John Groopman
Johns Hopkins University, Environmental Health Science, Faculty Member
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The assessment of aflatoxin B1 (AFB1) exposure using isotope-dilution liquid chromatography-mass spectrometry (LCMS) of AFB1-lysine adducts in human serum albumin (HSA) has proven to be a highly productive strategy for the biomonitoring... more
The assessment of aflatoxin B1 (AFB1) exposure using isotope-dilution liquid chromatography-mass spectrometry (LCMS) of AFB1-lysine adducts in human serum albumin (HSA) has proven to be a highly productive strategy for the biomonitoring of AFB1 exposure. To compare samples across different individuals and settings, the conventional practice has involved the normalization of raw AFB1-lysine adduct concentrations (e.g., pg/mL serum or plasma) to the total circulating HSA concentration (e.g., pg/mg HSA). It is hypothesized that this practice corrects for technical error, between-person variance in HSA synthesis or AFB1 metabolism, and other factors. However, the validity of this hypothesis has been largely unexamined by empirical analysis. The objective of this work was to test the concept that HSA normalization of AFB1-lysine adduct concentrations effectively adjusts for biological and technical variance and improves AFB1 internal dose estimates. Using data from AFB1-lysine and HSA me...
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Background In utero or early-life exposure to aflatoxin, which contaminates staple crops in disadvantaged settings, may compromise pregnancy and infant outcomes, but investigations into the extent, persistence, and determinants of... more
Background In utero or early-life exposure to aflatoxin, which contaminates staple crops in disadvantaged settings, may compromise pregnancy and infant outcomes, but investigations into the extent, persistence, and determinants of aflatoxin exposure at these life stages have lacked longitudinal data collection and broad geographic representation. Objectives Aflatoxin exposure and selected determinants thereof were characterized in mother–child dyads with serial plasma/serum samples in prenatal, perinatal, and early life in Malawi and Bangladesh. Methods Circulating aflatoxin B1 (AFB1)–lysine albumin adducts were measured in dyads from Bangladesh (n = 573; maternal first and third trimester, 3 mo postpartum, cord blood, infant 24 mo) and Malawi (n = 255; maternal second and third trimester, 6 mo postpartum, infant 6 and 18 mo) with isotope dilution mass spectrometry. We examined AFB1-lysine adduct magnitude, persistence, seasonality, and associations with infant feeding, and estimate...
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ObjectiveIn Guatemala, cirrhosis is among the 10 leading causes of death, and mortality rates have increased lately. The reasons for this heavy burden of disease are not clear as the prevalence of prominent risk factors, such as hepatitis... more
ObjectiveIn Guatemala, cirrhosis is among the 10 leading causes of death, and mortality rates have increased lately. The reasons for this heavy burden of disease are not clear as the prevalence of prominent risk factors, such as hepatitis B virus, hepatitis C virus and heavy alcohol consumption, appears to be low. Aflatoxin B1 (AFB1) exposure, however, appears to be high, and thus could be associated with the high burden of cirrhosis. Whether AFB1 increases the risk of cirrhosis in the absence of viral infection, however, is not clear.DesignCirrhosis cases (n=100) from two major referral hospitals in Guatemala City were compared with controls (n=200) from a cross-sectional study. Logistic regression was used to estimate the ORs and 95% CIs of cirrhosis and quintiles of AFB1 in crude and adjusted models. A sex-stratified analysis was also conducted.ResultsThe median AFB1 level was significantly higher among the cases (11.4 pg/mg) than controls (5.11 pg/mg). In logistic regression ana...
