Back to Search
Start Over
Influence of CCND1 G870A polymorphism on the risk of HBV-related HCC and cyclin D1 splicing variant expression in Chinese population
- Source :
- Tumour Biology
- Publisher :
- Springer Nature
-
Abstract
- The G870A polymorphism in the exon 4/intron 4 boundary of CCND1 gene is thought to influence the generation of two mRNAs (cyclin D1a and cyclin D1b). The “A” allele codes for a truncated variant, cyclin D1b, which may have higher transforming activity. Herein, the tumor relevance of G870A polymorphism, the association between cyclin D1 variant expression and G870A genotype, and the oncogenic potential of cyclin D1 variants in HBV-related hepatocellular carcinoma (HCC) were examined. We found that there is no significant difference of G870A distribution among the HCC, chronic HBV (CHB) infection, cirrhotic CHB, and healthy control groups. Stratification analysis revealed that in younger patients (ages ≤ 50), cirrhotic CHB patients with AA genotype had an increased risk of developing HCC with odds ratio of 1.943 (95 % CI 1.022–3.694, p = 0.0411) as compared with AG/GG genotypes. The two variants were both transcripted from “A” and “G” alleles, and neither cyclin D1a nor D1b production was influenced by G870A genotype in HCC. The expression of both cyclins D1a and D1b decreased in HCC tissues (p = 0.003, p = 0.005), while increased in adjacent nontumor tissues as compared with normal liver tissues (p = 0.045, p = 0.034). Overexpression of cyclin D1a or D1b could promote the cell proliferation and cell-cycle progression in Huh-7 and LO2 cell lines. Collectively, our data suggest that G870A polymorphism has only very limited predictive value for HBV-related HCC. Both cyclins D1a and D1b could promote cell proliferation, which might contribute to the potential oncogenic role of cyclin D1 variants during the precancerous cirrhotic stage of hepatocarcinogenesis. Electronic supplementary material The online version of this article (doi:10.1007/s13277-015-3401-7) contains supplementary material, which is available to authorized users.
- Subjects :
- Adult
Male
Hepatitis B virus
Cancer Research
Carcinoma, Hepatocellular
Genotype
Biology
medicine.disease_cause
Polymorphism, Single Nucleotide
Splicing variant
Exon
Cyclin D1
Asian People
Polymorphism (computer science)
medicine
Humans
Genetic Predisposition to Disease
Polymorphism
HCC
Allele
Genetic Association Studies
Cyclin
Liver Neoplasms
General Medicine
Middle Aged
medicine.disease
digestive system diseases
Alternative Splicing
Hepatocellular carcinoma
Cancer research
Female
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 10104283
- Volume :
- 36
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Tumor Biology
- Accession number :
- edsair.doi.dedup.....166945b407cd19fda407fa18ad38fb5f
- Full Text :
- https://doi.org/10.1007/s13277-015-3401-7