COLORECTAL CANCER GENETIC SYNDROMES

Gene/Chr Signaling pathway Criteria Manifestations Surveillance

FAP APC/5q21 Adenoma-carcinoma >100 polyps at age 15 Duodenal adenomas – Colorectal cancer:
Autosomal sequence. Spiegelman criteria (number, size, - Annual flexi sig from age 10-12 until polyps detected then annual colonoscopies until
dominant APC = tumour suppressor Gardners syndrome = Colonic polyps, histology, dysplasia). Incr risk of colectomy.
gene for Wnt/b-catenin Desmoids, Osetomas of jaw, duodenal cancer. - AFAP/FAP – TC + IRA ~18 years – surveillance flexi sign annually.
pathway leading to sebaceous cysts Gastric fundic polyps - FAP - Completion proctocolectomy + IPAA after childbearing to preserve fertility and
excessive b-catenin Desmoids erectile function.
accumulation and Turcott’s = colonic polyps + childhood Papillary Thyroid cancer Duodenal adenomas:
oncogenesis. medulloblastoma. - Gastroscopies from age 25, frequency dependent on Spiegelman.
Loss of APC  KRAS  Thyroid cancer:
SMAD2/4  p53 AFAP = <100 polyps - Thyroid US from age 18 then 2-5 yearly.
HNPCC dMMR = dMMR of MLH1, MSH2, Modified Amsterdam II: CEO-GUO – CR, Endometrial, Colorectal cancer:
MLH1, MSH2, MSH6 and PMS2  DNA - 3 family members effected with Ovarian, Gastric, Urothelial, - Annual colonoscopies from age 25 or 5 years earlier than youngest affected relative.
MSH6, MPS2 mismatch and frameshift HRC, 1 of whom is a first degree Other (Breast and Pancreas) - Aspirin chemoprophylaxis 300mg daily to decrease hance of cancer, not polyps.
errors  increased relative of the other two. cancers. - Segmental resection vs total colectomy + IRA and screening of rectal stump depends on
Autosomal microsatellites – - 2 successive generations compliance and other polyps.
dominant segments of repeated affected with HRC. Histology: LAMPS2 Endometrial cancer:
nucleotides (MSI) - 1 family member diagnosed age - Lymphoid aggregates - Recommend hysterectomy after childbearing complete or from age 40-50 years
 Incr MSI = cancer <50 - Assoc. extra colonic cancers Ovarian cancer:
- FAP is excluded. - Mucinous cancers - Consider risk-reducing salpingo-oophorectomy at time of risk-reducing hysterectomy.
- Tumours should be verified by - Poorly Gastric cancer:
pathological examination differentiated/Proximal - Annual gastroscopy from age 25 or 5 years earlier than youngest affected relative.
HRC*= HNPCC related cancers. cancers
- Synchronous and signet cell
Muir Torre – skin tumours and breast cancer.
cancer.
MUTYH MUTYH gene Germline MUTYH Colonic adenomas and/or CR cancer <age 40 Colorectal cancer:
mutation predispose to serrated/hyperplastic polyp. Duodenal adenomas - Annual or 2-yearly colonoscopies from age 20
Autosomal developing APC ‘Lynch’ like – right sided, synchronous, Ovarian, Endometrial, Breast, - Consider prophylactic subtotal colectomy depending on polyp burden and/or dysplasia.
recessive mutations and the KRAS mucinous, high grade tumour with Bladder, Thyroid (PTC) Duodenal adenomas:
‘hotspot’ mutation. lymphoid aggregates. - Gastroscopy at age 35 then as per Spigelman.
Cowdens PTEN Germline mutation in Multiple hamartomatous syndrome. BETRC – Breast, Endometrial, Breast cancer:
(PTEN) PTEN, PIK3CA, AKT1. Thyroid, Renal, Colorectal - Annual MRI +/- US from age 30-50.
Autosomal cancers. - 1-2 yearly MMG + US from age 50 onwards.
dominant Skin – Trichollemas, - Consider bilateral risk-reducing mastectomy age <40.
mucocutaneous papillomas, acral Endometrial cancer:
keratosis. - Recommend hysterectomy after childbearing complete or from age 40-50 years
Head - Macocephaly Thyroid cancer:
- Annual clinical examination from age 5
Colorectal cancer:
- Colonoscopy from age 35 then as per polyp burden.
Peutz STK11 LKB1 protein is a tumour Multiple GI hamartomatous polyps GI cancers (CRC > Gastric > Gastrointestinal cancers:
Jeghers suppressor. and mucocutaneous pigmentation. Pancreatic) - Gastroscopy and Colonoscopy at age 8
Autosomal Breast cancer - If no polyps – recommence G+C scopes at age 18 then as per polyp burden.
dominant Gynecological cancers Breast cancer:
Testicular cancers - Annual MRI +/- US from age 30
- Tamoxifen from age 30
- Consider bilateral risk-reducing mastectomy