AISP - 36^th National Congress. Bologna, Italy. October 4-6, 2012

Gene-Wide Association Study on the TERT Locus and PDAC Susceptibility. Results from the PANDoRA Consortium

Daniele Campa¹, Cosmeri Rizzato¹, Jens Werner², Gabriele Capurso³, William Greenhalf⁴, Renata Talar-Wojnarowska⁵, Krzysztof Jamroziak⁵, Raffaele Pezzilli⁶, Andrea Imbrogno⁶, Roberto Valente³, Eithne Costello⁴, Kay-Tee Khaw⁷, Tim Key⁸, Stefano Landi⁹, John P Neoptolemos⁴, Peter Bugert¹⁰, Pavel Vodicka¹¹, Pavel Soucek¹², Markus W Büchler², Nathalia Giese², Federico Canzian¹

¹German Cancer Research Center (DKFZ). Heidelberg, Germany. ²University of Heidelberg. Heidelberg, Germany. ³“Sapienza” University. Rome, Italy. ⁴National Institute for Health Research. Liverpool, United Kingdom. ⁵Medical University. Lodz, Poland. ⁶Sant’Orsola-Malpighi Hospital. Bologna, Italy. ⁷University of Cambridge. Cambridge, United Kingdom. ⁸University of Oxford. Oxford, United Kingdom. ⁹University of Pisa. Pisa, Italy. ¹⁰German Red Cross Blood Service. Mannheim, Germany. ¹¹Academy of Science of the Czech Republic. Prague, Czech Republic. ¹²National Institute of Public Health. Prague, Czech Republic

Context SNPs in the telomerase reverse transcriptase (TERT) locus were reported to be associated with pancreatic cancer risk in a genome-wide association study (GWAS). TERT is essential for maintaining telomere ends. Its over-expression in normal cells can lead to prolonged cell lifespan and transformation. While telomerase activity cannot be detected in most normal tissues, it is seen in approximately 90% of human cancers. Objective We attempted to replicate and expand the association with the locus in a series of PDAC and healthy controls of European ancestry within the PANcreatic Disease ReseArch (PANDoRA) consortium. Methods We genotyped 13 SNPs in 1,034 PDAC cases and 2,443 controls from the PANDoRA consortium. We tested each SNP for association with PDAC risk and also with survival of the patients. Results We replicated the association reported in the GWAS with rs401681 (OR=1.53; 95%C;I 1.22-1.92; P=0.0002) and found a novel association between rs2736098 and decreased PDAC risk (OR=0.75; 95%CI: 0.63-0.88; P=0.001). Another polymorphism (rs4246742) was associated with worse survival (HR=1.75, 95%CI: 1.15-2.67; P=0.009). Conclusion We report here two novel findings: an association with risk (rs2736098) and one with survival of the patients (rs4246742). These results further contribute to our understanding in the genetic etiology of pancreatic cancer and suggest a new marker for disease prognosis.