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Cancer Care Engineering: Studies on Oxidative Damage and SNPs

Cancer Care Engineering: Studies on Oxidative Damage and SNPs. Lisa M. Kamendulis, PhD James E. Klaunig, PhD Indiana University. Question: Is oxidative stress status altered in individuals with polyps or colorectal cancer?. Pro-oxidants H 2 O 2 , O 2 - , HO, 1 O 2. Antioxidants

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Cancer Care Engineering: Studies on Oxidative Damage and SNPs

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  1. Cancer Care Engineering:Studies on Oxidative Damage and SNPs Lisa M. Kamendulis, PhD James E. Klaunig, PhD Indiana University

  2. Question:Is oxidative stress status altered in individuals with polyps or colorectal cancer? Pro-oxidants H2O2, O2-, HO, 1O2 Antioxidants GSH, Vitamin E, VitC, SOD, Catalase, etc Approach • Whole blood collected and processed from 235 individuals for: • Comet Analysis (Direct and Oxidative DNA damage) • Total Antioxidant Capacity (TEAC) • Focused SNP analysis • Samples: • 104 controls • 92 polyps • 27 colon cancer • 11 with 1 follow-up; 4 with 2 follow-up • 12 rectal cancer • 3 with 1 follow-up; 2 with 2 follow-up • SNPs evaluated only on samples from the initial visit What Modulates Oxidative Stress? Dietary and lifestyle influences • high fat diet, alcohol, smoking, etc.  increased levels • Antioxidants  decreased levels Inflammation • Sources: • Mitochondria • Endothelial Cells • Immune Cells (including microglia) • Peroxisomes • Metabolism (P450) (Xenobiotics)

  3. Question:Is oxidative stress status altered in individuals with polyps or colorectal cancer? • Comet data (235 samples analyzed): • Total Antioxidant Capacity (TEAC) Data (235 samples analyzed):

  4. Question:Do differences exist in SNPs for oxidative stress and damage, and selective genes associated with colorectal cancer? • SNPs evaluated (129 samples analyzed) • Oxidative Stress • Catalase • SOD2 • NOS3 • GSTP • GSTM1 • DNA Damage/Repair • APEX1 • XRCC • OGG1 • TP53 • Inflammation • IL-6 • IL-8 • PTGS2 (COX2) • Vitamin D Status • VDR • CASR • CYP24A1 • Metabolism • CYP1A2 • CYP3A4

  5. Question:Do differences exist in SNPs for oxidative stress and damage, and selective genes associated with colorectal cancer?

  6. Question:Do differences exist in SNPs for oxidative stress and damage, and selective genes associated with colorectal cancer? GSTM1 null shown to be protective, % null population decreases in colorectal cancer Polymorphism in promoter region of COX2 reported to change transcriptional activity. Not previously reported in colon cancer I64V amino acid change, function unknown. No differences observed in this population.

  7. Next Steps • Complete sample and data analysis • 3 additional samples collected • SNPs completed on all 235 samples • Data Analysis/Evaluation • SNP tools • Correlation analysis with other endpoints

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