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SNP Array 6.0 Analysis in Advanced Gastric Cancer Patients Treated With 5-FU and Platinum or Irinotecan Based Chemoradiation
Peter P. Grimminger*1, Martin K. Maus1, Frederick Schumacher2, Ralf Metzger1, Jan Brabender3, Arnulf H. HöLscher1, Heinz-Joseph Lenz2
1Department of General-, Visceral- and Tumor surgery, University Clinic Cologne, Cologne, Germany; 2Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA; 3General- and Visceral Surgery, St. Antonius Hospital, Cologne, Germany
Background: Biochemical pathway SNP’s as possible molecular markers for response prediction in adjuvant chemotherapy in gastric cancer have already been reported. In our study we performed a systematic Single Nucleotide Polymorphism genotyping analysis by Affymetrix SNP 6.0 arrays that interrogates 906,600 single nucleotide polymorphisms.
Materials/Methods: Affymetrix SNP Array 6.0 analysis of 16 gastric cancer pts with response to chemotherapy (5FU + platinum or irinotecan and/or Radiation) and 30 gastric cancer pts with non-response to chemotherapy were performed. The Affymetrix assay was done by the guidelines provided by Affymetrix. For statistical evaluation a pathway analysis approach using the KEGG BIOCARTA REACTOM and AMBION database, including 1266 pathways, was performed.
Results: Several hundred SNP were identified with a possible association with response to chemotherapy. However, focusing on biochemical pathways with possible involvement in the efficiency of the chemotherapy treatment 6 pathways of the KEGG database were identified with an association to response to adjuvant treatment. The six identified pathways were: KEGG Colorectal Cancer Pathway (p=0.0001, FDR=0.343), Ambion Epithelial Tight Junctions (p=0.001, FDR=0.357), Reactome Muscle Contraction(p=0.001, FDR=0.331), KEGG Chronic Myeloid Leukemia (p=0.001, FDR=0.463), Ambion Transcritptional Regulatory Network in Embryonal Stem Cell (p=0.006, FDR=0.553 ) and Biocarta ALK Pathway (p=0.004, FDR=0.646).
Conclusion: The SNP’s of the six identified pathways have a possible impact on response to 5-FU and platinum/irinotecan based chemoradiation. Our future aim is to identify the key SNP in the pathways which may play the crucial role for treatment response. Future SNP array studies are in process to validate the identified pathways and also the single involved SNPs.
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