huang JeeFu,
Yu MinLung,
Chuang WanLong
Publication year - 2017
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1016/j.kjms.2017.04.009
Subject(s) - medicine , hepatocellular carcinoma , cirrhosis , gastroenterology , hepatitis b virus , genotype , odds ratio , tumor necrosis factor alpha , lymphotoxin , immunology , oncology , gene , virus , biochemistry , chemistry
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.