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Objective:Chronic aflatoxin exposure has been associated with childhood stunting (length-for-age/height-for-age < –2 sd), while data lacks for Bangladesh, a country with substantial burden of childhood stunting. This paper examined the... more
Objective:Chronic aflatoxin exposure has been associated with childhood stunting (length-for-age/height-for-age < –2 sd), while data lacks for Bangladesh, a country with substantial burden of childhood stunting. This paper examined the association between aflatoxin exposure and childhood stunting in a slum setting of Dhaka city.Design:In this MAL-ED aflatoxin birth cohort study, plasma samples were assayed for aflatoxin B1-lysine adduct (AFB1-lys) by MS at 7, 15, 24 and 36 months of age for 208, 196, 173 and 167 children to assess chronic aflatoxin exposure. Relationship between aflatoxin exposure and anthropometric measures was examined by mixed-effects logistic regression models.Setting and participants:The study was conducted in Mirpur, Dhaka, where children were followed from birth to 36 months.Results:Prevalence of stunting increased from 21 % at 7 months to 49 % at 36 months of age. Mean AFB1-lys concentrations at 7, 15, 24 and 36 months were 1·30 (range 0·09–5·79), 1·52 (r...
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Carotenoids are naturally occurring pigments that function as vitamin A precursors, antioxidants, anti-inflammatory agents or biomarkers of recent vegetable and fruit intake, and are thus important for population health and nutritional... more
Carotenoids are naturally occurring pigments that function as vitamin A precursors, antioxidants, anti-inflammatory agents or biomarkers of recent vegetable and fruit intake, and are thus important for population health and nutritional assessment. An assay approach that measures proteins could be more technologically feasible than chromatography, thus enabling more frequent carotenoid status assessment. We explored associations between proteomic biomarkers and concentrations of 6 common dietary carotenoids (α-carotene, β-carotene, lutein/zeaxanthin, β-cryptoxanthin, and lycopene) in plasma from 500 6-8 year old Nepalese children. Samples were depleted of 6 high-abundance proteins. Plasma proteins were quantified using tandem mass spectrometry and expressed as relative abundance. Linear mixed effects models were used to determine the carotenoid:protein associations, accepting a false discovery rate of q < 0.10. We quantified 982 plasma proteins in >10% of all child samples. Amo...
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Growth impairment is a major public health issue for children in Tanzania. The question remains as to whether dietary mycotoxins play a role in compromising children's growth. We examined children's exposures to dietary aflatoxin... more
Growth impairment is a major public health issue for children in Tanzania. The question remains as to whether dietary mycotoxins play a role in compromising children's growth. We examined children's exposures to dietary aflatoxin and fumonisin and potential impacts on growth in 114 children under 36 months of age in Haydom, Tanzania. Plasma samples collected from the children at 24 months of age (N = 60) were analyzed for aflatoxin B-lysine (AFB-lys) adducts, and urine samples collected between 24 and 36 months of age (N = 94) were analyzed for urinary fumonisin B(UFB). Anthropometric, socioeconomic, and nutritional parameters were measured and growth parameter z-scores were calculated for each child. Seventy-two percent of the children had detectable levels of AFB-lys, with a mean level of 5.1 (95% CI: 3.5, 6.6) pg/mg albumin; and 80% had detectable levels of UFB, with a mean of 1.3 (95% CI: 0.8, 1.8) ng/ml. This cohort had a 75% stunting rate [height-for-age z-scores (HAZ)...
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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... more
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%...
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Aflatoxin, which causes hepatocellular carcinoma, may also cause gallbladder cancer. We investigated whether patients with gallbladder cancer have higher exposure to aflatoxin than patients with gallstones. We measured aflatoxin B1... more
Aflatoxin, which causes hepatocellular carcinoma, may also cause gallbladder cancer. We investigated whether patients with gallbladder cancer have higher exposure to aflatoxin than patients with gallstones. We measured aflatoxin B1 (AFB1)-lysine adducts in plasma samples from the Shanghai Biliary Tract Cancer case-control study, conducted from 1997 through 2001. We calculated age- and sex-adjusted odds ratios (ORs) and 95% CIs and the population-attributable fraction for 209 patients with gallbladder cancer and gallstones vs 250 patients with gallstones without cancer (controls). In 54 patients with gallbladder cancer, tumor tissue was examined for the R249S mutation in TP53, associated with aflatoxin exposure, through targeted sequencing. The AFB1-lysine adduct was detected in 67 of 209 patients with gallbladder cancer (32%) and 37 of the 250 controls (15%) (χ(2) P <.0001), almost 3-fold more patients with gallbladder cancer than controls (OR, 2.71; 95% CI, 1.70-4.33). Among par...
