What is Cowden syndrome, the PTEN gene, and the associated cancer risks?

• A. PTEN hamartoma tumor syndrome; PTEN mutations increase risks of breast, thyroid, endometrial, kidney cancers, and benign hamartomas.
• B. Lynch syndrome; MMR genes; colorectal cancer.
• C. FAP; APC; colon cancer.
• D. BRCA1/BRCA2; breast/ovarian.

Answer: (A)

Cowden syndrome is a hereditary cancer predisposition caused by germline mutations in the PTEN gene, described as PTEN hamartoma tumor syndrome. PTEN normally functions as a tumor suppressor by inhibiting PI3K/AKT signaling; when PTEN is inactivated, cells can grow more readily, leading to hamartomas and increased cancer risk in multiple organs.

The cancer risks most associated with this syndrome include a substantially higher lifetime risk of breast cancer, thyroid cancer (especially follicular and papillary types), endometrial cancer, and renal cell carcinoma. People with Cowden may also develop mucocutaneous hamartomas and other benign lesions. In contrast, other hereditary cancer syndromes involve different genes and cancer patterns: Lynch syndrome involves mismatch repair genes and increased colorectal cancer risk; familial adenomatous polyposis involves APC and colon cancer; BRCA1/BRCA2 mutations are linked to breast and ovarian cancer risks.