Combined effects of p53 and MDM2 polymorphisms on susceptibility and surgical prognosis in hepatitis B virus-related hepatocellular carcinoma

Abstract

The p53 signaling pathway works as a potent barrier to tumor progression. Two single nucleotide polymorphisms (SNPs) in the gene loci of p53 pathway, p53 codon 72 Arg72Pro and MDM2 SNP309 (T > G), have been shown to cause perturbation of p53 function, but the effect of the two SNPs on the risk of hepatocellular carcinoma (HCC) remains inconsistent. This study investigated the influence of combined p53 Arg72Pro and MDM2 SNP309 on the risk of developing HCC in patients with chronic hepatitis B virus infection, and evaluated the significance of the two combined SNPs on patient prognosis. In total, 350 HCC patients, 230 non-HCC patients, and 96 healthy controls were genotyped for the p53 Arg72Pro and MDM2 SNP309. The combined p53 Pro/Pro and MDM2 G/G genotype was significantly associated with HCC risk (P = 0.047). Multivariate analysis indicated that combined p53 Pro/Pro and MDM2 G/G genotype was an independent factor affecting recurrence and survival (P < 0.05). Patients with combined p53 Pro/Pro and MDM2 G/G genotypes had a poorer prognosis than other genotypes, P < 0.01 for both disease-free survival (DFS) and overall survival (OS). DFS and OS rates also differed significantly between Barcelona Clinic Liver Cancer (BCLC) stage A patients with combined p53 Pro/Pro and MDM2 G/G and other genotypes (P < 0.05). Thus, the combined p53 Pro/Pro and MDM2 G/G genotype is associated with increased risk of developing HCC and is an independent adverse prognostic indicator in early stage HCC.

ASSOCIATION BETWEEN MURINE DOUBLE MINUTE 2 - T309G polymorphism and recurrence of hepatocellular carcinoma after surgical treatment

“…Concerning the association between SNP309 and prognostic factors related to HCC after surgical treatment, current literature is scarce. A single study conducted by Yang et al in 2003 (26) contemplated this association and noticed patients presenting G/G genotype had disease-free survival and global survival similar to other genotypes.…”

p53 R72P Alone and in Combination with MDM2 SNP T309G is Associated with Colon Carcinoma Incidence and Survival

“…p53 is one of the most studied proteins that plays fundamental role in regulating basic cellular function and because of this, it is an important target protein to study different polymorphic variants of p53 for their association with various diseases including colon carcinomas [10,[12][13][14]27]. A SNP in MDM2 (SNPT309G), a negative regulator of p53, alone or in combination with p53 has been reported to associate with different carcinomas and progression of disease [14,18,22,23,25,[27][28][29][30]. Over the last decade, studies have reported the role of p53 R72P and MDM2 T309G polymorphisms as risk factor for colorectal carcinoma [14,15,19,[23][24][25].…”

The MDM2 polymorphism SNP309 is associated with clinical characteristics and outcome in diffuse large B‐cell lymphoma

“…The impact of the T to G polymorphism in MDM2 SNP309 on cancer prognosis has been investigated in several studies in recent years where the G allele in MDM2 SNP309 is found to significantly correlate with long‐term survival in pancreatic cancer , chronic lymphocytic leukemia and possible hepatocellular carcinoma among others . That other studies found a correlation between MDM2 SNP309 polymorphism and long‐term survival strengthen our findings that there may be a plausible impact of the MDM2 SNP309 polymorphism on DLBCL prognosis for some patients.…”