@article{3033319,
    title = "Identification of Recessively Inherited Genetic Variants Potentially
Linked to Pancreatic Cancer Risk",
    author = "Lu, Ye and Gentiluomo, Manuel and Macauda, Angelica and Gioffreda, and Domenica and Gazouli, Maria and Petrone, Maria C. and Kelemen, Dezso and and Ginocchi, Laura and Morelli, Luca and Papiris, Konstantinos and and Greenhalf, William and Izbicki, Jakob R. and Kiudelis, Vytautas and and Mohelnikova-Duchonova, Beatrice and Bueno-de-Mesquita, Bas and Vodicka, and Pavel and Brenner, Hermann and Diener, Markus K. and Pezzilli, Raffaele and and Ivanauskas, Audrius and Salvia, Roberto and Szentesi, Andrea and and Aoki, Mateus Nobrega and Nemeth, Balazs C. and Sperti, Cosimo and and Jamroziak, Krzysztof and Chammas, Roger and Oliverius, Martin and and Archibugi, Livia and Ermini, Stefano and Novak, Janos and Kupcinskas, and Juozas and Strouhal, Ondrej and Soucek, Pavel and Cavestro, Giulia M. and and Milanetto, Anna C. and Vanella, Giuseppe and Neoptolemos, John P. and and Theodoropoulos, George E. and van Laarhoven, Hanneke W. M. and and Mambrini, Andrea and Moz, Stefania and Kala, Zdenek and Lovecek, Martin and and Basso, Daniela and Uzunoglu, Faik G. and Hackert, Thilo and Testoni, and Sabrina G. G. and Hlavac, Viktor and Andriulli, Angelo and Lucchesi, and Maurizio and Tavano, Francesca and Carrara, Silvia and Hegyi, Peter and and Arcidiacono, Paolo G. and Busch, Olivier R. and Lawlor, Rita T. and and Puzzono, Marta and Boggi, Ugo and Guo, Feng and Malecka-Panas, Ewa and and Capurso, Gabriele and Landi, Stefano and Talar-Wojnarowska, Renata and and Strobel, Oliver and Gao, Xin and Vashist, Yogesh and Campa, Daniele and and Canzian, Federico",
    journal = "Frontiers in Oncology",
    year = "2021",
    volume = "11",
    publisher = "Frontiers Media SA",
    doi = "10.3389/fonc.2021.771312",
    keywords = "pancreatic cancer; susceptibility; genome-wide association study;
recessive model; genetic polymorphisms",
    abstract = "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
(p<10(-5)) compared with the additive effects (p>10(-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."
}