Chemoprevention Against Environmental Carcinogens
More than 1.2 million Americans develop cancer every year, and almost half of the die of the disease. How do we decrease the cancer death ?
Treatment and control
Early detection and diagnosis
Incidence Mortality (600,000 new cases) (280,000) From: Breast Cancer Prognosis, Treatment and Prevention Examples of incidence and mortality of various women’s cancers in the United States (in percentages). Values for 1990.
The incidence of breast and prostate cancer is markedly higher in the Western world compared to Asian countries. Asian immigrants to the US who maintain an “Eastern” diet retain the lower rates of cancer development, while those who adopt a “Western” diet increase their cancer risk (WHO data as adapted by the American Cancer Society, 1992).
Fruit and Vegetable Consumption and Cancer Risk (Ames and Gold, Drug Metabolism Reviews 30 :201-223, 1998) Fraction of studies showing cancer protection Relative risk Cancer site (p < .05) (low vs. high quartile) Epithelial Pancreas 9/11 2.8 Stomach 17/19 2.5 Lung 24/25 2.2 Esophagus 15/16 2.0 Cervix 7/8 2.0 Colorectal 20/35 1.9 Hormone Dependent Ovary/endometrium 3/4 1.8 Breast 8/14 1.3 Prostate 4/14 1.3
The inhibition, reversal, or retardation of carcinogenesis by the administration of natural or synthetic agents is termed
Many phytochemicals are believed to affect every stage of the cancer process Chemopreventive Cancer Prevented Mechanisms Phytochemicals Source (animal models) of Action Alkyl sulfides and disulfides Allium Esophagus, Colon, Phase II, GST Sulfide volatiles Lung Allyl cystenes Monoterpenes Citrus Mammary, Pancreas, Phase II, GST, Lemonene Skin, Lung, Liver UDP-GT, Phase I Isothiocyanates Crucifers Liver, Lung, Phase II, GST Mammary Polyphenols Teas Colon, Lung, Phase II (GST, Epigallocatechin gallate Skin, Liver QR), Phase I, AP-1 Curcumin Turmeric Colon, Skin Phase II, GST, Cox II
Mechanisms of Action of Phytochemicals in Cancer Prevention
Large-scale demonstration trials aim to establish definitively the efficacy and toxicity of potential chemopreventive agents in a healthy population of subjects with a high risk of cancer.
Small Phase I and II chemoprevention trials are conducted in individuals with premalignant lesions or cancer to investigate mechanisms of action, pharmacokinetics, pharmacodynamics, and modulation of biomarkers.
CA Cancer J. Clin. 54:2004. N.B.: No benefit or harm
Carcinogenesis TCDD Gene Mutation Proto-oncogene Tumor Suppressor Angiogenesis Program Cell Death DNA Damage Normal Cells Promotion Mutant Cells Progression Benign Tumors Malignant Tumors Initiation BP DMBA Chemopreventive Agents X Phase I + Phase II –