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Discovering the causes of cancer and the means of prevention

Preetha Rajaraman Explores Environmental and Genetic Risk Factors

July 2011 - Linkage Newsletter

The only confirmed risk factors for brain tumors are exposure to ionizing radiation and certain rare genetic syndromes. With a strong background in environmental health and epidemiology, Preetha Rajaraman, Ph.D., a tenure-track investigator in the Radiation Epidemiology Branch (REB), is exploring how environmental and genetic risk factors interact in the etiology of brain tumors.

Photo of Preetha RajaramanDr. Rajaraman is especially interested in biological pathways related to the development of radiogenic brain cancer. She has examined the risk of brain tumors with respect to candidate gene variants in selected mechanisms, including apoptosis, oxidative response, cell-cycle control, and DNA repair. Dr. Rajaraman currently is conducting a genome-wide association study (GWAS) to identify genetic markers of susceptibility to glioma, the most common type of brain tumor. She believes that some of the pathways that she and others have identified through GWAS are "quite exciting." She plans to follow up these associations by looking for potential interactions with environmental risk factors.

Dr. Rajaraman took a circuitous route to get to where she is today. After college, she worked at a wildlife reserve and at the Ministry of Health in Botswana. Her growing interest in health research led her to pursue training in environmental health at the University of Washington and to work at the Washington State Department of Labor and Industries, where she managed the Adult Blood Lead Epidemiology and Surveillance Program. When she joined the Ph.D. program in epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, she pursued her interest in lead toxicity by examining data from an ongoing REB study of adult brain tumors, examining the unanswered question of whether lead exposure affects the risk of brain tumors. "The more I learned, the more I became intrigued by brain tumors themselves," Dr. Rajaraman said. "They can be such highly lethal tumors, and yet so little is known about them."

In 2004, Dr. Rajaraman completed her predoctoral fellowship in REB and became a postdoctoral fellow, where she enjoys the exciting intellectual environment offered at NIH. "Not only do you get to ask questions that may have a meaningful public health impact, but you're doing it in a great setting surrounded by many experts in different fields," she said.

Following her appointment in 2009 as a tenure-track investigator, Dr. Rajaraman joined the leadership team for the U.S. Radiologic Technologists Study, a cohort of approximately 150,000 technologists. In this study, Dr. Rajaraman is investigating the effects of low-dose fractionated exposure to ionizing radiation on the risk of breast and other cancers. The availability of blood samples within this cohort has allowed her to examine potential gene-radiation interactions in breast cancer. Dr. Rajaraman also is studying the risk of cancer and cardiovascular disease among technologists working with newer and higher dose radiological procedures, such as interventional fluoroscopy and nuclear medicine.

At the heart of many of Dr. Rajaraman's projects is the underlying theme of identifying susceptible populations. A particularly vulnerable population is young children. Thus, Dr. Rajaraman is examining the effects of radiation in population groups exposed early in life. Studies from the 1950s pointed to an increase in cancer risk for people who were exposed to diagnostic x-rays in utero. X-ray doses have decreased over time, and the risk of most cancers has followed suit. Nonetheless, using data from the United Kingdom Childhood Cancer Study, Dr. Rajaraman identified one type of cancer—acute myeloid leukemia—whose risk may still be increased by exposure to radiation.

To pursue her interest in the impact of radiation exposure in early life, Dr. Rajaraman is involved in the Childhood Cancer Survivor Study, in which a cohort of children exposed to cancer radiotherapy is being evaluated to identify potential gene-radiation interactions.

Dr. Rajaraman is developing a comprehensive strategy to identify both environmental and genetic risk factors for brain tumors. She believes that the discovery of heritable mechanisms may lead to potential drug targets that have preventive and/or therapeutic implications. Furthermore, the detection of lifestyle and other environmental factors in concert with genetic susceptibility may inform behavioral and other changes that reduce cancer risk.