Burkina Faso

Molecular Biomarkers for Environmental Carcinogens
(Grant: # P01ES006052 )  Publications
Groopman, John D (jgroopma@jhsph.edu ) - Johns Hopkins University
Abstract: This cohort of 804 healthy HBsAg-positive individuals (728 males and 76 females) and 882 HBsAg-negative individuals (820 males and 63 females) annually are contacted for blood and urine samples. These subjects were recruited into the study in May 1991 and ranged in age from 20-65 at the time of enrollment. Each subject donates blood and urine samples at yearly intervals since May 1991. The human subjects protocols have been approved by the committee on human research at the Johns Hopkins University Bloomberg School of Public Health and the committees at the Shnaghai Cancer Institute and Qidong Liver Cancer Institute. Specific aim 1: To determine the power of p53 mutations and other genetic alterations in sera using the Short Oligonucleotide Mass Analysis (SOMA) methodology combined with aflatoxin-DNA adducts in urine to predict cancer outcome and disease risk in cohorts in rural China and West Africa. We will (a) examine the predictive power of the aflatoxin specific p53 mutation in codon 249 as a biomarker for the early detection of liver cancer in a nested study within a cohort in Qidong, P.R.C. and also assess the prevalence of this mutation in blood samples from other highrisk areas of rural China; (b) establish the age-related prevalence of p53 codon 249 mutations in highly exposed children in West Africa and (c) apply a newly developed mass spectroscopic technique to sensitively measure aflatoxin N7-guanine and its imidazole ring opened derivative, AF-FAPyr, in urine of cohort samples. Specific aim 2: To extend our observations on the high level of aflatoxin biomarkers in West African children in order to assess the impact on growth and immune status, including susceptibility to hepatitis B virus (HBV) infection. West African children, unlike adults, have elevated aflatoxin biomarker levels when infected with HBV. We will examine in children (a) the unique HBV modulation of aflatoxin biomarkers, including DMA adducts in urine, serum albumin adducts and p53 mutations in sera and (b) the role of aflatoxin and other co-occurring dietary mycotoxins as modulators of growth and immune status. The possible modulation of the associations outlined in (a) and (b) by variations in aflatoxin metabolism, governed either genetically or environmentally, will be assessed.