Polygenic Risk Score and Lung Adenocarcinoma Risk Among Never-Smokers by EGFR Mutation Status: A Brief Report.

Area of Science:

• Genetics
• Oncology
• Epidemiology

Background:

• Lung adenocarcinoma (LUAD) is a significant health concern, particularly among never-smokers.
• Genetic factors, including germline susceptibility and somatic mutations like EGFR, play a role in LUAD development.
• Understanding the interplay between germline risk and specific mutations is crucial for personalized risk assessment.

Purpose of the Study:

• To investigate the association between a genome-wide polygenic risk score (PRS) for LUAD and EGFR gene mutations in East Asian never-smoking females.
• To determine if germline genetic susceptibility differs between EGFR-positive and EGFR-negative LUAD.
• To explore potential clinical and public health implications of these findings.

Main Methods:

• Case-case and multinomial regression analyses were employed.
• A genome-wide PRS for LUAD risk was assessed.
• The study included 998 East Asian never-smoking female LUAD cases (518 EGFR-positive; 480 EGFR-negative) and 4544 controls.

Main Results:

• The PRS showed a stronger association with EGFR-positive LUAD compared to EGFR-negative LUAD.
• The odds ratio for the highest PRS quartile was significantly higher for EGFR-positive LUAD (8.63) than for EGFR-negative LUAD (3.50).
• A significant heterogeneity (p = 3.66 × 10⁻³) was observed between the PRS associations with EGFR-positive and EGFR-negative LUAD.

Conclusions:

• Germline genetic susceptibility may be differentially associated with LUAD in never-smoking female East Asian patients based on EGFR mutation status.
• These findings highlight the importance of considering both germline genetic risk and tumor mutation status for a comprehensive understanding of LUAD.
• The results have potential public health and clinical implications for risk stratification and targeted prevention strategies.