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- Kananen, L, et al.
(author)
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Circulating cell-free DNA in health and disease - the relationship to health behaviours, ageing phenotypes and metabolomics
- 2023
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In: GeroScience. - : Springer Science and Business Media LLC. - 2509-2723 .- 2509-2715. ; 45:1, s. 85-103
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Journal article (peer-reviewed)abstract
- Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.
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| 5. |
- Marttila, S, et al.
(author)
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Methylation status of VTRNA2-1/nc886 is stable across populations, monozygotic twin pairs and in majority of tissues
- 2022
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In: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 14:18, s. 1105-1124
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Journal article (peer-reviewed)abstract
- Aims & methods: The aim of this study was to characterize the methylation level of a polymorphically imprinted gene, VTRNA2-1/ nc886, in human populations and somatic tissues.48 datasets, consisting of more than 30 tissues and >30,000 individuals, were used. Results: nc886 methylation status is associated with twin status and ethnic background, but the variation between populations is limited. Monozygotic twin pairs present concordant methylation, whereas ∼30% of dizygotic twin pairs present discordant methylation in the nc886 locus. The methylation levels of nc886 are uniform across somatic tissues, except in cerebellum and skeletal muscle. Conclusion: The nc886 imprint may be established in the oocyte, and, after implantation, the methylation status is stable, excluding a few specific tissues.
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| 6. |
- Ola, Idris, et al.
(author)
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Prostate cancer incidence in men with prostate-specific antigen below 3 ng/mL: The Finnish Randomized Study of Screening for Prostate Cancer
- 2022
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 152:4, s. 672-678
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Journal article (peer-reviewed)abstract
- Prostate-specific antigen (PSA)-based screening for prostate cancer (PCa) can reduce PCa mortality, but also involves overdetection of low-risk disease with potential adverse effects. We evaluated PCa incidence among men with PSA below 3 ng/mL and no PCa diagnosis at the first screening round of the Finnish Randomized Study of Screening for PCa. Follow-up started at the first screening attendance and ended at PCa diagnosis, emigration, death or the common closing date (December 2016), whichever came first. Cox regression analysis was used to estimate hazard ratios and their confidence intervals (CI). Among men with PSA <3 ng/mL, cumulative PCa incidence was 9.1% after 17.6 years median follow-up. Cumulative incidence was 3.6% among men with baseline PSA 0 to 0.99 ng/mL, 11.5% in those with PSA 1.0 to 1.99 ng/mL and 25.7% among men with PSA 2 to 2.99 ng/mL (hazard ratio 9.0, 95% CI: 7.9-10.2 for the latter). The differences by PSA level were most striking for low-risk disease based on Gleason score and EAU risk group. PSA values <1 ng/mL indicate a very low 20-year risk, while at PSA 2 to 2.99 ng/mL risks are materially higher, with 4- to 5-fold risk for aggressive disease. Using risk-stratification and appropriate rescreening intervals will reduce screening intensity and overdetection. Using cumulative incidence of clinically significant PCa (csPCa) as the criterion, rescreening intervals could range from approximately 3 years for men with initial PSA 2 to 2.99 ng/mL, 6 years for men with PSA 1 to 1.99 ng/mL to 10 years for men with PSA <1 ng/mL.
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- Hakamies-Blomqvist, L., et al.
(author)
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Driver ageing does not cause higher accident rates per km
- 2002
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In: Transportation Research Part F. - 1369-8478 .- 1873-5517. ; 5:4, s. 271-274
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Journal article (peer-reviewed)abstract
- Based on Finnish survey data, older (65+, n=1559) and younger (26-40, n=310) drivers' accident rates were compared. In accordance with earlier studies, the rates were similar per driver (0.1) but there was a non-significant trend towards older drivers having more accidents per distance driven (10.8 vs. 8.3 per 1 million km). However, when the accidents-per-km comparison was made in groups matched for yearly exposure, there is no evidence for higher risk with increasing age. In both age groups, risk per km decreased with increasing yearly driving distance. We suggest that the previous perception of an age-related risk increase of accidents per distance driven arises from a failure to control for low mileage bias at all ages. © 2003 Elsevier Science Ltd. All rights reserved.
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