Genetic polymorphisms involved in mitochondrial metabolism and pancreatic cancer risk.



Peduzzi, Giulia, Gentiluomo, Manuel, Tavano, Francesca, Arcidiacono, Paolo Giorgio, Ermini, Stefano, Vodicka, Pavel, Boggi, Ugo, Cavestro, Giulia Martina, Capurso, Gabriele, Morelli, Luca
et al (show 58 more authors) (2021) Genetic polymorphisms involved in mitochondrial metabolism and pancreatic cancer risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[img] Text
Peduzzi_Gentiluomo_mitocondrial_SNP_CEBP_v8.docx - Submitted Version

Download (85kB)

Abstract

<h4>Background</h4>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 aetiology. However, a systematic investigation of the genetic variability of mitochondrial genome (mtSNPs) and of all the nuclear genes involved in its functioning (n-mtSNPs) has never been reported.<h4>Methods</h4>We conducted a two-phase association study of mtSNPs and n-mtSNPs to assess their effect on PDAC risk. We analysed 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 MAGMA software.<h4>Results</h4>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 analysiswe observed that three genes (TERT, SUGCT and SURF1) involved in the mitochondrial metabolismshowed an association below the Bonferroni-corrected threshold of statistical significance (P=0.05/1588=3.1 x10-5).<h4>Conclusions</h4>Even though the mitochondrial metabolism might be involved in PDAC aetiology, 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.<h4>Impact</h4>This large case-control study does not support a role of the genetic variability of the mitochondrial function in PDAC risk.

Item Type: Article
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 18 Oct 2021 07:58
Last Modified: 19 Jan 2022 20:10
DOI: 10.1158/1055-9965.epi-21-0353
URI: https://livrepository.liverpool.ac.uk/id/eprint/3140793