Abstract
The comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan–Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p < 0.001). The effect of DNA damage on survival was modelled according to Cox proportional hazard regression model. The adjusted hazard ratio (HR) was 1.42 (1.06–1.90) for overall mortality, and 1.94 (1.04–3.59) for diseases of the circulatory system in subjects with the highest tertile of DNA damage. The findings of this study provide epidemiological evidence encouraging the implementation of the comet assay in preventive strategies for non-communicable diseases.
Highlights
The comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations
The association between mortality risk and tertile of DNA damage was further investigated with the Kaplan–Meier analysis, which indicated a worse outcome in subjects in the medium or high tertile of DNA damage, a result which was consistent over the follow-up time, as shown by Fig. 1 and Fig. 2 (%T; χ22 = 22.48, P < 0.001)
The results of the present study provide support for the hypothesis that an increased level of DNA damage represents a relevant event in the pathway leading to chronic disease and eventually to death
Summary
The comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Examples of biomarkers of genomic instability that have been linked to the risk of cancer with this study design include the frequency of chromosomal aberrations and micronuclei in peripheral lymphocytes[10,11,12,13,14,15,16] Other biomarkers such as DNA adducts have been positively investigated using a nested case–control design with analysis of stored s amples[17, 18], the historical cohort approach remains the most appropriate for those biomarkers that are preferably evaluated on fresh tissue. To individual data required for a follow-up of cancer incidence and mortality, and that—after receiving ethical approval—they could interrogate local/national cancer registries or registries of causes of death
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