Should a patient under 50 with more than five adenomatous colonic polyps or a family history of polyps or colorectal cancer be referred to a genetics service?

Genetic Referral for Multiple Colonic Polyps

Yes, a patient under 50 with more than five adenomatous polyps should be referred to genetics services, as this meets established criteria for hereditary polyposis syndromes that carry near-certain risk of colorectal cancer without intervention. 1

Clear Referral Thresholds for Adenomatous Polyps

The American College of Medical Genetics and Genomics (ACMG) establishes that ≥10 cumulative adenomatous colon polyps in the same person warrants immediate referral for cancer predisposition assessment, primarily to evaluate for familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). 1

For patients under 60 years with specific polyp burdens, the British Society of Gastroenterology provides additional guidance:

• Patients under 60 years with at least 10 adenomas require genetic referral 1
• Patients 60 years or older with at least 20 adenomas OR at least 10 adenomas plus a family history of colorectal cancer or polyposis require genetic referral 1

Age-Specific Considerations

The question specifies a patient under 50 with more than five adenomas. While this falls below the strict 10-polyp threshold, several factors make genetic referral appropriate:

• Any patient under 50 with colorectal cancer should be referred to genetics 1
• The presence of 5-9 adenomas in a young patient (<50 years) represents an intermediate risk group where genetic testing may identify mutations in 5-10% of cases 2, 3, 4
• APC mutations are found in 10% of patients with 20-99 adenomas and 5% of patients with 10-19 adenomas, establishing that genetic causes exist below the 100-polyp threshold for classic FAP 1

Family History as a Critical Modifier

If the patient has a family history of polyps or colorectal cancer in addition to their personal polyp burden, this substantially strengthens the indication for genetic referral: 1

• One first-degree relative with colorectal cancer diagnosed under age 50 warrants genetic assessment 1
• Two affected first-degree relatives with colorectal cancer at any age warrants genetic assessment 1
• Any number of juvenile polyps with a positive family history of juvenile polyposis syndrome warrants genetic referral 1

Syndromes to Consider

The genetic evaluation should assess for:

Familial Adenomatous Polyposis (FAP): Classic FAP presents with >100 adenomas and carries 100% lifetime colorectal cancer risk without intervention, while attenuated FAP presents with 30-100 adenomas and 70% cancer risk. 1, 2

MUTYH-Associated Polyposis (MAP): This recessively inherited condition typically presents with 10-100 adenomas and requires biallelic mutations for disease expression. 1

Lynch Syndrome: Should be considered if there is personal or family history of early-onset colorectal cancer, even with fewer polyps. 1

Practical Referral Algorithm

For a patient under 50 with >5 adenomatous polyps:

1. Document exact polyp count, size, histology (tubular vs villous features), and dysplasia grade 5
2. Obtain detailed three-generation family history focusing on colorectal cancer, polyps, and Lynch syndrome-associated cancers (endometrial, ovarian, gastric, urinary tract) 1, 6
3. Refer to genetics if ANY of the following apply:
   • ≥10 cumulative adenomas 1
   • 5-9 adenomas PLUS family history of colorectal cancer or polyposis 1
   • Any adenoma count with colorectal cancer diagnosed under age 50 1
   • Multiple polyp types (mixed polyposis) 1

Critical Pitfalls to Avoid

Do not wait until polyp count reaches 100 to refer for FAP evaluation, as attenuated FAP and MAP present with far fewer polyps but still carry substantial cancer risk. 1, 2

Do not dismiss family history as irrelevant if the patient is under 50 with multiple polyps—this combination significantly elevates hereditary syndrome probability. 1

Do not assume all polyposis is adenomatous—hamartomatous polyps (juvenile, Peutz-Jeghers) have different genetic causes and cancer risks, requiring histologic confirmation. 1, 7

Mortality and Morbidity Impact

FAP carries 100% colorectal cancer risk without prophylactic colectomy, but this risk is reduced significantly when patients enter screening-treatment programs. 2

Colorectal cancer in juvenile polyposis develops at a mean age of 34 years (range 15-59), with generally poor clinical outcomes, making early identification through genetic referral critical. 7

After total colectomy in FAP, duodenal cancer and desmoid tumors become the two main causes of mortality, requiring lifelong surveillance that begins with genetic diagnosis. 2