The research in my program involves the development and application of quantitative molecular biomarkers of exposure, dose and effect from environmental carcinogens using advanced mass spectrometry based technologies. The environmental carcinogens studied include agents that are naturally occurring in the diet as well as those produced as a result of mobile and stationary sources of air pollution. A prior major emphasis of the research had been in the elucidation of the role of aflatoxins, a common contaminate of the food supply, in the induction of liver cancer in high-risk populations living in Asia and Africa. This work has led to the identification of a very strong chemical-viral interaction between aflatoxin and the human hepatitis B virus in the induction of liver cancer. These biomarkers have also been used in many collaborative molecular epidemiology studies of liver cancer risk and recently employed to assess the efficacy of a number of chemopreventive agents in trials in high-risk aflatoxin-hepatitis B virus exposed populations. This research has been extended to develop genetic biomarkers of p53 mutations in human samples as early detection of disease biomarkers using a novel mass spectroscopy based method for genotyping developed in the laboratory. The following briefly describes some of our ongoing efforts.
Discovery and Characterization of the Synergy Between Hepatitis B Virus and Aflatoxin in Human Liver Cancer. We have conducted a number of international prospective epidemiological studies that has explored the role that aflatoxin and the hepatitis B virus plays in the risk of liver cancer. This work has deployed a series of validated analytical biomarkers that has led to the discovery of the synergy between the virus and the environmental chemical in liver cancer and this then established the foundation for the prevention trials.
Development of Isotope-Dilution Mass Spectrometry (ID-MS) Methods for DNA Mutation Analysis. Our laboratory has played a central role in the development of ID-MS methods for the quantitation of mutations induced by environmental carcinogens. These novel analytic tools have been critical for the measurement of specific hepatitis B virus mutations formed following integration of the HBV X-gene into hepatocytes and the formation of an aflatoxin specific p53 mutation at codon 249.
Application of Analytical Biomarkers to Epidemiology of Cancer. These biomarkers have been used to demonstrate a striking association between diminishing exposures to aflatoxin-contaminated maize and subsequent drop in age-standardized rates of primary liver cancer. These studies, conducted in a liver cancer endemic region of China, demonstrate the dramatic power of primary prevention in cancer risk reduction. Recent work in Chile has also established the role of aflatoxin in gall bladder cancer.
Translation of Biomarkers to Clinical Intervention Trials. I have been central collaborator on a series of chemoprevention trials in Qidong, China, an area of eastern China where exposures to dietary carcinogens (aflatoxin) and airborne pollutants (including benzene and PAHs) have been, or are currently exceedingly high, respectively. Results from several of these trials (oltipraz, chlorophyllin, broccoli sprouts) have led to expanded evaluation of their chemopreventive efficacy in many settings.
Nogueira L, Foerster C, Groopman J, Egner P, Koshiol J, Ferreccio C; Gallbladder Cancer Chile Working Group.. Association of aflatoxin with gallbladder cancer in Chile. JAMA. 2015 PubMed PMID: 26010638.
Groopman JD, Egner PA, Schulze KJ, Wu LS, Merrill R, Mehra S, Shamim AA, Ali H, Shaikh S, Gernand A, Khatry SK, LeClerq SC, West KP Jr, Christian P. Aflatoxin exposure during the first 1000 days of life in rural South Asia assessed by aflatoxin B₁-lysine albumin biomarkers. Food Chem Toxicol. 2014 PubMed PMID: 25308602.
Wu Y, Gan Y, Gao F, Zhao Z, Jin Y, Zhu Y, Sun Z, Wu H, Chen T, Wang J, Sun Y, Fan C, Xiang Y, Qian G, Groopman JD, Gu J, Tu H. Novel natural mutations in the hepatitis B virus reverse transcriptase domain associated with hepatocellular carcinoma. PLoS One. 2014 PubMed PMID: 24788140.
Chen JG, Egner PA, Ng D, Jacobson LP, Muñoz A, Zhu YR, Qian GS, Wu F, Yuan JM, Groopman JD, Kensler TW. Reduced aflatoxin exposure presages decline in liver cancer mortality in an endemic region of China. Cancer Prev Res (Phila). 2013 PubMed PMID: 23963804.
Ortiz-Cuaran S, Villar S, Gouas D, Ferro G, Plymoth A, Khuhaprema T, Kalalak A, Sangrajrang S, Friesen MD, Groopman JD, Hainaut P. Association between HBX status, aflatoxin-induced R249S TP53 mutation and risk of hepatocellular carcinoma in a case-control study from Thailand. Cancer Lett. 2013 PubMed PMID: 23200676.