Prevalence of Aflatoxin-Associated TP53R249S Mutation in Hepatocellular Carcinoma in Hispanics in South Texas

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 somatic mutation, hallmark of aflatoxin etiology in HCC, using droplet digital PCR and RFLP. mutation was detected in 3 of 41 HCC tumors from Hispanics in South Texas (7.3%). We also measured 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 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 mutation. The E2F1 family members, E2F1 and E2F4, were identified as upstream regulators. 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. 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 mutation in plasma cfDNA is not a promising biomarker of risk assessment for HCC in subjects with cirrhosis or advanced fibrosis in this population. .

Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors

“…A prior study showed that circulating tumor DNA mutants could be readily detected in patients with HCC using ddPCR with a detection limit of 0.01% 16. We also recently reported the detection of TP53 R249S mutant in plasma cfDNA of patients with HCC using ddPCR 17. In our analysis, we confirmed that the detection of TERT promoter mutations in cfDNA was not dependent on the amount of cfDNA extracted.…”

Aflatoxin B1exposure and liver cirrhosis in Guatemala: a case–control study

“…22 In contrast, a US study reported that the AFB 1 signature mutation in TP53 was not evident in the tissue of individuals with cirrhosis. 23 In the current study, the AFB 1 biomarker used reflects the formation of mutagenic AFB 1 -DNA adducts, and the risk of liver carcinogenesis has been demonstrated to increase with the level of aflatoxin exposure. 24 A mechanism underlying the possible development of cirrhosis induced by AFB 1 is not clear.…”

Bioinformatics analysis of the interactions among lncRNA, miRNA and mRNA expression, genetic mutations and epigenetic modifications in hepatocellular carcinoma

“…Accumulating evidence demonstrated that genetic mutations are associated with the occurrence and prognosis of tumors (34)(35)(36), including HCC (37)(38)(39). In the present study, it was identified that mutations in miRNA-424 target genes were associated with biological features of HCC.…”