EGFR Q787Q Polymorphism Is a Germline Variant and a Prognostic Factor for Lung Cancer Treated With TKIs

Wen-Jui Wu; Sheng-Hsiung Yang; Hsin-Pei Chung; Chia-Te Yen; Yen-Ting Chen; Wei-Chin Chang; Jian Su; Hsuan-Yu Chen

doi:10.3389/fonc.2022.816801

EGFR Q787Q Polymorphism Is a Germline Variant and a Prognostic Factor for Lung Cancer Treated With TKIs

Front Oncol. 2022 Mar 21:12:816801. doi: 10.3389/fonc.2022.816801. eCollection 2022.

Authors

Wen-Jui Wu¹, Sheng-Hsiung Yang^{1

2}, Hsin-Pei Chung¹, Chia-Te Yen¹, Yen-Ting Chen¹, Wei-Chin Chang^{3

4}, Jian Su¹, Hsuan-Yu Chen^{2

5

6

7}

Affiliations

¹ Chest Division, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.
² Ph.D. Program in Translational Medicine, National Taiwan University and Academia Sinica, Taipei, Taiwan.
³ Department of Pathology, MacKay Memorial Hospital, Taipei, Taiwan.
⁴ Department of Pathology, MacKay Medical College and MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.
⁵ Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
⁶ Genome and Systems Biology Degree Program, National Taiwan University, Taipei, Taiwan.
⁷ Ph.D. Program in Microbial Genomics, National Chung Hsing University, Taichung, Taiwan.

Abstract

The prevalence and impact of epidermal growth factor receptor (EGFR) Q787Q polymorphism on the treatment of lung adenocarcinoma remains unclear. We retrospectively analyzed patients with stage IV lung adenocarcinoma to evaluate the prevalence of the EGFR Q787Q polymorphism and its influence on effects of tyrosine kinase inhibitor (TKI) treatment. A total of 333 patients were included in this study. The prevalence of the EGFR Q787Q polymorphism was 38%, 42%, and 35% in the total patients, EGFR mutation negative, and EGFR mutation positive groups, respectively. The prevalence of EGFR Q787Q polymorphism was significantly higher in EGFR wild-type patients than in the general non-cancerous population from Taiwan Biobank and 1000 Genome Project databases, respectively. EGFR Q787Q polymorphism had significant protective effects on the overall survival of EGFR-mutant lung adenocarcinoma treated with EGFR TKIs (aHR =0.61, p=0.03). Our study demonstrated that EGFR Q787Q polymorphism is a germline variant in the general population. It is a protective predictor of overall survival in patients with stage IV EGFR-mutated lung adenocarcinoma treated with TKIs.

Keywords: EGFR; Q787Q; TKI; lung adenocarcinoma; polymorphism; survival benefit.