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Exposure to aflatoxin, a mycotoxin common in many foods, has been associated with child growth impairment in sub-Saharan Africa. To improve our understanding of growth impairment in relation to aflatoxin and other risk factors, we... more
Exposure to aflatoxin, a mycotoxin common in many foods, has been associated with child growth impairment in sub-Saharan Africa. To improve our understanding of growth impairment in relation to aflatoxin and other risk factors, we assessed biospecimens collected in Nepalese children at 15, 24, and 36 months of age for aflatoxin exposure. Children (N = 85) enrolled in the Bhaktapur, Nepal MAL-ED study encompassed the cohort analysed in this study. Exposure was assessed through a plasma biomarker of aflatoxin exposure: the AFB1-lysine adduct. The aflatoxin exposures in the study participants were compared to anthropometrics at each time period (length-for-age [LAZ], weight-for-age [WAZ], and weight-for-length [WLZ] z-scores), growth trajectories over time, age, and breastfeeding status. Results demonstrated chronic aflatoxin exposure in this cohort of children, with a geometric mean of 3.62 pg AFB1-lysine/mg albumin. However, the chronic aflatoxin exposure in this cohort was not signi...
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Inflammation is a condition stemming from complex host defense and tissue repair mechanisms, often simply characterized by plasma levels of a single acute reactant. We attempted to identify candidate biomarkers of systemic inflammation... more
Inflammation is a condition stemming from complex host defense and tissue repair mechanisms, often simply characterized by plasma levels of a single acute reactant. We attempted to identify candidate biomarkers of systemic inflammation within the plasma proteome. We applied quantitative proteomics using isobaric mass tags (iTRAQ) tandem mass spectrometry to quantify proteins in plasma of 500 Nepalese children 6-8 years of age. We evaluated those that co-vary with inflammation, indexed by α-1-acid glycoprotein (AGP), a conventional biomarker of inflammation in population studies. Among 982 proteins quantified in >10% of samples, 99 were strongly associated with AGP at a family-wise error rate of 0.1%. Magnitude and significance of association varied more among proteins positively (n = 41) than negatively associated (n = 58) with AGP. The former included known positive acute phase proteins including C-reactive protein, serum amyloid A, complement components, protease inhibitors, tr...
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Mycotoxins are toxic and carcinogenic metabolites produced by fungi that colonize food crops. The most agriculturally important mycotoxins known today are aflatoxins, which cause liver cancer and have also been implicated in child growth... more
Mycotoxins are toxic and carcinogenic metabolites produced by fungi that colonize food crops. The most agriculturally important mycotoxins known today are aflatoxins, which cause liver cancer and have also been implicated in child growth impairment and acute toxicoses; fumonisins, which have been associated with esophageal cancer (EC) and neural tube defects (NTDs); deoxynivalenol (DON) and other trichothecenes, which are immunotoxic and cause gastroenteritis; and ochratoxin A (OTA), which has been associated with renal diseases. This review describes the adverse human health impacts associated with these major groups of mycotoxins. First, we provide background on the fungi that produce these different mycotoxins and on the food crops commonly infected. Then, we describe each group of mycotoxins in greater detail, as well as the adverse effects associated with each mycotoxin and the populations worldwide at risk. We conclude with a brief discussion on estimations of global burden of...
