Elevated HPRT mutation frequencies in aflatoxin-exposed residents of Daxin, Qidong County, People's Republic of China

Molecular biomarkers are becoming increasingly important tools to identify people who are at highest risk of developing cancer. For many years we have been studying residents of Qidong County, People's Republic of China, to e xamine the combined impact of aflatoxin exposure with other risk factors as contributors to the high liver cancer incidence rates in this region. This study was conducted to determine the effects of aflatoxin exposure, as mea sured by serum aflatoxin-albumin adduct levels, on somatic mutation frequen cy in the human hypoxanthine guanine phosphoribosyl transferase gene (HPRT) , Subjects were assigned as low or high according to a dichotomization arou nd the population mean of aflatoxin-albumin adducts, HPRT mutant frequency was determined in individuals by a T cell clonal assay and the samples were categorized as low or high according to mean values, Separate analyses wer e also conducted for the small set of hepatitis B virus surface antigen (HB sAg)-positive and the larger set of HBsAg-negative individuals, known risk factors for liver cancer. An odds ratio of 19.3 (95% confidence interval 2. 0, 183) was demonstrated for a high HPRT mutation frequency in individuals with high aflatoxin exposure compared with those with low aflatoxin exposur e. This association indicates that aflatoxin-induced DNA damage in T lympho cytes, assessed using the validated surrogate albumin adduct markers, leads to increased mutations reflected as elevated HPRT gene mutations. This cro ss-sectional study suggests the potential use of mutation frequency of the HPRT gene as a long-term biomarker of aflatoxin exposure in high risk popul ations.