At what age can germline genetic testing be ordered?

Germline Genetic Testing Age Criteria

Germline genetic testing can be ordered at any age when clinically indicated, with specific age thresholds varying by gene and clinical context—most commonly testing is appropriate from age 18 years onward for adult-onset cancers, though testing for certain high-penetrance genes like TP53, APC, RB1, and PTEN should be considered under age 30 years when tumor pathogenic variants are identified. 1

Age-Specific Testing Thresholds by Gene

Testing Under Age 30 Years

For patients with tumor pathogenic variants identified through tumor testing, germline follow-up testing should be offered specifically for:

• TP53, APC, RB1, and PTEN: Test only if patient is <30 years of age 1
• CDKN2A and SMARCA4: Test only if patient is <30 years of age 1

Critical caveat for TP53: Testing in older patients (>45 years) without suspicious family history requires careful consideration to balance the risk of identifying TP53 as a variant of clonal hematopoiesis of indeterminate potential (CHIP) rather than true germline inheritance 1

Testing for Breast Cancer Patients

Age ≤65 years: BRCA1/2 testing should be offered to all newly diagnosed breast cancer patients aged 65 years or younger without requiring additional risk factors 1, 2, 3

Age >65 years: Testing should be offered selectively based on:

• Triple-negative breast cancer subtype 1, 2
• Personal or family history suggesting hereditary predisposition 1, 2
• Ashkenazi Jewish ancestry 1, 2
• Candidacy for PARP inhibitor therapy 1, 2

Women over 65 meeting NCCN criteria have a 9.0% likelihood of carrying pathogenic variants compared to 3.5% in those not meeting criteria 2, 3

Testing for Ovarian Cancer Patients

Any age: All women with high-grade non-mucinous epithelial ovarian cancer should be offered germline BRCA1/2 testing regardless of age 1

Testing for Lynch Syndrome

Starting age 25-35 years: Surveillance with urinalysis and cytology is recommended for at-risk individuals, though strong evidence for this specific age threshold is lacking 1

Age <60 years: European guidelines favor germline genetic testing in patients with upper tract urothelial carcinoma (UTUC) who present at age 60 years or less 1

Average age at diagnosis: Colorectal cancer in Lynch syndrome averages 44 years, substantially younger than sporadic cases (64 years), though cancers before age 25 years are very unusual even in hereditary syndromes 4

Testing in Unaffected Individuals

With Known Family Mutation

Any age (typically ≥18 years): If a first-degree relative has a known Lynch syndrome mutation, germline genetic testing for that specific mutation should be offered 1

Without Known Family Mutation

Any age when family history is suggestive: Risk prediction models (PREMM 1,2,6 or MMRpro) should be used to estimate mutation probability, with a threshold of >5% predicted probability prompting germline testing 1

Testing can be performed on deceased affected individuals if appropriate tissue is available and no affected living relative is available for testing 1

Pediatric Considerations

Generally not recommended for adult-onset cancers: Testing in children is typically deferred until adulthood unless:

• The child has developed cancer requiring genetic evaluation 5
• Testing results would change medical management during childhood 6
• Specific syndromes with childhood manifestations are suspected 7

In one pediatric series undergoing diagnostic exome sequencing for hereditary cancer, 40% of pediatric patients had findings in novel candidate genes 5

Key Implementation Points

Informed consent requirement: All patients undergoing germline testing should receive adequate pretest information for informed consent, with those having pathogenic variants receiving individualized post-test counseling 1

Genetic counseling access: Referral to providers experienced in clinical cancer genetics facilitates patient selection, interpretation of expanded testing, and counseling of individuals without pathogenic variants but with significant family history 1

Variants of uncertain significance: These should not impact management, and patients must be followed for potential reclassification 1, 3

Timing consideration: Primary cancer treatment should not be delayed for genetic counseling referral 1