Correlation Of MDR1Gene C3435T Polymorphism And Survival Of Gastric Cancer Patients Treated With Postoperative Adjuvant Chemotherapy

Objective:To evaluate the impact of MDR1gene C3435T polymorphism on survival ofgastric cancer patients treated with postoperative adjuvant chemotherapy.Methods:From January2005to December2008, patients with surgically resected gastriccancer received adjuvant chemotherapy in the Affiliated Jiangsu Cancer Hospital ofNanjing Medical University. MDR1gene C3435T polymorphism was tested by usingreal time quantitative polymerase chain reaction (RT-PCR). The relationship betweenMDR1gene C3435T polymorphism and survival after postoperative adjuvantchemotherapy was analyzed by SPSS17.0.Results:(1) Genotype frequenciesOne hundred and two patients were enrolled in this study. Among these patients,the genotypes of MDR1in codon C3435T were C/C40(39.2%), C/T44(43.1%) andT/T18(17.7%), respectively.(2) Associations between MDR1C3435T polymorphism and clinical pathologicalcharacteristics No significant associations were found between age, gender, pathologicaldifferentiation, metastatic lymphonode status, TNM stage or chemotherapy regimensand genotypes of MDR1gene C3435T (P＞0.05).(3) Associations between MDR1C3435T gene polymorphism and survivalAmong102patients,24were treated with5-FU/leucovorin/oxaliplatin(FOLFOX4) regimen,47with5-FU/paclitaxel/oxaliplatin and31with5-FU/docetaxol/oxaliplatin regimen.In this study, the median PFS for patients with C/C genotype was42months(95%CI=22.4-61.6), whereas that for patients with C/T+T/T genotypes was16months (95%CI=11.2-20.8; χ2=3.967, P=0.046). The median OS was64months(95%CI=50.7-77.3) for patients with C/C, and33months (95%CI=21.1-44.9) forthose with C/T or T/T genotype (χ2=6.407, P=0.011).Stratified by TNM stage, we found that the survival advantage was moresignificant for those with C/C genotype in stage Ⅲ patients (for PFS, P=0.002; forOS, P=0.005).Cox multivariate analysis showed that, after adjustment for age, gender,differentiation, TNM stage and chemotherapy regimens, patients with T alleleappeared to be an independent risk factor for PFS (adjusted HR=2.01,95%CI=1.17-3.45, P=0.012) and OS (adjusted HR=2.37,95%CI=1.31-4.28, P=0.004),compared to those with C allele.TNM stage was also an independent risk factor for PFS (adjusted HR=2.33,95%CI=1.34-4.05, P=0.003) and OS (adjusted HR=2.62,95%CI=1.44-4.76, P=0.002).Conclusion:MDR1gene C3435T polymorphism is associated with the prognosis of gastriccancer patients treated with postoperative adjuvant chemotherapy. Individuals with 3435CC genotype had a longer PFS and OS compared to those with CT or TTgenotype.