Article
Identification of recessively inherited genetic variants potentially linked to pancreatic cancer risk
Registro en:
LU, Ye et al. Identification of recessively inherited genetic variants potentially linked to pancreatic Cancer Risk. Frontiers in Immunology, v. 11, n. 771312, p. 1–11, 2021.
2234-943X
10.3389/fonc.2021.771312
Autor
Lu, Ye
Gentiluomo, Manuel
Macauda, Angelica
Gioffreda, Domenica
Gazouli, Maria
Petrone, Maria C.
Kelemen, Dezsö
Ginocchi, Laura
Morelli, Luca
Papiris, Konstantinos
Greenhalf, William
Izbicki, Jakob R.
Kiudelis, Vytautas
Mohelníková -Duchoñova, Beatrice
Bueno-de-Mesquita, Bas
Vodicka, Pavel
Brenner, Hermann
Diener, Markus K.
Pezzilli, Raffaele
Ivanauskas, Audrius
Salvia, Roberto
Szentesi, Andrea
Aoki, Mateus Nóbrega
Németh, Balázs C.
Sperti, Cosimo
Jamroziak, Krzysztof
Chammas, Roger
Oliverius, Martin
Archibugi, Livia
Ermini, Stefano
Novák, János
Kupcinskas, Juozas
Strouhal, Ondrej
Soucek, Pavel
Cavestro, Giulia M.
Milanetto, Anna C.
Vanella, Giuseppe
Neoptolemos, John P.
Theodoropoulos, George E.
Laarhoven, Hanneke W. M. van
Mambrini, Andrea
Moz, Stefania
Kala, Zdenek
Lovecek, Martin
Basso, Daniela
Uzunoglu, Faik G.
Hackert, Thilo
Testoni, Sabrina G. G.
Hlavác, Viktor
Andriulli, Angelo
Lucchesi, Maurizio
Tavano, Francesca
Carrara, Silvia
Hegyi, Péter
Arcidiacono, Paolo G.
Busch, Olivier R.
Lawlor, Rita T.
Puzzono, Marta
Boggi, Ugo
Guo, Feng
Małecka-Panas, Ewa
Capurso, Gabriele
Landi, Stefano
Talar-Wojnarowska, Renata
Strobel, Oliver
Gao, Xin
Vashist, Yogesh
Campa, Daniele
Canzian, Federico
Resumen
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 < 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.