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Your Environment. Your Health.

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
taylor@niehs.nih.gov
P.O. Box 12233
Mail Drop A3-05
Research Triangle Park, North Carolina 27709
Delivery Instructions

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 ("/Rhythmyx/assembler/render?sys_contentid=36586&sys_revision=2&sys_variantid=1173&sys_context=0&sys_authtype=0&sys_siteid=&sys_folderid=" sys_dependentvariantid="1173" sys_dependentid="36586" inlinetype="rxhyperlink" rxinlineslot="103" sys_dependentid="36586" sys_siteid="" sys_folderid="") 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
    ("/Rhythmyx/assembler/render?sys_contentid=35609&sys_revision=1&sys_variantid=639&sys_context=0&sys_authtype=0&sys_siteid=&sys_folderid=" sys_dependentvariantid="639" sys_dependentid="35609" inlinetype="rxhyperlink" rxinlineslot="103" sys_dependentid="35609" sys_siteid="" sys_folderid="")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


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Software

  • mPopTag
    ("/Rhythmyx/assembler/render?sys_contentid=35063&sys_revision=6&sys_variantid=639&sys_context=0&sys_authtype=0&sys_siteid=&sys_folderid=" sys_dependentvariantid="639" sys_dependentid="35063" inlinetype="rxhyperlink" rxinlineslot="103" sys_dependentid="35063" sys_siteid="" sys_folderid="")A tool used to select or evaluate linkage disequilibrium tag SNPs for multiple populations.
  • SNP Selection and Functional Information

  • TAGster ("/Rhythmyx/assembler/render?sys_contentid=35267&sys_revision=3&sys_variantid=639&sys_context=0&sys_authtype=0&sys_siteid=&sys_folderid=" sys_dependentvariantid="639" sys_dependentid="35267" inlinetype="rxhyperlink" rxinlineslot="103" sys_dependentid="35267" sys_siteid="" sys_folderid="")
    A tool to select, evaluate and visualize LD tag SNPs for single or multiple populations.


