AUTHOR=Zheng Jian , Cui Ning-hua , Zhang Shuai , Wang Xue-bin , Ming Liang 

TITLE=Leukocyte Mitochondrial DNA Copy Number and Risk of Thyroid Cancer: A Two-Stage Case-Control Study

JOURNAL=Frontiers in Endocrinology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00421

DOI=10.3389/fendo.2019.00421

ISSN=1664-2392

ABSTRACT=<p><bold>Background:</bold> Mitochondrial DNA copy number (mtDNA-CN) may contribute to the development of various cancer types in a tumor-specific manner. However, little is known about whether leukocyte mtDNA content confers susceptibility to thyroid cancer (TC). This study aimed to investigate the associations of leukocyte mtDNA-CN with the risk and clinicopathological features of TC in a Chinese population.</p><p><bold>Methods:</bold> In this two-stage case-control study with a total of 402 TC patients and 406 controls, leukocyte mtDNA-CN content was measured with a quantitative PCR method. In a subset of 100 cases and 100 controls, levels of leukocyte 8-hydroxy-2′-deoxyguanosine (8-OHdG) and plasma malondialdehyde, as two biomarkers for oxidative stress, were determined by ELISA and colorimetric kits, respectively.</p><p><bold>Results:</bold> In a combined analysis of discovery and validation sets, high mtDNA-CN content was positively associated with increased TC risk, after adjusting for confounders (OR for per SD increment: 1.43; 95%CI, 1.23–1.66; <italic>P</italic> &lt; 0.001; OR for tertile 3 vs. tertile 1: 2.10; 95%CI, 1.48–3.00; <italic>P</italic><sub>trend</sub> &lt; 0.001). This linear dose-response relationship was more pronounced in subtype analyses for papillary and follicular thyroid carcinoma (<italic>P</italic> &lt; 0.001 for all), as well as in subgroup analyses for subjects with overweight and obesity (<italic>P</italic><sub>interaction</sub> = 0.015). In TC patient, we observed the positive correlations of mtDNA-CN with advanced TNM stage (<italic>P</italic> = 0.006) and the presence of lymph node metastasis (<italic>P</italic> = 0.012). Leukocyte mtDNA-CN content was also identified to increase with the levels of leukocyte 8-OHdG (<italic>P</italic> &lt; 0.001), a biomarker for oxidative DNA damage.</p><p><bold>Conclusion:</bold> Our data suggest that the increase in leukocyte mtDNA-CN content may correlate with oxidative DNA damage, and serve as an independent risk factor for TC.</p>