Dataset Information

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

ABSTRACT: Background: 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. Methods: 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. Results: 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; P < 0.001; OR for tertile 3 vs. tertile 1: 2.10; 95%CI, 1.48-3.00; P _trend < 0.001). This linear dose-response relationship was more pronounced in subtype analyses for papillary and follicular thyroid carcinoma (P < 0.001 for all), as well as in subgroup analyses for subjects with overweight and obesity (P _interaction = 0.015). In TC patient, we observed the positive correlations of mtDNA-CN with advanced TNM stage (P = 0.006) and the presence of lymph node metastasis (P = 0.012). Leukocyte mtDNA-CN content was also identified to increase with the levels of leukocyte 8-OHdG (P < 0.001), a biomarker for oxidative DNA damage. Conclusion: 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.

SUBMITTER: Zheng J

PROVIDER: S-EPMC6614343 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Zheng Jian J Cui Ning-Hua NH Zhang Shuai S Wang Xue-Bin XB Ming Liang L

Frontiers in endocrinology 20190702

<b>Background:</b> 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. <b>Methods:</b> In this two-stage case-control study with a total of 402 TC patients and 406 co ...[more]

PMID: 31312182

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Project description:Background:Mitochondrial dysfunction is an important component of the aging process and has been implicated in the development of many human diseases. Mitochondrial DNA copy number (mtDNAcn), an indirect biomarker of mitochondrial function, is sensitive to oxidative damage. Few population-based studies have investigated the impact of fruit and vegetable consumption and cigarette smoke (2 major sources of exogenous antioxidants and oxidants) on leukocyte mtDNAcn. Objectives:We investigated the association between fruit and vegetable consumption, cigarette smoke, and leukocyte mtDNAcn based on data from the Nurses' Health Study (NHS). Methods:Data from 2769 disease-free women in the NHS were used to examine the cross-sectional associations between dietary sources of antioxidants, cigarette smoke, and leukocyte mtDNAcn. In vitro cell-based experiments were conducted to support the findings from the population-based study. Results:In the multivariable-adjusted model, both whole-fruit consumption and intake of flavanones (a group of antioxidants abundant in fruit) were positively associated with leukocyte mtDNAcn (P-trend = 0.005 and 0.02, respectively), whereas pack-years of smoking and smoking duration were inversely associated with leukocyte mtDNAcn (P-trend = 0.01 and 0.007, respectively). These findings are supported by in vitro cell-based experiments showing that the administration of naringin, a major flavanone in fruit, led to a substantial increase in mtDNAcn in human leukocytes, whereas exposure to nicotine-derived nitrosamine ketone, a key carcinogenic ingredient of cigarette smoke, resulted in a significant decrease in mtDNAcn of cells (all P < 0.05). Further in vitro studies showed that alterations in leukocyte mtDNAcn were functionally linked to the modulation of mitochondrial biogenesis and function. Conclusions:Fruit consumption and intake of dietary flavanones were associated with increased leukocyte mtDNAcn, whereas cigarette smoking was associated with decreased leukocyte mtDNAcn, which is a promising biomarker for oxidative stress-related health outcomes.

Project description:Abnormalities in the mitochondria have been linked to psoriasis, a chronic immune-mediated inflammatory skin disease. The mitochondrial DNA (mtDNA) is present in thousands of copies per cell and altered mtDNA copy number (mtDNA-CN), a common indicator of mitochondrial function, has been proposed as a biomarker for several diseases including autoimmune diseases. In this case-control study, we investigated whether the mtDNA-CN is related to psoriasis, correlates with the disease duration and severity, and can serve as a disease biomarker. Relative mtDNA-CN as compared with nuclear DNA was measured by a quantitative real-time polymerase chain reaction in peripheral blood buffy coat samples from 56 patients with psoriasis and 44 healthy controls. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the value of mtDNA-CN as a biomarker. We found that the mtDNA-CN was significantly decreased in patients with psoriasis compared to healthy controls (93.6±5.3 vs. 205±71; P = 0.04). Sub-group analyses with stratification of patients based on disease duration under or over 10 years and disease severity indicated that the mtDNA-CN was significantly lower in patients with longer disease duration (74±4.3 in disease duration >10 years vs. 79±8.3 in disease duration <10 years, P = 0.009), and higher disease severity (72±4.3 in moderate-to-severe index vs. 88.3 ± 6 in mild index, P = 0.017). Moreover, the mtDNA-CN was negatively correlated with the disease duration and disease severity (r = -0.36, P = 0.006; r = -0.41, P = 0.003 respectively). The ROC analysis of mtDNA-CN showed an area under the curve (AUC) of 0.84 (95% confidence interval: 0.69-0.98; P = 0.002) for differentiating patients from healthy controls. Our study suggests that low mtDNA-CN may be an early abnormality in psoriasis and associates with the disease progression. Our study also suggests that mtDNA-CN may be a novel blood-based biomarker for the early detection of psoriasis.

Dataset Information

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

Publications

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

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