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Gene Abnormalities Linked to Survival in Colon Cancer

Study suggests mutation status may also be associated with response to chemotherapy

TUESDAY, Nov. 3 (HealthDay News) -- Abnormalities in four genes can predict survival and possibly response to treatment in patients with advanced colon cancer, according to two studies published online Nov. 2 in the Journal of Clinical Oncology.

Pierre Laurent-Puig, Ph.D., from the Institut National de la Sante et de la Recherche Medicale in Paris, and colleagues retrospectively assessed genetic abnormalities in four genes in tumors from 173 patients with metastatic colon cancers, nearly all of whom had received cetuximab-based chemotherapy. They found that in patients with a wild-type KRAS gene, BRAF mutations were associated with a lack of response and shorter overall survival, EGFR amplification was associated with response, and lower PTEN expression was associated with shorter overall survival.

Susan D. Richman, Ph.D., from the University of Leeds in the United Kingdom, and colleagues assessed KRAS and BRAF mutations in tumors from 711 patients with advanced colon cancer who had been assigned to fluorouracil alone or combined with irinotecan or oxaliplatin as part of a clinical trial. They found that mutations in either gene were associated with poor overall survival (hazard ratio, 1.40), but mutation status was not associated with the impact of irinotecan or oxaliplatin on progression-free survival or overall survival.

"The EGFR/K-Ras story is an excellent example of how understanding the signaling pathways involved in clinical response to a targeted agent leads to successful identification of patients most likely to benefit from treatment," writes the author of an accompanying editorial. "As demonstrated by the two reports, once a pathway member is implicated, then the remainder can be tested, and even events of low overall frequency can be understood in clinical context."

Two authors of the first study are employed by Myriad Genetics and several authors of the first study and editorial reported financial relationships with drug companies.

Abstract - Laurent-Puig
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Abstract - Richman
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