SNP of phospholipase D1 gene as a predictive marker of response to chemotherapy in metastatic colorectal carcinoma Free

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Phospholipase D (PLD) is activated in response to stimulators of vesicle transport, endocytosis, exocytosis, cell migration, and mitosis, and these cellular biological processes have been known to be deregulated in the development of various human tumors. Pharmacogenetics focuses on the prediction of the response of tumor and normal standard therapy by genetic profiling and, thereby, to select the most appropriate medication at optimal doses for each individual patient. Single nucleotide polymorphisms (SNPs) are extensively used in case-control studies of practically all cancer types. The identification of polymorphisms in patients undergoing chemotherapy may help the clinician prescribe the optimal drug combination or schedule and predict with more accuracy the response to these prescriptions. The purpose of this study was to analyze genetic polymorphisms of Phospholipase D1 gene as a Predictive marker of response to chemotherapy in metastatic colorectal carcinoma. We identified two SNPs at exon 14, one SNP at exon 16 and two SNP at exon 23 which were novel. Two single nucleotide polymorphisms of PLD1 with highest heterozygosites were selected; (exon 23, rs2663,allele G/T: Exon 23-38), (exon 23, rs 2669,allele C/A: Exon 23-74). The allelic frequencies of exon 23-38 were 16% and exon 23-74 were 18% in 50 metastatic colorectal carcinoma patients. The allelic frequencies of exon 23-38 (rs2663) polymorphism showed significant association between responders (partial response) and non-responders (stable disease and progression) to chemotherapy (p=0.068), but allele frequencies of exon 23-74(re2669) polymorphism showed no significant differences between responders and non-responders (p=0.410). The genotype frequencies of exon 23-74 polymorphism showed significant association with gender in metastatic colorectal carcinoma (p=0.038). Overall survival was analyzed using the Kaplan-Meier method, verified by the log-rank test. Overall survival rate was not significant between groups with polymorphism of exon 23-38(p=0.9120) or exon23-74(p=0.8846) and without polymorphism. From our results, we suggest that PLD1 genetic polymorphism (exon 23-38, exon 23-74) might be a predictive marker of response to chemotherapy in metastatic colorectal carcinoma. Further studies with large number of cases will be needed