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Research Interests: Biology, Medicine, Molecular Epidemiology, Humans, Animals, and 15 moreHepatocellular Carcinoma, Cohort Study, Risk factors, Aflatoxin, Aspergillus flavus, Total Synthesis, Aflatoxins, Quantitative risk assessment, Structure Elucidation, Food Contamination, Food Sciences, Risk Factors, Carcinogen, Serum albumin, and Liver neoplasms
Research Interests: Food Safety, Environmental Health, Developing Countries, Public Health, Surveillance, and 15 moreMedicine, Environmental Sciences, Humans, Developing Country, Biomonitoring, Hepatocellular Carcinoma, Workgroup, Hepatitis, Aflatoxin, Aflatoxins, World Health Organization, Food Contamination, Outbreak, Medical and Health Sciences, and Population surveillance
Research Interests: Environmental Health, Biology, Environmental Sciences, Humans, Female, and 15 moreMale, Hepatocellular Carcinoma, Infant, Gambia, Aged, Aflatoxins, Adult, Cross Section, Hepatitis B virus, Asymptomatic, Cross Sectional Studies, chronic hepatitis B, Confidence Interval, HBsAg, and Case Control Studies
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Essential to the conduct of epidemiologic studies examining aflatoxin exposure and the risk of heptocellular carcinoma, impaired growth, and acute toxicity has been the development of quantitative biomarkers of exposure to aflatoxins,... more
Essential to the conduct of epidemiologic studies examining aflatoxin exposure and the risk of heptocellular carcinoma, impaired growth, and acute toxicity has been the development of quantitative biomarkers of exposure to aflatoxins, particularly aflatoxin B1. In this study, identical serum sample sets were analyzed for aflatoxin-albumin adducts by ELISA, high-performance liquid chromatography (HPLC) with fluorescence detection (HPLC-f), and HPLC with isotope dilution mass spectrometry (IDMS). The human samples analyzed were from an acute aflatoxicosis outbreak in Kenya in 2004 (n = 102) and the measured values ranged from 0.018 to 67.0, nondetectable to 13.6, and 0.002 to 17.7 ng/mg albumin for the respective methods. The Deming regression slopes for the HPLC-f and ELISA concentrations as a function of the IDMS concentrations were 0.71 (r2 = 0.95) and 3.3 (r2 = 0.96), respectively. When the samples were classified as cases or controls, based on clinical diagnosis, all methods were...
Research Interests: Chemistry, Chromatography, Fluorescence, Kenya, Comparative Study, and 15 moreHumans, Albumin, Hepatocellular Carcinoma, Exploration, Incidence, Aflatoxin, High Performance Liquid Chromatography, High Pressure Liquid Chromatography, Isotope Dilution, Isotope Dilution Mass Spectrometry, Enzyme Linked Immunosorbent Assay, Environmental Exposure, Adduct, Liver neoplasms, and HPLC Chromatography
Metabolic activation of the hepatocarcinogenic mycotoxin aflatoxin B1 (AFB1) results in the covalent attachment of AFB1 to serum albumin. Digestion of adducted albumin releases AFB1-lysine, a biomarker of exposure status. AF-albumin... more
Metabolic activation of the hepatocarcinogenic mycotoxin aflatoxin B1 (AFB1) results in the covalent attachment of AFB1 to serum albumin. Digestion of adducted albumin releases AFB1-lysine, a biomarker of exposure status. AF-albumin adducts have been most frequently measured in precipitated serum albumin using an immunoassay (ELISA); however, a sensitive and specific isotope dilution mass spectrometric (IDMS) assay for measurement of AFB1-lysine in serum has recently been developed. The ELISA and IDMS methods were compared using 20 human sera collected in Guinea, West Africa, where AF exposure is endemic. Measurement of AFB1-lysine adduct concentrations by IDMS in serum and albumin precipitated from the same sample revealed that precipitation has no effect on the measured adduct levels. The concentration of AF-albumin adducts measured by ELISA and AFB1-lysine measured by IDMS in 2 mg of albumin were well correlated (R = 0.88, P < 0.0001); however, AF-albumin adduct concentrations...
