Genetic Mutation Tied to Lung Cancer Prognosis

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http://www.cancerpage.com/news/article.asp?id=8999

By David Douglas

NEW YORK OCT 31, 2005 (Reuters Health) - A polymorphism of the fibroblast growth factor receptor 4 (FGFR4) gene appears to be associated with cancer cell migration in patients with lung adenocarcinoma, according to Italian researchers.

"We showed that a single change in the DNA sequence coding for FGFR4 is responsible for the differences in the prognosis observed among patients," senior investigator Dr. Tommaso A. Dragani told Reuters Health. "This DNA variation was found to produce two FGFR4 proteins which only differ by a single amino acid but display a different capacity to affect the migration of cancer cells -- that is, the ability to produce metastasis."

In the October 10th issue of the Journal of Clinical Oncology, Dr. Dragani of the Instituto Nazionale Tumori, Milan and colleagues note that the Gly388Arg polymorphism of the FGFR4 gene has been shown in vitro to modulate cancer cell migration.

To investigate further, the researchers compared the clinical stage and the survival of 274 Italian lung adenocarcinoma patients in relation to their genetic characteristics. Some 401 healthy subjects acted as controls.

Compared to those with the Gly/Gly genotype, in patients who carried the Arg388 allele, cancer onset was earlier (60.2 versus 63.4 years). They also had a 2.3-times increased hazard ratio for higher clinical stage disease and 1.9-times increased hazard ratio for lymph node involvement. This was also true of mortality at 63 months of follow-up, with a 1.7-times increased hazard ratio.

Thus, continued Dr. Dragani, "the differences in lung cancer aggressiveness and malignancy not only depend on somatic mutations occurring in the tumor itself which have been considered until now the main cause of variation in neoplastic progression."

"These findings," he concluded, "represent an important breakthrough in the understanding of the individual genetic elements that can control cancer progression and in the development of new diagnostic and therapeutics treatments based not only on the tumor but also on the patient's genetic characteristics."

SOURCE:

J Clin Oncol 2005;23:7307-7311.