Prevalence of aflatoxin-associated TP53R249S mutation in hepatocellular carcinoma in Hispanics in South Texas

Jingjing Jiao, Weibo Niu, Ying Wang, Keith Baggerly, Yuanqing Ye, Xifeng Wu, Dewitt Davenport, Jose Luis Almeda, Monica M. Betancourt-Garcia, R. Armour Forse, Heather Stevenson-Lerner, Gordon P. Watt, Joseph B. McCormick, Susan P. Fisher-Hoch, Laura Beretta

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Abstract

We aimed to determine whether aflatoxin dietary exposure plays a role in the high incidence of hepatocellular carcinoma (HCC) observed among Hispanics in South Texas. We measured TP53R249S somatic mutation, hallmark of aflatoxin etiology in HCC, using droplet digital PCR and RFLP. TP53R249S mutation was detected in 3 of 41 HCC tumors from Hispanics in South Texas (7.3%). We also measured TP53R249S mutation in plasma cell-free DNA (cfDNA) from 218 HCC patients and 96 Hispanic subjects with advanced fibrosis or cirrhosis, from South Texas. The mutation was detected only in Hispanic and AsianHCCpatients, and patients harboring TP53R249S mutation were significantly younger and had a shorter overall survival. The mutation was not detected in any Hispanic subject with advanced fibrosis or cirrhosis. Genes involved in cell-cycle control of chromosomal replication and in BRCA1-dependent DNA damage response were enriched in HCCs with TP53R249S mutation. The E2F1 family members, E2F1 and E2F4, were identified as upstream regulators. TP53R249S mutation was detected in 5.7% to 7.3% of Hispanics with HCC in South Texas. This mutation was associated with a younger age and worse prognosis. TP53R249S was however not detected in Hispanics in South Texas with cirrhosis or advanced fibrosis. Aflatoxin exposure may contribute to a small number of HCCs in Hispanics in South Texas, but the detection of TP53R249S mutation in plasma cfDNA is not a promising biomarker of risk assessment for HCC in subjects with cirrhosis or advanced fibrosis in this population. Cancer Prev Res; 11(2); 103-12.

Original languageEnglish (US)
Pages (from-to)103-112
Number of pages10
JournalCancer Prevention Research
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2018

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Jiao, J., Niu, W., Wang, Y., Baggerly, K., Ye, Y., Wu, X., Davenport, D., Almeda, J. L., Betancourt-Garcia, M. M., Forse, R. A., Stevenson-Lerner, H., Watt, G. P., McCormick, J. B., Fisher-Hoch, S. P., & Beretta, L. (2018). Prevalence of aflatoxin-associated TP53R249S mutation in hepatocellular carcinoma in Hispanics in South Texas. Cancer Prevention Research, 11(2), 103-112. https://doi.org/10.1158/1940-6207.CAPR-17-0235