PIN1 genetic polymorphisms and the susceptibility of HBV-related hepatocellular carcinoma in a Guangxi population.

Abstract

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) plays a critical role in different signaling pathways, cell cycle progression and proliferation, and gene expression, and it has been found to overexpress in many tumor tissues. Recently, researchers have found that PIN1 gene polymorphisms may alter the function of protein and be associated with the risk of cancer. The present study analyzed three common polymorphisms in promoter regions (rs2233678 and rs2233679) and in exon2 (rs2233682) of the PIN1 gene in 254 patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and 235 healthy controls in a Guangxi study population to determine whether any relationship exists between the polymorphisms and the risk of HBV-related HCC. The results revealed that the rs2233679 TT genotype was associated with increased risk of HCC with HBV infection [odds ratio (OR) = 2.04, 95% confidence interval (95% CI) = 1.13-3.69, p = 0.019]. This association was stronger in men than in women (OR = 2.17, 95% CI = 1.09-4.34, p = 0.028) as well as in men 50years of age and older (OR = 3.91, 95% CI = 1.29-11.80, p = 0.016); moreover, for alcohol drinkers, being a carrier of the PIN1 rs2233679 CT genotype had a moderately increased risk of HCC (OR = 3.98, 95% CI = 1.02-15.57, p = 0.047). In contrast, people carrying the rs2233682 GA genotype and A alleles were 0.23 times more likely to develop HCC (OR = 0.23, 95% CI = 0.06-0.87, p = 0.031 and OR = 0.23, 95% CI = 0.06-0.87, p = 0.030). No such associations were found in the PIN1 rs2233678 polymorphisms between the HBV-related HCC cases and the controls. In addition, the haplotype GCA was found to be a high protection factor for HCC with HBV infection (OR = 0.14, 95% CI = 0.03-0.62, p = 0.003). In conclusion, this study's findings suggest that the PIN1 rs2233679 TT genotype, the rs2233682GA genotype, and A alleles might be associated with the HBV-related HCC in a Guangxi study population.