谷胱甘肽S-转移酶P1基因多态性与散发性结直肠腺癌易感性的关系

Relationship between Gene Polymorphism of Glutathione S-transferase P1 and Susceptibility to Sporadic Colorectal Adenocarcinoma

背景:谷胱甘肽S-转移酶(GST)属Ⅱ相代谢酶,在人体内参与多种致癌物的解毒作用。目的:探讨GSTP1基因多态性与散发性结直肠腺癌(SCRAC)遗传易感性的关系。方法:118例SCRAC患者和140名健康对照者纳入研究。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测GSTP1基因第5外显子105位密码子单核苷酸多态性,分析两组间GSTP1等位基因和基因型的差异。结果:SCRAC组GSTP1突变型等位基因(Val)频率显著高于健康对照组(57.6%对40.7%,P=0.000);纯合突变基因型(Val/Val)频率亦高于健康对照组,但差异无统计学意义(44.1%对30.7%,P=0.027)。根据临床病理特征对SCRAC患者进行分层分析,Dukes C期和低分化腺癌Val/Val基因型频率分别显著高于Dukes A、B期(P=0.007)和高、中分化腺癌(P=0.002)。结论:GSTP1基因多态性与SCRAC相关,纯合突变基因型携带者对SCRAC的易感性增加。

Background： Glutathione S-transferase （GST） is a family of phase H metabolic enzymes involved in the detoxification of carcinogens. Aims： To investigate the relationship between gene polymorphism of GSTP1 and genetic susceptibility to sporadic colorectal adenocarcinoma （SCRAC）. Methods： One hundred and eighteen SCRAC patients and 140 healthy controls were enrolled in this study. Single nucleotide polymorphism at exon 5 codon 105 of the gene GSTP1 was detected using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） with restriction enzyme BsmA I. The discrepancies of GSTP1 alleles and genotypes between the two groups were analyzed. Results： The frequency of GSTP1 mutant allele （Val） was significantly higher in SCRAC patients than that in healthy controls （57.6% vs. 40.7%, P=0.000）. The frequency of GSTP1 homozygous mutant genotype （Val/Val） was also higher in SCRAC patients than that in healthy controls, but was not statistically significant （44.1% vs. 30.7%, P=0.027）. By stratifying the SCRAC patients with their clinicopathologic characteristics, the frequency of GSTP1 Val/Val genotype was significantly higher in Dukes C stage and poorly-differentiated adenocarcinoma than that in Dukes A, B stages （P=0.007） and well- and moderately-differentiated adenocarcinoma （P=0.002）, respectively. Conclusions： Gene polymorphism of GSTP1 is correlated with the development of SCRAC. The genetic susceptibility to SCRAC is high in population carrying GSTP1 homozygous mutant genotype.