School of Medicine Publications and Presentations
Document Type
Article
Publication Date
10-31-2017
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 Asian HCC patients, 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. ©2017 AACR.
Recommended Citation
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, H. L., 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 (Philadelphia, Pa.), 11(2), 103–112. https://doi.org/10.1158/1940-6207.CAPR-17-0235
Publication Title
Cancer prevention research (Philadelphia, Pa.)
DOI
10.1158/1940-6207.CAPR-17-0235
Academic Level
faculty
Comments
©2017 American Association for Cancer Research.