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Absence of TP53 Codon 249 Mutations in Young Guinean Children with High Aflatoxin Exposure

¹ 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; ² Institut Pasteur de Guinée, Kindia, Republic of Guinea; ³ Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; and ⁴ Infectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, University of London, London, United Kingdom

Requests for reprints: Christopher P. Wild, Molecular Epidemiology Unit, Centre for Epidemiology and Biostatistics, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, United Kingdom LS2 9JT. Phone: 44-113-343-6601; Fax: 44-113-343-6603. E-mail: c.p.wild{at}leeds.ac.uk

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 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.

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