Biography

Dr. Taylor received his medical degree from the University of Iowa in 1973 and completed his residency in internal medicine at Vanderbilt University in 1976. He joined the Centers for Disease Control in 1976 as an EIS officer and while there completed a residency in preventive medicine. He received his master’s and doctoral degrees in epidemiology from the Harvard School of Public Health, and came to the NCI in 1983. He was chief of the Cancer Prevention Studies Branch from 1987 – 2004 before joining the Genetic Epidemiology Branch in 2005. His research interests focus on developing cancer prevention strategies.

Research Interests

Upper Gastrointestinal Cancer Research

My current primary research interest is in the development of prevention strategies for cancers of the upper gastrointestinal (UGI) tract, including esophageal and gastric cancers, although I retain interest in prevention of other cancers, including prostate, lung, and breast. My work has involved a variety of different research approaches, including the conduct of cancer prevention trials, early detection studies, etiologic studies, laboratory-based molecular research, and clinical nutrition studies.

Beginning with the Nutrition Intervention Trials (NIT) in over 32,000 residents of Linxian, China, started in 1985, my research on esophageal cancer has evolved through the years into an integrated, highly collaborative, interdisciplinary, international research program that includes studies of etiology, genetics, early detection, and intervention, all emphasizing prevention. My research is conducted primarily as part of the three UGI cancer projects described here, but is inter-connected with a number of other studies directed by others within our UGI Cancer Research Group ( http://dceg.cancer.gov/neb/research/ugcrg).

The original goal of the Nutrition Intervention Trials (NIT) in Linxian, China was to evaluate the role of nutrition in the etiology and prevention of UGI cancers. With the conclusion of the intervention phase in 1991, and the determination that the micronutrient combination of selenium/vitamin E/ß-carotene reduced total mortality, total cancer mortality, and gastric cancer mortality, objectives now include:

• Determination of post-trial effects of the interventions;
• Evaluation of etiologic hypotheses, including nutrition, carcinogens, infections, genetics, and other exposures;
• Studies of natural history; and
• Examination of interactions (gene-environment, gene-gene, and gene-intervention).

In collaboration with the Cancer Institute of the Chinese Academy of Medical Sciences (CICAMS) in Beijing, we continue to follow trial participants to ascertain endpoints, and conduct nested case-control and case-cohort studies using baseline serum. In 1999 and 2000 we collected additional blood samples to permit expanded DNA and biochemical analyses.

The Upper Gastrointestinal Cancer Genetic Studies were started in 1995 to look for major susceptibility genes for UGI cancers and identify the genetic changes associated with their development. To accomplish this:

• We identify somatic genetic alterations, emphasizing recessive loss-of-function changes that might point us to tumor suppressor genes;
• We search for dominant gain-of-function changes associated with oncogenes that might potentially serve as early detection markers; and
• We examine germ-line genetic variants in relation to cancer to identify major risk (high penetrance, low prevalence) susceptibility genes, as well as moderate risk (low penetrance, high prevalence) susceptibility genes to enable development of risk stratification strategies and better understand cancer biology.

  This project was initiated to study esophageal squamous cell carcinomas (ESCC), but also includes other UGI cancers (gastric cardia cancer or GCC and gastric non-cardia cancer or GNCC). Following a pilot study in 1995, we initiated a collaboration with the Shanxi Cancer Hospital and Institute (SCHI), Taiyuan, Shanxi Province, China in 1996 to perform clinical and field studies:

• To enable study of somatic alterations in tumors, we developed a “tumor/non-tumor study” by recruiting cancer cases surgically resected at the Shanxi Cancer Hospital who answer a standardized risk factor questionnaire and provide a blood sample and tumor/non-tumor surgical specimens.
• To permit evaluation of somatic molecular markers in pre-malignant tissues in our search for early detection markers, we added an “endoscopy study” in 2006 which targets collection of esophageal biopsies, blood, and risk factor questionnaire data on patients presenting to the Endoscopy Clinic at the Shanxi Cancer Hospital.
• To examine germ-line genetic variants in relation to cancer in our search for major risk susceptibility genes, we developed a “family study” which recruits highly informative multiplex families (pedigrees with 2+ UGI cancer cases and available DNA) and obtains blood samples and questionnaire-based risk factor information on all living first-degree relatives over 20 years of age for linkage (and association study) analysis.
• To evaluate germ-line genetic variants in relation to cancer in our search for moderate risk susceptibility genes, as well as study environment, gene-environment, and gene-gene interactions, we developed a “case-control study” which enrolls histologically-confirmed UGI cancer cases and neighborhood-matched controls, obtains information from a structured risk factor questionnaire, and collects biologic samples (a venous blood sample, a finger stick blood sample, a buccal smear, and a tumor specimen from surgical resections of cases).

