Table 1.

Summary statements

Standard for minimal cancer family history assessment in gastrointestinal (GI) practice

A family history of cancer and premalignant GI conditions that provides sufficient information to develop a preliminary determination of the risk of a familial predisposition to cancer should be obtained for all patients being evaluated in outpatient gastroenterology and endoscopy practices.

Essential elements of a family history include presence and type of cancer diagnoses in first- and second-degree relatives, and presence and (ideally) type of polyps in first-degree relatives; age and lineage should be noted for each diagnosis.

Lynch syndrome (LS)

All newly diagnosed colorectal cancers (CRCs) should be evaluated for mismatch repair deficiency.

Analysis may be done by immunohistochemical testing for the MLH1/MSH2/MSH6/PMS2 proteins and/or testing for microsatellite instability. Tumors that demonstrate loss of MLH1 should undergo BRAF testing or analysis for MLH1 promoter hypermethylation.

Individuals who have a personal history of a tumor showing evidence of mismatch repair deficiency (and no demonstrated BRAF mutation or hypermethylation of MLH1), a known family mutation associated with LS, or a risk of ≥5% chance of LS based on risk prediction models should undergo genetic evaluation for LS.

Genetic testing of patients with suspected LS should include germline mutation genetic testing for the MLH1, MSH2, MSH6, PMS2, and/or EPCAM genes or the altered gene(s) indicated by immunohistochemical (IHC) testing.

Adenomatous polyposis syndromes

Familial adenomatous polyposis (FAP)/MUTYH-associated polyposis/attenuated polyposis

Individuals who have a personal history of >10 cumulative colorectal adenomas, a family history of one of the adenomatous polyposis syndromes, or a history of adenomas and FAP-type extracolonic manifestations (duodenal/ampullary adenomas, desmoid tumors (abdominal>peripheral), papillary thyroid cancer, congenital hypertrophy of the retinal pigment epithelium ((CHRPE), epidermal cysts, osteomas) should undergo assessment for the adenomatous polyposis syndromes.

Genetic testing of patients with suspected adenomatous polyposis syndromes should include APC and MUTYH gene mutation analysis.

Hamartomatous polyposis syndromes

Peutz–Jeghers syndrome (PJS)

Individuals with perioral or buccal pigmentation and/or two or more histologically characteristic gastrointestinal hamartomatous polyp(s) or a family history of PJS should be evaluated for PJS.

Genetic evaluation of a patient with possible PJS should include testing for STK11 mutations.

Juvenile polyposis syndrome (JPS)

Individuals with five or more juvenile polyps in the colorectum or any juvenile polyps in other parts of the GI tract should undergo evaluation for JPS.

Genetic evaluation of a patient with possible JPS should include testing for SMAD4 and BMPR1A mutations.

Cowden syndrome (PTEN hamartoma tumor syndrome)

Individuals with multiple gastrointestinal hamartomas or ganglioneuromas should be evaluated for Cowden syndrome and related conditions.

Genetic evaluation of a patient with possible Cowden syndrome should include testing for PTEN mutations.

Serrated/hyperplastic polyposis syndrome

Individuals who meet at least one of the following criteria have the clinical diagnosis of serrated polyposis syndrome (SPS): (i) at least 5 serrated polyps proximal to the sigmoid colon with ≥2 of these being >10 mm; (ii) any number of serrated polyps proximal to the sigmoid colon in an individual who has a first-degree relative (FDR) with serrated polyposis; and (iii) >20 serrated polyps of any size, distributed throughout the large intestine.

A clear genetic etiology has not yet been defined for SPS, and therefore genetic testing is currently not routinely recommended for SPS patients; testing for MUTYH mutations may be considered for SPS patients with concurrent adenomas and/or a family history of adenomas.

Hereditary pancreatic cancer

Individuals should be considered to be at risk for familial pancreatic adenocarcinoma if they (i) have a known genetic syndrome associated with pancreatic cancer, including hereditary breast—ovarian cancer syndrome, familial atypical multiple melanoma and mole syndrome (FAMMM), PJS, LS, or other gene mutations associated with an increased risk of pancreatic adenocarcinoma; or (ii) have two relatives with pancreatic adenocarcinoma, where one is a FDR; (iii) have three or more relatives with pancreatic cancer; or (iv) have a history of hereditary pancreatitis.

Genetic testing of patients with suspected familial pancreatic cancer should include analysis of BRCA1/2, CDKN2A, PALB2, and ATM. Evaluation for PJS, LS, and hereditary pancreatitis-associated genes should be considered if other component personal and/or family history criteria are met for the syndrome.

Hereditary gastric cancer

Hereditary diffuse gastric cancer (HDGC)

Individuals with (i) ≥2 cases of diffuse gastric cancer, with at least one diagnosed at <50 years; (ii) ≥3 cases of documented diffuse cancer in first- or second degree relatives independent of age of onset; (iii) diffuse gastric cancer diagnosed at <40 years; (iv) a personal or family history of diffuse gastric cancer and lobular breast cancer with one diagnosed at <50 years should be evaluated for HDGC.

Genetic testing of individuals who fulfill HDGC clinical criteria should include analysis of CDH1 mutations.