Genetic Study of Young Patients With Colorectal Cancer

RATIONALE: Identifying genemutations (microsatellite instability) may allow doctors to plan effective treatment for patients who develop colorectal cancer at an early age.

Official Title

Genetic Study of the Prognostic Significance of Microsatellite Instability in Patients With Early Age-of-Onset Stage I-III Colorectal Cancer

Conditions

– Colon Cancer- hereditary non-polyposis colon cancer (hMSH2, hMLH1, hPMS1, hPMS2)- Rectal Cancer

Study Type

Interventional

Study Design

Diagnostic

Further Details

PURPOSE: Genetictrial to determine the significance of gene mutations in helping predict the outcome of treatment in patients who develop stage I, stage II, or stage III colorectal cancer at an early age. OBJECTIVES:Evaluate the prognostic significance (e.g., overall survival) of microsatellite instability (MSI) status in patients with early age-of-onset stage I-III colorectal cancer, assuming the presence of a quantitative interaction between MSI status and family history of cancer. Evaluate the development of metachronous neoplasms in this patient population. Evaluate the histologic features and genetic changes associated with hereditary nonpolyposis colorectal cancer in this patient population. OUTLINE: This is a multicenter study. Patients are stratified according to family history using the Amsterdam II criteria for hereditary nonpolyposis colorectal cancer (positive vs negative). Patients undergo baseline colonoscopy before or within 6 months of initial curative resection and then surveillance colonoscopy at 1, 3, and 5 years (+/- 6 months) after resection. The number, size, location, histology, and method of removal of polyps are documented at the time of colonoscopy. Patients also undergo microsatellite instability (MSI) status testing at baseline and complete family history questionnaires at baseline and then at 3 months. Markers used to determine MSI status include BAT loci (BAT-26 [MSH2 intragenic repeat] and BAT-25), D5S346, D2S123, and D17S50.The prognostic significance of family history and MSI status is evaluated. The individual histologic features of the tumors are compared with the MSI status to determine their predictive value. The histologic features are also correlated with outcome to determine their prognostic significance. Patients may be referred for genetic counseling.A certificate of confidentiality protecting the identity of research participants in this project has been issued by the National Cancer Institute. PROJECTED ACCRUAL: A total of 3,000 patients will be accrued for this study within 6 years.

Study Start

Eligibility & Criteria

Ages Eligible for Study: 18 Years – 49 Years, Genders Eligible for Study: Both Criteria DISEASE CHARACTERISTICS:Diagnosis of stage I-III adenocarcinoma of the colon or rectum Must have undergone an initial curative resection within the past year No colon or rectal cancer resection that does not allow for definitive T or N staging No initial post-surgical surveillance colonoscopy prior to study entry Must have a pathology specimen, with representative normal and tumor tissues, available for submission to the ACOSOG Central Specimen Bank prior to study entry No personal or family history of familial adenomatous polyposis No recurrent colorectal cancer PATIENT CHARACTERISTICS: Age18 to 49 at first diagnosis Performance statusNot specified Life expectancyNot specified HematopoieticNot specified HepaticNot specified RenalNot specified OtherMust be willing to provide a family cancer history to the study team and continue with follow-up colonoscopic surveillance No other malignancy within the past 5 years except completely resected cervical cancer or nonmelanoma skin cancer No evidence of recurrence of other prior malignancy PRIOR CONCURRENT THERAPY: Biologic therapyNot specified ChemotherapyNot specified Endocrine therapyNot specified RadiotherapyNo prior pelvic radiotherapy for rectal cancer No concurrent preoperative pelvic radiotherapy for rectal cancer SurgerySee Disease Characteristics

Total Enrolment

Contact Details

[1] Jose G. Guillem, MD, Study Chair, Memorial Sloan-Kettering Cancer Center