title: Mitochondrial DNA copy number and pancreatic cancer in the alpha-tocopherol beta-carotene cancer prevention study.
abstract: Diabetes, obesity, and cigarette smoke, consistent risk factors for pancreatic cancer, are sources of oxidative stress in humans that could cause mitochondrial DNA (mtDNA) damage and increase mtDNA copy number. To test whether higher mtDNA copy number is associated with increased incident pancreatic cancer, we conducted a nested case-control study in the Alpha-Tocopherol Beta Carotene Cancer Prevention (ATBC) Study cohort of male smokers, aged 50 to 69 years at baseline. Between 1992 and 2004, 203 incident cases of pancreatic adenocarcinoma occurred (follow-up: 12 years) among participants, with whole blood samples used for mtDNA extraction. For these cases and 656 controls, we calculated ORs and 95% CIs using unconditional logistic regression, adjusting for age, smoking, and diabetes history. All statistical tests were two sided. Higher mtDNA copy number was significantly associated with increased pancreatic cancer risk (highest vs. lowest mtDNA copy number quintile, OR = 1.64, 95% CI = 1.01-2.67, continuous OR = 1.14, 95% CI 1.06-1.23), particularly for cases diagnosed during the first 7 years of follow-up (OR = 2.14, 95% CI = 1.16-3.96, P(trend) = 0.01, continuous OR = 1.21, 95% CI = 1.10-1.33), but not for cases occurring during follow-up of 7 years or greater (OR = 1.14, 95% CI = 0.53-2.45, continuous OR = 1.05, 95% CI = 0.93-1.18). Our results support the hypothesis that mtDNA copy number is associated with pancreatic cancer and could possibly serve as a biomarker for pancreatic cancer development.
authors.affiliation: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Rockville, MD 20852, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Lynch
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.forename: Chin-San
authors.initials: CS
authors.lastname: Liu
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Cheng
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Rachael Z
authors.initials: RZ
authors.lastname: Stolzenberg-Solomon
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology* / Q000517:prevention & control*; D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D048909:Diabetes Complications; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000517:prevention & control*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D024502:alpha-Tocopherol; D019207:beta Carotene
chemical_list: D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial; D019207:beta Carotene; D004247:DNA; D024502:alpha-Tocopherol