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Mark Purdue Seeks the Causes of Cancer

July 2011 - Linkage Newsletter

According to Mark Purdue, Ph.D., a tenure-track investigator in the Occupational and Environmental Epidemiology Branch (OEEB), "My interest is in combining environmental epidemiology with molecular techniques to study the causes of cancer. DCEG and OEEB are on the cutting edge of such research." For Dr. Purdue, this is the ideal training and research environment.

After completing his doctorate in epidemiology at the University of Toronto in Ontario, Canada, with an investigation into how exposure to sunlight affects molecular subtypes of melanoma, Dr. Purdue came to OEEB as a postdoctoral fellow in 2004 and was promoted to tenure-track investigator in 2009. He is the co-principal investigator for DCEG research in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and oversees use of its biospecimens for etiologic and early disease marker studies.

Dr. Purdue has been interested in investigating the causes of non-Hodgkin lymphoma (NHL), a cancer whose incidence has increased rapidly in recent decades. Patients with severe immune dysregulation, such as those who have HIV infection or are receiving strong immunosuppressive drugs for an organ transplant, have a high risk of NHL, and thus immunologic alterations may be an important mechanism driving increased risk. Because of this, "We were interested in conducting research within the general population to see if more subtle changes in immune regulation influence NHL risk," Dr. Purdue explained.

In a prospective study of 297 cases and 297 matched controls from the PLCO cohort, Dr. Purdue and his colleagues examined serum levels of soluble CD30, a suspected marker of B-lymphocyte activity. A strong dose-response relationship was seen between soluble CD30 serum levels and NHL risk; strikingly, the risk was increased significantly even 6 to 10 years after blood collection. As Dr. Purdue noted, "This finding is consistent with an etiologic association, not simply a disease-induced effect."

Dr. Purdue also is interested in investigating whether occupational and environmental exposures influence NHL risk. In particular, he is leading research into the effects of trichloroethylene (TCE), a solvent used to clean metal parts. TCE currently is classified by the International Agency for Research on Cancer (IARC) in group 2A (i.e., probably carcinogenic to humans). The evidence for this classification was based on studies in laboratory animals and was last reviewed by IARC in 1995.

In a case-control study of NHL within NCI's Surveillance, Epidemiology, and End Results (SEER) program, Dr. Purdue found that a high level of estimated occupational TCE exposure was significantly associated with increased risk. A particular strength of this study was the detailed methods used to estimate exposure. As Dr. Purdue explained, "It will be particularly important for IARC to have additional data from human studies for its next review of TCE, so our study should make an important contribution to this evaluation."

Dr. Purdue recently has expanded his work into studies of kidney cancer, another malignancy with increasing incidence. As with NHL, early evidence suggests an association between TCE and kidney cancer, and thus he is currently pursuing that lead. Recently, Dr. Purdue and colleagues published the first genome-wide association study of renal cell carcinoma (RCC), the most common type of kidney cancer. In a study of 3,772 cases and 8,505 controls, Dr. Purdue joined forces with IARC investigators to identify two chromosomal regions associated with RCC susceptibility at a level of genome-wide significance. One locus, on chromosome 2p21, maps to the gene EPAS1, which has been found experimentally to influence RCC development. "The second locus is in 11q13.3, which has no characterized genes, so it is not clear what underlies the association," Dr. Purdue noted. "We are following up on these findings to seek a better understanding of the underlying mechanisms."

Dr. Purdue and his wife, Melissa, a sales representative for a company that markets laboratory instruments to clinical microbiology labs, have a daughter who is nearly 5 years old and an 8-month-old son. In his admittedly limited spare time, Dr. Purdue "shuttles the kids around," reads, and hikes. "It's a challenge juggling work and family, especially with small children," he said. "I find it rewarding and exhausting in equal measure."

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