Abstract 4668: Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2011-04, Vol.71 (8_Supplement), p.4668-4668
• Main Authors: Zeng, Hongmei, Yu, Herbert, Lu, Lingeng, Jain, Dhanpat, Kidd, Mark S., Saif, M Wasif, Chanock, Stephen J., Hartge, Patricia, Risch, Harvey A.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-4668

Purpose: Germline genetic variation may affect clinical outcomes of cancer patients. Using an existing genome-wide association study (GWAS) data set, we applied a candidate-gene approach to evaluate the effect of putative markers on survival of patients with pancreatic cancer. We also examined gene-radiotherapy and gene-chemotherapy interactions, aiming to explain inter-individual differences in treatment outcomes. Patients, Materials and Methods: In total, 211 patients with pancreatic cancer were identified and recruited between February 2005 and June 2008 in a population-based study and followed through June 2010, an average follow-up of 3.4 years. Sixty-four candidate genes associated with cancer survival or treatment response were selected from existing publications. Genotype information was obtained from a previous GWAS analysis of the study subjects. The main effect of genetic variation and gene-specific treatment interactions on overall survival were examined by proportional hazards regression models. Results: Fourteen genes showed evidence of association with pancreatic cancer survival. Among these, rs1760217, located at the DPYD gene, rs17091162 at SERPINA3 and rs2231164 at ABCG2 had the lowest P-values of 10−4.60, 0.0013 and 0.0023, respectively. We also observed that two genes, RRM1 and IQGAP2, had significant interactions with radiotherapy in association with survival, and two others, TYMS and MET, showed evidence of interaction with the chemotherapeutic agents 5-FU and erlotinib, respectively. Conclusions: Our study revealed significant associations between germline genetic polymorphisms and overall survival in pancreatic cancer, as well as survival interactions between various genes and radiotherapy and chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4668. doi:10.1158/1538-7445.AM2011-4668