Several specific genetic alterations associated with development of smoking-related cancers

Preliminary research indicates that several specific genetic alterations are associated with the development of smoking-related head and neck skin cancers, according to a report in the January 10 issue of JAMA: The Journal of the American Medical Association.

Despite its slowly declining incidence rate and a modest improvement in 5-year survival, squamous cell carcinoma (SCC; a type of cancer similar to the common form of skin cancer) of the head and neck continues to be a clinical challenge. With a worldwide prevalence of more than 1.6 million, it is estimated that in 2006, about 30,990 new cases will be diagnosed in the United States. Even with the use of modern therapeutic options that include surgery, radiation therapy, and chemotherapeutic intervention, 50 percent of all patients will ultimately die of this disease, with more than 7,400 deaths projected for 2006 in the United States, according to background information in the article.

Charis Eng, M.D., Ph.D., of the Genomic Medicine Institute at the Cleveland Clinic Foundation, Cleveland, and colleagues conducted a study to determine the extent of genomic alterations in the stroma (connective tissue) of head and neck SCC. Tumor epithelium (the cancer itself) and surrounding stroma were isolated from 122 patients with oral cavity and oropharyngeal (relating to the mouth and pharynx) or hypopharyngeal (bottom part of throat) SCC and these tissues were subjected to whole genome analysis.

Tumor-associated stroma of head and neck SCC from smokers were found to have a high degree of genomic alterations. A correlation between tumor aggressiveness could be found for a specific set of 5 loci. Three stroma-specific loci were associated with tumor size and regional nodal (small mass) metastases. Also, 2 specific genomic alterations (markers termed "hot spots") were positively correlated with node metastases and clinical stage.

"Stroma-specific genetic alterations are associated with smoking-related head and neck SCC genesis," the authors write. "We hope that our genomic observations, which point to genomic regions that may harbor many genes, will guide future in-depth functional and mechanistic studies. Nevertheless, our current observations can be used to identify new biomarkers for prediction of clinical outcome and potentially novel compartments for targeted therapy and prevention."