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 50 years 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.

A Guide to PIN1 Function and Mutations Across Cancers

“…Carriers of the −842C variant in the PIN1 promoter have low PIN1 protein levels and low risk for developing cancer (Li et al, 2013). Contrasting evidence has been reported for the −667C variant in the PIN1 promoter, which was found to associate with a low risk of developing nasopharyngeal carcinoma (Li et al, 2013), but a high risk for oral squamous cell carcinoma and HCC (Yao et al, 2014; Huang et al, 2016).…”

“…Finally, the synonymous change Gln33Gln was not found to associate with the risk of breast cancer (Han et al, 2010), or squamous cell carcinoma of the head and neck (Lu et al, 2009). However, a higher risk of HCC was found among carriers of the Gln33Gln variant in a Chinese population (Huang et al, 2016).…”

“…However, it is still not fully understood how this enzyme participates in cancer development and progression. Several studies showed that some single nucleotide polymorphisms (SNPs) in PIN1 gene increase the risk of cancer whereas other variants operate as protective factors (Segat et al, 2007; Lu et al, 2009; Han et al, 2010; Li et al, 2013; Huang et al, 2016). Little has been reported so far about PIN1 somatic mutations and cancer.…”

Chemical or genetic Pin1 inhibition exerts potent anticancer activity against hepatocellular carcinoma by blocking multiple cancer-driving pathways

“…Pin1 might play different roles in HCC cells depending on status of TP53 gene mutation42. Pin1 single nucleotide promoter and exon polymorphisms are associated with the susceptibility of HBV-related HCC43. Interestingly, Pin1 also physically interacts with and increases hepatitis B virus X-protein (HBx) protein stability to enhance hepatocarcinogenesis44.…”

The association between PIN1 genetic polymorphisms and the risk of chronic hepatitis B and hepatitis B virus-related liver cirrhosis

“…[12–15] Interestingly, we recently found that PIN1 genetic polymorphisms might affect the occurrence and development progress of HBV-related HCC in Guangxi. [13] Nonetheless, so far, no research has been carried out on the role of PIN1 genetic polymorphisms in CHB and LC susceptibility. Therefore, we further examined whether the PIN1 promoter single-nucleotide polymorphisms (SNPs) (842G>C, rs2233678 and 667T>C, rs2233679) and the exon 2 synonymous SNP (Gln33Gln, G>A, rs2233682) influence one's susceptibility to CHB and HBV-related LC in a Guangxi population.…”