Christian Abnet: Seeking to Understand Cancer Risk

“Essentially, I couldn’t decide what I wanted to do,” recalled Christian C. Abnet, Ph.D., M.P.H., Nutritional Epidemiology Branch (NEB), as he discussed his colorful background as an owl caller in Oregon for the U.S. Forest Service. “This work, censusing Northern Spotted Owls on Mt. Hood, allowed me time to think about a direction for my graduate education.”

Deciding to pursue his interest in freshwater pollution, Dr. Abnet went on to complete his Ph.D. in environmental toxicology at the University of Wisconsin–Madison. After graduation, Dr. Abnet saw an advertisement in Science for the NCI Cancer Prevention Fellowship Program and thought it would be an interesting opportunity to move away from laboratory work. Because he had no epidemiology experience, he spent his first year completing an M.P.H. at the University of Minnesota in Minneapolis.

For the second year of the fellowship, he came to the Center for Cancer Research in the Cancer Prevention Studies Branch, where he later took a position as staff scientist. He joined NEB with his appointment as a tenure-track investigator in 2005.

Thanks to the enduring relationships he formed during his fellowship, Dr. Abnet continues to collaborate with mentors Sanford M. Dawsey, M.D. (NEB), and Philip R. Taylor, M.D., Sc.D., Genetic Epidemiology Branch. Working with Dr. Dawsey, Farin Kamangar, M.D., Ph.D. (NEB), and Iranian colleagues, Dr. Abnet recently completed accrual of a case-control study of esophageal squamous cell carcinoma (ESCC) in a high-risk population of northeastern Iran. Dr. Abnet’s first analysis in the study found a strong association between tooth loss and increased risk of ESCC. This finding is similar to that of Dr. Abnet’s previous prospective study of a high-risk rural population in China. Both studies show this association even in the absence of the two main etiologic factors for this disease in industrialized countries, alcohol and tobacco use. As Dr. Abnet explained, “the idea of tooth loss being related to cancer is not new, but relatively few epidemiological studies have looked at it, and there were no good data.” This finding is important, he believes, because “dental hygiene is a modifiable risk factor. You can intervene to improve oral health.” And, he pointed out, “our study areas in China and this region of Iran have the highest incidence of esophageal cancer in the world but have little else in common except limited alcohol and tobacco use.”

Dr. Abnet plans to follow up these findings with a search for the biological mechanisms underlying the association between tooth loss and esophageal cancer risk. He is delighted with the possibilities offered by the NIH Roadmap Human Microbiome Project to explore this topic. Along with a postdoctoral research fellow, Neal D. Freedman, Ph.D., M.P.H. (NEB), Dr. Abnet is currently at work on a pilot study using saliva samples to study the contribution of oral flora to this association.

In another investigation of a large cohort of Chinese men and women, Dr. Abnet and his colleagues found an association between higher 25-hydroxyvitamin D (25[OH]D) serum concentrations and ESCC. This association appeared to be limited to males, however, and study participants exhibited serum 25(OH)D concentrations below the “normal” range. Dr. Abnet noted that when “esophageal squamous dysplasia (the precursor lesion to ESCC) was substituted as the end point, higher serum 25(OH)D was associated with higher risk of disease in both sexes. We’d like to see an association like this many times before we know it is meaningful, especially because vitamin D is currently a hot topic in cancer prevention.” Dr. Abnet and his colleagues are working with the NCI Cohort Consortium to examine the potential association between higher serum 25(OH)D levels and ESCC across a range of populations. “This will allow us to examine groups with much higher vitamin D levels but will also include a population in Finland, where there is not as much sunlight as in the United States. Our previous results might be relevant only in the rural Chinese communities we were studying.”

Using data collected as part of the Chinese cohort study, Dr. Abnet has expanded the use of x-ray fluorescence spectroscopy in epidemiologic studies to include direct measures of zinc concentrations in baseline tissue samples. He explained that “inadequate zinc has been clearly linked to esophageal cancer in elegant rodent studies, but this is difficult to examine in humans because of homeostasis and because zinc’s bioavailability is strongly dependent on other food components.” With biopsy specimens from the Chinese cohort and access to the powerful supercollider at Argonne National Laboratory, Dr. Abnet and his colleagues showed that hazard ratios for ESCC were significantly lower for subjects in the highest tissue zinc concentration quartile compared to those in the lowest quartile. “These are very valuable, prospective samples,” Dr. Abnet said. “This study allowed us to use sections only five micrometers thick and examine zinc and four other elements as well. This got me really interested in assessing other nutritional and toxic elements in epidemiologic studies.” He acknowledged that his work was the first to apply this technology in such a study and that others are also now using the tool.

Dr. Abnet finds a great deal of satisfaction in his contributions to NCI’s mission to better understand the etiology and prevention of cancers. “My work advances knowledge just as much when working in China as when it involves Americans. NCI must go where the disease is.” Outside of his work, Dr. Abnet enjoys drawing and spending time with his wife of 11 years, Dr. Rebecca Holden, and their two children, Clara, 10, and Soren, 7.

—Terry Taylor, M.A.

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