| Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide in terms of numbers of cases(626,000 or 5.7% of new cancer cases) but because of the very poor prognosis, the number of deaths is almost the same (598,000). It is therefore the third most common cause of death from cancer. The incidence rate of HCC varies considerably worldwide, with the highest incidence rates in East and Southeast Asia and Sub-Saharan Africa, and China alone accounted for approximately 55% of all HCC malignancies. Chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is the most important risk factor for development of HCC. Overall, 75%–80% of cases of HCC are attributable to persistent viral infections with either HBV (50%–55%) or HCV (25%–30%). It is estimated that 2 billion people have been infected with HBV, with an estimated 300 million persons with chronic infection worldwide. However, it also is known that only a minority of lifelong chronic carriers of HBV eventually will develop HCC, thus implicating the importance of cofactors (environmental or genetic) in HBV-related HCC.Cell-mediated immunity (CMI) is thought to play a critical role in viral clearance and disease pathogenesis during HBV infection. Interleukin-12 (IL12) is a heterodimeric pro-inflammatory cytokine formed by a 35-kDa light chain (known as p35 encoded by IL12A) and a 40-kDa heavy chain (known as p40 encoded by IL12B), which induces the production of interferon-gamma (IFN-γ), favors the differentiation of Th1 cells and forms a link between innate resistance and adaptive immunity. Studies showed that IL12 had a central role in Th1 responses. Besides the activity of antivirus, IL12 is also important for host resistance to tumors. The antitumor activity of IL12 has been extensively reported in mouse models of cancer, where it has been shown to inhibit tumorigenesis and induce regression of established tumors. The major antitumor activities of IL12 rely on its ability to promote Th1 adaptive immunity and CTL responses. Because of the functional relevance of IL12, several molecular epidemiological studies were performed to investigate the relationship between the IL12A and IL12B polymorphisms and risk of cancers, including Cervical Cancer, gastric cancer , lung cancer, non-Hodgkin lymphoma and others. Few studies evaluated IL12A and IL12B polymorphisms and risk of cervical cancer. The aim of this case-control study is to investigate the associations of IL12A and IL12B polymorphisms with HCC risk.In the present study, we searched all the common potentially functional SNPs in IL12A and IL12B. As a result, we selected three common SNPs, that is, rs2243115 (5'UTR T>G) and rs568408 (3'UTR G>A) in IL12A and rs3212227 (3'UTR A>C) in IL12B. This case-control study included 869 confirmed HCC patients and 891 cancer-free controls frequency-matched to the cases on age (±5 years), sex, and residential areas. We genotyped the three polymorphisms by PCR-RFLP (PCR- Restriction Fragment Length Polymorphism) and PCR-PIRA (PCR-Primer Introduced Restriction Analysis) method. In addition, genotyping was performed blindly and 10% of the samples were randomly selected for repeated assays.In this case-control study, we found that the IL12A rs568408 GA/AA variant genotypes were associated with a significantly increased risk of HCC [adjusted odds ratio (OR) =1.53, 95% confidence interval (CI) = 1.17-2.00], compared with the wild-type GG homozygote. In the stratified analyses, this increased risk associated with rs568408 GA/AA was more pronounced in patients who were negative for HBsAg (adjusted OR=1.71, 95% CI =1.23-2.39).Our findings indicate that IL12A rs568408 may contribute to the risk of HCC, and modify HCC risk associated with HBV infection. |
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