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The measurement of the aflatoxin B1-lysine serum albumin adduct in human blood samples is the most facile biomarker for the assessment of chronic exposure to aflatoxin B1. Many technologies have been developed for the measurement of this... more
The measurement of the aflatoxin B1-lysine serum albumin adduct in human blood samples is the most facile biomarker for the assessment of chronic exposure to aflatoxin B1. Many technologies have been developed for the measurement of this protein adduct including immunoassays, high-performance liquid chromatography (HPLC) with fluorescence detection, and a newly developed isotope-dilution mass spectrometry method. Irrespective of the technology used to determine this adduct level, an important question remains about the long-term stability of this damage product in stored samples. To address this issue, 19 human serum samples that had been previously analyzed for the aflatoxin B1-lysine adduct by high-performance liquid chromatography–fluorescence in 1989 were re-analyzed by isotope dilution mass spectrometry after storage at −80°C. The adduct concentrations measured by these two techniques were identical within 4% over the range 5 to 100 pg of aflatoxin B1-lysine/mg albumin. In addi...
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The public health impact of aflatoxin exposure is pervasive in economically developing countries; consequently, we need to design intervention strategies for prevention that are practicable for these high-risk populations. The adverse... more
The public health impact of aflatoxin exposure is pervasive in economically developing countries; consequently, we need to design intervention strategies for prevention that are practicable for these high-risk populations. The adverse health consequences of aflatoxins in populations are quite varied, eliciting acute effects, such as rapid death, and chronic outcomes, such as hepatocellular carcinoma. Furthermore, a number of epidemiological studies describe a variety of general adverse health effects associated with aflatoxin, such as impaired growth in children. Thus, the magnitude of the problem is disseminated across the entire spectrum of age, gender, and health status in the population. The aflatoxins multiplicatively increase the risk of liver cancer in people chronically infected with hepatitis B virus (HBV), which illustrates the deleterious impact that even low toxin levels in the diet can pose for human health. Thus other aflatoxin interactions, which likely contribute to ...
Research Interests: Environmental Health, Developing Countries, Environmental Monitoring, Public Health, Medicine, and 14 moreHumans, Social Science Research Network, Developing Country, Animals, Hepatocellular Carcinoma, Carcinogens, Risk factors, Aflatoxin, Aflatoxins, Public health systems and services research, Food Contamination, Risk Factors, Clinical Trials as Topic, and Liver neoplasms
An estimated 500 million of the poorest people in sub-Saharan Africa, Latin America, and Asia are exposed to mycotoxins at levels that substantially increase mortality and morbidity (Pitt et al., 2012). The problem is not newly... more
An estimated 500 million of the poorest people in sub-Saharan Africa, Latin America, and Asia are exposed to mycotoxins at levels that substantially increase mortality and morbidity (Pitt et al., 2012). The problem is not newly recognized. Shortly after the discovery of aflatoxins, the impact on child health was brought into immediate focus. After the reporting of several deaths in children in Africa due to consumption of aflatoxin- contaminated meal, a decision was made in 1966 by the FAO/WHO/ UNICEF Protein Advisory Group to set a limit of 30 ppb aflatoxin in protein supplements made from groundnuts (Anonymous, 1966). In contrast to the situation today, in 1966 throughout most of Africa the proportion of calories from maize was modest, with a greater proportion coming from sorghum, millet, and cassava. Executive summary The International Agency for Research on Cancer (IARC) of the World Health Organization convened a Working Group Meeting in Lyon from 30 June to 3 July 2014. This ...
