DNA modification seen in colorectal tumors helps predict outcomes, John Wayne Cancer Institute researchers find

May 21 2008

An international study led by researchers at the John Wayne Cancer Institute at Saint John's Health Center has found that modifications to DNA found on multiple chromosomes in tumors can help to predict outcomes in patients with early-stage rectal cancer.

The study, published in the May 10, 2008, issue of the Journal of Clinical Oncology, also suggests that classification of rectal cancer based upon these genetic changes should be evaluated as means of predicting reoccurrence and perhaps re-evaluating treatment strategies.

Cancer of the rectum, which is diagnosed in more than 40,000 people each year, is characterized by the development of malignant cells near the end of the large colon. While rectal cancer often is discussed along with colon cancer as one group, clinical management of rectal cancer is different. This study demonstrates that the genetic changes in rectal cancer also are different than those in the colon.

The study, titled, "Quantitative Analysis of Methylation of Genomic Loci in Early-Stage Rectal Cancer Predicts Distant Recurrence," was one of the first to identify prognostic biomarkers for rectal cancer. Using cancerous rectal tissues from patients, the group assessed alternative forms of genetic aberrations on several chromosomes in an effort to identify biomarkers that could identify changes from normal to precancerous to malignant cells. Genetic findings were then validated in a large multi-center clinical trial that examined the primary tumor rectal cancer tissues of 251 patients who underwent tumor removal without pre-surgical radiotherapy.

The study demonstrated that DNA modification at several genetic aberrations on different chromosomal sites showed significant changes. In analyses of patients with early-stage disease without lymph node metastasis, the genetic subclassifications could predict for distant recurrence, the authors said.

"This was one of the larger genetic biomarker studies to predict outcomes for patients with early-stage primary rectal cancer," said Dave S.B. Hoon, Ph.D., Director of the Department of Molecular Oncology at the John Wayne Cancer Institute and an investigator for the Santa Monica study. "Our results don't currently have specific implication regarding treatment, however they do help to predict which early-stage patients will have aggressive disease and which will not. The key to effective disease management is being able to identify at an early stage what tumors will reoccur and be lethal rather than the conventional wait-and-see approach."

According to Hoon, the study is significant for one overriding reason: "Our results were validated in a multi-center trial with long-term follow-up and focused on rectal cancer tissue," he said. "This is therefore somewhat of a unique study."

"While our results can't be directly applied to therapy, in the future our findings will perhaps be used to make decisions regarding disease management. Those whose biomarkers indicate more aggressive cancer will perhaps be treated more aggressively at early stages. Those who don't have these biomarkers will perhaps have a greater likelihood of long-term survival and may avoid unnecessary treatment."

According to Hoon, the next step would be to apply these findings to the overall rectal cancer patient population and integrate them into better classifications of rectal cancer.

Funding for this study was provided by the Ruth and Martin H. Weil Fund at John Wayne Cancer Institute, the Gonda Foundation and the Roy E. Coats Memorial Fund.

Since 1981, the John Wayne name has been committed by the Wayne family to groundbreaking cancer research and education in memory of their father who died of cancer. The John Wayne Cancer Institute at Saint John's Health Center has received worldwide acclaim for advances in melanoma (skin cancer), breast and colon cancer as well as immune therapy of cancer. Other areas of research include prostate and liver cancer. Their unique ability to rapidly turn scientific breakthroughs into innovative approaches to treatment and early detection provides immediate hope to cancer patients from around the globe.

Michael F.G. de Maat, Cornelis J.H. van de Velde, Martijn P.J. van der Werff, Hein Putter, Naoyuki Umetani, Elma Meershoek Klein-Kranenbarg, Roderick R. Turner, J. Han J.M. van Krieken, Anton Bilchik, Rob A.E.M. Tollenaar and Dave S.B. Hoon, "Quantitative Analysis of Methylation of Genomic Loci in Early-State Rectal Cancer Predicts Distant Recurrence," Journal of Clinical Oncology, Volume 26, No. 14, May 10, 2008.