title: Absence of TP53 codon 249 mutations in young Guinean children with high aflatoxin exposure.
abstract: Infection with hepatitis viruses and chronic exposure to high levels of dietary aflatoxins are the major etiologic agents for hepatocellular carcinoma in west Africa. A challenge for the prevention of hepatocellular carcinoma in this region is that both hepatitis B virus and aflatoxin exposures start early in life; indeed, aflatoxin exposures can start in utero and continue unabated throughout childhood. A mutation in the TP53 tumor suppressor gene at codon 249 (TP53 Ser249 mutation) has been reported previously for hepatocellular carcinoma tumors and matched plasma DNA samples in individuals from areas with high aflatoxin exposure. We examined whether the TP53 Ser249 mutation could be observed in DNA found in plasma of young children (ages 2-5 years) from Guinea, west Africa, a region of high aflatoxin exposure. Plasma aflatoxin-albumin adducts were present in 119 of 124 (96%) of the children, geometric mean of positives 9.9 pg/mg albumin (95% confidence interval, 8.8-11.0 pg/mg). This is the level and prevalence of exposure observed previously in adults. Following PCR amplification of plasma-derived DNA and detection using mass spectrometry, none of the samples were found to contain the TP53 Ser249 mutation. Because approximately 50% of the hepatocellular carcinomas in adults in west Africa have this specific TP53 Ser249 mutation, a lack of detection in samples from children ages <5 years may indicate that a window of opportunity for intervention exists that could be exploited to lower hepatocellular carcinoma risk.
authors.affiliation: Molecular Epidemiology Unit, Centre for Epidemiology and Biostatistics, Leeds Institute of Genetics, Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom LS2 9JT.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Turner
authors.forename: Abdoulaye
authors.initials: A
authors.lastname: Sylla
authors.forename: Shuang-Yuan
authors.initials: SY
authors.lastname: Kuang
authors.forename: Clare L
authors.initials: CL
authors.lastname: Marchant
authors.forename: Mamadou S
authors.initials: MS
authors.lastname: Diallo
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hall
authors.forename: John D
authors.initials: JD
authors.lastname: Groopman
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Wild
mesh_terms: D018248:Adenoma, Liver Cell / Q000139:chemically induced* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000348:Aflatoxins / Q000009:adverse effects* / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D016701:Guinea; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation
chemical_list: D000348:Aflatoxins; D004273:DNA, Neoplasm