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Molecular & Genetic Epidemiology Group

Environmental Exposure & Carcinogenesis

Jack A. Taylor, M.D., Ph.D.
Jack A. Taylor, M.D., Ph.D.
Principal Investigator



Tel (919) 541-4631
Fax (919) 541-2511
taylor15@niehs.nih.gov

Curriculum Vitae (http://www.niehs.nih.gov/research/atniehs/labs/epi/molecular/taylor_cv.pdf)  Download Adobe Reader
P.O. Box 12233
Mail Drop A3-05
Research Triangle Park, North Carolina 27709
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Research Summary

The Molecular & Genetic Epidemiology Group works toward understanding the interaction between genes and environmental exposures in human carcinogenesis. The group’s research has two main elements: investigating the role of environmental exposure in critical target gene mutation and investigating the role of genetic susceptibility and environmental exposure in cancer risk. Jack A. Taylor, M.D., Ph.D., is head of the Molecular and Genetic Epidemiology Group.

Taylor’s research on critical target genes addresses the hypothesis that different environmental exposures cause different patterns of mutation in genes that are important in carcinogenesis. The initial focus has been on mutational activation of oncogenes and deactivation of tumor suppressor genes. Much of this work has been on lung and bladder cancer, two tumors types that have strong environmental determinants. Recent studies have focused on normal and preneoplastic tissue. This includes a study using fluorescent light bronchscopy to identify and collect samples of normal, dysplastic, and neoplastic bronchial tissue from patients at high risk for lung cancer. Samples are being analyzed for a variety of molecular changes and specific lesions were followed over time with periodic biopsy. This work seeks to identify early molecular changes in normal lung epithelium following environmental exposures, and to identify mutations and other changes that may be prognostic markers. Such mutations can be used both to identify novel critical target genes and to suggest mechanisms by which an environmental agent causes cancer. If specific carcinogens produce characteristic patterns of gene mutation in tumors, the detection of those patterns would be a powerful tool in studies of environmental risk and for use in prevention and early diagnosis.

The research on genetic susceptibility tests the hypothesis that commonly inherited allelic variants of selected candidate genes, in conjunction with environmental exposures, affect a person's risk of developing cancer. This research has largely focused on cancers of the bladder, prostate and lung with efforts directed at genes involved in carcinogen metabolism. Current efforts are focused on polymorphisms in genes involved in DNA synthesis and repair and on the development of a functional assay for DNA repair that can be applied in population-based studies. Working with genetically susceptible subgroups may allow identification of the environmental exposures that cause disease and the true risks associated with exposure. It could also lead to the development of public health programs for protecting susceptible populations, and for targeted screening of groups at higher risk of disease.

Taylor received a B.A. from Carleton College, an M.D. from the University of Wisconsin and a Ph.D. in epidemiology from the School of Public Health at the University of North Carolina at Chapel Hill. Taylor is licensed in North Carolina, and holds board certifications in Public Health and General Preventive Medicine. He holds Adjunct Professorships in the Department of Epidemiology, Department of Medicine and the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill, as well as in the Department of Medicine at Duke University. He serves as Senior Researcher in the U.S. Public Health Service at NIEHS, and holds a joint appointment (http://www.niehs.nih.gov/research/atniehs/labs/lmc/molecular/index.cfm) in the Laboratory of Molecular Carcinogenesis at NIEHS.

Studies

  • Bladder Cancer Study
  • Fried Meat Study
  • Haplotypes in Environmental Genome Project
  • LIFE and VALID Lung Studies (http://www.niehs.nih.gov/research/atniehs/labs/epi/studies/life/index.cfm)
    The LIFE study's objective is to evaluate the effectiveness of Lung Imaging Fluorescence Endoscopy (LIFE) in detecting and following early lung lesions in patients at high risk for developing lung cancer. The VALID study, a companion to the LIFE study, evaluates the effect of initial arterial ligation versus venous ligation during surgery on the risk of distant metastases in lung cancer patients.
  • Prostate Cancer Consortium

Software

  • TAGSter is a software tool to select, evaluate and visualize LD tag SNPS for single or multiple populations.   http://www.niehs.nih.gov/research/resources/software/tagster/
  • mPopTag is a tool used to select or evaluate linkage disequilibrium (LD) tag SNPs for multiple populations.   http://www.niehs.nih.gov/research/resources/software/mpoptag/

