Urinary 8-isoprostane levels and occurrence of lung, colorectal, prostate, breast and overall cancer: Results from a large, population-based cohort study with 14 years of follow-up

Wilsgaard

Jansen

et al. 2019

Intl Journal of Cancer

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Oxidative stress may be involved in carcinogenesis and biomarkers of oxidative stress like derivatives of reactive oxygen metabolites (d‐ROM) may be useful for cancer prediction. However, no previous study assessed the association of pre‐diagnostic d‐ROM measurements with cancer incidence. We measured serum d‐ROM levels in a cohort sample of n = 4,345 participants of the German ESTHER study and in a case‐cohort sample of the Norwegian Tromsø study (cancer cases: n = 941; subcohort: n = 1,000). Moreover, d‐ROM was repeatedly measured at follow‐ups of both studies. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were derived by (weighted) multivariable‐adjusted Cox regression with time‐dependent modeling of d‐ROM levels for incident lung, colorectal, breast and prostate cancer. Individual study results were pooled by random effects meta‐analysis. The HRs (95% CI) for comparison of top and bottom d‐ROM tertile were statistically significant for lung (1.90 [1.25–2.89]), colorectal (1.70 [1.15–2.51]) and breast cancer incidence (1.45 [1.01–2.09]) but not for prostate cancer incidence (1.20 [0.84–1.72]). In conclusion, this individual participant data meta‐analysis of two large population‐based cohort studies with repeated d‐ROM measurements yielded evidence for an involvement of high oxidative stress in carcinogenesis. Given the observed associations of pre‐diagnostic d‐ROM measurements with lung, colorectal and breast cancer incidence, subjects with increased serum d‐ROM levels should be recommended to reduce these levels by lifestyle changes including smoking cessation, a healthy diet and an increase in physical activity.

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 74%

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Pre‐diagnostic derivatives of reactive oxygen metabolites and the occurrence of lung, colorectal, breast and prostate cancer: An individual participant data meta‐analysis of two large population‐based studies

Wilsgaard

Jansen

et al. 2019

Intl Journal of Cancer

Self Cite

“…Nonphysiologically high levels of free radicals oxidatively damage DNA, proteins and cell membranes and can subsequently promote cancer development. A population‐based study has shown that the lipid peroxidation end‐product 8‐isoprostane is an independent risk factor for various types of cancer . Therefore, the antioxidant system may be essential for maintaining redox harmony and prevention of carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Serum total thiol levels and the risk of lung, colorectal, breast and prostate cancer: A prospective case–cohort study

Wilsgaard

Jansen

et al. 2019

Intl Journal of Cancer

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Free thiol groups of intra and extracellular molecules are considered to be antioxidative and to protect cells from damage caused by free radicals. However, the associations of serum total thiol levels (TTL) with the incidences of the four most frequent cancer sites have not yet been investigated in a large population‐based, prospective study. TTL was measured in case–cohort design in a sample from the population‐based, Norwegian Tromsø 3 study (cancer cases: n = 941; random subcohort: n = 1,000) and was repeatedly measured at Tromsø 5. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by weighted multivariable‐adjusted Cox regression with time‐dependent modeling of TTL for incident lung, colorectal, breast and prostate cancer. High serum TTL were associated with a reduced risk of all four major cancers. The associations with lung (top vs. bottom tertile: HR, 0.64; 95% CI, 0.41, 0.99) and breast cancer (top vs. bottom tertile: HR, 0.64; 95% CI, 0.42, 0.96) were statistically significant, whereas associations with colorectal (top vs. bottom tertile: HR, 0.79; 95% CI, 0.54, 1.16) and prostate cancer (top vs. bottom tertile: HR, 0.79; 95% CI, 0.53, 1.17) were not statistically significant but pointed in the same protective direction. These findings from a large, prospective Norwegian cohort study suggest a preventive role of thiols against the development of the four most frequent cancers. Whereas associations with breast and lung cancer could be shown with statistical significance, larger studies are needed to corroborate potential associations of TTL with colorectal and prostate cancer.

Associations of urinary 8‐iso‐prostaglandin F_2α levels with all‐cause dementia, Alzheimer's disease, and vascular dementia incidence: results from a prospective cohort study

Trares

Perna

et al. 2020

Alzheimer's & Dementia

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Introduction: Prospective studies on a potential association of 8-iso-prostaglandin F 2 (8-iso-PGF 2) levels, a biomarker of lipid peroxidation, with dementia are limited. Methods: Multivariate Cox regression models were used to assess potential associations of urinary 8-iso-PGF 2 levels with all-cause, Alzheimer's disease (AD), and vascular dementia (VD) incidence in 5853 older adults from a German, population-based cohort. Results: Over 14 years of follow-up, 365 all-cause dementia cases including 127 VD and 109 AD cases were diagnosed. Participants in the top compared to the bottom 8iso-PGF 2 tertile had a 45% increased risk of all-cause dementia incidence (hazard ratio [95% confidence interval]: 1.45 [1.12 to 1.88]). Interaction with the apolipoprotein E (APOE) ԑ4/ԑ4 genotype was detected (P = .02). Furthermore, continuously modeled, logarithmized 8-iso-PGF 2 levels were statistically significantly associated with all-cause dementia and AD incidence. Discussion: Oxidative stress may be involved in the pathogenesis of dementia. Individuals with increased 8-iso-PGF 2 levels and the APOE ԑ4/ԑ4 genotype showed a considerably increased dementia risk. K E Y W O R D S 8-iso-prostaglandin F 2 , Alzheimer's disease, cohort study, dementia, oxidative stress, vascular dementia 1 BACKGROUND Growing evidence shows that oxidative stress (OS) plays an important role in the development of dementia, especially of Alzheimer's disease (AD) and vascular dementia (VD). 1 OS occurs if the production of oxidants exceeds antioxidant defenses, causing a disruption of redox This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. c ○ 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association signaling and control. 2 Reactive oxygen species (ROS), the most abundantly produced oxidants, are increasingly produced and damage proteins and lipids in the brain. Consequently, neurodegeneration and cell death occur. 1,3 However, it has been observed that OS is not only associated with dementia, but also with its risk factors, including hypertension, diabetes, hypercholesterolemia, obesity, depression,