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Improving child cognition in impoverished countries is a public health priority. Yet, biological pathways and associated biomarkers of impaired cognition remain poorly understood and largely unknown, respectively. This study aimed to... more
Improving child cognition in impoverished countries is a public health priority. Yet, biological pathways and associated biomarkers of impaired cognition remain poorly understood and largely unknown, respectively. This study aimed to explore and quantify associations between functional plasma protein biomarkers and childhood intellectual test performance. We applied proteomics to quantify proteins in plasma samples of 249 rural Nepalese children, 6-8 years of age who, 1 year later at 7-9 years of age, were administered the Universal Nonverbal Intelligence Test (UNIT). Among 751 plasma proteins quantified, 22 were associated with UNIT scores, passing a false discovery rate threshold of 5.0% (q<0.05). UNIT scores were higher by 2.3-9.2 points for every 50% increase in relative abundance of two insulin-like growth factor binding proteins (IGFBPs), six subclasses of apolipoprotein (Apo) and transthyretin, and lower by 4.0-15.3 points for each 50% increase in relative abundance of 13 ...
Research Interests: Psychology, Immunology, Intelligence, Inflammation, Proteomics, and 9 moreNepal, Medicine, Humans, Child, Female, Blood, Male, Nutritional Status, and Neurosciences
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Research Interests: Biology and Micronutrient
Micronutrient deficiencies are common in undernourished societies yet remain inadequately assessed due to the complexity and costs of existing assays. A plasma proteomics-based approach holds promise in quantifying multiple... more
Micronutrient deficiencies are common in undernourished societies yet remain inadequately assessed due to the complexity and costs of existing assays. A plasma proteomics-based approach holds promise in quantifying multiple nutrient:protein associations that reflect biological function and nutritional status. To validate this concept, in plasma samples of a cohort of 500 6- to 8-y-old Nepalese children, we estimated cross-sectional correlations between vitamins A (retinol), D (25-hydroxyvitamin D), and E (α-tocopherol), copper, and selenium, measured by conventional assays, and relative abundance of their major plasma-bound proteins, measured by quantitative proteomics using 8-plex iTRAQ mass tags. The prevalence of low-to-deficient status was 8.8%…
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Background Cervical cancer is common in Kenyan women. Cofactors in addition to infection with oncogenic human papillomavirus (HPV) are likely to be important in causing cervical cancer, because only a small percentage of HPV-infected... more
Background Cervical cancer is common in Kenyan women. Cofactors in addition to infection with oncogenic human papillomavirus (HPV) are likely to be important in causing cervical cancer, because only a small percentage of HPV-infected women will develop this malignancy. Kenyan women are exposed to dietary aflatoxin, a potent carcinogen and immunosuppressive agent, which may be such a cofactor. Methods Demographics, behavioral data, plasma, and cervical swabs were collected from 88 human immunodeficiency virus-uninfected Kenyan women without cervical dysplasia. Human papillomavirus detection was compared between women with or without plasma aflatoxin B1-lysine (AFB1-lys) and evaluated in relation to AFB1-lys concentration. Results Valid HPV testing results were available for 86 women (mean age 34.0 years); 49 women (57.0%) had AFB1-lys detected and 37 (43.0%) had none. The AFB1-lys detection was not associated with age, being married, having more than secondary school education, home ...
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A review of the literature discloses no cases of contact sensitivity due to thiamine (vitamin B 1 ), and personal communication, so far as practicable, with other dermatologists fails to elicit any cases of allergic contact dermatitis due... more
A review of the literature discloses no cases of contact sensitivity due to thiamine (vitamin B 1 ), and personal communication, so far as practicable, with other dermatologists fails to elicit any cases of allergic contact dermatitis due to it. Within the past two years we have observed 2 cases of such contact sensitivity. Both occurred in persons who worked in a pharmaceutical establishment, filling ampuls containing injectable materials, one of which was vitamin B 1 . The patients' sole duties in these establishments were the filling of ampuls and vials, without actually handling the contents, although from time to time the contents splashed onto their fingers and hands. The interval of time elapsing between the initial handling of the substances and the appearance of a dermatitis was three months and eight months, respectively. In each instance the original site of involvement was on the back of the hands and fingers, with