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

Clinical trial: Screening and Risk Factors of Colon Neoplasia

Summary: The investigators propose a screening population-based study to systematically evaluate the accuracy and clinical relevance of sDNA testing as a potential alternative to colonoscopy screening. In addition, the investigators propose a genetic epidemiologic study of the relation between colon polyps, an established precursor of colon cancer, and two factors that may influence risk for colon cancer: candidate genes and diet.

Detailed description: Colorectal carcinoma is currently the second most common fatal cancer in the United States, and is largely preventable through the use of screening in the asymptomatic population. Although colonoscopy is considered to be the most accurate 'gold standard' screening test, there are a significant proportion of eligible patients who decline colonoscopy or in whom colonoscopy is not readily available. More recently, testing for aberrant molecular/genetic markers in stool DNA (sDNA) is emerging as a promising alternative to colonoscopy, and some professional society guidelines have endorsed the use of sDNA testing in the early detection of colorectal cancer. However, despite some guidelines that endorse sDNA testing primarily for the detection of colorectal cancer, data on the efficacy of sDNA testing for advanced adenomas, and hence prevention of colorectal cancer, are limited.
  Colon carcinogenesis is a multifactorial and multistep process that involves both genetic and environmental influences. Diet clearly plays an important role. However, despite extensive research, there has been limited success in identifying such specific dietary and nutritional factors. In particular, a number of within-population studies, including several randomized trials, have yielded conflicting results and cast serious doubt on the hypothesized central role of dietary fat and fiber in colon carcinogenesis. In contrast, there is increasing evidence relating colon neoplasia to obesity, type 2 diabetes and related metabolic abnormalities. These results, together with the marked and consistent similarities in the dietary and lifestyle risk factors for type 2 diabetes and colon neoplasia have led to the notion that insulin resistance resulting from energy imbalance (excess energy intake, physical inactivity, and obesity) may be the underlying link between these two entities. Indeed, the insulin resistance-colon neoplasia hypothesis could account for many of the dietary and lifestyle risk factors of colon neoplasia and for its high incidence in Western countries. The fact that the incidences of obesity, insulin resistance syndrome, and type 2 diabetes are escalating at epidemic pace in the Western societies makes the exploration of the insulin resistance-colon neoplasia hypothesis a subject of pressing priority.
  A Food Frequency Questionnaire (FFQ), a Meat Preparation Questionnaire (MPQ), and a Physical Activity Questionnaire (PAQ), all developed at the University of Arizona Cancer Center will be used to collect dietary and physical activity data.The FFQ, MPQ and PAQ questionnaires will be self-administered by each subject according to detailed written instructions, and they are mailed to the participant with the consent forms. Subjects will be asked to donate whole blood and urine samples on the day of routine colonoscopy exams. These samples will be looked at for disease markers. Stool samples will be collected to evaluate its use at detecting colon polyps using the sDNA Test and 2 FIT tests (fecal immunochemical test).

Eligibility: Inclusion Criteria:
  -  patients undergoing routine colonoscopy at University Hospitals, Cleveland Ohio
  Exclusion Criteria:
  -  Unable to give written consents
  -  Unable to fill the questionnaires
  -  A history of polyps within the past 10 years (except hyperplastic polyps)
  -  Family history of Familial Adenomatous Polyposis (FAP) or Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
  -  Personal history of inflammatory bowel disease
  -  Personal diagnosis of any cancer, with the exception of non-melanoma skin cancer
  -  Any major colon surgeries (e.g. resectioning)

Relevance to patient case: not relevant