BACKGROUND: Hepatocellular carcinoma (HCC) is a neoplasm for which the 
prevalence and mortality rates are very high in Taiwan. The DNA non-homologous 
end-joining repair gene XRCC6/Ku70 plays an important role in the repair of DNA 
double-strand breaks (DSBs) induced by both exogenous and endogenous 
DNA-damaging agents. Defects in overall DSB repair capacity can lead to genomic 
instability and carcinogenesis. In this study, we investigated the contribution 
of variant XRCC6 in relation to the risk of HCC, from the levels of DNA, RNA and 
protein.
MATERIALS AND METHODS: In this hospital-based case-control study, we collected 
298 patients with HCC and 298 cancer-free controls, with frequency matched by 
age and gender. Firstly, the associations of XRCC6 promoter T-991C (rs5751129), 
promoter G-57C (rs2267437), promoter A-31G (rs132770), and intron-3 (rs132774) 
polymorphisms with HCC risk in this Taiwanese population were evaluated. 
Secondly, 30 HCC tissue samples with variant genotypes were tested to estimate 
the XRCC6 mRNA expression by real-time quantitative reverse transcription. 
Finally, the HCC tissue samples of variant genotypes were examined by 
immunohistochemistry and western blotting to estimate their XRCC6 protein 
expression levels.
RESULTS: Compared with the TT genotype, the TC and CC genotypes conferred a 
significantly increased risk of HCC [adjusted odds ratio (aOR)=2.43 and 3.52, 
95% confidence interval (CI)=1.52-4.03 and 1.18-13.36, p=0.0003 and 0.0385, 
respectively]. The mRNA and protein expression levels in HCC tissues revealed 
statistically significantly lower XRCC6 mRNA and protein expressions in the HCC 
samples with TC/CC genotypes compared with those with the TT genotype (p=0.0037 
and 0.0003, respectively).
CONCLUSION: Our multi-approach findings at the DNA, RNA and protein levels 
suggested that XRCC6 may play an important role in HCC carcinogenesis in the 
Taiwanese population.