| Autor: |
Ye Lu, Manuel Gentiluomo, Angelica Macauda, Domenica Gioffreda, Maria Gazouli, Maria C. Petrone, Dezső Kelemen, Laura Ginocchi, Luca Morelli, Konstantinos Papiris, William Greenhalf, Jakob R. Izbicki, Vytautas Kiudelis, Beatrice Mohelníková-Duchoňová, Bas Bueno-de-Mesquita, Pavel Vodicka, Hermann Brenner, Markus K. Diener, Raffaele Pezzilli, Audrius Ivanauskas, Roberto Salvia, Andrea Szentesi, Mateus Nóbrega Aoki, Balázs C. Németh, Cosimo Sperti, Krzysztof Jamroziak, Roger Chammas, Martin Oliverius, Livia Archibugi, Stefano Ermini, János Novák, Juozas Kupcinskas, Ondřej Strouhal, Pavel Souček, Giulia M. Cavestro, Anna C. Milanetto, Giuseppe Vanella, John P. Neoptolemos, George E. Theodoropoulos, Hanneke W. M. van Laarhoven, Andrea Mambrini, Stefania Moz, Zdenek Kala, Martin Loveček, Daniela Basso, Faik G. Uzunoglu, Thilo Hackert, Sabrina G. G. Testoni, Viktor Hlaváč, Angelo Andriulli, Maurizio Lucchesi, Francesca Tavano, Silvia Carrara, Péter Hegyi, Paolo G. Arcidiacono, Olivier R. Busch, Rita T. Lawlor, Marta Puzzono, Ugo Boggi, Feng Guo, Ewa Małecka-Panas, Gabriele Capurso, Stefano Landi, Renata Talar-Wojnarowska, Oliver Strobel, Xin Gao, Yogesh Vashist, Daniele Campa, Federico Canzian |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Frontiers in Oncology, Vol 11 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2234-943X |
| DOI: |
10.3389/fonc.2021.771312 |
| 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 < 5×10−8). 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: |
Directory of Open Access Journals |
| Externí odkaz: |
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