TY - JOUR
TI - Genetic Polymorphisms Involved in Mitochondrial Metabolism and
Pancreatic Cancer Risk
AU - Peduzzi, Giulia
AU - Gentiluomo, Manuel
AU - Tavano, Francesca and
AU - Arcidiacono, Paolo Giorgio
AU - Ermini, Stefano
AU - Vodicka, Pavel and
AU - Boggi, Ugo
AU - Cavestro, Giulia Martina
AU - Capurso, Gabriele and
AU - Morelli, Luca
AU - Milanetto, Anna Caterina
AU - Pezzilli, Raffaele and
AU - Lawlor, Rita T.
AU - Carrara, Silvia
AU - Lovecek, Martin
AU - Souc, Pavel
AU - and Guo, Feng
AU - Hackert, Thilo
AU - Uzunoglu, Faik G.
AU - Gazouli,
AU - Maria
AU - Parniczky, Andrea
AU - Kupcinskas, Juozas
AU - Bijlsma, Maarten
AU - F.
AU - Bueno-de-Mesquita, Bas
AU - Vermeulen, Roel
AU - van Eijck, Casper
AU - H. J.
AU - Jamroziak, Krzysztof
AU - Talar-Wojnarowska, Renata and
AU - Greenhalf, William
AU - Gioffreda, Domenica
AU - Petrone, Maria C. and
AU - Landi, Stefano
AU - Archibugi, Livia
AU - Puzzono, Marta
AU - Funel,
AU - Niccola
AU - Sperti, Cosimo
AU - Piredda, Maria L. and
AU - Mohelnikova-Duchonova, Beatrice
AU - Lu, Ye
AU - Hlavac, Viktor
AU - Gao,
AU - Xin
AU - Schneider, Martin
AU - Izbicki, Jakob R.
AU - Theodoropoulos,
AU - George
AU - Bunduc, Stefania
AU - Kreivenaite, Edita
AU - Busch, Olivier R.
AU - and Malecka-Panas, Ewa
AU - Costello, Eithne
AU - Perri, Francesco and
AU - Testoni, Sabrina Gloria Giulia
AU - Vanella, Giuseppe
AU - Pasquali,
AU - Claudio
AU - Oliverius, Martin
AU - Brenner, Hermann
AU - Loos, Martin and
AU - Gotz, Mara
AU - Georgiou, Konstantinos
AU - Eross, Alint
AU - Maiello,
AU - Evaristo
AU - Szentesi, Andrea
AU - Bazzocchi, Francesca
AU - Basso,
AU - Daniela
AU - Neoptolemos, John P.
AU - Hegyi, P. Eter
AU - Kiudelis,
AU - Vytautas
AU - Canzian, Federico
AU - Campa, Daniele
JO - Cancer Epidemiology, Biomarkers & Prevention
PY - 2021
VL - 30
TODO - 12
SP - 2342-2345
PB - AMER ASSOC CANCER RESEARCH
SN - 1055-9965, 1538-7755
TODO - 10.1158/1055-9965.EPI-21-0353
TODO - null
TODO - 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.
ER -