The Barrett’s Esophagus Early Detection Study was initiated in July 2006, with the primary goal of identifying a practical blood-based biomarker to distinguish persons with Barrett’s esophagus (BE) from those without it. This BE case-control study is being conducted as a collaboration with investigators at the National Naval Medical Center in Bethesda among Barrett’s Esophagus Registry patients and non-BE patients endoscoped in the Gastroenterology Clinic.

Other Research

Clinical Nutrition Studies:Over the years we have conducted nearly a dozen controlled clinical nutrition feeding studies in collaboration with colleagues at the US Department of Agriculture’s Beltsville Human Nutrition Research Center to evaluate modifiable dietary risk factors for cancer. Studies have emphasized research on potential chemopreventive antioxidants (selenium, ß-carotene, vitamin C); fat, fiber, and energy; and alcohol. Active research studies include: (i) a controlled dietary (alcohol) intervention study conducted in 1999, the Postmenopausal Women’s Alcohol Study (WAS), which evaluated potential mechanisms by which controlled alcohol ingestion (zero, one, or two drinks/day) might influence breast cancer risk factors (eg, sex hormones); and (ii) a study which characterizes and compares the metabolism of inorganic and organic selenium compounds before and after two years of supplementation.

The Alpha-Tocopherol Beta-Carotene (ATBC) Cancer Prevention Trial and Follow-up Study: I am a Co-PI for the ATBC Cancer Prevention Trial, a large intervention study conducted between 1984 and 1993 in Finland in over 29,000 male smokers to test the effect of vitamin E and ß-carotene on the prevention of lung and other cancers; and the ATBC Cohort Follow-up Study, the ongoing follow-up of trial participants that is evaluating post-trial effects and studying nutritional, other environmental, and genetic etiologic factors in the development of lung, prostate, gastric, and other cancers.

Selenium and Vitamin E Prostate Chemoprevention Trial (SELECT): I serve on the Steering Committee for SELECT (SELenium and vitamin E Cancer prevention Trial), a large-scale study in 35,000+ men to test selenium and vitamin E for the prevention of prostate cancer.

Keywords

• Esophageal cancer, gastric cancer, cancer prevention, intervention, clinical trial, early detection, epidemiology, nutrition, genetics, prostate cancer, lung cancer, breast cancer, selenium, alcohol

Selected Publications

• Kamangar F, Qiao YL, Blaser MJ, Sun XD, Katki H, Fan JH, Perez-Perez GI, Abnet CC, Zhao P, Mark SD, Taylor PR, Dawsey SM. Helicobacter pylori and oesophageal and gastric cancers in a prospective study in Chiana. Br J Cancer 2007;96:172-176.
• Abnet CC, Fagundes RB, Strickland PT, Kamangar F, Roth MJ, Taylor PR, Dawsey SM. The influence of genetic polymorphisms in Ahr, CYP1A1, CYP1A2, CYP1B1, GST M1, GST T1, and UGT1A1 on urine 1-hydroxypyrene glucuronide concentrations in healthy subjects from Rio Grande do Sul, Brazil. Carcinogenesis 2007;28:112-117.
• Wright ME, Virtamo J, Hartman AM, Pietinen P, Edwards BK, Taylor PR, Huttunen JK, Albanes D. Effects of alpha-tocopherol and beta-carotene supplementation on upper aerodigestive tract cancers in a large, randomized controlled trial. Cancer 2007;109:891-898.
• Mahabir S, Baer D, Johnson LL, Roht M, Campbell W, Clevidence B, Taylor PR. Body mass index, percent body fat, and regional body fat distribution in relation to leptin concentrations in healthy, non-smoking postmenopausal women in a feeding study. Nutr J 2007;6:3.
• Chen W, Dawsey SM, Qiao YL, Mark SD, Dong ZW, Taylor PR, Zhao P, Abnet CC. Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers. Br J Cancer 2007;97:123-128.
• Qu CX, Kamangar F, Fan JH, Yu B, Sun XD, Taylor PR, Chen BE, Abnet CC, Qiao YL, Mark SD, Dawsey SM. Chemoprevention of primary liver cancer: a randomized, double-blind trial in Linxian, China. J Natl Cancer Inst 2007;99:1240-1247.
• Kadota M, Yang HH, Hu N, Wang C, Hu Y, Taylor PR, Buetow KH, Lee MP. Allele-specific chromatin immunoprecipitation studies show genetic influence on chromatin state in human genome. PloS Genetics 2007;3:e81.
• Abnet CC, Chen W, Dawsey SM, Wei WQ, Roth MJ, Liu B, Lu N, Taylor PR, Qiao YL. Serum 25(OH)-vitamin D concentration and risk of esophageal squamous dysplasia. Cancer Epidemiol Biomarkers Prev 2007;16:1889-1893.
• Koshiol J, Qiao YL, Mark SD, Dawsey SM, Abnet CC, Kamangar F, Lennette ET, Dong ZW, Taylor PR. Epstein-Barr virus serology and gastric cancer incidence and survival. Br J Cancer 2007;97:1567-1569.
• Endogenous Hormones and Prostate Cancer Collaborative Group. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 2008;100:170-183.
• Dawsey SP, Roth MJ, Adams L, Hu N, Wang OH, Taylor PR, Woodson K. COX-2 (PTGS2) gene methylation in epithelial, subepithelial lymphocyte and stromal tissue compartments in a spectrum of esophageal squamous neoplasia. Cancer Detect Prev 2008;32:135-139

