title: The association between exposure to aflatoxin, mutation in TP53, infection with hepatitis B virus, and occurrence of liver disease in a selected population in Hyderabad, India.
abstract: Aflatoxin B1 is a carcinogen produced by Aspergillus flavus and a few related fungi that are often present in many food substances. It interacts synergistically with Hepatitis B or C virus (HBV, HBC) infection, thereby increasing the risk of hepatocellular carcinoma (HCC). The G to T transversion at the third position of codon 249 (AGG) of the TP53 gene, substituting arginine to serine, is the most common aflatoxin-induced mutation linked to HCC. This study examined mutations in TP53 by PCR-RFLP analysis and by measurement of an aflatoxin-albumin adduct as a biomarker for human exposure of aflatoxin B1 by indirect-competitive ELISA, in samples collected from healthy controls as well as patients with hepatitis in Hyderabad, Andhra Pradesh, India. A total of 238 blood samples were analyzed the presence of the G to T mutation. Eighteen of these samples were from HBV-positive subjects, 112 of these were from subjects who had HBV-induced liver cirrhosis, and 108 samples were taken from subjects without HBV infection or liver cirrhosis (control group). The G to T mutation was detected in 10 samples, 8 of which were from subjects positive to both HBV and aflatoxin-albumin adduct in blood (p=0.07); whilst two were from individuals who were HBV-negative, but positive for the aflatoxin-albumin adduct (p=0.14). The aflatoxin-albumin adduct was detected in 37 of 238 samples, 29 samples were from HBV-positive subjects and eight were from individuals who were positive for both HBV and the TP53 mutation (p=0.07). The concentration of aflatoxin-albumin adduct ranged from 2.5 to 667pg/mg albumin. Despite low incidence of the G to T mutation, its detection in subjects positive to aflatoxin-adducts is indicative of a strong association between the mutation and aflatoxin exposure in India.
authors.affiliation: International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), Patancheru 502 324, Andhra Pradesh, India. Electronic address: s.anitha@cgiar.org.
authors.forename: S
authors.initials: S
authors.lastname: Anitha
authors.affiliation: Department of Medical Oncology, Nizam's Institute of Medical Sciences (NIMS), Hyderabad 500 082, India.
authors.forename: D
authors.initials: D
authors.lastname: Raghunadharao
authors.affiliation: ICRISAT, Niamey BP 12404, Niger.
authors.forename: F
authors.initials: F
authors.lastname: Waliyar
authors.affiliation: International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), Patancheru 502 324, Andhra Pradesh, India.
authors.forename: H
authors.initials: H
authors.lastname: Sudini
authors.affiliation: Department of Medical Gastroenterology, PGIMS, Rohtak 124001, India.
authors.forename: M
authors.initials: M
authors.lastname: Parveen
authors.affiliation: Department of Microbiology and Immunoserology, Apollo Health City, Jubilee Hills, Hyderabad 500 033, India.
authors.forename: Ratna
authors.initials: R
authors.lastname: Rao
authors.affiliation: International Institute of Tropical agriculture (IITA), PMB 5320, Ibadan, Nigeria.
authors.forename: P Lava
authors.initials: PL
authors.lastname: Kumar
mesh_terms: D000348:Aflatoxins / Q000009:adverse effects*; D001231:Aspergillus flavus; D002273:Carcinogens / Q000633:toxicity; D005260:Female; D006509:Hepatitis B / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D006515:Hepatitis B virus; D006801:Humans; D015994:Incidence; D007194:India / Q000453:epidemiology; D008297:Male; D017354:Point Mutation; D011042:Poisons / Q000009:adverse effects*; D012150:Polymorphism, Restriction Fragment Length; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000348:Aflatoxins; D002273:Carcinogens; D011042:Poisons; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Aflatoxins; Biomarker; Hepatitis virus; Hepatocellular carcinoma; TP53 mutation