What testing is recommended for an 18-year-old patient with a family history of pancreatic cancer in a relative?

Testing for an 18-Year-Old with a Family History of Pancreatic Cancer

Your 18-year-old patient does not yet qualify for pancreatic surveillance imaging, but you should obtain a detailed three-generation family history now and consider genetic testing of the affected relative first, which will determine if and when this young patient needs future screening.

Immediate Priority: Test the Affected Relative, Not the 18-Year-Old

• The affected family member with pancreatic cancer should undergo germline genetic testing first, as this is the critical step that determines appropriate surveillance criteria and timing for at-risk relatives 1, 2.
• Universal genetic testing is recommended for all patients with pancreatic cancer to identify pathogenic variants in genes including BRCA1, BRCA2, CDKN2A, ATM, PALB2, STK11, Lynch syndrome genes (MLH1, MSH2, MSH6, PMS2), and TP53 1, 2.
• Testing should ideally occur near the time of the relative's diagnosis, as pancreatic cancer has high mortality rates and the opportunity to test may not be available long-term 2.
• Approximately 10% of pancreatic cancers have a hereditary component, with germline mutations found in 5-10% of apparently sporadic cases 1.

Obtain a Comprehensive Three-Generation Pedigree Now

• Take a thorough family history documenting pancreatic cancer, pancreatitis, melanoma, and cancers of the colorectum, breast, and ovaries on both sides of the family 1.
• Specifically document the degree of relationship (first-degree vs. second-degree), age at diagnosis, and which side of the family (maternal vs. paternal) for all affected relatives 1.
• Note if the patient is of Ashkenazi Jewish ancestry, as this population has higher prevalence of BRCA1/2 mutations 1, 2.
• Use the free online PancPRO risk prediction tool to help determine risk 1.

When This 18-Year-Old Would Qualify for Future Surveillance

If a Pathogenic Germline Variant is Found in the Affected Relative:

• STK11/LKB1 (Peutz-Jeghers syndrome): Begin surveillance at age 30-35 years regardless of family history 2, 3.
• CDKN2A/p16 carriers: Begin surveillance at age 40 years, or 10 years younger than the earliest pancreatic cancer diagnosis in the family 1, 2, 3.
• BRCA2, ATM, or PALB2 carriers: Begin surveillance at age 50 years if they have at least one affected first-degree relative 1, 2.
• Lynch syndrome gene carriers: Begin surveillance at age 50 years if they have at least one affected first-degree relative 2.

If No Mutation is Found but Strong Family History Exists:

• At least 2 affected first-degree relatives who are first-degree relatives to each other: Begin surveillance at age 50 years, or 10 years younger than the youngest affected relative 1, 2.
• At least 3 affected blood relatives with at least one being a first-degree relative: Begin surveillance at age 50 years 1, 2.

What Testing is NOT Indicated Now for This 18-Year-Old

• No pancreatic imaging surveillance (MRI/MRCP or endoscopic ultrasound) is indicated at age 18, as even the highest-risk genes don't warrant screening until age 30-35 at the earliest 1, 2.
• Genetic testing of the 18-year-old should wait until the affected relative is tested first, unless the relative is deceased or unavailable for testing 2.
• If the affected relative cannot be tested, consider genetic counseling referral to discuss whether testing the 18-year-old is appropriate based on the complete family history 1.

Critical Pitfalls to Avoid

• Do not screen family members without first testing the affected patient for germline mutations, as this determines appropriate surveillance criteria and timing 2.
• Do not start surveillance before the recommended age even with a strong family history, as most pancreatic cancers in high-risk individuals under surveillance are diagnosed after age 55 in those without known mutations 1.
• Do not offer surveillance to individuals who are not surgical candidates, as screening should only be performed in those who could tolerate pancreatic resection 2.
• Do not perform surveillance at low-volume centers; all screening should occur at high-volume specialty centers with multidisciplinary expertise when the time comes 2, 3.

Actionable Next Steps for This Patient

• Refer the affected relative with pancreatic cancer for genetic counseling and germline testing if not already done 1, 2.
• Document the complete family pedigree in the 18-year-old's chart for future reference 1.
• Counsel the 18-year-old on risk-reducing strategies including smoking cessation and weight maintenance 1.
• Plan to reassess for genetic counseling referral when the patient reaches the appropriate age for surveillance based on the affected relative's genetic testing results 1, 2.
• If the affected relative tests positive for a pathogenic variant, refer the 18-year-old for genetic counseling to discuss cascade testing at the appropriate time 1, 2.