Περίληψη:
Background: The mitochondrial metabolism has been associated with
pancreatic ductal adenocarcinoma (PDAC) risk. Recent evidence also
suggests the involvement of the genetic variability of the mitochondrial
function in several traits involved in PDAC etiology. However, a
systematic investigation of the genetic variability of mitochondrial
genome (mtSNP) and of all the nuclear genes involved in its functioning
(n-mtSNPs) has never been reported.
Methods: We conducted a two-phase association study of mtSNPs and
n-mtSNPs to assess their effect on PDAC risk. We analyzed 35,297
n-mtSNPs and 101 mtSNPs in up to 55,870 individuals (12,884 PDAC cases
and 42,986 controls). In addition, we also conducted a gene-based
analysis on 1,588 genes involved in mitochondrial metabolism using
Multi-marker Analysis of GenoMic Annotation (MAGMA) software.
Results: In the discovery phase, we identified 49 n-mtSNPs and no mtSNPs
associated with PDAC risk (P < 0.05). In the second phase, none of the
findings were replicated. In the gene-level analysis, we observed that
three genes (TERT, SUGCT, and SURF1) involved in the mitochondrial
metabolism showed an association below the Bonferroni-corrected
threshold of statistical significance (P = 0.05/1588 - 3.1 x 10(-5)).
Conclusions: Even though the mitochondrial metabolism might be involved
in PDAC etiology, our results, obtained in a study with one of the
largest sample sizes to date, show that neither n-mtSNPs nor mtSNPs are
associated with PDAC risk.
Συγγραφείς:
Peduzzi, Giulia
Gentiluomo, Manuel
Tavano, Francesca and
Arcidiacono, Paolo Giorgio
Ermini, Stefano
Vodicka, Pavel and
Boggi, Ugo
Cavestro, Giulia Martina
Capurso, Gabriele and
Morelli, Luca
Milanetto, Anna Caterina
Pezzilli, Raffaele and
Lawlor, Rita T.
Carrara, Silvia
Lovecek, Martin
Souc, Pavel
and Guo, Feng
Hackert, Thilo
Uzunoglu, Faik G.
Gazouli,
Maria
Parniczky, Andrea
Kupcinskas, Juozas
Bijlsma, Maarten
F.
Bueno-de-Mesquita, Bas
Vermeulen, Roel
van Eijck, Casper
H. J.
Jamroziak, Krzysztof
Talar-Wojnarowska, Renata and
Greenhalf, William
Gioffreda, Domenica
Petrone, Maria C. and
Landi, Stefano
Archibugi, Livia
Puzzono, Marta
Funel,
Niccola
Sperti, Cosimo
Piredda, Maria L. and
Mohelnikova-Duchonova, Beatrice
Lu, Ye
Hlavac, Viktor
Gao,
Xin
Schneider, Martin
Izbicki, Jakob R.
Theodoropoulos,
George
Bunduc, Stefania
Kreivenaite, Edita
Busch, Olivier R.
and Malecka-Panas, Ewa
Costello, Eithne
Perri, Francesco and
Testoni, Sabrina Gloria Giulia
Vanella, Giuseppe
Pasquali,
Claudio
Oliverius, Martin
Brenner, Hermann
Loos, Martin and
Gotz, Mara
Georgiou, Konstantinos
Eross, Alint
Maiello,
Evaristo
Szentesi, Andrea
Bazzocchi, Francesca
Basso,
Daniela
Neoptolemos, John P.
Hegyi, P. Eter
Kiudelis,
Vytautas
Canzian, Federico
Campa, Daniele
