title: The contribution of caveolin-1 genotype and phenotype to hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors worldwide, for which the prevalence and mortality rates are very high in Taiwan. Caveolin-1 (CAV-1) is a main structural protein of caveolae and plays a regulatory role in signaling pathways and tumorigenesis. High expression of Cav-1 in mouse HCC is positively correlated with higher cell invasive capacity, but the contribution of CAV-1 genetic variants during HCC progression is still largely unknown. In this study, we investigated the contribution of CAV-1 variant to the risk of HCC from the analyses of DNA, RNA and proteins.
  
  
  METHODS
  We enrolled 298 patients with HCC and 298 cancer-free controls, frequency-matched by age and gender in this case-control study. Firstly, the associations of six single nucleotide polymorphisms (SNPs) of the Cav-1 gene at C521A (rs1997623), G14713A (rs3807987), G21985A (12672038), T28608A (rs3757733), T29107A (rs7804372), and G32124A (rs3807992) with HCC risk in a Taiwanese population were evaluated. Secondly, thirty HCC tissue samples with variant genotypes were tested to estimate for CAV-1 mRNA expression by real-time quantitative reverse transcription. Finally, the HCC tissue samples of variant genotypes were examined by western blotting to estimate their CAV-1 protein expression patterns.
  
  
  RESULTS
  There were significant differences between the HCC and control groups in the distributions of the CAV-1 G14713A genotypes (p=0.0124), and these carrying AG and AA genotypes had a higher risk for HCC, compared with those with the GG genotype (odds ratio=1.51 and 1.94, respectively). Patients with CAV-1 G14713A AG or AA genotype had higher levels of mRNA (p=0.0001) and protein (p=0.0019) than those with the GG genotype.
  
  
  CONCLUSIONS
  Our multi-approach findings at the DNA, RNA and protein levels suggest that CAV-1 may play a critical role in HCC carcinogenesis, and serve as a target for HCC therapy.
authors: Department of Medical Research, Terry Fox Cancer Research Lab, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404 Taiwan.
authors: Chin-Mu
authors: CM
authors: Hsu
authors: Mei-Due
authors: MD
authors: Yang
authors: Chia-Wen
authors: CW
authors: Tsai
authors: Chien-Yi
authors: CY
authors: Ho
authors: Wen-Shin
authors: WS
authors: Chang
authors: Sheng-Chi
authors: SC
authors: Chang
authors: Long-Bin
authors: LB
authors: Jeng
authors: Yuhsin
authors: Y
authors: Tsai
authors: Fuu-Jen
authors: FJ
authors: Tsai
authors: Da-Tian
authors: DT
authors: Bau
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D051242:Caveolin 1