| Autor: |
Lu, Ye Gentiluomo, Manuel Macauda, Angelica Gioffreda, Domenica Gazouli, Maria Petrone, Maria C. Kelemen, Dezso and Ginocchi, Laura Morelli, Luca Papiris, Konstantinos and Greenhalf, William Izbicki, Jakob R. Kiudelis, Vytautas and Mohelnikova-Duchonova, Beatrice Bueno-de-Mesquita, Bas Vodicka, Pavel Brenner, Hermann Diener, Markus K. Pezzilli, Raffaele and Ivanauskas, Audrius Salvia, Roberto Szentesi, Andrea and Aoki, Mateus Nobrega Nemeth, Balazs C. Sperti, Cosimo and Jamroziak, Krzysztof Chammas, Roger Oliverius, Martin and Archibugi, Livia Ermini, Stefano Novak, Janos Kupcinskas, Juozas Strouhal, Ondrej Soucek, Pavel Cavestro, Giulia M. and Milanetto, Anna C. Vanella, Giuseppe Neoptolemos, John P. and Theodoropoulos, George E. van Laarhoven, Hanneke W. M. and Mambrini, Andrea Moz, Stefania Kala, Zdenek Lovecek, Martin and Basso, Daniela Uzunoglu, Faik G. Hackert, Thilo Testoni, Sabrina G. G. Hlavac, Viktor Andriulli, Angelo Lucchesi, Maurizio Tavano, Francesca Carrara, Silvia Hegyi, Peter and Arcidiacono, Paolo G. Busch, Olivier R. Lawlor, Rita T. and Puzzono, Marta Boggi, Ugo Guo, Feng Malecka-Panas, Ewa and Capurso, Gabriele Landi, Stefano Talar-Wojnarowska, Renata and Strobel, Oliver Gao, Xin Vashist, Yogesh Campa, Daniele and Canzian, Federico |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Popis: |
Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p10(-3)), although none of the six SNPs reached the conventional threshold for genome-wide significance (p < 5x10(-8)). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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