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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 ][Full Text ][PDF ]
  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 ][Full Text ][PDF ]
  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 ][Full Text ][PDF ]
  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 ][Full Text ][PDF ]
  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 ][Full Text ][PDF ]
  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 ][Full Text ][PDF ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  18. Markunas CA, Umbach DM, Xu Z, Taylor JA. Assessing candidate gene nsSNPs for phenotypic differences in double-strand break repair using radiation-induced gamma H2A.X foci. Journal of cancer epidemiology 2008 2008:387423-8 pages.[Abstract ]
  19. Xu Z, Taylor JA. SNPInfo: integrating GWAS and candidate gene information into functional SNP selection for genetic association studies. Nucleic Acids Res.2009 Jul;37(Web Server issue):W600-5. Epub 2009 May 5.[Abstract ]
  20. Stern MC, Lin J, Figueroa JD, Kelsey KT, Kiltie AE, Yuan JM, Matullo G, Fletcher T, Benhamou S, Taylor JA, Placidi D, Zhang ZF, Steineck G, Rothman N, Kogevinas M, Silverman D, Malats N, Chanock S, Wu X, Karagas MR, Andrew AS, Nelson HH, Bishop DT, Sak SC, Choudhury A, Barrett JH, Elliot F, Corral R, Joshi AD, Gago-Dominguez M, Cortessis VK, Xiang YB, Gao YT, Vineis P, Sacerdote C, Guarrera S, Polidoro S, Allione A, Gurzau E, Koppova K, Kumar R, Rudnai P, Porru S, Carta A, Campagna M, Arici C, Park SS, Garcia-Closas M, International Consortium of Bladder Cancer. Polymorphisms in DNA repair genes, smoking, and bladder cancer risk: findings from the International Consortium of Bladder Cancer. Cancer research 2009 69(17):6857-64.[Abstract ]
  21. N Rothman, M Garcia-Closas, N Chatterjee, N Malats, X Wu, J Figueroa, V Cortessis, G Matullo, D Baris, M Thun, LA Kiemeney, P Vineis, I De Vivo, F X Real, D Albanes, M Purdue, T Rafnar, M Hildebrandt, AE Kiltie, O Cussenot, K Golka, R Kumar, JA Taylor, JI Mayordomo, KB Jacobs, M Kogevinas, A Hutchinson, Z Wang, YP Fu, L Prokunina-Olsson, L Burdett, M Yeager, W Wheeler, A Tardon, C Serra, A Carrato, R Garcia-Closas, J Lloreta, A Johnson, M Schwenn, MR Karagas, A Schned, G Andriole Jr, R Grubb 3rd, A Black, EJ Jacobs, WR Diver, SM Gapstur, SJ Weinstein, J Virtamo, VK Cortessis, M Gago-Dominguez, MC Pike, MC Stern, JM Yuan, DJ Hunter, M McGrath, CP Dinney, B Czerniak, M Chen, H Yang, SH Vermeulen, KK Aben, JA Witjes, RR Makkinje, P Sulem, S Besenbacher, K Stefansson, E Riboli, P Brennan, S Panico, C Navarro, NE Allen, HB Bueno-de-Mesquita, D Trichopoulos, N Caporaso, MT Landi, F Canzian, B Ljungberg, A Tjonneland, F Clavel-Chapelon, DT Bishop, MT Teo, MA Knowles, S Guarrera, S Polidoro, F Ricceri, C Sacerdote, A Allione, G Cancel-Tassin, S Selinski, JG Hengstler, H Dietrich, T Fletcher, P Rudnai, E Gurzau, K Koppova, S Bolick, A Godfrey, Z Xu, JI Sanz-Velez, M D Garcia-Prats, M Sanchez, G Valdivia, S Porru, S Benhamou, RN Hoover, JF Fraumeni Jr., DT Silverman, SJ Chanock. A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. Nature Genetics 2010 42(11):978-84.[Abstract ]
  22. Xu Z, Bensen JT, Smith GJ, Mohler JL, Taylor JA. GWAS SNP Replication among African American and European American men in the North Carolina-Louisiana prostate cancer project (PCaP). Prostate 2011 71(8):881-91.[Abstract ]
  23. Meadows KL, Andrews DM, Xu Z, Carswell GK, Laughlin SK, Baird DD, Taylor JA. Genome-wide analysis of loss of heterozygosity and copy number amplification in uterine leiomyomas using 100K single nucleotide polymorphism array. Experimental and molecular pathology 2011 91(1):434-9.[Abstract ]
  24. Shaughnessy DT, Gangarosa LM, Schliebe B, Umbach DM, Xu Z, MacIntosh B, Knize MG, Matthews PP, Swank AE, Sandler RS, DeMarini DM, Taylor JA. Inhibition of fried meat-induced colorectal DNA damage and altered systemic genotoxicity in humans by crucifera, chlorophyllin, and yogurt. PLOS ONE 2011 6(4):e18707-.[Abstract ]
  25. Kim S, Sandler DP, Carswell G, De Roo LA, Parks CG, Cawthon R, Weinberg CR, Taylor JA. Telomere length in peripheral blood and breast cancer risk in a prospective case-cohort analysis: results from the Sister Study. Cancer causes & control 2011 22(7):1061-6.[Abstract ]
  26. Kim S, Sandler DP, Carswell G, Weinberg CR, Taylor JA. Reliability and short-term intra-individual variabiltiy of telomere length measurement using monochrome multiplexing quantitative PCR. PloS one 6(9):e25774, 2011.[Abstract ]
  27. Kim S, Parks CG, Xu Z, Carswell G, DeRoo LA, Sandler DP, Taylor JA. Association between genetic variants in DNA and histone methylation and telomere length. PloS one 7(7):e40504-, 2012.[Abstract ]
  28. Sucheston LE, Bensen JT, Xu Z, Singh PK, Preus L, Mohler JL, Su LJ, Fontham ET, Ruiz B, Smith GJ, TaylorJA. Genetic ancestry, self-reported race and ethnicity in African and European Americans in the PCaP cohort. PLOS ONE 7(3):e30950-, 2012.[Abstract ]
  29. Fang F, Umbach DM, Xu Z, Ye W, Sandler DP, Taylor JA, Kamel F. No association between DNA repair gene XRCC1 and amyotrophic lateral sclerosis. Neurobiology of aging 33(5):1015.e25-1015.e26, 2012. [Abstract ]
  30. Bensen JT, Xu Z, Smith GJ, Mohler JL, Fontham ET, Taylor JA. Genetic polymorphism and prostate cancer aggressiveness: A case-only study of 1,536 GWAS and candidate SNPs in African-Americans and European-Americans. The Prostate 2013 73(1):11-22.[Abstract ]
  31. White AJ, Sandler DP, Bolick SCE, Xu Z, Baldwin K, Taylor JA, DeRoo LA. Recreational and household physical activity at different time points and DNA global methylation. 2013 European journal of cancer.  49:2199-2206.[Abstract ]
  32. Xu Z, Bolick SCE, DeRoo LA, Weinberg CR, Sandler DP, Taylor JA. DNA methylation in blood is associated with breast cancer: A study in prospective samples from the Sister Study. Journal of the National Cancer Institute. 2013 105(10):694-700.[Abstract ]
  33. Kim S, Taylor JA, Milne GL, Sandler DP. Association between Urinary Prostaglandin E2 Metabolite and Breast Cancer Risk: A Prospective, Case-Cohort Study of Postmenopausal Women. Cancer prevention research (Philadelphia, Pa.) 2013 6(6):511-518.[Abstract ]
  34. Bensen JT, Xu Z, McKeigue PM, Smith GJ, Fontham ET, Mohler JL, Taylor JA. Admixture mapping of prostate cancer in African Americans participating in the North Carolina-Louisiana Prostate Cancer Project (PCaP). The Prostate 2014 74(1):1-9.[Abstract ]
  35. DeRoo LA, Bolick SCE, Xu Z, Umbach DM, Shore D, Weinberg CR, Sandler DP, Taylor JA. Global DNA methylation and one-carbon metabolism gene polymorphisms and the risk of breast cancer in the Sister Study. Carcinogenesis 35(2):333-338, 2014.[Abstract ]
  36. Xu Z, Taylor JA. Genome-wide age-related DNA methylation changes in blood and other tissues relate to histone modification, expression and cancer. Carcinogenesis 2014 35(2):356-364.[Abstract ]
  37. Weinberg CR, Shi M, DeRoo L, Taylor JA, Sandler DP, Umbach DM. Asymmetry in family history implicates nonstandard genetic mechanisms: application to the genetics of breast cancer. PLoS genetics 10(3):e1004174, 2014.[Abstract ]

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