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Background. The chromobox (CBX) proteins CBX2, CBX4, CBX6, CBX7, and CBX8, also known as Polycomb (Pc) proteins, are canonical components of the Polycomb repressive complex 1 (PRC1). Abundant evidence indicates that abnormal expression of Pc proteins is associated with a variety of tumors, but their role in the pathogenesis of hepatocellular carcinoma (HCC) has not been fully elucidated. In the present study, we performed a case-control study to investigate the relationship between single nucleotide polymorphisms (SNPs) of CBX genes and HCC. Methods. Nine SNPs on CBX genes (rs7217395, rs2036316 of CBX2; rs3764374, rs1285251, rs2289728 of CBX4; rs7292074 of CBX6; and rs710190, rs139394, rs5750753 of CBX7) were screened and genotyped using MassARRAY technology in 334 HCC cases and 321 controls. The association between SNPs and their corresponding gene expressions was analyzed through bioinformatics methods using the Ensembl database and Blood eQTL browser online tools. Results. The results indicated that rs2289728 (G>A) of CBX4 (P = 0.03, OR = 0.56, 95% CI: 0.33-0.94) and rs139394 (C>A) of CBX7 (P = 0.02, OR = 0.55, 95% CI: 0.33-0.90) decreased the risk of HCC. Interaction between rs2036316 and HBsAg increased the risk of HCC (P = 0.02, OR = 6.88, 95% CI: 5.20-9.11), whereas SNP-SNP interaction between rs710190 and rs139394 reduced the risk of HCC (P = 0.03, OR = 0.33, 95% CI: 0.12-0.91). Gene expression analyses showed that the rs2289728 A allele and the rs139394 A allele significantly reduced CBX4 and CBX7 expression, respectively. Conclusion. Our findings suggest that CBX4 rs2289728 and CBX7 rs139394 are protective SNPs against HCC. The two SNPs may reduce the risk of HCC while suppressing the expression of CBX4 and CBX7. [ABSTRACT FROM AUTHOR]

Polymorphisms in genes may affect its expression and alter individual susceptibility to cancer. In this study, we investigate associations between CMTM family gene polymorphisms and hepatocellular carcinoma (HCC) in a southern Chinese population. Ten selected single-nucleotide polymorphisms (SNPs) in CMTM family genes were genotyped in 315 HCC patients and 315 cancer-free controls using Sequenom MassARRAY platform and the associations of the selected SNPs with HCC risk were evaluated. We found individuals with the rs164207 AA genotypes had a significantly increased risk of HCC than those with CC genotypes (adjusted OR = 2.794, 95% CI = 1.143–6.828). Also, individuals with the rs3811178 GG genotypes showed a significant association with increased risk of HCC when compared with the AA genotypes (adjusted OR = 2.578, 95% CI = 1.114–5.969). Furthermore, there was also a significantly increased risk of HCC when combined risk genotypes of these loci, i.e., rs164207 AA, CA and rs3811178 GG, GA. Compared with the low-risk group (0 risk genotypes), the high-risk group (2 risk genotypes) was at significantly increased risk of HCC (adjusted OR = 3.339, 95% CI = 1.119–9.964, p = 0.031). Our results suggest that polymorphisms of rs3811178 in CMTM5 and rs164207 in CMTM6 might contribute to the genetic susceptibility of HCC in the southern Chinese population. Further well-designed studies with larger sample sizes are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

The defects of DNA repair genes may lead to genomic instability and cancer. As an important DNA mismatch repair gene that maintains genomic stability from DNA replication errors, genetic variants of mutS homolog 2 (MSH2) are associated with some cancers. In this study, 1021 hepatocellular carcinoma (HCC) cases and 1021 non-HCC controls from Guangxi were included to explore the association between MSH2 single-nucleotide polymorphisms (SNPs) and HCC. Among the eight MSH2 SNPs, only genotype distribution of rs2303428 was significantly different from HCC and non-HCC patients ( p < 0.05). Moreover, CT, TT, and CT/TT genotype of rs2303428 could increase HCC risk [OR (95% CI) = 1.758 (1.195-2.657), 1.846 (1.213-2.896), and 1.823 (1.219-2.763), respectively] and decrease the survival time of HCC patients [codominant, HR (95% CI) = 1.267 (1.046-1.535); dominant, HR (95% CI) = 1.675 (1.162-2.414)]. In addition, rs2303428 was found to interact with HBV infection and family history to increase HCC risk by gene-environment analysis ( p < 0.05). Finally, multivariate COX regression analysis showed that rs2303428, tumor number, tumor staging, and metastasis had a significant influence on HCC prognosis. Our results provide MSH2 SNP, rs2303428, as a new prognostic biomarker for HCC patients. [ABSTRACT FROM AUTHOR]

The forkhead box O (FOXO) transcription factors play important roles in various cancer development including Hepatocellular Carcinoma (HCC). In this study we conducted a hospital-based case control study including 1049 cases (HCC patients) and 1052 controls (non-tumor patients) to examine whether single nucleotide polymorphisms (SNPs) within microRNA (miRNA) target sites of FOXO genes confer HCC susceptibility. A total of three miRNA target site SNPs in the 3’ untranslated regions (UTR) of FOXO1 (rs17592236), FOXO3 (rs4946936) and FOXO4 (rs4503258) were analyzed. No statistically significant differences were found in genotype distribution for rs17592236, rs4946936, and rs4503258 between the HCC patient group and the tumor-free control group using single factor chi-square analysis (P>0.05). However, multivariate logistic regression analysis showed that the CT/TT genotype in rs17592236 was significantly associated with decreased risk of HCC development (P = 0.010, OR = 0.699, 95% CI: 0.526–0.927) as compared to the CC genotype in rs17592236. Additionally, a genetic interaction was found between rs17592236 and rs4503258 (P = 0.003, OR = 0.755, 95% CI: 0.628–0.908). Functional dual luciferase reporter assays verified that the rs17592236 SNP was a target site of human miRNA miR-137. Together, these results indicate that the rs17592236 polymorphism is associated with decreasing of HCC hereditary susceptibility likely through modulating the binding affinity of miR-137 to the 3’UTR in FOXO1 messenger RNA (mRNA). Further knowledge obtained from this study may provide important evidence for the prevention and targeted therapy of HCC. [ABSTRACT FROM AUTHOR]