James M., a 62-year-old male, presents with a 3-month history of intermittent blood in his stool, fatigue, and unintentional weight loss of 8 kg. He also reports changes in bowel habits, including alternating diarrhea and constipation. James denies abdominal pain, fever, or vomiting. He has a significant smoking history (20 pack-years), a diet high in processed meats, and a sedentary lifestyle. He has never undergone colorectal cancer screening, and there is no family history of colorectal cancer or other malignancies. On physical examination, James’s vitals are stable. Abdominal examination reveals mild tenderness in the lower abdomen without palpable masses. Rectal examination shows blood in the stool, but no obvious masses are felt. A colonoscopy is performed, revealing an ulcerating mass in the sigmoid colon. Biopsy of the lesion confirms moderately differentiated adenocarcinoma. Immunohistochemistry (IHC) testing of the biopsy specimen reveals nuclear beta-catenin accumulation. What is the primary cause of beta-catenin accumulation in colorectal cancer?
