title: Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas.
abstract: Hepatocellular carcinoma is one of the most common cancers worldwide. Infection with hepatitis B virus and exposure to aflatoxins in the diet act synergistically to amplify risk. From a public health perspective, hepatitis virus vaccination programs and efforts to both reduce aflatoxin exposures and to attenuate the toxicological consequences of unavoidable exposures should have major impacts on the global incidence of this disease. Experimentally, aflatoxin-induced hepatocarcinogenesis can be inhibited by over a score of different chemopreventive agents with multiple mechanisms of action. One agent, oltipraz, is a potent inducer of phase 2 enzymes involved in the detoxication of carcinogens including aflatoxin. A second agent, chlorophyllin, impedes the bioavailability of carcinogens by forming molecular complexes and enhances their elimination in the fecal stream. This review highlights the findings of recent randomized clinical trials with oltipraz and chlorophyllin conducted in individuals exposed to dietary aflatoxins and at high risk for development of liver cancer. Both chemopreventive agents modulated levels of aflatoxin biomarkers in the study participants in manners consonant with protection. Although pharmacological approaches establish proof of principle and help identify key molecular targets for interventions, food-based approaches that also use these molecular targets may be the most practical for widespread application in high-risk populations.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, Maryland 21205, USA. tkensler@jhsph.edu
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kensler
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Egner
authors.forename: Jin-Bing
authors.initials: JB
authors.lastname: Wang
authors.forename: Yuan-Rong
authors.initials: YR
authors.lastname: Zhu
authors.forename: Bao-Chu
authors.initials: BC
authors.lastname: Zhang
authors.forename: Pei-Xin
authors.initials: PX
authors.lastname: Lu
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chen
authors.forename: Geng-Sun
authors.initials: GS
authors.lastname: Qian
authors.forename: Shuang-Yuan
authors.initials: SY
authors.lastname: Kuang
authors.forename: Peta E
authors.initials: PE
authors.lastname: Jackson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Alvaro
authors.initials: A
authors.lastname: Muñoz
authors.forename: John D
authors.initials: JD
authors.lastname: Groopman
mesh_terms: D000348:Aflatoxins / Q000009:adverse effects*; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D016587:Antimutagenic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000517:prevention & control*; D018890:Chemoprevention; D004032:Diet; D005506:Food Contamination; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D000348:Aflatoxins; D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents