Aflatoxin and viral hepatitis exposures in Guatemala: Molecular biomarkers reveal a unique profile of risk factors in a region of high liver cancer incidence

Abstract

Liver cancer is an emerging global health issue, with rising incidence in both the United States and the economically developing world. Although Guatemala experiences the highest rates of this disease in the Western hemisphere and a unique 1:1 distribution in men and women, few studies have focused on this population. Thus, we determined the prevalence and correlates of aflatoxin B1 (AFB1) exposure and hepatitis virus infection in Guatemalan adults. Healthy men and women aged ≥40 years (n = 461), residing in five departments of Guatemala, were enrolled in a cross-sectional study from May-October of 2016. Serum AFB1-albumin adducts were quantified using isotope dilution mass spectrometry. Multivariate linear regression was used to assess relationships between AFB1-albumin adduct levels and demographic factors. Biomarkers of hepatitis B virus and hepatitis C virus infection were assessed by immunoassay and analyzed by Fisher's exact test. AFB1-albumin adducts were detected in 100% of participants, with a median of 8.4 pg/mg albumin (range, 0.2-814.8). Exposure was significantly higher (p<0.05) in male, rural, low-income, and less-educated participants than in female, urban, and higher socioeconomic status participants. Hepatitis B and C seropositivity was low (0.9% and 0.5%, respectively). Substantial AFB1 exposure exists in Guatemalan adults, concurrent with low prevalence of hepatitis virus seropositivity. Quantitatively, AFB1 exposures are similar to those previously found to increase risk for liver cancer in Asia and Africa. Mitigation of AFB1 exposure may reduce liver cancer incidence and mortality in Guatemala, warranting further investigation.

Fig 1. Flow-chart of recruitment.

Numbers of households or participants at each stage of recruitment, for each department and for the final sample.

Fig 2. Unadjusted serum aflatoxin B₁-albumin adduct levels (pg/mg) in study participants.

Unadjusted serum AFB₁-albumin adducts overall and with stratification by sex, residence location, or ethnicity. All data are plotted on a base-10 logarithmic scale; dotted scale lines are drawn at 0.05, 0.5, 5, 50, and 500 pg/mg. Whiskers on boxplots extend to the 5^th and 95^th percentiles, with individual observations beyond those cutoffs plotted. *, p = 0.009 vs. male; †, p ≤ 0.0001 vs. rural; §, p ≤ 0.0001 vs. indigenous by multiple linear regression of unadjusted adduct values. Sample size n is displayed below each group. Non-I., non-indigenous; Indig., indigenous.