Genetic Polymorphisms Involved in Mitochondrial Metabolism and Pancreatic Cancer Risk

0552789 - ÚEM 2022 RIV US eng J - Článek v odborném periodiku
Peduzzi, G. - Gentiluomo, M. - Tavano, F. - Arcidiacono, P.G. - Ermini, S. - Vodička, Pavel - Boggi, U. - Cavestro, G.M. - Capurso, G. - Morelli, L. - Milanetto, A.C. - Pezzilli, R. - Lawlor, R.T. - Carrara, S. - Loveček, M. - Souč, P. - Guo, F. - Hackert, T. - Uzunoglu, F.G. - Gazouli, M. - Parniczky, A. - Kupcinskas, J. - Bijlsma, M.F. - Bueno-de-Mesquita, B. - Vermeulen, R. - van Eijck, C.H.J. - Jamroziak, K. - Talar-Wojnarowska, R. - Greenhalf, W. - Gioffreda, D. … celkem 68 autorů
Genetic Polymorphisms Involved in Mitochondrial Metabolism and Pancreatic Cancer Risk.
Cancer Epidemiology Biomarkers & Prevention. Roč. 30, č. 12 (2021), s. 2342-2345. ISSN 1055-9965. E-ISSN 1538-7755
Institucionální podpora: RVO:68378041
Klíčová slova: genome-wide association * susceptibility
Obor OECD: Genetics and heredity (medical genetics to be 3)
Impakt faktor: 4.090, rok: 2021
Způsob publikování: Omezený přístup

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.
Trvalý link: http://hdl.handle.net/11104/0330170