hcc_prevention

hcc_prevention - Strategies for Prevention of HCC Molecular...

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Strategies for Prevention of HCC
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May 2nd, 2005 Megan McBee-BE.450 2 Molecular Epidemiology • Identify risk factors and outcome •B iomarkers •Carcinogen-macromolecular adducts •Normal DNA sequence variants •Mutations in target genes • Measure in urine, serum or tissue •Immunoassays •GC/MS, LC/MS
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May 2nd, 2005 Megan McBee-BE.450 3 HCC Epidemiology • Annual new cases ~600,000 • ~600,000 annual deaths – 80% burden in Asia and sub- saharan Africa – 300,000+ cases in People’s Republic of China • High risk areas early age of onset 20’s • Low risk areas early age of onset 50’s
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May 2nd, 2005 Megan McBee-BE.450 4 HCC Epidemiology • Main causes in high risk areas – HBV infection – Aflatoxins in diet • Synergism leading to increased risk Impact on HCC incidence HBV vaccination aflatoxin exposure
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May 2nd, 2005 Megan McBee-BE.450 5 HCC Epidemiology: Aflatoxin Studies •Ta iwan 1 : BsAg+ males with HCC compared to control subjects •OR = 2.8 detectable vs. nondetectable aflatoxin metabolites •OR = 5.5 high vs. low urinary metabolite levels • Shanghai 2 : relative risk for HCC with presence aflatoxin metabolites = 3.8 1. Wang LY et al. Int J Cancer. 1996 Sep 4;67(5):620-5. 2.
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May 2nd, 2005 Megan McBee-BE.450 6 Aflatoxins • Produced by fungi – 1960 outbreak of “Turkey ‘X’ disease” in UK Aspergillus flavus •C omm o n i n c o r n , p e a n u t s , fermented soy products H H Aflatoxin B 1 Cytochrome P450 Active DNA-modifying agent
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May 2nd, 2005 Megan McBee-BE.450 7 HCC Prevention/Intervention • Primary –Vacc inat ion – Reduced contamination •Secondary
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May 2nd, 2005 Megan McBee-BE.450 8 HCC Prevention/Intervention chlorophyllin oltipraz, ITCs antioxidants antiviral drugs green tea polyphenols, COX-2 inhibitors, ITCs, vitamin K analogs, retinoids green tea polyphenols, COX-2 inhibitors, ITCs, vitamin K analogs, retinoids oltipraz vaccination Aflatoxin B 1 Reactive Intermediates Aflatoxin-Mercapturic Acid (urine) Promutagenic DNA Lesions
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This note was uploaded on 11/11/2011 for the course BIO 20.410j taught by Professor Rogerd.kamm during the Spring '03 term at MIT.

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hcc_prevention - Strategies for Prevention of HCC Molecular...

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