# Association of p53 Pro72Arg Polymorphism with Hepatocellular Carcinoma Risk in Hepatitis B Across Multiethnic Populations

## TL;DR

This study examines how a genetic variation in the p53 gene affects liver cancer risk in hepatitis B patients from Indonesia, finding ethnic and clinical subgroup differences.

## Contribution

The study identifies ethnic-specific and clinical subgroup associations of the p53 Pro72Arg polymorphism with hepatocellular carcinoma in a multiethnic Indonesian population.

## Key findings

- No overall association between p53 Pro72Arg and HCC risk was found in the general population.
- Madurese patients with Pro/Arg or Arg/Arg genotypes showed increased HCC susceptibility.
- Pro/Arg carriers with decompensated cirrhosis were more likely to develop HCC.

## Abstract

Hepatocellular carcinoma (HCC) is a complex, multistage disease influenced by viral and genetic factors. The tumor suppressor p53 gene, located on chromosome 17p13.1, plays a central role in genome protection through cell cycle arrest, apoptosis, senescence, and Deoxyribonucleic Acid (DNA) repair. A common single-nucleotide polymorphism at codon 72 (Pro72Arg, rs1042522) alters p53 function, with the arginine variant favoring apoptosis and the proline variant enhancing cell cycle arrest. To investigate its role in the diverse multiethnic population of Indonesia, we analyzed Pro72Arg polymorphism on 140 Chronic Hepatitis B (CHB) patients (79 with HCC, 61 controls) by direct DNA sequencing. Genotype frequencies were 12.9% Pro/Pro, 31.4% Arg/Arg, and 55.7% Pro/Arg. No overall association with HCC risk was observed; however, Madurese patients carrying Pro/Arg or Arg/Arg genotypes showed increased susceptibility, and Pro/Arg carriers with decompensated cirrhosis were more likely to develop HCC. These findings highlight ethnic and clinical subgroups where p53 Pro72Arg may contribute to hepatocarcinogenesis.

Introduction: Mounting evidence indicates that the p53 Pro72Arg single-nucleotide polymorphisms (SNPs) may play a role in modulating hepatocarcinogenesis in the setting of chronic HBV infection. However, there is currently a lack of studies focusing on this genetic variant in Indonesia, a country characterized by its diverse genetic landscape comprising over 1300 distinct ethnic groups. We aimed to investigate the association between the p53 Pro72Arg polymorphism and the risk of hepatocellular carcinoma (HCC) among Indonesian patients with chronic HBV infection. Methods: A total of 140 patients with chronic hepatitis B (CHB) were recruited, including 79 with HCC and 61 without HCC serving as controls. We used direct sequencing of DNA extracted from peripheral blood to analyze the SNPs of p53 codon 72. Results: The distribution of p53 Pro72Arg genotypes among Indonesian CHB patients was 12.9% for proline homozygotes (Pro/Pro), 31.4% for arginine homozygotes (Arg/Arg), and 55.7% for proline/arginine heterozygotes (Pro/Arg). Despite the lack of association between the SNPs and HCC risk in the overall population, both the Pro/Arg and Arg/Arg genotypes demonstrate an increased susceptibility to HCC compared to Pro/Pro genotypes exclusively in the Madurese ethnic group. Additionally, we discovered that in those with decompensated cirrhosis, the heterozygote Pro/Arg was more likely to develop HCC than the homozygous Pro/Pro. No significant association was found between the SNPs of p53 Pro72Arg and the clinicopathological characteristics of HCC. Conclusions: The p53 Pro72Arg polymorphism might contribute to hepatocarcinogenesis in Indonesian chronic hepatitis B patients, particularly Madurese and those with liver decompensation.