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

Manuel Gentiluomo; Verena A Katzke; Rudolf Kaaks; Anne Tjonneland; Gianluca Severi; Vittorio Perduca; Marie-Christine Boutron-Ruault; Elisabete Weiderpass; Pietro Ferrari; Theron Johnson; Matthias B Schulze; Manuela Bergmann; Antonia Trichopoulou; Anna Karakatsani; Carlo La Vecchia; Domenico Palli; Sara Grioni; Salvatore Panico; Rosario Tumino; Carlotta Sacerdote; Bas Bueno-de-Mesquita; Roel Vermeulen; Torkjel M Sandanger; J Ramón Quirós; Miguel Rodríguez-Barranco; Pilar Amiano; Sandra Colorado-Yohar; Eva Ardanaz; Malin Sund; Kay-Tee Khaw; Nicholas J Wareham; Julie A Schmidt; Paula Jakszyn; Luca Morelli; Federico Canzian; Daniele Campa

doi:10.1158/1055-9965.EPI-19-0868

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

Manuel Gentiluomo, Verena A Katzke, Rudolf Kaaks, Anne Tjonneland, Gianluca Severi, Vittorio Perduca, Marie-Christine Boutron-Ruault, Elisabete Weiderpass, Pietro Ferrari, Theron Johnson, Matthias B Schulze, Manuela Bergmann, Antonia Trichopoulou, Anna Karakatsani, Carlo La Vecchia, Domenico Palli, Sara Grioni, Salvatore Panico, Rosario Tumino, Carlotta SacerdoteBas Bueno-de-Mesquita, Roel Vermeulen, Torkjel M Sandanger, J Ramón Quirós, Miguel Rodríguez-Barranco, Pilar Amiano, Sandra Colorado-Yohar, Eva Ardanaz, Malin Sund, Kay-Tee Khaw, Nicholas J Wareham, Julie A Schmidt, Paula Jakszyn, Luca Morelli, Federico Canzian, Daniele Campa

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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 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 OR=0.35 (95% C.I 0.16-0.79), p=0.01 when comparing the 5th quintile with the 1st using an unconditional logistic regression and OR=0.19 (95% C.I 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.

Original language	English
Pages (from-to)	681-686
Number of pages	6
Journal	Cancer Epidemiology Biomarkers and Prevention
Volume	29
Issue number	3
Early online date	13 Jan 2020
DOIs	https://doi.org/10.1158/1055-9965.EPI-19-0868
Publication status	Published - Mar 2020

Access to Document

10.1158/1055-9965.EPI-19-0868

1055-9965.EPI-19-0868.fullFinal published version, 314 KBLicence: Taverne

Cite this

Gentiluomo, M., Katzke, V. A., Kaaks, R., Tjonneland, A., Severi, G., Perduca, V., Boutron-Ruault, M.-C., Weiderpass, E., Ferrari, P., Johnson, T., Schulze, M. B., Bergmann, M., Trichopoulou, A., Karakatsani, A., La Vecchia, C., Palli, D., Grioni, S., Panico, S., Tumino, R., ... Campa, D. (2020). Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort. Cancer Epidemiology Biomarkers and Prevention, 29(3), 681-686. https://doi.org/10.1158/1055-9965.EPI-19-0868

@article{0b281be1ea9f4797ac73f9a37abfac42,

title = "Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort",

abstract = "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 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 OR=0.35 (95% C.I 0.16-0.79), p=0.01 when comparing the 5th quintile with the 1st using an unconditional logistic regression and OR=0.19 (95% C.I 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.",

author = "Manuel Gentiluomo and Katzke, {Verena A} and Rudolf Kaaks and Anne Tjonneland and Gianluca Severi and Vittorio Perduca and Marie-Christine Boutron-Ruault and Elisabete Weiderpass and Pietro Ferrari and Theron Johnson and Schulze, {Matthias B} and Manuela Bergmann and Antonia Trichopoulou and Anna Karakatsani and {La Vecchia}, Carlo and Domenico Palli and Sara Grioni and Salvatore Panico and Rosario Tumino and Carlotta Sacerdote and Bas Bueno-de-Mesquita and Roel Vermeulen and Sandanger, {Torkjel M} and Quir{\'o}s, {J Ram{\'o}n} and Miguel Rodr{\'i}guez-Barranco and Pilar Amiano and Sandra Colorado-Yohar and Eva Ardanaz and Malin Sund and Kay-Tee Khaw and Wareham, {Nicholas J} and Schmidt, {Julie A} and Paula Jakszyn and Luca Morelli and Federico Canzian and Daniele Campa",

note = "Copyright {\textcopyright}2020, American Association for Cancer Research.",

year = "2020",

month = mar,

doi = "10.1158/1055-9965.EPI-19-0868",

language = "English",

volume = "29",

pages = "681--686",

journal = "Cancer Epidemiology Biomarkers and Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "3",

}

Gentiluomo, M, Katzke, VA, Kaaks, R, Tjonneland, A, Severi, G, Perduca, V, Boutron-Ruault, M-C, Weiderpass, E, Ferrari, P, Johnson, T, Schulze, MB, Bergmann, M, Trichopoulou, A, Karakatsani, A, La Vecchia, C, Palli, D, Grioni, S, Panico, S, Tumino, R, Sacerdote, C, Bueno-de-Mesquita, B, Vermeulen, R, Sandanger, TM, Quirós, JR, Rodríguez-Barranco, M, Amiano, P, Colorado-Yohar, S, Ardanaz, E, Sund, M, Khaw, K-T, Wareham, NJ, Schmidt, JA, Jakszyn, P, Morelli, L, Canzian, F & Campa, D 2020, 'Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort', Cancer Epidemiology Biomarkers and Prevention, vol. 29, no. 3, pp. 681-686. https://doi.org/10.1158/1055-9965.EPI-19-0868

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 - Tjonneland, 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 - Rodríguez-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

PY - 2020/3

Y1 - 2020/3

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 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 OR=0.35 (95% C.I 0.16-0.79), p=0.01 when comparing the 5th quintile with the 1st using an unconditional logistic regression and OR=0.19 (95% C.I 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 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 OR=0.35 (95% C.I 0.16-0.79), p=0.01 when comparing the 5th quintile with the 1st using an unconditional logistic regression and OR=0.19 (95% C.I 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.

U2 - 10.1158/1055-9965.EPI-19-0868

DO - 10.1158/1055-9965.EPI-19-0868

M3 - Article

C2 - 31932413

SN - 1055-9965

VL - 29

SP - 681

EP - 686

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

IS - 3

ER -

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

Abstract

Access to Document

Fingerprint

Cite this