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Impact of smoking on frequency and spectrum of K-RAS and EGFR mutations in treatment naive Indonesian lung cancer patients

Authors Masykura N, Zaini J, Syahruddin E, Andarini SL, Hudoyo A, Yasril R, Ridwanuloh A, Hidajat H, Nurwidya F, Utomo A

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 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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