TY - JOUR

T1 - Urinary markers of nucleic acid oxidation and cancer in type 2 diabetes

AU - Broedbaek, Kasper

AU - Siersma, Volkert

AU - Henriksen, Trine Foged

AU - Weimann, Allan

AU - Petersen, Morten

AU - Andersen, Jon T.

AU - Solem, Espen Victor Jimenez

AU - Hansen, Lars J

AU - Henriksen, Jan Erik

AU - Bonnema, Steen J

AU - de Fine Olivarius, Niels

AU - Friis, Søren

AU - Poulsen, Henrik E

N1 - Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

PY - 2015/4

Y1 - 2015/4

N2 - AIMS/HYPOTHESIS: We investigated whether urinary markers of nucleic acid oxidation are associated with an increased risk of cancer in type 2 diabetes patients.METHODS: Urine samples from 1381 newly diagnosed diabetes patients were assayed for the oxidatively modified guanine nucleosides 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo). Cox proportional hazards regression was used to examine the relationship between the urinary markers and cancer incidence.RESULTS: The crude analyses showed an association between overall cancer and urinary excretion of the RNA oxidation marker 8-oxoGuo (unadjusted hazard ratio for cancer per natural log increase in 8-oxoGuo 1.35 [95% CI, 1.01-1.81]), however, in the adjusted analyses, no significant associations between 8-oxodG or 8-oxoGuo and overall cancer were found. For site-specific cancers 8-oxodG was associated with breast cancer in the crude analyses (unadjusted hazard ratio for breast cancer per natural log increase in 8-oxodG was 2.37 [95% CI, 1.07-5.26]), although the association was attenuated in the adjusted analyses (sex- and age-adjusted hazard ratio 2.15 [95% CI, 0.92-5.02] and multivariate adjusted hazard ratio1.98 [95% CI, 0.95-4.10]).CONCLUSIONS: Urinary excretion of the nucleic acid oxidation markers 8-oxodG and 8-oxoGuo at the time of diagnosis was not associated with cancer overall in type 2 diabetes patients. For site-specific cancers, risk elevations were seen for breast cancer (8-oxodG). These findings should be examined in future and larger studies.

AB - AIMS/HYPOTHESIS: We investigated whether urinary markers of nucleic acid oxidation are associated with an increased risk of cancer in type 2 diabetes patients.METHODS: Urine samples from 1381 newly diagnosed diabetes patients were assayed for the oxidatively modified guanine nucleosides 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo). Cox proportional hazards regression was used to examine the relationship between the urinary markers and cancer incidence.RESULTS: The crude analyses showed an association between overall cancer and urinary excretion of the RNA oxidation marker 8-oxoGuo (unadjusted hazard ratio for cancer per natural log increase in 8-oxoGuo 1.35 [95% CI, 1.01-1.81]), however, in the adjusted analyses, no significant associations between 8-oxodG or 8-oxoGuo and overall cancer were found. For site-specific cancers 8-oxodG was associated with breast cancer in the crude analyses (unadjusted hazard ratio for breast cancer per natural log increase in 8-oxodG was 2.37 [95% CI, 1.07-5.26]), although the association was attenuated in the adjusted analyses (sex- and age-adjusted hazard ratio 2.15 [95% CI, 0.92-5.02] and multivariate adjusted hazard ratio1.98 [95% CI, 0.95-4.10]).CONCLUSIONS: Urinary excretion of the nucleic acid oxidation markers 8-oxodG and 8-oxoGuo at the time of diagnosis was not associated with cancer overall in type 2 diabetes patients. For site-specific cancers, risk elevations were seen for breast cancer (8-oxodG). These findings should be examined in future and larger studies.

U2 - 10.1016/j.redox.2014.11.010

DO - 10.1016/j.redox.2014.11.010

M3 - Journal article

C2 - 25498965

VL - 4

SP - 34

EP - 39

JO - Redox Biology

JF - Redox Biology

SN - 2213-2317

ER -