Researchers Investigate the Roles of Genes in Head and Neck Cancer
School researchers are leading an inter-institutional effort to determine the role of specific genes on the formation of head and neck cancer. Karl Kelsey, professor in the Departments of Cancer Cell Biology and Environmental Health, is the primary investigator of the five-year, $500,000-per-year grant. His colleague in this investigation is research associate Edward Peters.
In 1994, Peters was a newly admitted doctoral student in epidemiology. He also worked part time as a dental consultant at Dana-Farber Cancer Institute treating patients who had cancer of the head and neck.
Head
and neck cancer, also known as oral cancer, is diagnosed in about 30,000
Americans each year. It comprises cancers of the tongue, jaw, larynx,
pharynx, and the hard and soft palettes. And while it is relatively uncommon,
it is particularly distressing to those afflicted by it: late-stage surgery
may require removal of the cancerous area. Sufferers may be forced to
give up their tongues, their jaws, or their voices in attempts to stop
the cancer from spreading.
Not only is it disfiguring, it is deadly. While the survival rates have been improving marginally for the past two decades, the average newly diagnosed patient has only a slightly better than one-in-two chance of living beyond five years.
Three-quarters of those with head and neck cancer have histories of using tobacco and/or alcohol, and 95% of new diagnoses are of people over age 55. Yet Peters, at the clinic, saw patients who didn't fit this model. He said, "I was seeing patients who didn't smoke, who didn't drink, and who were young."
As he progressed in his doctoral studies, Peters began learning more about genetic and molecular epidemiology. He began to wonder if there might not be a genetic difference in people that made some more susceptible than others to head and neck cancers.
Peters took his knowledge, newly gained from such HSPH cancer luminaries as Nancy Mueller and Fred Li, and began to design a thesis that would attempt to identify some of the genetic factors involved in head and neck cancer. A review of similar approaches to other cancers, in addition to referrals within the school, led Peters to Kelsey, a molecular biologist who has been investigating the roles of specific genes in the development of lung cancer.
Peters, with Kelsey's guidance, identified a handful of genes that were likely suspects in carcinogenesis. While Peters was particularly interested in why those at low risk (nonsmokers and nondrinkers) were developing cancer, it seemed wise to begin to understand the genetic basis of what was known--that smokers and drinkers were at higher risk for head and neck cancer--and then use that knowledge as a foothold to investigate the cancers that occur in low-risk patients.
For his
thesis, "Genetic Susceptibility to Cancers of the Head and Neck,"
Peters looked at five genes that are involved in the metabolism of tobacco
and alcohol. He obtained his cancer cases from five Boston-area hospitals.
Each participating case member submitted a questionnaire that gathered
data on smoking, drinking, and diet. In addition, each participant also
submitted either blood or cells gently scraped from within the mouth.
Randomly selected control subjects also answered the questionnaire and provided similar genetic material. The genes were processed in Kelsey's laboratory and the five genes of interest were compared between the case and control groups.
The results were at once both promising and disappointing. "We found what seemed to be interesting associations between normal genetic variation, tobacco exposure, and likelihood of cancer," said Peters, "but our sample size was so small that those correlations were not statistically significant."
With his thesis successfully defended and his doctorate hanging on his wall, Peters now refers to that research as a pilot project. It's the expanded project that occupies Peters now.
"We're now working with eight hospitals," said Peters, "and plan to obtain 800 cases and 1,600 controls."
A frustration for Peters has been the lack of public attention to head and neck cancer. "It makes sense for things like lung cancer and breast cancer to get a lot of attention--they're common, and they kill or harm a lot of people. But head and neck cancer should be publicized, too. Most cases can be prevented by avoidance of tobacco and alcohol. And even if oral cancers form, they may be easily detectable during a dental exam and can be successfully treated if caught early."
Kelsey adds, "there isn't a lot of research being done on head and neck cancer in the Boston area, but there is some being done in our backyard. There are projects underway at the dental school [Harvard School of Dental Medicine] and at the medical school [Harvard Medical School]. One of the goals of this project is to pull this community of interested researchers together so that we can share what we know and help each other."
While Peters plans to use this project as a framework upon which to
build additional investigations of head and neck cancer, Kelsey emphasizes
that the knowledge they gain from this project will be helpful to other
diseases. "The more we know about genetic processes and how they're
affected by exposures to tobacco and alcohol," said Kelsey,"the
better off we are. The effects of these exposures are likely going to
be applicable to cardiovascular disease and other things that are influenced
by tobacco or alcohol. "If we can learn how to modify the toxic by-products
of tobacco, we can do a lot of good for a lot of people," said Kelsey.
