title: Influence of CCND1 G870A polymorphism on the risk of HBV-related HCC and cyclin D1 splicing variant expression in Chinese population.
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.
authors: Department of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors: Zhenzhen
authors: Z
authors: Zeng
authors: Department of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors: Jing
authors: J
authors: Tu
authors: Department of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors: Jin
authors: J
authors: Cheng
authors: Department of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors: Mingjie
authors: M
authors: Yao
authors: Department of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors: Yali
authors: Y
authors: Wu
authors: Department of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors: Xiangbo
authors: X
authors: Huang
authors: Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, China.
authors: Xiaomeng
authors: X
authors: Xie
authors: Department of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors: Xiaolei
authors: X
authors: Zhang
authors: Department of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors: Fengmin
authors: F
authors: Lu
authors: Department of Microbiology and Infectious Disease Center, School of Basic Medical Science, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. xm_chen6176@bjmu.edu.cn.
authors: Xiangmei
authors: X
authors: Chen
mesh_terms: D000328:Adult; D017398:Alternative Splicing / Q000235:genetics; D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006515:Hepatitis B virus / Q000472:pathogenicity; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C530104:CCND1 protein, human; D019938:Cyclin D1
keywords: Cyclin D1; HCC; Hepatitis B virus; Polymorphism; Splicing variant