Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort

Background: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited. Methods: To further our knowledge on this topic, we measured relative mtDNA copy...

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Main Authors: Gentiluomo, M, Katzke, V, Kaaks, R, Schmidt, J, Et al.
Format: Journal article
Language:English
Published: American Association for Cancer Research 2020
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author Gentiluomo, M
Katzke, V
Kaaks, R
Schmidt, J
Et al.
author_facet Gentiluomo, M
Katzke, V
Kaaks, R
Schmidt, J
Et al.
author_sort Gentiluomo, M
collection OXFORD
description Background: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited. Methods: To further our knowledge on this topic, we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Results: We observed lower mtDNA copy number with advancing age (P = 6.54 × 10−5) and with a high body mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.16–0.79; P = 0.01] when comparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 (95% CI, 0.07–0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses. Conclusions: Our results suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk. Impact: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer.
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spelling oxford-uuid:5e0d9f5c-ca83-4f28-8211-e9e51b5df17f2022-03-26T17:38:10ZMitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohortJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5e0d9f5c-ca83-4f28-8211-e9e51b5df17fEnglishSymplectic Elements at OxfordAmerican Association for Cancer Research2020Gentiluomo, MKatzke, VKaaks, RSchmidt, JEt al.Background: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited. Methods: To further our knowledge on this topic, we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Results: We observed lower mtDNA copy number with advancing age (P = 6.54 × 10−5) and with a high body mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.16–0.79; P = 0.01] when comparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 (95% CI, 0.07–0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses. Conclusions: Our results suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk. Impact: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer.
spellingShingle Gentiluomo, M
Katzke, V
Kaaks, R
Schmidt, J
Et al.
Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort
title Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort
title_full Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort
title_fullStr Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort
title_full_unstemmed Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort
title_short Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort
title_sort mitochondrial dna copy number variation and pancreatic cancer risk in the prospective epic cohort
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AT kaaksr mitochondrialdnacopynumbervariationandpancreaticcancerriskintheprospectiveepiccohort
AT schmidtj mitochondrialdnacopynumbervariationandpancreaticcancerriskintheprospectiveepiccohort
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