title: Urinary markers of nucleic acid oxidation and cancer in type 2 diabetes.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark. Electronic address: kasper.broedbaek.02@regionh.dk.
authors.forename: Kasper
authors.initials: K
authors.lastname: Broedbaek
authors.affiliation: The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Volkert
authors.initials: V
authors.lastname: Siersma
authors.affiliation: Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Henriksen
authors.affiliation: Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Weimann
authors.affiliation: Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Petersen
authors.affiliation: Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Jon T
authors.initials: JT
authors.lastname: Andersen
authors.affiliation: Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Espen
authors.initials: E
authors.lastname: Jimenez-Solem
authors.affiliation: The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lars J
authors.initials: LJ
authors.lastname: Hansen
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark.
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Henriksen
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark.
authors.forename: Steen J
authors.initials: SJ
authors.lastname: Bonnema
authors.affiliation: The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: de Fine Olivarius
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Friis
authors.affiliation: Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark; Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Poulsen
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000652:urine*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000473:pathology / Q000652:urine*; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives* / Q000652:urine; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D012313:RNA / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D006151:Guanosine; C046215:8-hydroxyguanosine; D012313:RNA; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine
keywords: 8‐oxo‐7,8‐dihydroguanosine; 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine; Cancer; DNA oxidation; RNA oxidation; Type 2 diabetes