Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, EPS 8003, MSC 7240, Bethesda, MD 20892, USA.
Cancer Epidemiol Biomarkers Prev. 2011 Sep;20(9):1944-9. doi: 10.1158/1055-9965.EPI-11-0379. Epub 2011 Jul 22.
Mitochondrial DNA (mtDNA) is an approximately 16,000-bp circular double-stranded DNA molecule that is a prime target of oxidative damage. Several somatic mutations in mtDNA have been observed in gastric tumors, suggesting an involvement in gastric cancer risk and progression. mtDNA copy number in leukocyte DNA has also been linked to several other cancers, although the temporal relationship between mtDNA and cancer has not been adequately explored.
Using a nested case-control study design, we examined the association between mtDNA copy number in 162 gastric cancer cases and 299 matched controls within the Shanghai Women's Health Study, a large population-based prospective cohort. Relative mtDNA copy number was measured in triplicate by a quantitative real-time PCR assay in peripheral leukocytes.
mtDNA copy number levels were comparable among cases and controls, with a median of 1.04 [interquartile range (IQR), 0.87-1.25] and 1.06 (IQR, 0.88-1.29), respectively. Overall, mtDNA was not associated with gastric cancer risk. However, the association differed when stratified by the time between sample collection and cancer diagnosis. An association between low levels of mtDNA copy number (<median) and gastric cancer risk was apparent among earlier diagnosed cases, in particular, those diagnosed within 2 years of sample collection (OR = 5.32; 95% CI = 1.03-27.60). This association was not present as the time between sample collection and cancer diagnosis increased.
Our findings suggest that there is no association between leukocyte mtDNA copy number and risk of developing gastric cancer; however, we observed a possible early disease effect on mtDNA copy number levels.
线粒体 DNA（mtDNA）是一个大约 16000bp 的圆形双链 DNA 分子，是氧化损伤的主要靶点。在胃肿瘤中已经观察到 mtDNA 的几个体细胞突变，提示其参与胃癌的风险和进展。白细胞 DNA 中的 mtDNA 拷贝数也与其他几种癌症有关，尽管 mtDNA 与癌症之间的时间关系尚未得到充分探讨。
我们采用巢式病例对照研究设计，在上海妇女健康研究中，对 162 例胃癌病例和 299 例匹配对照者的 mtDNA 拷贝数进行了研究，该研究是一项大型基于人群的前瞻性队列研究。通过外周白细胞定量实时 PCR 检测 mtDNA 拷贝数。
病例组和对照组的 mtDNA 拷贝数水平相当，中位数分别为 1.04（四分位距，0.87-1.25）和 1.06（四分位距，0.88-1.29）。总体而言，mtDNA 与胃癌风险无关。然而，当按样本采集与癌症诊断之间的时间进行分层时，这种关联就有所不同。在早期诊断的病例中，尤其是在样本采集后 2 年内诊断的病例中，低水平的 mtDNA 拷贝数（<中位数）与胃癌风险之间存在关联（OR=5.32；95%CI=1.03-27.60）。随着样本采集与癌症诊断之间的时间增加，这种关联并不存在。
我们的研究结果表明，白细胞 mtDNA 拷贝数与发生胃癌的风险之间没有关联；然而，我们观察到 mtDNA 拷贝数水平可能与早期疾病有关。
