Tumor testing for DNA mismatch repair (MMR) deficiency with immunohistochemistry for MMR proteins and/or microsatellite instability should be assessed in all CRC patients. As an alternate strategy, tumor testing should be carried out in individuals with CRC younger than 70 years, or those older than 70 years who fulfill any of the revised Bethesda guidelines.

Individuals with familial CRC X syndrome are recommended to have a colonoscopy at 3 to 5 year intervals, starting 5 to 10 years earlier than the youngest case in the family.

In families with classic familial adenomatous polyposis, sigmoidoscopy (or colonoscopy) should be carried out every 1 to 2 years starting at the age of 10 to 11 years and continued lifelong in mutation carriers. Surgery is indicated if there are large numbers of adenomas including adenomas showing a high degree of dysplasia.

In families with attenuated familial adenomatous polyposis (AFAP), colonoscopy should be carried out every 2 years starting at the age of 18 to 20 years and continued lifelong in mutation carriers. Surgery is indicated if there are large numbers of adenomas, including adenomas showing a high degree of dysplasia. Some patients with AFAP can be conservatively managed with a colonoscopy every 1 to 2 years and polypectomy.

Full germline genetic testing for Lynch Syndrome should include DNA sequencing and large rearrangement analysis.

Patients with multiple colorectal adenomas (>10), should be considered for germline genetic testing of APC and/or MUTYH.

Full germline genetic testing of APC should include DNA sequencing and large rearrangement analysis.

Germline testing of MUTYH can be initiated by screening for the most common mutations (G396D, Y179C) in the Caucasian population followed by analysis of the entire gene in heterozygotes. Founder mutations among ethnic groups should be taken into account. For non-Caucasian individuals, full sequencing of MUTYH should be considered.

In both classic and attenuated familial adenomatous polyposis, screening for extracolonic manifestations (gastroduodenal polyposis, thyroid cancer, desmoid tumors) should be considered when colorectal polyposis is diagnosed or at the age of 25 to 30 years, whichever comes first.

If loss of MLH1/PMS2 protein expression is observed in the tumor, analysis of BRAF V600E mutation or analysis of methylation of the MLH1 promoter should be carried out first to rule out a sporadic case. If tumor is MMR deficient and somatic BRAF mutation is not detected or MLH1 promoter methylation is not identified, testing for germline mutations is indicated.

If loss of any of the other proteins (MSH2, MSH6, PMS2) is observed, germline genetic testing should be carried out for the genes corresponding to the absent proteins (e.g. MSH2, MSH6, EPCAM, PMS2, or MLH1).

The decision on the type of colorectal surgery in FAP (total colectomy + ileorectal anastomosis vs proctocolectomy + ileal pouch anal anatomosis) depends on the age of the patient, the severity of rectal polyposis, the wish to have children, the risk of developing desmoids and possibly the site of the mutation in the APC gene.

Follow-up recommendations in mutation carriers include colonoscopy every 1 to 2 years, and gynecological examination (with transvaginal ultrasound and aspiration biopsy) on a yearly basis. Prophylactic gynecological surgery might be an option in female carriers from age 35 and after childbearing is completed.

After colorectal surgery, surveillance of the rectum or pouch should be carried out every 6 to 12 months if rectal tissue remains and every 6 months to 5 years if ileoanal pouch, depending on polyp burden. Surveillance of the gastroduodenum should be performed every 6 months to 5 years depending on the polyp burden.

The suggested surveillance protocol for MUTYH-associated polyposis patients is similar to that for patients with attenuated familial adenomatous polyposis.

Colon and rectum: Colonoscopy every 1 to 2 years, starting at age 20 to 25 or 5 years before the youngest case in the family. No upper limit is established.

Endometrium and ovary: Gynecological examination, pelvic ultrasound (not CA 125), and aspiration biopsy every year, from age 30 to 35 years. Consider prophylactic hysterectomy and salpingoophorectomy when childbearing is completed.

Gastric cancer: For gastric cancer, the search for the presence of Helicobacter pylori and subsequent eradication is recommended in mutation carriers. In case of a high incidence of gastric cancer in some populations, some experts recommend upper GI endoscopy every 1 to 3 years.

Other Lynch-associated cancers: Surveillance is not recommended due to the low sensitivity and specificity. (Although there are insufficient data supporting surveillance for other target organs, it may be considered in the context of family history.)

Colon and rectum: Sigmoidoscopy (or colonoscopy) every 1 to 2 years, starting at age 10 to 11 years and continued lifelong in mutation carriers. Once adenomas are detected, annual colonoscopy should be carried out until colectomy is planned. Surgery is indicated if there are large numbers of adenomas, including adenomas showing a high degree of dysplasia.

Gastroduodenal adenomas: Gastroduodenal endoscopy using both front and side-view scopes starting when colorectal polyposis is diagnosed or at age 25 to 30 years, whichever comes first. Surveillance intervals are based on the Spigelman stage.

Thyroid cancer: Annual cervical ultrasonography may be considered starting at age 25 to 30 years.

Desmoid tumors: A baseline CT or MRI scan should be considered if risk factors (positive family history for desmoids and site of the mutation in APC).

Colon and rectum: Colonoscopy every 1 to 2 years, starting at age 18 to 20 years and continued lifelong in mutation carriers. Once adenomas are detected, colonoscopy should be carried out annually.

Gastroduodenal adenomas: Gastroduodenal endoscopy using both front and side-view scopes starting when colorectal polyposis is diagnosed or at age 25 to 30 years, whichever comes first. Surveillance intervals are based on the Spigelman stage.

Thyroid cancer: Annual cervical ultrasonography may be considered starting at age 25 to 30 years.

Desmoid tumors: A baseline CT scan or MRI should be considered if risk factors (positive family history for desmoids and site of the mutation in APC).