Selected Publications

  1. Stern MC, Umbach DM, van Gils CH, Lunn RM, Taylor JA. DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk. Cancer Epidemiology Biomarkers and Prevention 10:125-131, 2001.  [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11219769) Exit NIEHS [Full Text] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11219769http://cebp.aacrjournals.org/cgi/content/full/10/2/125) Exit NIEHS [PDF] (http://cebp.aacrjournals.org/cgi/reprint/10/2/125) Download Adobe Reader Exit NIEHS
  2. Thompson TE, Rogan PK, Risinger JI, Taylor JA. Splice variants, but not mutations, of DNA Polymerase b are common in bladder cancer. Cancer Research 62:3251-3256, 2002.  [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12036941) Exit NIEHS [Full Text] (http://cancerres.aacrjournals.org/cgi/content/full/62/11/3251) Exit NIEHS [PDF] (http://cancerres.aacrjournals.org/cgi/reprint/62/11/3251) Download Adobe Reader Exit NIEHS
  3. Slebos JC, Oh DS, Umbach DM, Taylor JA. Mutations in tetranucleotide repeats following DNA damage depend on repeat sequence and carcinogenic agent. Cancer Research 2002; 62:6052-60, 2002.  [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12414628) Exit NIEHS [Full Text] (http://cancerres.aacrjournals.org/cgi/content/full/62/21/6052) Exit NIEHS [PDF] (http://cancerres.aacrjournals.org/cgi/reprint/62/21/6052) Download Adobe Reader Exit NIEHS
  4. Stern MC, Johnson LR, Bell DA, Taylor JA. XPD codon 751 polymorphism, metabolism genes, smoking, and bladder cancer risk. Cancer Epidemiology Biomarkers and Prevention 11:1004-1011, 2002.  [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12376500) Exit NIEHS [Full Text] (http://cebp.aacrjournals.org/cgi/content/full/11/10/1004) Exit NIEHS [PDF] (http://cebp.aacrjournals.org/cgi/reprint/11/10/1004) Download Adobe Reader Exit NIEHS
  5. Schroeder JC, Conway K, Li Y, Mistry K, Bell DA, Taylor JA. P53 mutations in bladder cancer: evidence for exogenous versus endogenous risk factors. Cancer Research 63:7530-8, 2003.  [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14612556) Exit NIEHS [Full Text] (http://cancerres.aacrjournals.org/cgi/content/full/63/21/7530) Exit NIEHS [PDF] (http://cancerres.aacrjournals.org/cgi/reprint/63/21/7530) Download Adobe Reader Exit NIEHS
  6. Slebos RJC, Umbach DM, Sommer CA, Horner GA, Choi JY, Taylor JA Analytical and statistical methods to evaluate microsatellite allelic imbalance in small amounts of DNA. Lab. Invest. 2004 84:648-57.  [Abstract] (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=15048133) Exit NIEHS
  7. Li L, Umbach DM, Terry P, Taylor JA. Application of the GA/KNN method to SELDI proteomics data. Bioinformatics 2004 20:1638-40.  [Abstract] (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=14962943) Exit NIEHS
  8. Slebos RJC, Little RE, Umbach DM, Antipkin Y, Zadaorozhnaja TD, Mendel NA, Sommer CA, Conway K, Parrish E, Gulino S, Taylor JA. Mini- and microsatellite mutations in children from Chernobyl accident cleanup works. Mut. Research 2004 559:143-51.  [Abstract] (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=15066582) Exit NIEHS
  9. Slebos RJC, Livanos E, Yim H-W, Randell SH, Parsons AM, Detterbeck FC, Rivera MP, Taylor JA. Chromosomal abnormalities in bronchial epithelium from smokers, non-smokers and lung cancer patients. Cancer Genetics and Cytogenetics. 2005 159:137-42.  [Abstract] (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=15899385) Exit NIEHS
  10. Taylor JA, Xu ZL, Kaplan NL, Morris RW. How well do HapMap haplotypes identify common haplotypes of genes? A comparison with haplotypes of 334 genes resequenced in the Environmental Genome Project. Cancer Epidemiology Biomarkers and Prevention. 2006 15:133-7.  [Abstract] (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16434598) Exit NIEHS
  11. Terry PD, Umbach DM, Taylor JA. APE1 genotype and risk of bladder cancer: Evidence for effect modification by smoking. Int J Cancer 2006 31:516-8.  [Abstract] (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16425270) Exit NIEHS
  12. Stern MC, Conway K, Li Y, Mistry K, Taylor JA. DNA repair gene polymorphisms and probability of p53 mutation in bladder cancer. Molecular Carcinogenesis 2006 45:715-719.  [Abstract] (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16652373) Exit NIEHS
  13. Yim HW, Slebos RJC, Randell SH, Umbach DM, Parsons AM, Rivera MP, Detterbeck FC, Taylor JA. Smoking is associated with increased telomerase activity in short-term cultures of human bronchial epithelial cells. Cancer Letters 2007 246:24-33.  [Abstract] (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16517060) Exit NIEHS
  14. Flake GP, Rivera MP, Funkhouser WK, Slebos RJC, Maygarden SJ, Meadows KL, Long EH, Stockton PS, Jones TC, Taylor JA. Detection of pre-invasive lung cancer: Technical aspects of the LIFE Project. Toxicologic Pathology 2007 35:65-74.  [Abstract] (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17325974) Exit NIEHS
  15. Xu Z, Kaplan NL, Taylor JA. Tagster: Efficient selection of LD tag SNPs in single or multiple populations. Bioinformatics (Oxford, England) 2007 23(23):3254-3255. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17827206) Exit NIEHS
  16. Xu Z, Kaplan NL. Tag SNP selection for candidate gene association studies using HapMap and gene resequencing data. European journal of human genetics : EJHG 2007 15(10):1063-1070. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17568388) Exit NIEHS
  17. Flake GP, Rivera MP, Funkhouser WK, Maygarden SJ, Meadows KL, Long EH, Stockton PS, Jones TC, Yim HW, Slebos RJC, Taylor JA. Detection of pre-invasive lung cancer: technical aspects of the LIFE project. Toxicologic pathology 2007 35(1):65-74. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17325974) Exit NIEHS

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Last Reviewed: August 26, 2008