Association of TP53 gene codon 72 polymorphism with Helicobacter pylori-positive non-cardia gastric cancer in Vietnam

Introduction: This research aimed to determine the association of the combination of H. pylori infection and TP53 codon 72 polymorphism with non-cardia gastric cancer (GC) in Vietnam. Methodology: A total of 164 patients with non-cardia GC and 164 patients with peptic ulcer disease or functional dyspepsia in controls matched by sex and age were enrolled. H. pylori infection was diagnosed by rapid urease test and polymerase chain reaction (PCR). The cagA gene-positivity and vacA sm subtypes were determined by multiplex PCR. Genotypes of TP53 codon 72 polymorphism were determined by PCR-restriction fragment length polymorphism. Results: The prevalence of H. pylori infection in GC and control group were 61.6% and 55.4%, respectively. The rates of cagA-positive strains in the two H. pylori-positive groups were 80.2% and 71.4%, respectively. There was no statistically significant difference in TP53 codon 72 genotype distribution between GC group (frequencies of Arg/Arg, Arg/Pro and Pro/Pro genotypes were 31.1%, 43.3% and 25.6%, respectively) and controls (29.3%, 52.4% and 18.3%, respectively), p = 0.172. The significant difference in genotype distribution was observed in recessive model (Pro/Pro vs Arg/Arg + Arg/Pro) when stratifying by H. pylori infection (OR = 2.02, 95% CI 1.03–3.96, p = 0.041) and by cagA-positivity (OR = 2.33, 95% CI 1.07–5.07, p = 0.032). Conclusions: This study suggests a synergistic interaction between H. pylori infection, especially cagA-positive H. pylori, and Pro/Pro genotype of TP53 codon 72 polymorphism might play a significant role in the pathogenesis of GC in the Vietnamese population.

Recurrence risk evaluation in stage IB gastric cancer with TP53 codon 72 polymorphism.

4044 Background: Post-operative adjuvant chemotherapy is not currently indicated for Stage IB gastric cancer. However, about 10% of these patients experience recurrence and metastasis. Our previous study on a panel of gastric cancer cell lines indicated that TP53 codon 72 polymorphisms may affect the degree of biological malignancy. Hence, we hypothesized that the TP53 codon 72 polymorphisms may have been associated with post-operative survival without adjuvant chemotherapy. In this study, we investigated the risk of recurrence after treatment of Stage IB gastric cancer patients carrying the TP53 codon 72 polymorphism and attempted to identify a subpopulation that should receive post-operative adjuvant chemotherapy. Methods: Among 658 gastric cancer patients who received gastrectomy with curative-intent, 130 Stage IB patients were enrolled in the present study. The TP53 codon 72 polymorphisms of formalin-fixed paraffin-embedded cancer tissue sections were assessed by direct sequencing using originally designed primers. Overall survival rate (OS) and relapse-free survival rate (RFS) were analyzed based on the status of TP53 codon 72 polymorphism "Arg/Arg", "Arg/Pro" and "Pro/Pro". The hazard ratio for each subgroup was compared by TP53 codon 72 polymorphism. All interaction p values were calculated using the likelihood test. Results: Of the 125 patients for whom polymorphism analysis results were available, the 5- and 10-year OS was 84.5% and 63.9%, respectively. The 5- and 10-year RFS was 82.2% and 64.3%, respectively. When the study cohort was divided into two groups according to polymorphism status (i.e., Arg/Arg and Arg/Pro vs. Pro/Pro), both the OS (hazard ratio [HR], 1.968; 95% confidence interval [CI], 0.770-7.430, p = 0.045) and RFS (HR, 1.976; 95% CI, 0.778-7.515, p = 0.033) of the Pro/Pro group across the entire observation period were significantly lower than those for the Arg/Arg and Arg/Pro group. The majority of recurrences in Pro/Pro occurred within three years from the operation. Conclusions: Among Stage IB gastric cancer patients that underwent gastrectomy with curative-intent, post-operative adjuvant chemotherapy may be considered immediately after surgery for patients carrying the TP53 codon 72 Pro/Pro polymorphism.