<p>Impact of smoking on frequency and spectrum of <em>K-RAS</em> and <em>EGFR </em>mutations in treatment naive Indonesian lung cancer patients</p>

Abstract

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.

The role of oncogenes and tumor suppressor genes in determining survival rates of lung cancer patients in the population of North Sumatra, Indonesia

“…23 In addition, Syahruddin et al, as the first study to identify KRAS mutations in lung cancer in Indonesia, showed a lower incidence of KRAS mutations compared with populations worldwide (7% vs 31%). 24,25 The occurrence of KRAS mutations also often coincides with mutations in other oncogenes or tumor suppressor genes. Co-mutations between KRAS and TP53 were the most prevalent and were related to the poorest outcomes in all pharmacological approaches including targeted therapy, chemotherapy, and radiotherapy.…”

Molecular Biology and Therapeutic Perspectives for K-Ras Mutant Non-Small Cell Lung Cancers

“…Several studies show that Asian populations have significant lower KRAS mutation incidence than that in the Caucasian and Afro-American populations [ 37 , 38 ]. As for Europe, even in Asia there is a wide range in the mutation frequencies among countries, with the highest values in Vietnam (21%, close to European populations) and the lowest in China (8.4–13%), Japan (10%) and Indonesia (7%) [ 33 , 39 , 40 , 41 , 42 ].…”

The Absence of Mutations in the Exon 2 KRAS Gene in Several Ethnic Groups in North Sumatra May Not the Main Factor for Lung Cancer

“…Apart from relating the nature of disease and prognosis of lung cancer, KRAS mutation exhibit an association with several clinical and demographic factors, including ethnic variability and environmental alteration ( 5 - 8 ). Several studies showed that the Asian population has lower KRAS mutation incidence compare with the Western and Black populations ( 7 ).…”

“…Apart from relating the nature of disease and prognosis of lung cancer, KRAS mutation exhibit an association with several clinical and demographic factors, including ethnic variability and environmental alteration ( 5 - 8 ). Several studies showed that the Asian population has lower KRAS mutation incidence compare with the Western and Black populations ( 7 ). In the Chinese population, the prevalence of KRAS mutation was 13.1% in lung adenocarcinoma ( 9 ), wherein Indonesian population, KRAS mutation was about 7% in all types of lung cancer ( 10 ).…”