Dataset Information

Pre-diagnostic leukocyte mitochondrial DNA copy number and skin cancer risk.

ABSTRACT: No previous study has examined the association between mitochondrial DNA copy number (mtCN) and skin cancer risk prospectively. We examined the associations between peripheral blood leukocytes mtCN level and the risks of skin cancers in a case-control study nested within the Nurses' Health Study of non-Hispanic White women, including 272 melanoma cases and 293 controls, 508 squamous cell carcinoma (SCC) cases and 550 controls, and 515 basal cell carcinoma (BCC) cases and 536 controls. Relative mtCN in peripheral blood leukocytes was measured by quantitative PCR-based assay. Unconditional logistic regression models were used to examine the associations between mtCN and skin cancer risks. Compared with those with high mtCN, the risk for melanoma was 1.06 [95% confidence interval (CI) = 0.70-1.62] in the median group and 1.19 (95% CI = 0.78-1.81) for the low group. There was suggestive evidence that increased risk for melanoma was apparent among low constitutional susceptibility group [odds ratio (OR)low versus high = 1.80, 95% CI = 0.95-3.39, P for trend = 0.07, P for interaction = 0.06]. The increased risk of melanoma was also apparent among high cumulative UV exposure group (ORlow versus high = 3.40, 95% CI = 1.46-7.92, P for trend = 0.004, P for interaction = 0.01). For non-melanoma skin cancers, compared with high-mtCN group, low-mtCN group had an increased risk for SCC (OR = 1.26, 95% CI = 0.93-1.71) and BCC (OR = 1.35; 95% CI = 1.00-1.82). Because some of the associations were marginally significant, the results only provided suggestive evidence. Further studies are warranted to replicate these findings and better understand the underlying mechanisms.

SUBMITTER: Meng S

PROVIDER: S-EPMC5008249 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Pre-diagnostic leukocyte mitochondrial DNA copy number and skin cancer risk.

Meng Shasha S De Vivo Immaculata I Liang Liming L Giovannucci Edward E Tang Jean Y JY Han Jiali J

Carcinogenesis 20160705 9

No previous study has examined the association between mitochondrial DNA copy number (mtCN) and skin cancer risk prospectively. We examined the associations between peripheral blood leukocytes mtCN level and the risks of skin cancers in a case-control study nested within the Nurses' Health Study of non-Hispanic White women, including 272 melanoma cases and 293 controls, 508 squamous cell carcinoma (SCC) cases and 550 controls, and 515 basal cell carcinoma (BCC) cases and 536 controls. Relative m ...[more]

PMID: 27381830

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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

Pre-diagnostic leukocyte mitochondrial DNA copy number and skin cancer risk.

Publications

Pre-diagnostic leukocyte mitochondrial DNA copy number and skin cancer risk.

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