Collaborators

DCEG Collaborators

• Christian Abnet, Ph.D, M.P.H.; Demetrius Albanes, M.D.; Stephen Chanock, M.D.; Wong-Ho Chow, Ph.D.; Sandy Dawsey, M.D.; Neal Freedman, Ph.D.; Ying Gao, M.D., Ph.D.; Alisa Goldstein, Ph.D.; Farin Kamangar, M.D., Ph.D.; Jill Koshiol, Ph.D.; Maria Teresa Landi, M.D., Ph.D.; Katherine McGlynn, Ph.D.; Thomas O'Brien, M.D.; Ruth Pfeiffer, Ph.D.; Mark Roth, M.D.; Sharon Savage, M.D.; Rachael Stolzenberg-Solomon, Ph.D.; Jorge Toro, M.D.

Other NCI Collaborators

• Paul Albert, Ph.D.; Michael Emmert-Buck, M.D., Ph.D.; Stephen Hewitt, M.D., Ph.D.; Ed Korn, PhD.; Maxwell Lee, Ph.D.; Stephen Meltzer, M.D.; Blossom Patterson, Ph.D.; Mimi Poirier, Ph.D.

Other Scientific Collaborators

• Laura Lee Johnson, PhD., NCCAM, NIH
• Franco Marincola, M.D., Clinical Center, NIH
• Steven Mark, M.D., ScD., University of Colorado
• Paul Limburg, M.D., Mayo Clinic
• Martin Blaser, M.D., NYU
• Patti Gravitt, Ph.D, Johns Hopkins
• Yun-Ling Zheng, Ph.D., Georgetown University
• Brooks Cash, M.D., NNMC
• David Baer, Ph.D., USDA
• Joseph Judd, Ph.D., USDA
• Beverly Clevidence, Ph.D., USDA
• Orville Levander, Ph.D., USDA
• Gerald Combs, Ph.D., USDA
• Somdat Mahabir, Ph.D., MD Anderson Cancer Center
• Joanne Dorgan, Ph.D., Fox Chase Cancer Center
• Terryl Hartman, Ph.D., Penn State University
• Richard Stevens, Ph.D., University of Connecticut
• Scott Lippman, M.D., MD Anderson Cancer Center
• Eric Klein, M.D., Cleveland Clinic
• Phyllis Goodman, M.S., Fred Hutchinson Cancer Research Center
• Charles Coltman, M.D., University of Texas, San Antonio, TX
• You-Lin Qiao, M.D., Ph.D., CICAMS, China
• Zhi-Wei Dong, M.D., CICAMS, China
• Guo-Qing Wang, M.D., CICAMS, China
• Wen-Qiang Wei, M.D., CICAMS, China
• Ning Lu, M.D., CICAMS, China
• Ning-Zhi Xu, Ph.D., CICAMS, China
• Ti Ding, M.D., SCHI, China
• Xiao-You Han, M.D., SCHI, China
• Quan-Hong Wang, M.D., SCHI, China
• Reza Malekzadeh, M.D., DDRC, Iran
• Jarmo Virtamo, M.D., NPHI, Finland
• Pirjo Pietinen, Ph.D., NPHI, Finland
• Renato Fagundes, M.D., University of Santa Maria, Brazil

Staff

• Nan Hu, M.D., Ph.D. , Staff Scientist
• Chaoyu Wang, M.S., Laboratory Biologist
• Lemin Wang, B.A., Research Technician