Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
Dig Dis Sci. 2012 Feb;57(2):573-9. doi: 10.1007/s10620-011-1893-6. Epub 2011 Sep 16.
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.
胰腺癌的高死亡率是进一步治疗和长期疗效的一个瓶颈。因此，迫切需要寻找新的方法来准确预测胰腺癌的早期发病。我们假设阳离子胰蛋白酶原（PRSS1）基因的不同基因型可能使汉族人群易患或抵抗胰腺癌。
我们在 154 例胰腺癌患者和 520 例汉族健康对照者中确定了 PRSS1 基因型。获取临床信息，通过直接测序分析 PRSS1 基因的单核苷酸多态性（SNP），并检测基因型的分布是否符合 Hardy-Weinberg 平衡。通过 logistic 回归分析计算比值比和 95%置信区间，以评估不同基因型或单倍型与胰腺癌风险之间的关联。
鉴定出三个 SNP（-409 C/T、-204 A/C 和 c.486 C/T）。病例对照分析显示，个体携带这些 SNP 时，患胰腺癌的风险分别降低 0.118 倍（95%CI：0.037-0.653）、0.842 倍（95%CI：0.177-4.010）和 0.750 倍（95%CI：0.519-1.085）。与携带-409 T/T 基因型的个体相比，携带-409 C/T 基因型的个体患胰腺癌的风险降低。与 T(-409)-A(-204)-T(486) 单倍型相比，C(-409)-A(-204)-C(486) 单倍型具有保护作用（OR=0.115，95%CI：0.016-0.849）或与 T(-409)-A(-204)-C(486) 单倍型相比（OR=0.090，95%CI：0.012-0.667）。-409 C/T 基因型患者的血清胰蛋白酶水平仅为-409 T/T 基因型患者的四分之一，仅为健康对照组的三分之一。
PRSS1 的-409 C/T 基因型被揭示为汉族人群胰腺癌的保护因素。
