Germline Variants in Indian Non-Small Cell Lung Cancer Patients With Familial Aggregation: A Prospective Cohort Study

Area of Science:

• Oncology
• Genetics
• Cancer Research

Background:

• Increasing lung cancer incidence in never-smokers suggests genetic predisposition.
• Familial aggregation of cancer is a key indicator for genetic testing.
• Germline variants in cancer predisposition genes contribute to lung cancer risk.

Purpose of the Study:

• To determine the prevalence of pathogenic germline variants (PGVs) in Indian lung cancer patients with a family history.
• To evaluate the role of genetic predisposition in lung cancer among Indian patients.

Main Methods:

• Screening of non-small cell lung cancer (NSCLC) patients for family history.
• Next-generation sequencing (NGS) analysis of 143 cancer predisposition genes in germline DNA.
• Analysis of clinical, pathological, demographic, and survival data.

Main Results:

• 18.26% of 750 patients had a significant family history; 16.5% of those tested had PGVs.
• Mutations were found in 12 genes, including ATM and BRCA2, often linked to DNA damage repair.
• 8 out of 12 first-degree relatives carried the same mutation as the index patient.

Conclusions:

• The frequency of PGVs in Indian NSCLC patients with a family history is 16.5%.
• Genetic testing can identify high-risk individuals for targeted screening strategies.
• Familial aggregation is a significant factor in lung cancer etiology and warrants genetic evaluation.