Numerous research projects have been supported by the Hereditary Colorectal Cancer Family Registry. Notable is the MSH2A636P gene mutation study in Ashkenazi Jewish patients with early age-of-onset colorectal cancer. This study demonstrated that this mutation is found in colorectal cancer patients of Ashkenazi descent, and in particular those with early age-of-onset colorectal cancer or a strong family history of colorectal cancer. The identification and characterization of this novel mutation has been greatly facilitated by the study of patients with Hereditary Nonpolyposis Colorectal Cancer (HNPCC) and early age-of-onset CRC participating in the Registry.
The reputation of the Hereditary Colorectal Cancer Family Registry has prompted Pfizer, Inc. to invite MSKCC to participate in a new clinical trial entitled “A Phase III Placebo-Controlled Trial of Celecoxib in Genotype Subjects with FAP.” Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome characterized by polyposis of the colon and rectum and a near 100% progression to colorectal cancer at a very early age. The overall goal of this study is to attempt to delay prophylactic surgical removal of the colon and rectum by reducing the number of polyps. This study may provide an important option for delaying surgery until patients are older and able to cope with the complexities of major surgery. The Registry will serve as a valuable resource for identifying eligible patients.
We have recently completed a study titled “The Prospective Immunohistochemical Analysis of Primary Colorectal Cancers for Loss of Mismatch Repair Protein Expression”, which was presented during the 2008 annual meeting of the American Society of Colon and Rectal Surgeons. This study, addressing the diagnosis of HNPCC in early age-of-onset colorectal cancer patients, investigates the utility of routine testing of colorectal cancer specimens for proteins involved in DNA repair. We have shown that assessment of family cancer history alone may be inadequate for identifying this genetic syndrome in young patients with colorectal cancer. We believe that this technique may improve identification of patients with HNPCC.
Some of our studies are multi-centered and are supported, in part, by the National Cancer Institute (NCI). One study aims to prospectively determine the diagnostic accuracy of careful pathologic review to predict HNPCC. This study has the potential to change the standard of care for patients with early age-of-onset CRC. Similarly, a second study involves the genome-wide DNA analysis by single nucleotide polymorphism arrays, which provides very high-resolution analysis of both DNA copy number alterations and loss of heterozygosity events in cancer cells. This technique can accurately map genetic changes present across the entire genome, allowing for focused evaluation of novel candidate genes in patients with colorectal cancer.
We are also interested in patients with Hyperplastic Polyposis Syndrome (HPS). This rare and poorly understood condition is characterized by the development of numerous small hyperplastic polyps throughout the colon and rectum. Some patients also develop polyps in other parts of the gastrointestinal tract, and there are reports of an association with colorectal cancer. Recent studies have identified potential genetic mutations responsible for this syndrome. However, given the rarity of this disease, it is difficult for any single institution to assemble enough patients to perform large-scale investigations. This has led us to begin collaborations with other academic institutions. Our hope is to initiate multi-center studies to better define the natural history of this disease, as well as to investigate the potential role of medications that may delay the onset of or prevent polyp formation.
Information on the natural history of hereditary forms of colorectal cancer, gleaned from maintaining the Registry, has facilitated the development of recommendations for screening and surveillance. Recently, Dr. Guillem assembled a panel of experts to author a standard of care document on Risk-Reducing Surgery for Hereditary Cancers, for the widely read 8th edition of Cancer: Principles & Practice of Oncology, by DeVita, Hellman and Rosenberg.
Dr. Guillem is a founding member and Past-President of the Collaborative Group of the Americas on Inherited Colorectal Cancer (CGA-ICC). This organization was established in 1995 to improve understanding of the causes and natural history of inherited colorectal cancer as well as the clinical management of affected families. This organization provides opportunities for participation in multi-institutional collaborative studies, locates resources and provides support to patients and their families.
The high level of clinical research and patient care that The Hereditary Colorectal Cancer Family Registry is able to provide is made possible by the support of a diverse research team. Below is a brief list of our current members:
Jose G. Guillem, M.D., M.P.H., Attending Physician
Arnold Markowitz, M.D., Attending Physician
Udo Rudloff, M.D., Ph.D., Clinical Research Fellow
Steven Lee-Kong, M.D., Clinical Research Fellow
Stephanie Hauck, R.N., Clinical Nurse
Zana Correa, N.P., Nurse Practicioner
Christopher Papadopoulos, B.A., Registrar