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. 2021 Dec;30(12):2342-2345.
doi: 10.1158/1055-9965.EPI-21-0353. Epub 2021 Sep 15.

Genetic Polymorphisms Involved in Mitochondrial Metabolism and Pancreatic Cancer Risk

Giulia Peduzzi #  1 , Manuel Gentiluomo #  1 , Francesca Tavano  2 , Paolo Giorgio Arcidiacono  3 , Stefano Ermini  4 , Pavel Vodicka  5   6 , Ugo Boggi  7 , Giulia Martina Cavestro  8 , Gabriele Capurso  3   9 , Luca Morelli  10 , Anna Caterina Milanetto  11 , Raffaele Pezzilli  12 , Rita T Lawlor  13 , Silvia Carrara  14 , Martin Lovecek  15 , Pavel Souček  16 , Feng Guo  17 , Thilo Hackert  18 , Faik G Uzunoğlu  19 , Maria Gazouli  20 , Andrea Párniczky  21   22 , Juozas Kupcinskas  23   24 , Maarten F Bijlsma  25 , Bas Bueno-de-Mesquita  26 , Roel Vermeulen  27 , Casper H J van Eijck  28 , Krzysztof Jamroziak  29 , Renata Talar-Wojnarowska  30 , William Greenhalf  31 , Domenica Gioffreda  2 , Maria C Petrone  3 , Stefano Landi  1 , Livia Archibugi  3   9 , Marta Puzzono  8   32 , Niccola Funel  33 , Cosimo Sperti  34 , Maria L Piredda  13 , Beatrice Mohelnikova-Duchonova  35 , Ye Lu  36   37 , Viktor Hlaváč  16 , Xin Gao  17   38 , Martin Schneider  18 , Jakob R Izbicki  19 , George Theodoropoulos  39 , Stefania Bunduc  21   40 , Edita Kreivenaite  23   24 , Olivier R Busch  41 , Ewa Małecka-Panas  30 , Eithne Costello  31 , Francesco Perri  2 , Sabrina Gloria Giulia Testoni  3 , Giuseppe Vanella  3   9 , Claudio Pasquali  11 , Martin Oliverius  42 , Hermann Brenner  17   38   43 , Martin Loos  18 , Mara Götz  19 , Konstantinos Georgiou  39 , Bálint Erőss  21 , Evaristo Maiello  44 , Andrea Szentesi  21   45 , Francesca Bazzocchi  46 , Daniela Basso  47 , John P Neoptolemos  18 , Péter Hegyi  21   45 , Vytautas Kiudelis  23   24 , Federico Canzian #  36 , Daniele Campa #  48
Affiliations

Genetic Polymorphisms Involved in Mitochondrial Metabolism and Pancreatic Cancer Risk

Giulia Peduzzi et al. Cancer Epidemiol Biomarkers Prev. 2021 Dec.

Abstract

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 × 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.

Impact: This large case-control study does not support a role of the genetic variability of the mitochondrial function in PDAC risk.

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References

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