A Case of APC Gene Mutation-Associated Familial Adenomatous Polyposis With Multiple System Malignancies

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disorder, with a nearly 100% risk of developing colorectal cancer by the age of 40. The primary gene mutated in FAP is APC, and mutations in certain regions of the APC gene may be associated with thyroid disorders, including malignant neoplasms, benign nodules, and endocrine diseases of the thyroid. FAP-associated colorectal cancer (FAP-CRC) demonstrates poorer treatment outcomes compared to sporadic colorectal cancer, which may be attributed to several factors such as distinct molecular pathogenesis, chromosomal instability (CIN), and tumor microenvironment (TME).

We describe the case of a 30-year-old female patient with a history of papillary thyroid carcinoma who presented with abdominal pain. Gastrointestinal endoscopy revealed multiple polyps in the stomach and colon. Additionally, the patient was found to have metastatic colorectal cancer with hepatic and pulmonary involvement. Further genetic testing revealed a deletion mutation in the APC gene at exon 16, c.1974_1975del (p.Asn659Glnfs*14). Despite the implementation of multiple therapeutic regimens, the patient's condition showed a poor response, ultimately leading to her demise. We conducted an in-depth analysis of the potential factors contributing to this outcome.

APC gene mutations lead to FAP and subsequent colorectal cancer, and may also predispose individuals to thyroid disorders, including malignancies, benign nodules, and endocrine dysfunction. Therefore, we recommend that young patients diagnosed with thyroid cancer undergo a thorough evaluation of family history for hereditary conditions. Additionally, consideration should be given to gastrointestinal endoscopic and ophthalmologic screening, as well as molecular genetic testing. When multiple gastric and colorectal polyps are detected, genetic alterations in APC or MUTYH should be suspected. In particular, female patients diagnosed with FAP before the age of 31 should undergo annual thyroid ultrasound surveillance.