title: Hepatocellular carcinoma and liver cirrhosis TP53 mutation analysis reflects a moderate dietary exposure to aflatoxins in Espírito Santo State, Brazil.
abstract: The close relationship between aflatoxins and 249ser TP53 gene mutation (AGG to AGT, Arg to Ser) in hepatocellular carcinoma (HCC) makes this mutation an indirect indicator of dietary contamination with this toxin. We have examined the prevalence of codon 249 TP53 mutation in 41 HCC and 74 liver cirrhosis (without HCC) cases diagnosed at the HUCAM University Hospital in Vitoria, Espírito Santo State, Brazil. DNA was extracted from paraffin sections and from plasma. The mutation was detected by DNA amplification, followed by restriction endonuclease digestion and confirmed by direct sequencing. DNA restriction showed 249ser mutation in 16 HCC and 13 liver cirrhosis, but sequencing confirmed mutations in only 6 HCC and 1 liver cirrhosis. In addition, sequencing revealed 4 patients with mutations at codon 250 (250ser and 250leu) in HCC cases. The prevalence of TP53 mutation was 10/41 (24.3%) in HCC and 1/74 (1.4%) in liver cirrhosis. No relationship between the presence of mutations and the etiology of HCC was observed. TP53 exon 7 mutations, which are related to aflatoxins exposure, were found at 14.6% (249ser), 7.3% (250leu) and 2.4% (250ser) in 41 cases of HCC and 1.4% in 74 liver cirrhosis (without HCC) cases, suggesting a moderate dietary exposure to aflatoxins in the Espírito Santo State, Brazil.
authors: Núcleo de Genética Humana e Molecular, Departamento de Ciências Biológicas, Centro de Ciências Humanas e Naturais, Universidade Federal do Espírito Santo, Av. Marechal Campos 1468, Campus de Maruípe, Vitória, Espírito Santo, CEP 29040-090, Brazil.
authors: Fernanda Magri
authors: FM
authors: de Carvalho
authors: Thiago
authors: T
authors: de Almeida Pereira
authors: Patrícia Lofego
authors: PL
authors: Gonçalves
authors: Robson Dettmann
authors: RD
authors: Jarske
authors: Fausto Edmundo Lima
authors: FE
authors: Pereira
authors: Iuri Drumond
authors: ID
authors: Louro
mesh_terms: D000348:Aflatoxins / Q000633:toxicity*; D001483:Base Sequence; D001938:Brazil; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005506:Food Contamination; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000348:Aflatoxins; D017931:DNA Primers; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
references: World J Gastroenterol. 1999 Aug;5(4):324-326
references: 11819458
references: Cancer Epidemiol Biomarkers Prev. 2001 Jun;10(6):617-25
references: 11401911
references: Oncologist. 2010;15 Suppl 4:5-13
references: 21115576
references: Food Addit Contam. 2001 Nov;18(11):981-6
references: 11665739
references: J Natl Cancer Inst. 1997 Dec 17;89(24):1844-51
references: 9414172
references: Cancer. 1994 Jul 1;74(1):30-7
references: 8004579
references: Nat Rev Gastroenterol Hepatol. 2010 Aug;7(8):448-58
references: 20628345
references: Carcinogenesis. 1996 May;17(5):1007-12
references: 8640905
references: J Natl Cancer Inst. 2000 Jan 19;92(2):148-53
references: 10639517
references: Oncogene. 2005 Sep 1;24(38):5858-67
references: 16007211
references: World J Gastroenterol. 2003 Apr;9(4):692-5
references: 12679912
references: Cancer Res. 1997 Aug 15;57(16):3471-7
references: 9270015
references: Vaccine. 1986 Dec;4(4):253-6
references: 3799019
references: Int J Cancer. 2003 Jan 10;103(2):149-52
references: 12455027
references: Br J Cancer. 1993 Jun;67(6):1395-7
references: 8390289
references: Int J Cancer. 1996 Sep 27;68(1):21-5
references: 8895534
references: Clinics (Sao Paulo). 2010;65(12):1285-90
references: 21340216
references: World J Gastroenterol. 1998 Apr;4(2):125-127
references: 11819254
references: Liver. 1993 Oct;13(5):279-81
references: 8259041
references: N Engl J Med. 2011 Sep 22;365(12):1118-27
references: 21992124
references: Mutat Res. 1999 Apr 6;425(2):205-11
references: 10216213
references: World J Gastroenterol. 1998 Feb;4(1):28-29
references: 11819223
references: BMC Cancer. 2009 Jun 26;9:204
references: 19558663
references: Am J Surg Pathol. 1993 Dec;17(12):1244-51
references: 8238731
references: J Gastroenterol Hepatol. 2005 Aug;20(8):1185-90
references: 16048565
references: Rev Inst Med Trop Sao Paulo. 1997 May-Jun;39(3):165-70
references: 9460258