Evaluation of the Association between Programmed Cell Death-1 Gene Polymorphisms and Hepatocellular Carcinoma Susceptibility in Turkish Subjects. A Pilot Study

Abstract

Background and Aims: Programmed cell death-1 (PD-1) has a vital role in regulating T-cell function, and immune escape mechanism of cancer cells. It was shown that there could be a relationship between single nucleotide polymorphisms (SNPs) in the PD-1 gene and susceptibility to hepatocellular carcinoma (HCC) based on various studies. We aimed to investigate the role of three SNPs within the PD-1 gene in susceptibility to HCC in the Turkish population.
 Methods: Single nucleotide polymorphisms of PD-1.1, 1.5, and 1.6 were genotyped by using TaqMan Allelic Discrimination Assays in blood samples of 137 HCC and 136 control subjects, matched for age and gender. The genotype, allele and haplotype frequencies were compared in HCC and control groups using logistic regression analysis.
 Results: Genotype distributions of PD-1.1, PD-1.5 and PD-1.6 SNPs were in Hardy-Weinberg equilibrium. No significant difference was observed in the genotype distribution of PD-1.1, PD-1.5 and PD-1.6 polymorphisms among gender and age-matched HCC (M/F: 96/41; mean age: 61.4 ±11.7 years) and control group (M/F: 94/42; mean age: 61.4±10.1). In the haplotype analysis of PD-1.1/PD-1.5/PD-1.6, no significant difference was found among HCC and control group adjusted for sex and age (all p values>0.1).
 Conclusion: Our findings, firstly reporting the association of PD-1.5 polymorphism with HCC, and PD-1.1 and PD-1.6 with HCC in the Turkish population, suggest that PD-1 polymorphisms are not predisposing factors for HCC development. Future studies with larger sample sizes and different ethnic populations are required to validate our findings.

Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells

“…A study performed in 2015 also found no significant differences in the genotype distributions of PD-1 rs11568821 and rs41386439 in chronic HBV patients compared to the spontaneously recovered control group[ 138 ], indicating the possibility of lack of association between PD-1 gene polymorphisms and HBV infection susceptibility and HBV-related HCC progression in Turkish patients. These findings were confirmed in a more recent study investigating three PD-1 gene polymorphisms and HCC progression; again no significant distribution of rs36084323, rs2227981, and rs10204525 genotypes were observed in HCC cases in Turkish patients[ 139 ].…”

Evaluation of the possible association of PDCD-1 and LAG3 gene polymorphisms with hepatocellular carcinoma risk

“…Another research has previously reported PDCD-1 rs10204525 C > T SNP acquired significance after adjusting for other risks, being most notable in the smaller numbers of women with NAFLD-HCC in Caucasian patients [ 22 ]. Contrary to these studies, the rs10204525 SNP was found to have an insignificant role in patients with HCV-related hepatic disorders (chronic infection, cirrhosis, and HCC) in the Italian cohort [ 23 ] and was not a predisposing factor for HCC development in the Turkish population [ 11 ]. In the present study, our results also demonstrated no association between rs10204525 T > C and HCC risk, which was consistent with De Re V’s study in the Italian cohort and Demirci AF’s study in the Turkish population [ 11 , 23 ].…”

“…Contrary to these studies, the rs10204525 SNP was found to have an insignificant role in patients with HCV-related hepatic disorders (chronic infection, cirrhosis, and HCC) in the Italian cohort [ 23 ] and was not a predisposing factor for HCC development in the Turkish population [ 11 ]. In the present study, our results also demonstrated no association between rs10204525 T > C and HCC risk, which was consistent with De Re V’s study in the Italian cohort and Demirci AF’s study in the Turkish population [ 11 , 23 ]. Although the allele distribution of the PDCD-1 rs10204525 genotype in the control group in this study was not similar to the distribution of the previously studied Northwest China and other population, it had no differences with the distribution of CDX and KHV populations ( http://asia.ensembl.org/Homo_sapiens/Variation/Population?db=core;v=rs10204525;vdb=variation , P = 0.89 and P = 0.78, respectively).…”

“…The rs36084323 is located at -606 base pairs upstream of the promoter region at position 242801596 and the rs10204525 G/A (C/T, PDCD-1.6) is located at + 8669 base pairs in the 3’ UTR at position 241,850,169. The relationship between the two SNP and susceptibility to HCC has been reported in several studies [ 8 – 11 ]. However, these conclusions are not always consistent.…”

“…The SNPs of rs36084323 and rs10204525 were significantly associated with HBV-related cirrhosis and HCC in Chinese Han individuals [ 8 – 10 ]. But no significant association was observed in the gene polymorphisms of rs36084323 and rs10204525 with HCC in the Turkish population [ 11 ]. It suggested that ethnicity might play a role in the observed frequencies of PDCD-1 polymorphisms in relation to HCC susceptibility.…”