The effect of cytochrome P450 2A6 gene rs8192725 polymorphism on clinical outcomes of chemotherapy in postoperative gastric cancer patients / 中华普通外科杂志

ABSTRACT

Objective To investigate the associations between CYP2A6 polymorphisms and treatment outcomes of adjuvant S-1 in postoperative gastric cancer patients.Methods 188 patients after D2 radical resection received S-1 based adjuvant chemotherapy.PBMC cell specimen were collected for the genotyping of genetic variation and CYP2A6 gene mRNA expression.Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis,and multivariate analysis were adjusted by COX regression analysis.Results The polymorphisms included in this study were collected in the NCBI database with the minor allele frequency ＞ 10％ in Chinese population (rs8192725,rs8192720 and rs28399433),with rs8192725 only of clinical significance.The prevalence of rs8192725 in CYP2A6 were CC genotype 131 cases (69.7％),CT genotype 51 cases (27.1％),TT genotype 6 cases (3.2％),minor allele frequency of rs8192725 was 0.17.The 3 year disease-free survival (DFS) rate in patients with CT/TT genotype and CC genotype were 61.5％ and 72.5％,respectively (x2 =8.233,P =0.004).The 3 year overall survival rate of the two genotypes were 73.7％ and 79.4％ (x2 =4.863,P =0.021).CT/TT genotypes were an independent factor for DFS (OR =1.81,P =0.012).The expression of CYP2A6 in PBMC of the patients with CT/TT genotypes were significantly lower than those of the CC genotype patients (P ＜ 0.001).Conclusions After D2 gastric cancer patients treated by S-1,the polymorphism rs8192725 of CYP2A6 may effect the clinical outcomes of adjuvant chemotherapy S-1 treatment through influencing the mRNA expression of CYP2A6.