Mitochondrial DNA copy number and pancreatic cancer in the alpha-tocopherol beta-carotene cancer prevention study.
Mitochondrial DNA copy number and pancreatic cancer in the alpha-tocopherol beta-carotene cancer prevention study.
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DOI：
10.1158/1940-6207.capr-11-0002
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发表时间：
2011-11
期刊：
影响因子：
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通讯作者：
Stolzenberg-Solomon RZ
中科院分区：
文献类型：
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作者：
Lynch SM;Weinstein SJ;Virtamo J;Lan Q;Liu CS;Cheng WL;Rothman N;Albanes D;Stolzenberg-Solomon RZ
糖尿病、肥胖和吸烟是胰腺癌的一贯危险因素，是人类氧化应激的来源，可能导致线粒体DNA（mtDNA）损伤并增加mtDNA拷贝数。为了测试较高的mtDNA拷贝数是否与胰腺癌发病率增加相关，我们在α-生育酚β-胡萝卜素癌症预防（ATBC）研究队列中进行了一项巢式病例对照研究，研究对象为基线年龄为50-69岁的男性吸烟者。在1992年至2004年期间，在使用全血样本进行mtDNA提取的参与者中发生了203例胰腺癌事件（随访：12年）。对于这些病例和656例对照，我们使用非条件logistic回归计算了比值比（OR）和95%置信区间，并调整了年龄、吸烟和糖尿病史。所有统计学检验均为双侧检验。线粒体DNA拷贝数增加与胰腺癌风险增加显著相关（最高与最低mtDNA拷贝数五分位数，OR=1.64，95%CI=1.01-2.67，连续OR=1.14，95%CI 1.06-1.23），特别是在随访的前7年内诊断的病例（OR= 2.14，95% CI=1.16-3.96，p-trend=0.01，连续OR=1.21，95% CI 1.10-1.33），但对于随访7年或更长时间内发生的病例则不存在（OR= 1.14，95% CI=0.53-2.45，连续OR=1.05，95% CI 0.93-1.18）。我们的研究结果支持线粒体DNA拷贝数与胰腺癌相关的假设，并可能作为胰腺癌发展的生物标志物。
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 50-69 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 odds ratios (OR) and 95% confidence intervals 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.