941 Genetic Polymorphisms as Predictive/prognostic Biomarkers in Esophageal Cancer Patients Receiving Cisplatin/5-Fluorouracil-based Neoadjuvant Chemotherapy

Abstract

Introduction: Esophageal cancer is a particularly aggressive tumor with poor prognosis, and represents the eight most common cancer in the world. At present, no consensus exists on the benefit of preoperative cisplatin/5- fluorouracil-based chemotherapy in association with radiation in esophageal cancer patients. Aim of our study was to evaluate the predictive and/or prognostic value of some relevant genetic polymorphisms, in an attempt to identify those patients who could benefit more from the neoadjuvant treatment. Material and Methods: Using peripheral blood as surrogate for target tissues, DNA from 143 esophageal cancer patients, 63 receiving neoadjuvant radio-chemotherapy and 80 primary surgery, was analyzed for the following polymorphisms: ERCC1 Asn118Asn (rs11615), ERCC1 C8092A (rs3212986), XPD/ERCC2 Asp312Asn (rs1799793), XPD/ERCC2 Lys751Gln (rs13181), of the Nucleotide Excision Repair (NER) pathway; three polymorphisms within genes of the glutathione S-transferase (GST) family: GSTM1 null, GSTT1 null and GSTP1 single nucleotide polymorphism (SNP) Ile105Val (rs1695); two polymorphisms in the thymidylate synthase (TS) gene: the 28-bp variable repeat in the 5-untranslated region and the G/C SNP in the second repeat of the 3R allele. Results:We found that, in the neoadjuvant radio-chemotherapy group, ERCC1 8092 C/A and A/A genotypes, although not associated with therapeutic response, are prognostic markers of better outcome, compared to the C/C genotype (P = 0.01, HR: 2.69, 95% CI: 1.25-5.76). On the contrary, no association was observed in the primary surgery group (P = 0.40, HR: 1.35, 95% CI: 0.67-2.71). Conclusion: Our study, despite its retrospective nature, strongly suggests the ERCC1 C8092A polymorphism as a possible indicator of better outcome in esophageal cancer patients who undergo neoadjuvant treatment and, once validated in further analyses, as a marker that could be taken into account for therapeutic decision making.