Advances in molecular and genetic epidemiology have increased our knowledge of the mechanisms underlying hepatocarcinogenesis and the relationships between susceptibility and individual genetic variations [
17]. Based on the genetic information, we determine the disease etiology in terms of genetic determinants to be used for identifying the high-risk individuals and perform targeting therapy to the individual’s genetic make-up.
TNF-α is a member of the TNF/TNFR cytokine superfamily, and is an intercellular communicating molecule involved in building transient or long-lasting multicellular structures [
18]. It interacts with receptors TNFR1 and TNFR2, which participate in cellular signal transduction pathways [
19]. TNF-α plays an important role in the regulation of cell differentiation, proliferation and death as well as in inflammation and the innate and adaptive immune response. It has also been implicated in a wide variety of human diseases. The presence of DNA sequence variations in the regulatory region might interfere with transcription of the TNF gene, influencing the circulating level of TNF and thus increasing susceptibility to human diseases, such as cancer. The TNF enhancer polymorphism has been implicated in several diseases, and the TNF-a −308 polymorphism has been described as the most important TNF polymorphism in human disease susceptibility. The significance of these polymorphisms reflects their possible influence on the transcription of the TNF gene. TNF-α −308 G > A polymorphism involves the substitution of a guanine (G) by an adenine (A) and is associated with an increase in TNF-α expression levels [
7]. TNF-α −308G > A polymorphism has been reported to alter the risk of several types of cancers, such as breast cancer, lung cancer, non-Hodgkin lymphomas, and prostate cancer [
8]-[
11]. For example, Jin et al. found that the TNF- α −308G > A polymorphism was not associated with breast cancer risk in the overall population but that the A allele might be a protective factor for breast cancer in postmenopausal women, and the AA genotype might be a breast cancer risk factor in premenopausal women [
8]. In Ma et al’ study, a significantly increased prostate cancer risk was found to be associated with the TNF-α-308 G > A polymorphism (AA + AG vs. GG: OR = 1.531, 95% CI = 1.093–2.145;
P = 0.013; AG vs. GG: OR = 1.477, 95% CI = 1.047–2.085;
P = 0.026). Their results suggested that the TNF-α-308 G > A polymorphism might significantly contribute to prostate cancer susceptibility [
11]. However, the association between TNF-α −308 G > A polymorphism and risk of HCC is controversial [
12]-[
15]. The present case–control study was performed to assess the association of HCC risk and TNF-α −308 G > A polymorphism in a Han Chinese population. We found that the genotypic frequencies in the cases were not similar to that of the controls. We then analyzed the effects of the tested genotypes under different genetic models. Using the GG genotype as the reference genotype, AA was significantly associated with increased risk of HCC. Similarly, AG + AA genotype showed 5.59-fold increased HCC risk in a dominant model. Furthermore, we found A allele was significantly associated with increased risk of HCC, compared with G allele. Our results were consistent with the findings previously reported by Heneghan et al. and Ho et al. [
20],[
21], but different from Chen et al’s study [
22].