Biography

Dr. Hayes received a D.D.S. from the School of Dental and Oral Surgery at Columbia University. As a Cancer Epidemiology Research Fellow, he earned an M.P.H. and Ph.D. from The Johns Hopkins School of Hygiene and Public Health. Dr. Hayes practiced clinical dentistry for two years, taught epidemiology and public health at the University of Maryland School of Dentistry, and worked as a cancer epidemiologist at the Dutch Cancer Foundation and the Medical School of the Erasmus University, Rotterdam, before joining the NCI in 1985. He received the PHS Special Recognition Award for work on fluoride, the Alice Hamilton Science Award for Occupational Safety and Health for the study of occupational exposure to ethylene oxide, and the NIH Merit Award for investigations of prostate cancer. Dr. Hayes serves on the editorial board of several scientific journals in epidemiology and cancer research.

Research Interests

Our research involves large-scale, population based studies into the genetic and environmental determinants of cancer. Investigations of occupational cohorts provide unique opportunities to study cancer risks associated with high level exposure to chemicals that are also found in the general environment, but at substantially lower levels. Cohort and case control studies in the general population are undertaken to investigate factors influencing cancer risks, including gene environment interactions.

Chemical Carcinogens in the Workplace

The spectrum of disease and level of risk associated with benzene exposure are not well understood, although the chemical is an important environmental and occupational exposure. Results from our epidemiologic investigations of benzene exposed workers in China suggest that benzene is associated with a variety of hematologic neoplasms besides leukemia, and that excess risks occur at lower exposure levels than previously established. Myelodysplastic syndromes were also linked to benzene exposure. Furthermore, biochemical studies in this population identified benzene related cytogenetic effects and genetic susceptibility factors. The studies also showed that the proportion of benzene metabolized to toxic compounds decreases as exposure increases. Work is continuing to evaluate risk of non hematologic neoplasms and to characterize dose response patterns at relatively low levels of exposure.

1,3 Butadiene is used in the production of synthetic rubber and found in automobile exhaust and cigarette smoke. The chemical is genotoxic and carcinogenic in experimental animals, but there is only limited evidence of its carcinogenicity in humans. To elucidate further the effects of 1,3-butadiene in humans, we conducted a study that found increased lymphocyte and platelet counts and higher levels of a butadiene associated hemoglobin adducts in exposed workers. However, no differences were found in cytogenetic abnormalities (measured by fluorescence in situ hybridization) and somatic mutations (measured by glycophorin A and hprt assays). We are continuing to develop biologic markers of exposure to 1,3-butadiene and to evaluate its cytogenetic effects.

Formaldehyde exposure occurs among pathologists, anatomists, and workers in the funeral industry. It is also a ubiquitous environmental chemical, which has been found to cause nasal carcinomas in laboratory rats. We showed that workers in the funeral industry have excess malignancies of the lymphatic and hematopoietic systems, including myeloid leukemia and multiple myeloma. Our studies of embalming identified work practices associated with high exposure to formaldehyde, which increased risks of nasal epithelial and lymphocyte micronuclei and decreased lymphocyte O6 alkylguanine DNA alkyltransferase activity. An ongoing case control study of leukemia and related disorders is assessing risk in relation to work practices in the funeral industry and formaldehyde exposure.

Genes and the Environment

We are examining risk factors for prostate cancer in a large case control study among African-American and white men in three regions of the United States. The study has thus far shown that risk increases among men whose brothers and fathers have a history of prostate cancer. Also, heavy alcohol use appears to be a risk factor. We recently showed a relationship between increased risk of prostate cancer and sexual behavior and sexually transmitted diseases, suggesting that a sub set of this cancer may be due to a sexually transmissible agent.

In a case control study in Puerto Rico, we found that risk of alcohol-related oral cancer was magnified among persons who had the ADH31 1 genotype, a trait associated with efficient metabolism of alcohol to the toxic metabolite acetaldehyde. A sub study showed that smokers are at an increased risk of salivary gland tumors. We are investigating other genetic factors associated with the metabolism of alcohol and tobacco related compounds in relation to risk of oral cancer.

A large cohort study of cancer etiology is being carried out within the NCI Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The screening arm is examining the 74,000 participants over a 6 year period, and following them for cancer occurrence for 13 years through annual follow up mailings. Thus far, more than 65,000 participants have had an initial screen. Biologic samples are collected at each screening exam. By the study's conclusion, we expect to observe more than 1,500 cases of prostate, lung, and colorectal cancers in the screened arm. Because of the prospective design, screening exams, and sequential pre-diagnostic blood sample collections, we will be able to evaluate temporal changes in biomarkers to the subsequent development of cancer. Our initial analyses are focusing on genetic and environmental determinants of adenomatous polyps and colorectal cancer, with additional studies being planned for other cancers.

Keywords

adenomatous polyps, African-Americans, alcohol, benzene, butadiene, cigarette smoking, colorectal cancer, dietary factors, gene-environment interactions, formaldehyde, genetic susceptibility, industrial exposures, oral cancer, prostate cancer, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Selected Publications

• Hayes RB, et al. "Tobacco and alcohol use and oral cancer in Puerto Rico." Cancer Causes Control 1999; 10:27-33.
• Hayes RB, et al. "Sexual behaviour, STDs and risks for prostate cancer." Br J Cancer 2000; 82:718-725.
• Hayes RB, et al. "Genotoxic markers among butadiene polymer workers in China." Carcinogenesis 2000; 21:55-62.
• Marcus PM, et al. "Cigarette smoking, N acetyltransferase 2 acetylation status, and bladder cancer risk: a case series meta analysis of a gene environment interaction." Cancer Epidemiol Biomark Prev 2000; 9:461-467.

Collaborators

DCEG Collaborators

• Andrew Flood, Ph.D.; Ruthann Giusti, M.D.; Wen-Yi Huang, Ph.D.; Bu-Tian Ji, M.D., Dr.P.H.; Katherine. McGlynn, Ph.D.; Pamela Mink, Ph.D., M.P.H.; Ulrike Peters, Ph.D.; Nathaniel Rothman, M.D.; Rashmi Sinha, Ph.D.; Jim Vaught, Ph.D.; Tara Vogt, Ph.D.; Stephanie Weinstein, Ph.D.; Regina Ziegler, Ph.D., M.P.H.

Other NCI Collaborators

• Lori Beth Dixon, Ph.D.; Amy Subar, Ph.D.

Other Scientific Collaborators

• Robert Bresalier, M.D.; Christine Cole Johnson, Ph.D., M.P.H., Henry Ford Health System, Detroit, MI
• Charlotte Mayo, Ph.D., University of Alabama, Birmingham, AL
• Robert Schoen, M.D.; Joel Weissfeld, M.D., Dr.P.H., University of Pittsburgh, Pittsburgh, PA
• Ellen Velie, Ph.D., Michigan State University, East Lansing, MI