Table 1.
Genes involved in different CRC syndromes and associated clinical symptoms.
| Syndrome | Genetic Defects | Clinical Manifestations | References |
|---|---|---|---|
| Hereditary nonpolyposis cancer syndromes | |||
| Lynch syndrome | MLH1, MSH2, MSH6, MSH3, and PMS2 | Increased risk for CRC, (10–47%) depending on gene mutated; asymptomatic unless altered bowel habits, GI bleeding due to tumors/polyps occurs; increased risk for endometrial cancer; extracolonic manifestations are associated as Muir-Torre, Turcot. | [44,46,47] |
| Muir-Torre syndrome (HNPCC + Sebaceous gland malignancies) | MLH1, MSH2, MSH6, and PMS2 | Sebaceous skin tumor/keratoacanthoma and Lynch syndrome features. | [48,49] |
| Turcot syndrome type 1 (HNPCC with primary brain tumors) | MMR, MLH1, and PMS2 | Features of Lynch syndrome + primary brain tumors. | [50,51,52,53] |
| Hereditary polyposis colorectal cancers | |||
| Familial adenomatous polyposis (FAP) syndrome | APC | More than colorectal adenomatous polyps; 100% cancer risk | [50,54] |
| Turcot syndrome type II (FAP with Primary Brain tumors) | APC | FAP syndrome + primary brain tumors, medulloblastoma, glioblastoma, astrocytoma. | [50,51,52,53] |
| Gardner syndrome | APC | FAP syndrome+ extraintestinal manifestations of desmoid tumors; sebaceous cysts; osteomas of mandible, skull, fibromatosis, congenital hypertrophy of retinal pigment epithelium (CHRPE); adrenal adenomas. | [55,56] |
| Adenomatous polyposis syndromes | APC and MUTYH | Increased number of colorectal adenomas (10–100 s), serrated polyposis, mixed polyps; duodenal adenomas are common; 43–33% increased risk of CRC; increased thyroid nodules, adrenal lesions, jawbone cysts. | [50,57,58,59] |
| Juvenile polyposis coli | BMPR1A and SMAD4 | Multiple hamartomatous polyps in the GI tract- mainly colorectum; rectal bleeding due to polyps is a common presenting symptom; anemia due to bleeding is common; extracolonic manifestations hereditary hemorrhagic Telangiectasia (HHT) telangiectasias of buccal mucosa and skin, epistaxis, and anemia, with AV malformations; colorectal cancer risk 38.7% increased. | [60,61,62] |
| Peutz-Jeghers syndrome | STK11 | Mucocutaneous pigmentation; hamartomatous polyps; 39% increased risk for CRC. | [63,64] |
| Cowden syndrome (multiple hamartomasyndrome) | PTEN | Mucocutaneous lesions and macrocephaly; skin manifestations; uterine leiomyomas, ovarian cysts; multiple hamartomas on any organ; increased risk of breast, thyroid, renal, endometrial, and colorectal cancer; 9–16% risk of CRC.; increased risk for malignant melanomas; specific dysplastic gangliocytoma of the cerebellum; Lhermitte-Duclos disease is specific to Cowden disease. | [65,66] |
Abbreviations: MUTYH, mutY DNA glycosylase; STK11, serine/threonine kinase; 11SMAD4, mothers against decapentaplegic homolog 4; PTEN, phosphate and tensin homolog; BMPR1A, bone morphogenic protein receptor type 1A; MLH, MutL homolog; MSH, MutS homolog; MMR, mismatch repair.