The National Comprehensive Cancer Network (NCCN v 3.2019 and v1.2020) guidelines recommend referral to a cancer genetics professional for an individual with one or more of the following:

AFFECTED WITH COLON CANCER

  • Colon cancer diagnosed at or before age 50
  • Colon cancer at any age AND any of the following
    • Tumor showing mismatch repair (MMR) deficiency, either by microsatellite instability (MSI) or loss of MMR protein expression
    • Tumor with MSI-high (MSI-H) histology (ex presence of tumor infiltrating lymphocytes, Chron’s like lymphocytic reaction, mucinous/signet ring differentiation, or medullary growth pattern)
    • Personal history of synchronous or metachronous Lynch syndrome related cancer**
    • > 1 first or second-degree relative with a Lynch syndrome related cancer** diagnosed before age 50. 
    • >2 first or second-degree relative with a Lynch syndrome related cancer** diagnosed at any age.
    • PTEN Hamartoma Tumor syndrome related featuresᅀ.
  • Increased model-predicted risk for Lynch syndrome
    • An individual with a 5% or greater risk of having an MMR gene pathogenic variant based on predictive models (ie, PREMM5, MMRpro, MMRpredict)
  • Family history of any blood relative with a known pathogenic/likely pathogenic variant in a cancer susceptibility gene
  • Genetic counseling/patient education is highly recommended when genetic testing is offered and when results are disclosed.
  • If no pathogenic/likely pathogenic variant is found, consider referral for expert genetics evaluation if not yet performed; testing for other hereditary cancer syndromes may be appropriate. 

FAMILY HISTORY OF COLON CANCER

  • > 1 first-degree relatives with colorectal diagnosed before age 50
  • > 1 first-degree relatives with colorectal and another synchronous or metachronous Lynch syndrome-related cancer**
  • >2 first or second-degree relatives with Lynch syndrome-related cancer**, including > 1 relatives diagnosed before age 50
  • > 3 first or second-degree relatives with Lynch syndrome-related cancers, regardless of age
  • Family history of any blood relative with a known pathogenic/likely pathogenic variant in a cancer susceptibility gene
  • Increased model-predicted risk for Lynch syndrome
    • An individual with a 5% or greater risk of having an MMR gene pathogenic variant based on predictive models (ie, PREMM5, MMRpro, MMRpredict)
  • Family history of any blood relative with a known pathogenic/likely pathogenic variant in a cancer susceptibility gene
  • Genetic counseling/patient education is highly recommended when genetic testing is offered and when results are disclosed.

**Lynch syndrome-related cancers include colorectal, gastric, ovarian, pancreas, ureter and renal pelvis, brain (usually glioblastoma), biliary tract, small intestinal cancers, as well as sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas as seen in Muir-Torre syndrome

ᅀ PTEN Hamartoma Tumor syndrome related features can include breast cancer, endometrial cancer, follicular thyroid cancer, ganglioneuromas, macrocephaly, macular pigmentation of glans penis, trichilemmomas, multiple palmoplantar keratosis, multifocal or extensive oral mucosal papillomatosis, multiple cutaneous facial papules, autism, colon cancer, >3 esophageal glycogenic acanthosis, lipomas, intellectual disability (IQ < 75, thyroid lesions (adenomas, nodules, goiter), renal cell carcinoma, testicular lipomatosis, and/or vascular anomalies.

CONDITIONS TO CONSIDER