The −409 C/T Genotype of PRSS1 Protects Against Pancreatic Cancer in the Han Chinese Population

Abstract

The high mortality rate of pancreatic cancer is a bottleneck for further treatment with long-term efficacy. Thus, it is urgent to identify new methods to accurately predict the early onset of pancreatic cancer. We hypothesized that the different genotypes of cationic trypsinogen (PRSS1) gene could confer susceptibility and/or resistance to pancreatic cancer in the Han Chinese population. The genotypes of PRSS1 were determined in 154 patients with pancreatic cancer and in a control group of 520 healthy individuals of Han Chinese descent. Clinical information was obtained, single-nucleotide polymorphisms (SNPs) of the PRSS1 gene were analyzed by direct sequencing, and the distribution of the genotypes were tested for Hardy-Weinberg equilibrium. Odds ratios and 95% confidence intervals were calculated by logistic regression analysis to estimate the associations between the different genotypes or haplotypes and the risk of pancreatic cancer. Three SNPs (-409 C/T, -204 A/C, and c.486 C/T) were identified. A case-control analysis revealed a 0.118-fold (95% CI: 0.037-0.653), 0.842-fold (95% CI: 0.177-4.010), and 0.750-fold (95% CI: 0.519-1.085) change in risk of developing pancreatic cancer for individuals harboring these SNPs, respectively. The individuals with the -409 C/T genotype tended to have a reduced risk compared to those who carried the -409 T/T genotype. A protective effect was observed for the C(-409)-A(-204)-C(486) haplotype compared to the T(-409)-A(-204)-T(486) haplotype (OR = 0.115, 95% CI: 0.016-0.849) or compared to the T(-409)-A(-204)-C(486) haplotype (OR = 0.090, 95% CI: 0.012-0.667). Serum levels of trypsin in patients with the -409 C/T genotype were only one-fourth that of those with the -409 T/T genotype and only one-third that of the healthy controls. The -409 C/T genotype of PRSS1 was revealed to be a protective factor against pancreatic cancer in the Han Chinese population.