• Rev Invest Clin · May 2020

    Metabolic Syndrome Instead of Aflatoxin-Related TP53 R249S Mutation as a Hepatocellular Carcinoma Risk Factor.

    • Estefanie N Valdés-Peregrina, Beatriz E Sánchez-Hernández, and Armando Gamboa-Domínguez.
    • Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
    • Rev Invest Clin. 2020 May 7; 72 (5).

    BackgroundHepatocarcinogenesis has a variety of risk factors. In Mexico City, autopsies found 14% of hepatocellular carcinomas (HCCs) without cirrhosis.ObjectiveThe objective of the study was to explore if HCCs carry the TP53 R249S mutation that has linked them to aflatoxin exposure and describe the associated risk factors.MethodsA retrospective review of consecutive cases of HCC was performed. Exposure to hepatotropic viruses, alcoholism, metabolic diseases, diabetes mellitus, and hypertension, as well as episodes of ascites, portal hypertension, and body mass index were retrieved. Slides were re-reviewed, macrodissected and DNA was extracted. TP53 exon 7 was amplified, purified, and used as a template for sequencing.ResultsIn 14 years, 74 HCCs were identified in 1863 (4%) consecutive liver biopsies. No data were available in five excluded patients; the rest was submitted to exon 7 screening. Patients had a median age of 62 years, and 46 (67%) were male. Stage 4 fibrosis was observed in 46 patients (67%) and their associated risk factors were hepatitis C virus (39%, 18/46), alcoholism (20%, 9/46), hepatitis B virus (2%, 1/46), and 18 were cryptogenic. Fibrosis stage 3 or lower was observed in 23 (33%) patients without demonstrated liver disease; 8/23 had diabetes and 6/23, systemic hypertension. Steatohepatitic variants of HCC were observed in 4 and in 5, the remnant liver had steatohepatitis. A 238-bp fragment was obtained in each tumor without the expected TP53 R249S mutation.ConclusionsThere was no evidence of aflatoxin exposure in HCCs, with and without the known "classical" risk factors. One-third of non-cirrhotic HCCs had steatohepatitis or conditions associated to metabolic syndrome.

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