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Association of interleukin-6 polymorphisms with susceptibility to hepatocellular carcinoma.

ABSTRACT: TARGET:Our study was to investigate the effects of interleukin-6 (IL-6) polymorphisms (rs2069837 and rs17147230) on the risk for hepatocellular carcinoma (HCC). METHODS:A total of 226 HCC cases and 220 healthy controls were admitted into the study and genomic DNA was extracted from the peripheral blood. The genotyping was conducted by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the relationship of IL-6 rs2069837 and rs17147230 polymorphisms with HCC susceptibility. RESULTS:The frequency of GG genotype of rs2069837 was higher in HCC patients, compared with controls (P < 0.05). Moreover, the results indicated that GG genotype was related with increased risk for HCC (OR = 2.303, 95% CI = 1.056-5.025). Similarly, the risk for G allele carriers was higher than that of A allele (OR = 1.392, 95% CI = 1.046-1.852). For rs17147230, TT genotype showed strong effect on HCC susceptibility (OR = 2.089, 95% CI = 1.135-3.845) and T allele appeared to be a risk factor for HCC (OR = 1.326, 95% CI = 1.010-1.740). Further analysis showed that G-T haplotype was associated with increased risk for HCC (OR = 3.125, 95% CI = 1.845-5.294, P = 0.000). CONCLUSION:IL-6 rs2069837 as well as rs17147230 were associated with HCC susceptibility. In addition, G-T haplotype also served as a genetic-susceptibility factor for HCC.

SUBMITTER: Zheng X

PROVIDER: S-EPMC4483998 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: Inflammation is a response of body tissues to injury or irritation. Small RNAs, such as miR-146a and miR-499, participate in various processes of tumorigenesis. A recent study indicates that inflammation and abnormal immune responses may promote malignant progression in cancer development, indicating that inflammation-related polymorphisms such as miR-146a rs2910164 and miR-499 rs3746444 are crucial. However, studies on the association of these two polymorphisms with hepatocellular carcinoma (HCC) are inconclusive and inconsistent. We aimed at accessing the combined result of reported studies and make a more precise estimate of the relationship. METHODS: Meta-analysis was performed on the associations between the miR-146a rs2910164 C?>?G and miR-499 rs3746444 T?>?C polymorphisms and hepatocellular carcinoma, using: allele contrast, dominant, and recessive models. A total of 12 studies(8 on miR-146a rs2910164 and 4 on miR-499 rs3746444) with three populations (Chinese, Korean, Turkish) were included in this study. RESULTS: Results show that both allele frequency and genotype distributions of miR-146a rs2910164 polymorphism are significantly associated with susceptibility to HCC (G versus C: OR?=?1.153, 95% CI 1.083-1.228, P?<?0.001; GC versus CC: OR?=?1.165, 95% CI 1.054-1.286, P?=?0.003; GG versus CC: OR?=?1.361, 95% CI 1.192-1.553, P?<?0.001; GG/GC versus CC: OR?=?1.213, 95% CI 1.104-1.333, P?<?0.001; GG versus GC/CC: OR?=?1.210, 95% CI 1.080-1.356, P?<?0.001). Our data suggest that people with G allele have a higher susceptibility to HCC as compared to those with C allele. However, meta-analysis failed to detect associations between miR-499 rs3746444 and HCC risk under each genetic model tested. Subgroup analysis showed that Chinese population with CC genotype are more vulnerable to HCC (OR?=?2.171, 95% CI?=?1.149-4.104, P?=?0.017) than those with TT genotype. CONCLUSIONS: We conclude that rs2910164 in miR-146a may confer susceptibility to HCC, especially in the Chinese population. No significant association was found between miR-499 rs3746444 and HCC, but subgroup study showed that subjects with CC genotype are more vulnerable to HCC than TT genotype in the Chinese population.

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Association of interleukin-6 polymorphisms with susceptibility to hepatocellular carcinoma.

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