Study of p53 gene polymorphism and risk of hepatocellular carcinoma: in a Bangladeshi cohort

Abstract

Hepatocellular carcinoma (HCC) is the number one malignancy of the liver, the 5th leading cancer death throughout the world. Most liver cancers are related to gene polymorphism, specifically the p53 tumor suppressor gene (TP53). The study aims to investigate the association of TP53 gene polymorphism with the risk of liver cancer in the Bangladeshi cohort. It was a case-control study with 119 HCC patients and 150 healthy controls. The genetic polymorphism of TP53 was determined by polymerase chain reaction- based restriction fragment length polymorphism (PCR-RFLP) method using restriction enzyme digestion with BustUI for exon 4 and HaeIII for exon 7. Appropriate statistical analysis was performed to determine the association of genotypes with gender, smoking status, tumor stage, tumor grade, and family history of cancer. The demographic data showed a significant difference between the age of HCC and control subjects (49.8±1.2 and 35.8±1.1, respectively). Among the patients, males were much higher than females (83.2% vs 16.8% respectively). Smoking status was significantly higher in the HCC group than in the control group. In contrast, there was no significant difference in the family history of cancer and alcohol consumption between the two groups. Among the hepatocellular carcinoma subjects (n=119), the homozygous wild type was 20.17%, the homozygous mutant was 49.58%, and the heterozygous mutant was 30.25% at codon 72 in exon 4. Homozygous mutant variants (CC) and heterozygous mutant (GC) of TP53 at 72 position were substantially related to liver cancer risk when compared with the controls (OR=0.17; 95% CI=0.09-0.31; p<0.001 and OR =0.11; 95% CI =0.06-0.23; p<0.001) considering GG as reference group. On the other hand, at codon 249 in exon 7 genotype, the homozygous wild type was 48.74%, the heterozygous mutant was 42.86 %, and the homozygous mutant was 8.40%. Heterozygous mutant (GT) of TP53 at 249 positions were significantly associated with liver cancer risk when compared with the controls (OR=0.19; 95% CI=0.10-0.35; p<0.001), whereas no association was found with homozygous mutant variants (TT) (OR=0.43; 95% CI=0.18-1.17; p=0.124) when GG was considered as the reference group. TP53 genome analysis of exon 4, an association of CC and GC variation with the risk of cancer was found when GG genotype was considered as a reference group. On the other hand, the TP53 genome analysis of exon 7, GT, and TT variants was significantly associated with male cancer patients. The genetic linkage evaluation of the TP53 gene (exon 4 and exon 7) suggested that polymorphism of G to C and G to T showed a high risk for HCC in the study subjects. Therefore, this study can conclude that TP53 gene polymorphisms are highly associated with hepatocellular carcinoma in the Bangladeshi cohort.