Patient case: 68-year-old male with colon cancer; genetic feature: MLH1 methylation suppression (microsatellite instability)

Clinical trial: Evaluation of Stool Based Markers for the Early Detection of Colorectal Cancers and Adenomas

Summary: Colonoscopy is the current state-of-the-art screening procedure for detecting colorectal cancers. However, compliance with this screening procedure by the public is very low for a variety of reasons. New screening tools are needed to improve detection of colon cancer. Biomarkers from stool, urine, serum, tissue and plasma may provide valuable initial screening tools to sort the population into those that need colonoscopy and those that most likely do not. This is a cross-sectional study of subjects undergoing clinically-indicated colonoscopy or who have diagnosed colorectal cancer who are willing to provide biospecimens.

Detailed description: In recognition of the fact that novel potential biomarkers are continually being identified and will need to be validated in a rapid, efficient and scientifically rigorous manner, the NCI has made an enormous commitment to the development of a network that will facilitate biomarker development and validation in multiple organ sites. As part of the National Cancer Institute-funded Early Detection Research Network (EDRN), the Great Lakes-New England Clinical Epidemiological Center (GLNE CEC) proposes a research study that validates potential molecular markers ("biomarkers") for the detection of precancerous and cancerous conditions and cancer risk assessment. Although examples of such biomarkers are currently in clinical use (i.e. CEA, CA-125), there are limitations to all of them. Our consortium focuses on gastrointestinal neoplasia. The goals of this phase of the proposed research are:
  1. Assessment of the utility of individual stool-based, serum-based and urine-based biomarkers for discriminating between patients with adenocarcinomas, patients with adenomas, patients without adenomas and normal subjects.
  2. Assessment of the utility of individual stool-based, serum-based and urine-based biomarkers for detecting indicators of carcinogenesis known to be present or not present in adenomas, adenocarcinomas, and normal mucosa.
  3. Construction of a panel of markers from those considered in Objectives 1 and 2 to discriminate, under a number of assumptions concerning prevalence and cost of misclassification, between:
  a Subjects with normal colons versus patients without adenomas, patients with adenomas and patients with cancers; b Subjects with normal colons, patients without adenomas and patients with adenomas, versus subjects with cancers; c Subjects with normal colons versus patients without and patients with adenomas versus patients with cancers.
  4. Comparison of the characteristics of individual markers and panels as discriminators to those of the established current standard, Fecal Occult Blood test (FOBT).
  5. Development of a bank of stool samples linked to serum, tissue, urine and clinical data from patients with colorectal cancer, adenomas and normal controls for validation of stool-based markers that may be developed in the future.
  To meet our goals the investigators propose to collect stool, rectal mucus, serum, plasma, and urine samples from 800 subjects (200 colorectal cancers, 200 adenomas, 200 higher risk normals and 200 normal colons for controls). The stool samples will be assayed for stool-based biomarkers. EDRN Common Data Elements (CDEs) will be completed by the recruiting sites and provided for the laboratories developing the assay.

Eligibility: Inclusion Criteria:
  -  Willing to sign informed consent
  -  Able to physically tolerate removal of up to 58 ml of blood at one to two different time points
  -  Adults at least 18 years old
  -  Willing to collect 1-2 stool samples and prepare a FOBT card and five specimen vials from each stool sample
  -  Pregnant or nursing women who otherwise meet the eligibility criteria may participate
  -  Subjects with one of the following:
  -  Colorectal adenocarcinoma—not treated and in colon at time of stool collection (CRC bin)
  -  Adenoma-pathologically confirmed adenoma present in colon at time of stool collection (Adenoma Bin)
  -  Higher Risk Normal Bin Subjects with a personal history of adenomas (confirmed by pathology) with none present on qualifying colonoscopy Subjects with a personal history of CRC (longer than 3 years ago because of exclusion criteria of cancer within last 3 years) with none present at time of qualifying colonoscopy Any family history of CRC (1st degree relative)
  -  Normal Control Bin
  -  No history or current finding of any colon neoplasia including CRC, adenomas, no personal or family history of HNPCC or FAP
  -  Subjects who had CRC that was successfully treated at least three years ago may be considered eligible for the adenoma bin if their polyps are adenomas and there is no evidence of CRC or for the higher risk normal bin as noted above.
  -  Subjects whose screening colonoscopy shows any of these types of polyps may be included in the normal or the higher risk normal bin if they meet the other criteria noted above.
  -  Hyperplastic polyps
  -  Benign mucosal polyps
  -  Polypoid granulation tissue
  -  Prolapsed mucosal polyps
  -  Inflammatory polyp
  -  Transitional mucosal polyp
  -  Lipoma
  -  Gangleoneuroma
  -  Neuroma
  -  Hamartomatous polyp
  Exclusion Criteria:
  -  Cancer patients who have had any surgery, radiation, or chemotherapy for their current colorectal cancer prior to collecting the baseline samples
  -  Patients with a history of or clinically active Inflammatory Bowel Disease
  -  Patients with known HNPCC or FAP
  -  Inability to provide informed consent.
  -  Other active malignancy within 3 years of enrollment except any of the following:
  -  Squamous cell carcinoma of the skin
  -  Basal cell carcinoma of the skin
  -  Carcinoma in situ of the cervix, Stages Ia or Ib invasive squamous cell carcinoma of the cervix treated by surgery only. (Excluded if had pelvic radiation)
  -  Stage Ia Grade 1 adenocarcinoma of the endometrium treated with surgery
  -  Subjects with known HIV or chronic viral hepatitis

Relevance to patient case: not relevant