Success of chemotherapy tied to genetics

Genetics may play a role in the success of anti-cancer therapy, according to researchers at the Research Institute of the McGill University Health Centre (MUHC) and the Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis – Jewish General Hospital. Their study, published in today’s issue of Clinical Cancer Research, shows that some colorectal cancer patients with a particular gene mutation respond much better to therapy than those without this genetic change.

“Our findings are important,” says Dr. Rima Rozen acting Scientific Director of the Research Institute of the MUHC and senior author. “They demonstrate that colorectal cancer patients who have a particular genetic change, the MTHFR variant, will respond better to fluoropyrimidine-based chemotherapy than those patients without this genetic mutation. This suggests that therapy should be individualized. Patients with the MTHFR variant should be identified and appropriate chemotherapy should be administered.”

“This finding may provide hope to the 10% to 15% of colorectal cancer patients who have the MTHFR variant” says co-author Dr. Victor Cohen, oncologist at the Sir Mortimer B. Davis-Jewish General Hospital (JGH) and researcher at the JGH’s Lady Davis Institute (LDI) for Medical Research. “Although these are preliminary findings, they suggest these patients will respond well to fluoropyrimidine-based chemotherapy and consequently may have a better prognosis. Larger scale studies are needed to determine the long term consequence of having this gene variant.”

“Perhaps as important, the MTHFR enzyme may be an important target to inhibit and thus sensitize the majority of patients to this chemotherapy,” adds co-author Dr. Gerald Batist, oncologist at the JGH and researcher at the LDI.

Dr. Rima Rozen’s laboratory is currently conducting research to evaluate MTHFR as a novel target for anti-cancer chemotherapy.

Both Dr. Batist and Dr. Cohen are members of the Montreal Centre for Experimental Therapeutics in Cancer. Based at the JGH, this centre groups together scientific investigators from all of Quebec’s major universities, representing a major leap forward in the battle against cancer.

Colon and rectal cancers, referred to as colorectal cancer, are life-threatening tumors that develop in the large intestine. The Canadian Cancer Society estimates that 18 000 people will be diagnosed with the disease this year. Only lung cancer is responsible for more cancer deaths.

Drs. Rozen, Cohen and Batist, who are also professors in the Faculty of Medicine at McGill University, analyzed 43 patients with advanced colorectal cancer. All patients were administered fluoropyrimidine-based chemotherapy. Tumour progression and survival rate was recorded, and their DNA analyzed. The 26 patients with a copy of the MTHFR variant responded better to fluoropyrimidine-based chemotherapy than those without the variant.

This research was funded by Variagenics, Inc.

About the Research Institute of the MUHC The Research Institute of the McGill University Health Centre (MUHC) located in Montreal, Quebec, is Canada’s largest concentration of biomedical and health-care researchers. The institute has over 500 researchers, nearly 650 graduate and post-doctoral students and 306 laboratories devoted to research. The mission of the institute is to facilitate investigator-initiated and discovery-driven research that creates new knowledge. This research is inextricably linked to the clinical programs of the MUHC, a full service academic hospital for patients of all ages.

About the Lady Davis Institute for Medical Research The Lady Davis Institute for Medical Research (LDI) located in Montreal, Quebec, is the research arm of the Sir Mortimer B. Davis – Jewish General Hospital and has strong academic links with McGill University. The LDI occupies an important position among major biomedical research institutions in Canada because of major discoveries in AIDS research, Aging, Cancer and Human Genetics. The LDI is currently the second largest biomedical research institute in the Province of Quebec as measured by the total value of peer reviewed grants and awards recognized by the Fonds de la Recherche en Santé du Québec (FRSQ).