Background Guatemala has the highest incidence of hepatocellular carcinoma (HCC), the dominant type of liver cancer, in the Western Hemisphere. The major risk factors in Guatemala are not well-characterized, but the prevalence of hepatitis B (HBV) and hepatitis C virus (HCV) appear to be low, while the prevalence of aflatoxin (AFB 1 ) exposure appears to be high. To examine whether AFB 1 could be a risk factor for HCC in Guatemala, this study examined the frequency of the AFB 1 -signature mutation in the TP53 gene (R249S) as well as other somatic mutations.Methods Ninety-one formalin-fixed, paraffin-embedded (FFPE) HCC tissues were obtained from three hospitals in Guatemala City. An additional, eighteen tumor tissues preserved in RNAlater were also obtained. Targeted sequencing of TP53 was successfully performed in 89 of the FFPE samples, and a panel of 245 genes were sequenced in the RNAlater samples.Results Overall, 47% of HCCs had a TP53 mutation. The AFB 1 -signature R249S mutation was present in 24%. Among the RNAlater samples, 44% had any TP53 mutation and 33% had the R249S mutation. Other somatic mutations were identified in known HCC driver genes such as ARID1A , ARID2 , and CTNNB1 .Conclusions The presence of the TP53 R249S mutation indicates that AFB 1 is a risk factor for HCC in Guatemala. The proportion of HBV positive tumors was low, suggesting that AFB 1 is associated with HCC in the absence of concomitant HBV infection. To decrease the risk of HCC in Guatemala, AFB 1 abatements efforts are warranted.
