A 50-year-old woman comes to the office for an annual wellness check. The patient is asymptomatic and feels well. She follows a high-fiber diet and eats red meat once a week. The patient drinks at least 3 cups of coffee a day. Medical history is significant for obesity, type 2 diabetes mellitus, osteoarthritis, and cervical intraepithelial neoplasia treated with surgical excision. In addition to insulin, the patient takes ibuprofen every day for knee pain. Family history is unremarkable. She does not use tobacco, alcohol, or illicit drugs. Vital signs are within normal limits. BMI is 35 kg/m². Cardiopulmonary and abdominal examinations are unremarkable. The patient is referred for a screening colonoscopy, which reveals a large villous adenoma within the ascending colon. Which of the following is the greatest risk factor predisposing this patient to this abnormality?

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11ec25c8_d863_0e2b_bc81_2d8e035bc183_MD0003_00 This patient has a villous adenoma, a high-risk precursor for colorectal cancer (CRC). Major risk factors for CRC include a personal or family history of adenomatous polyps or colon cancer, inherited CRC syndromes (eg, Lynch syndrome, familial adenomatous polyposis), ulcerative colitis, prior abdominopelvic radiation therapy, and tobacco and alcohol use. In addition, obesity and type 2 diabetes are associated with increased risk for CRC, especially early-onset (ie, age <50) cancer, likely due to insulin resistance and hyperinsulinemia. Hyperinsulinemia results in increased circulating levels of insulin-like growth factor-1, which inhibits colorectal epithelial cell apoptosis and promotes neoplastic progression. In addition, obesity is associated with increased expression of inflammatory cytokines (eg, tumor necrosis factor-alpha), which may promote development of CRC. (Choice A) A high intake of coffee and tea is associated with a modestly decreased risk of CRC, possibly due to antioxidant and antimutagenic compounds or effects on the gut microbiome. (Choice B) Although human papillomavirus can cause anal and cervical squamous cell carcinoma, it does not lead to adenomatous colon polyps or CRC. (Choice C) Nonsteroidal anti-inflammatory drugs (eg, ibuprofen) and aspirin inhibit cyxlooxygenase-2, an enzyme thought to be involved in colon carcinogenesis. Chronic use of these medications can lower the risk of CRC, although it is not usually recommended due to the risk of gastrointestinal bleeding and renal failure. (Choice E) Several compounds found in red meat and processed foods can promote colon tumorigenesis. Frequent (eg, daily) consumption of red meat has been associated with increased risk of CRC, but intermittent consumption, as in this patient, is not a significant risk factor. Educational objective: Obesity and type 2 diabetes are associated with an increased risk of colorectal adenocarcinoma, likely due to hyperinsulinemia. Hyperinsulinemia results in increased circulating levels of insulin-like growth factor-1, which inhibits colorectal epithelial cell apoptosis and promotes neoplastic progression. References: The mechanisms linking obesity to colon cancer: An overview. (http://www.ncbi.nlm.nih.gov/pubmed/29428365)

A 50-Year-Old Woman Comes to the Office for an Annual