Influence of CCND1 G870A polymorphism on the risk of HBV infection related HCC and cyclin D1 splicin

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  Background Cyclin D1 is encoded by CCND1 gene which generates 2 alternative splice variants (D1a and D1b).A common polymorphism (G870A) is thought to influence the splicing of CCND1 which has been reported to associate with variety of human malignancies.Herein, we examined the association between CCND1 polymorphism, variant expression and HCC risk in a Chinese population.Methods The CCND1 G870A genotype was determined by Taqman SNP genotyping assay and the impact of this polymorphism on HBV infection related HCC risk was assessed in a large case-control study.The relative expression of both cyclin D1 variants was detected by real-time qRT-PCR and demonstrated by westem blot.Results After adjusting for age and gender, the genotype and allele distribution showed no significant difference among the HBV infection related HCC, chronic hepatitis B virus infection (CHB), cirrhotic CHB and healthy control groups.Stratification analysis revealed that compared with the combined AG/GG variant genotypes, cirrhotic CHB patients with the AA genotype had 1.943-fold odds of developing HCC (P =0.0411).Compared to non-tumor tissues, the expression levels of cyclin D 1 a and D 1 b were significantly decreased in tumor tissues (P =0.004 andP =0.001, respectively).Unexpectedly, neither cyclin D1a nor D1b production was influenced by G870A genotype in HCC tissues.Conclusion Our results suggest that CCND1 G870A polymorphism is not a strong predictor of the HBV-related HCC risk in Chinese population.Both cyclin D1 variants are decreased in HCC tissues with a similar expression profile independent of influence of A allele.
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