Jansen Rick J, Fonseca-Williams Sharon, Bamlet William R, Ayala-Peña Sylvette, Oberg Ann L, Petersen Gloria M, Torres-Ramos Carlos A
Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
Department of Physiology and Biophysics, University of Puerto Rico, San Juan, Puerto Rico.
Mol Carcinog. 2015 Oct;54(10):1220-6. doi: 10.1002/mc.22189. Epub 2014 Aug 11.
DNA repair is a key mechanism in maintaining genomic stability: repair deficiencies increase DNA damage and mutations that lead to several diseases, including cancer. We extracted DNA from peripheral blood mononuclear cells (PBMCs) of 48 pancreatic adenocarcinoma cases and 48 healthy controls to determine relative levels of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage by QPCR. All participants were never smokers and between the ages of 60 and 69. Average levels among cases were compared to controls using a rank sum test, and logistic regression adjusted for potential confounding factors (age, sex, and diabetes mellitus). Cases had less DNA damage, with a significant decrease in mtDNA damage (P-value = 0.03) and a borderline significant decrease in nDNA damage (P = 0.08). Across samples, we found mtDNA abundance was higher among non-diabetics compared to diabetics (P = 0.04). Our results suggest that patients with pancreatic adenocarcinoma have less DNA damage in their PBMCs, and that having diabetes, a known pancreatic cancer risk factor, is associated with lower levels of mtDNA abundance.
DNA修复是维持基因组稳定性的关键机制:修复缺陷会增加DNA损伤和突变,进而导致包括癌症在内的多种疾病。我们从48例胰腺腺癌患者和48例健康对照者的外周血单核细胞(PBMC)中提取DNA,通过定量聚合酶链反应(QPCR)测定核DNA(nDNA)和线粒体DNA(mtDNA)损伤的相对水平。所有参与者均为非吸烟者,年龄在60至69岁之间。使用秩和检验比较病例组和对照组的平均水平,并采用逻辑回归对潜在混杂因素(年龄、性别和糖尿病)进行校正。病例组的DNA损伤较少,mtDNA损伤显著降低(P值 = 0.03),nDNA损伤有临界显著降低(P = 0.08)。在所有样本中,我们发现非糖尿病患者的mtDNA丰度高于糖尿病患者(P = 0.04)。我们的结果表明,胰腺腺癌患者的PBMC中DNA损伤较少,并且作为已知胰腺癌风险因素的糖尿病与较低水平的mtDNA丰度相关。