Distribution of gemcitabine pathway genotypes in Han Chinese population and their association with s

来源 :第十五次全国临床药理学学术会议 | 被引量 : 0次 | 上传用户:magy_java2009
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  Purpose:Adjuvant chemotherapy using gemcitabine has been shown to prolong survival in patients after resection of pancreatic cancer.But tumor showed low response to gemcitabine.We conducted a retrospective study to investigate the association between genetic polymorphisms in the genes involved in gemcitabine and overall survival in patients with pancreatic cancer.Methods: Thirty-three patients with resectable pancreatic cancer from one institute were used for single nucleotide polymorphisms.UTR3,UTR5 and exon in five genes (CDA,dCK,RRM1,RRM2 and SCL29A1)were selected from pathway that may influence the metabolism or sensitivity of gemcitabine therapy.Germline DNA was extracted from Formalin-fixed,paraffin embedded (FFPE) rumor tissue and assayed by Targeted sequence.Results:Results shows 16 SNPs among 5 genes finally analysis for the 33 pancreatic cancer patients who received adjuvant gemcitabine therapy.All SNPS were found to be in Hardy-Weinberg equilibrium (p >0.05).Linkage disequilibrium was not observed.The data for all the genetic polymorphisms analyzed for OS are shown in Table 2.Log-rank analyses showed that OS in patients with CT genotype of the dCK rs67437265 polymorphism was significantly shorter than in those with the CC genotype (15.6 versus 30.1 months,HR=2.82,95%CI: 0.97-23.62);p=0.057).dCK exon genotypes (rs 67437265 and ch71859617) SNP were associated with a shorter OS compared with the wild genotype (15.3 versus 30.1 months,HR=3.16,95% CI:1.34-25.69;p=0.022).Kaplan-Meier survival analyses indicated that patients with SLC29A1 rs3734703 CA/AA status,CDA rs3215400-C/--had shorter OS (HR=1.63 and 2.38,respectively);but the difference did not meet statistical significance (p=0.323 and 0.077,respectively).Kaplan-Meier survival analyses indicated that patients with RRM2 rs1130609 TG/GG had longer OS (HR=0.60;95CI: 0.21-1.60,p=0.295) compared with TT genotype.Conclusion: Our study suggests that the dCK genotype in exon region may act as prognostic biomarkers in identifying patients who are likely to resistance from adjuvant gemcitabine therapy in pancreatic cancer patients.
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