Is lung cancer hereditary and is it included in the Ambry (Genetic Screening Test)?

Hereditary Lung Cancer and Inclusion in Ambry Genetic Testing

Yes, lung cancer has a hereditary component with approximately 18% heritability, and certain hereditary cancer syndromes that increase lung cancer risk are included in Ambry genetic testing panels. 1

Hereditary Factors in Lung Cancer

Lung cancer does have a significant hereditary component, though environmental factors (particularly smoking) remain the predominant risk factor. The evidence for hereditary risk includes:

• Family history is a well-established risk factor for lung cancer, with a meta-analysis of 28 case-control and 17 cohort studies showing a relative risk of 1.8 (95% CI, 1.6-2.0) for individuals with a first-degree relative with lung cancer 1
• The risk is higher for individuals with multiple affected family members or early-onset disease 1
• Heritability of lung cancer is estimated at approximately 18% 1
• The familial risk persists even after adjustment for smoking habits 1

Genetic Susceptibility Loci and Mutations

Several genetic factors have been identified that contribute to lung cancer risk:

• Genome-wide association studies have identified multiple lung cancer susceptibility loci, including:

  • CHRNA3, CHRNA5, TERT, BRCA2, CHEK2 and HLA regions 1
  • 15q24-25 region associated with increased lung cancer risk, nicotine dependence, and peripheral artery disease 1
  • 6q23-25 region identified in familial lung cancer studies 1

• Specific germline mutations associated with lung cancer include:

  • TP53 mutations (Li-Fraumeni syndrome) 1
  • EGFR germline mutations (particularly T790M) 1
  • Mutations in ATM, BRCA2, and CHEK2 1
  • Multiple other genes including APC, BLM, MSH6, RET, and SDHB 1

Ambry Genetic Testing for Lung Cancer Risk

Ambry Genetics offers several hereditary cancer panels that include genes associated with lung cancer risk. While lung cancer is not the primary focus of most hereditary cancer panels, genes that increase lung cancer risk are included in several of their comprehensive panels:

• Genes like TP53 (Li-Fraumeni syndrome), which significantly increases lung cancer risk, are included in most hereditary cancer panels
• BRCA2, CHEK2, and ATM, which have associations with lung cancer risk, are commonly included
• Comprehensive cancer panels from Ambry typically include testing for multiple genes associated with lung cancer susceptibility

Clinical Implications

• Individuals with a strong family history of lung cancer (especially multiple first-degree relatives or early-onset cases) should consider genetic counseling 1
• Patients with classic familial cancer susceptibility syndromes (such as Li-Fraumeni syndrome) have substantially increased risk for lung cancer, especially if they smoke 1
• The risk is particularly pronounced for lung adenocarcinoma in certain genetic syndromes 1
• Screening recommendations may be modified based on genetic risk factors and family history

Important Caveats

• Unlike some other cancers (breast, colorectal), lung cancer does not have a single high-penetrance hereditary syndrome specifically dedicated to it
• Environmental factors, particularly smoking, remain the dominant risk factors for lung cancer development
• Genetic testing should be considered particularly for:
  • Early-onset lung cancer (under age 50)
  • Multiple affected family members
  • Lung cancer in never-smokers
  • Presence of other cancers associated with hereditary syndromes

The identification of genetic risk factors for lung cancer is an evolving field, and testing recommendations may change as more evidence emerges about specific genetic variants and their impact on lung cancer risk.