Lung Cancer: Targets and Therapy (Jun 2019)

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

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

Journal volume & issue
Vol. Volume 10
pp. 57 – 66

Abstract

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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 Utomo1,51Cancer 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, IndonesiaBackground: 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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