ABSTRACT
Changes in whole blood (WB) mitochondrial DNA (mtDNA) content are associated with health and disease. Platelet-derived mtDNA can confound WB mtDNA content measurements. From a sample of 44 volunteers, we show that platelet mtDNA content and platelet:leukocyte ratio are both dependent predictors of WB mtDNA content, but that platelet count itself is not. Furthermore, when platelet:leukocyte ratio increased by <2-fold ex vivo, the effect on WB mtDNA content was minimal. Altogether, this study clarifies the contribution of platelet mtDNA content rather than platelet count on WB mtDNA content measurements, and identifies defined parameters for future research on WB mtDNA content.
Subject(s)
DNA, Mitochondrial/genetics , Leukocytes, Mononuclear/chemistry , Mitochondria/genetics , Adult , Female , Healthy Volunteers , Humans , Leukocyte Count , Male , Platelet Count , Real-Time Polymerase Chain Reaction , Young AdultABSTRACT
PURPOSE: A retrospective review of adolescent and young adult (AYA) head and neck cancer (HNC) patients treated with radiation therapy (RT) at British Columbia Cancer was performed to determine the incidence of late toxicities, the documented late side effects discussed and the screening recommendations provided at the time of transfer of care to primary care providers (PCPs). METHODS: Charts (n = 162) were reviewed for all patients 15 to 35 years at diagnosis with HNC treated with RT from 1960 to 2010 who survived > 5 years after diagnosis. RESULTS: A discussion regarding the risk of long-term side effects was documented in the initial consultation for 85% of patients. The majority of patients (78%) developed > 1 documented late effect. The most common were xerostomia (44%), skin changes (28%), neck fibrosis (22%), nasal crusting (16%), epistaxis (16%), and dental decay (14%). In all, 20% were currently followed or were followed until they died. Of the 80% transferred to their PCP, 14% had a formal discharge summary. For those discharged from British Columbia Cancer, documented recommendations included regular dental care (34%) and screening for hypothyroidism (5%) and second malignancy (4%). CONCLUSIONS: The majority of AYA HNC patients treated with RT developed late side effects, and most PCPs were not sent a discharge summary outlining screening recommendations for delayed late effects. IMPLICATIONS FOR CANCER SURVIVORS: AYA HNC survivors treated with RT are at high risk for late effects and would benefit from a survivorship care plan outlining these risks and screening recommendations.
Subject(s)
Cancer Survivors , Head and Neck Neoplasms/radiotherapy , Neoplasms, Radiation-Induced/diagnosis , Neoplasms, Radiation-Induced/etiology , Adolescent , British Columbia/epidemiology , Dental Caries/diagnosis , Dental Caries/epidemiology , Dental Caries/etiology , Documentation/methods , Female , Head and Neck Neoplasms/epidemiology , Humans , Hypothyroidism/diagnosis , Hypothyroidism/epidemiology , Hypothyroidism/etiology , Incidence , Male , Middle Aged , Neoplasms, Radiation-Induced/epidemiology , Neoplasms, Second Primary , Radiation Injuries/diagnosis , Radiation Injuries/epidemiology , Radiation Injuries/etiology , Radiotherapy/adverse effects , Retrospective Studies , Xerostomia/diagnosis , Xerostomia/epidemiology , Xerostomia/etiology , Young AdultABSTRACT
BACKGROUND: Increased cell-free DNA levels are associated with poor health outcomes, and cell-free mitochondrial DNA (cf-mtDNA) has proinflammatory properties. Given that HIV infection is associated with chronic inflammation, we investigated the relationship between cf-mtDNA and proinflammatory cytokine interleukin-6 (IL-6) in the context of HIV infection. We also optimized separation of cell-free plasma from blood. SETTING: In this retrospective cross-sectional study, we collected blood, demographic information, and clinical data from 99 HIV-infected and 103 HIV-uninfected adults and children enrolled in the Children and Women: AntiRetrovirals and Markers of Aging pan-Canadian (CARMA) cohort. METHODS: Plasma was separated from blood by 14,000g centrifugation followed by 0.45-µm filtration to remove cells and platelets. Cf-mtDNA and cell-free nuclear DNA were quantified simultaneously via monochrome, multiplex, quantitative polymerase chain reaction. IL-6 was measured using enzyme-linked immunosorbent assay. RESULTS: Higher speed centrifugation and filtration was necessary to isolate truly cell-free plasma. Higher cf-mtDNA levels were univariately associated with HIV infection, elevated IL-6 levels, younger age, higher white blood cell count, and higher cell-free nuclear DNA levels but not blood mtDNA content or HIV viral load. In a multivariable model, HIV infection (P < 0.001), elevated IL-6 (P = 0.021), younger age (P < 0.001), and higher blood nDNA levels (P = 0.007) were independently associated with higher cf-mtDNA. CONCLUSIONS: People living with HIV have higher levels of circulating cf-mtDNA than their uninfected peers. Increased levels of inflammatory marker IL-6 are associated with elevated cf-mtDNA, independent of the effect of HIV infection. Higher cf-mtDNA levels and white blood cell count in younger people may reflect higher cell turnover in that population.
