Event Title

Session 1K: Mitochondrial DNA Oxidative Damage May Predict Cancer Risk: The Normative Aging Study

Session Number

Session 1K: 3rd Presentation

Advisor(s)

Lifang Hou, Northwestern University

Location

Room A119

Start Date

28-4-2017 8:30 AM

End Date

28-4-2017 9:45 AM

Abstract

Oxidative stress (OS) in response to intra- and extracellular environmental stress can induce carcinogenic mechanisms such as DNA damage and defective DNA repair. 8-hydroxy- 2’deoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, is a marker of oxidative stress and has previously been measured in tissue samples only after cancer diagnosis. In this study, we examined the prospective and retrospective association between mitochondrial DNA (mtDNA) 8-OHdG in blood leukocytes and cancer risk. Our study population included a total of 443 participants in the Normative Aging Study who had blood drawn during 1-3 visits (mean follow up 9.0 years), prior to cancer diagnosis. We used retrospective analysis with mixed linear regression to determine whether OS levels differed by cancer status, and survival analysis with Cox model to examine associations between OS levels and cancer risk. Based on retrospective analysis, participants that eventually developed cancer had 2% less mitochondrial oxidative stress than their cancer- free counterparts (p=0.04). Survival analysis showed that for every 0.1 unit of increase in mitochondrial oxidative stress, cancer risk decreased by 23% (p=0.01). Further analysis revealed a positive association between mtDNA OS and activation of tumor suppressor genes (OGG1 and SIRT3) in the base-excision repair pathway which has been associated with reduced cancer risk. Out study suggests that mtDNA OS in leukocytes could be a potential biomarker for early cancer detection and prevention.

Comments

Additional team members: Yinan Zheng

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Apr 28th, 8:30 AM Apr 28th, 9:45 AM

Session 1K: Mitochondrial DNA Oxidative Damage May Predict Cancer Risk: The Normative Aging Study

Room A119

Oxidative stress (OS) in response to intra- and extracellular environmental stress can induce carcinogenic mechanisms such as DNA damage and defective DNA repair. 8-hydroxy- 2’deoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, is a marker of oxidative stress and has previously been measured in tissue samples only after cancer diagnosis. In this study, we examined the prospective and retrospective association between mitochondrial DNA (mtDNA) 8-OHdG in blood leukocytes and cancer risk. Our study population included a total of 443 participants in the Normative Aging Study who had blood drawn during 1-3 visits (mean follow up 9.0 years), prior to cancer diagnosis. We used retrospective analysis with mixed linear regression to determine whether OS levels differed by cancer status, and survival analysis with Cox model to examine associations between OS levels and cancer risk. Based on retrospective analysis, participants that eventually developed cancer had 2% less mitochondrial oxidative stress than their cancer- free counterparts (p=0.04). Survival analysis showed that for every 0.1 unit of increase in mitochondrial oxidative stress, cancer risk decreased by 23% (p=0.01). Further analysis revealed a positive association between mtDNA OS and activation of tumor suppressor genes (OGG1 and SIRT3) in the base-excision repair pathway which has been associated with reduced cancer risk. Out study suggests that mtDNA OS in leukocytes could be a potential biomarker for early cancer detection and prevention.