TY - JOUR
T1 - Mitochondrial DNA Copy-Number Variation and Pancreatic Cancer Risk in the Prospective EPIC Cohort.
AU - Gentiluomo, Manuel
AU - Katzke, Verena A.
AU - Kaaks, Rudolf
AU - Tjønneland, Anne
AU - Severi, Gianluca
AU - Perduca, Vittorio
AU - Boutron-Ruault, Marie-Christine
AU - Weiderpass, Elisabete
AU - Ferrari, Pietro
AU - Johnson, Theron
AU - Schulze, Matthias B.
AU - Bergmann, Manuela
AU - Trichopoulou, Antonia
AU - Karakatsani, Anna
AU - La Vecchia, Carlo
AU - Palli, Domenico
AU - Grioni, Sara
AU - Panico, Salvatore
AU - Tumino, Rosario
AU - Sacerdote, Carlotta
AU - Bueno-de-Mesquita, Bas
AU - Vermeulen, Roel
AU - Sandanger, Torkjel M.
AU - Quirós, J. Ramón
AU - Rodriguez-Barranco, Miguel
AU - Amiano, Pilar
AU - Colorado-Yohar, Sandra
AU - Ardanaz, Eva
AU - Sund, Malin
AU - Khaw, Kay-Tee
AU - Wareham, Nicholas J.
AU - Schmidt, Julie A.
AU - Jakszyn, Paula
AU - Morelli, Luca
AU - Canzian, Federico
AU - Campa, Daniele
N1 - Place: United States
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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 [95CI), 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 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.
AB - 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 [95CI), 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 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.
M3 - Article
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 3
ER -