title: The case for aflatoxins in the causal chain of gallbladder cancer.
abstract: Chronic aflatoxin exposure has long been related to hepatocellular carcinoma (HCC). Recently, its association with gallbladder cancer (GBC) was postulated. Here we present the data supporting this hypothesis in Chile, the country with the highest GBC mortality worldwide with age-standardized mortality rates (ASMR) of 10.3 in women and 5.04 in men. The highest GBC rates occur in Southern Chile (ASMR=18), characterized by: high Amerindian ancestry, associated with high bile acid synthesis and gallstones; high poverty and high cereal agriculture, both associated with aflatoxin exposure. Aflatoxins have been detected in imported and locally grown foods items. We estimated population dietary exposure ranging from 0.25 to 35.0 ng/kg-body weight/day. The only report on human exposure in Chile found significantly more aflatoxin biomarkers in GBC than in controls (Odds Ratio=13.0). The hypothesis of aflatoxin-GBC causal link in the Chilean population is supported by: genetically-determined rapid cholesterol excretion and high gallstones prevalence (49.4%); low prevalence of HCC (ASMR=4.9) and low HBV infection (0.15%) the main co-factor of aflatoxins in HCC risk. If the association between aflatoxins and GBC were confirmed, public health interventions based on food regulation could have a substantial public health impact.
authors.affiliation: Public Health Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; Advanced Center for Chronic Diseases (ACCDiS), FONDAP, Santiago, Chile.
authors.forename: Claudia
authors.initials: C
authors.lastname: Foerster
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, MD, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Koshiol
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), FONDAP, Santiago, Chile; Department of Pharmacological and Toxicological Chemistry, Pharmaceutical and Chemical Sciences Faculty, Universidad de Chile, Santiago, Chile.
authors.forename: Ariel R
authors.initials: AR
authors.lastname: Guerrero
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), FONDAP, Santiago, Chile; Department of Pharmacological and Toxicological Chemistry, Pharmaceutical and Chemical Sciences Faculty, Universidad de Chile, Santiago, Chile.
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Kogan
authors.affiliation: Public Health Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; Advanced Center for Chronic Diseases (ACCDiS), FONDAP, Santiago, Chile. Electronic address: cferrec@med.puc.cl.
authors.forename: Catterina
authors.initials: C
authors.lastname: Ferreccio
mesh_terms: D018450:Disease Progression; D019317:Evidence-Based Medicine; D005260:Female; D005506:Food Contamination / Q000706:statistics & numerical data*; D005706:Gallbladder Neoplasms / Q000139:chemically induced* / Q000401:mortality*; D006801:Humans; D015994:Incidence; D008297:Male; D008954:Models, Biological; D012307:Risk Factors; D015996:Survival Rate; D000096702:Aflatoxin Poisoning