Impact of smoking on frequency and spectrum of K-RAS and EGFR mutations in treatment naive Indonesian lung cancer patients
Received 25 July 2018
Accepted for publication 11 February 2019
Published 17 June 2019 Volume 2019:10 Pages 57—66
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 3
Editor who approved publication: Dr Sai-Hong Ignatius Ou
Najmiatul Masykura,1 Jamal Zaini,2 Elisna Syahruddin,2 Sita Laksmi Andarini,2 Achmad Hudoyo,2 Refniwita Yasril,2 Asep Ridwanuloh,3 Heriawaty Hidajat,4 Fariz Nurwidya,2 Ahmad Utomo1,5
1Cancer Diagnostic Research, Stem-cell and Cancer Institute, Jakarta, Indonesia; 2Department of Pulmonology and Respiratory Medicine Faculty of Medicine, Universitas Indonesia and Persahabatan Hospital, Jakarta, Indonesia; 3Research Center for Biotechnology, Indonesian Institute of Sciences, Bogor, Indonesia; 4Anatomic Pathology Laboratory, Persahabatan Hospital, Jakarta, Indonesia; 5Molecular Genetic Testing Services, Kalbe Genomics Laboratory, Jakarta, Indonesia
Background: Indonesia has the highest cigarette consumption in the world. We explored the clinical impact of smoking on the prevalence of EGFR and K-RAS mutations and survival in this prospective study.
Methods: 143 treatment naive lung cancer patients were recruited from Persahabatan Hospital, a national tertiary hospital. DNA from cytological specimens had been extracted and genotyped for both EGFR and K-RAS mutations using a combination of PCR high resolution melting, restriction fragment length polymorphism (RFLP) and direct DNA sequencing.
Results: EGFR mutation frequency in never smokers (NS) and ever smokers (ES) were 75% and 56% (p = 0.0401), respectively. In this cohort, the overall K-RAS mutation rate was 7%. Neither gender nor smoking history were associated with K-RAS mutation significantly. However, K-RAS transversion mutations were more common in male ES than transition mutations. Smoking history did not affect EGFR and K-RAS mutation frequencies in women. Concurrent EGFR/K-RAS mutation rate was 2.8% (4 of 143 patients). Four out of 91 EGFR mutation positive patients (4.4%) had simultaneous K-RAS mutation.
Conclusions: In region where cigarette consumption is prevalent, smoking history affected frequencies of EGFR and K-RAS mutations, mainly in males.
Keywords: lung cancer, Indonesia, K-RAS mutation, smoking
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