Frequency of EGFR Mutations in 907 Lung Adenocarcioma Patients of Indian Ethnicity

Abstract

BackgroundDuring the past decade, the incidence of EGFR mutation has been shown to vary across different ethnicities. It occurs at the rate of 10–15% in North Americans and Europeans, 19% in African-Americans, 20–30% in various East Asian series including Chinese, Koreans, and Japanese. Frequency of EGFR mutations in India however remains sparsely explored.Methodology/Principal FindingsWe report 23% incidence of Epidermal growth factor receptor (EGFR) mutations in 907 Non small cell lung cancer (NSCLC) patients of Indian ethnicity, in contrast to 10–15% known in Caucasians and 27–62% among East Asians. In this study, EGFR mutations were found to be more common in never-smokers 29.4% as compared to smokers 15.3%. Consistent with other populations, mutation rates among adenocarcinoma-males were predominantly lower than females with 32% incidence. However unlike Caucasians, EGFR mutation rate among adenocarcinoma-never-smoker females were comparable to males suggesting lack of gender bias among never smokers likely to benefit from EGFR targeted therapy.Conclusions/SignificanceThis study has an overall implication for establishing relevance for routine EGFR mutation diagnostics for NSCLC patients in clinics and emphasizes effectiveness for adoption of EGFR inhibitors as the first line treatment among Indian population. The intermediate frequency of EGFR mutation among Indian population compared to Caucasians and East Asians is reminiscent of an ancestral admixture of genetic influence from Middle Easterners, Central Asians, and Europeans on modern- Indian population that may confer differential susceptibility to somatic mutations in EGFR.

Drug-sensitiveFGFR3 mutations in lung adenocarcinoma

“…Based on the mutation profiling of 363 lung adenocarcinoma patients, we present the first portrait of activating mutations present in the Indian lung cancer genome (Figure 1B), wherein 160 of 363 patients were found to harbor activating mutations across 8 genes at following frequency: EGFR (28.4%), KRAS (13%), ALK (3.8%), AKT1 (2.5%), PIK3CA (1.4%), FGFR4 (0.4%) and ERBB2 (0.3%) as shown in Figure 1A, consistent with earlier reports [6, 8, 9]. In addition, 3 of 79 patients were found to harbor EML4-ALK translocation as determined by FISH.…”

Epidermal growth factor receptor exon 20 mutation in lung cancer: types, incidence, clinical features and impact on treatment

“…The demographic profile of our population did not reveal an association between gender, smoking status and exon 20 mutations, although, in certain reports, a higher proportion of patients with exon 20 mutation was found to be nonsmokers 7,10. In general, the incidence of nonsmokers in Indian non-small cell lung cancer (NSCLC) patients is relatively high in the range of 40%–50% 1. Our data too showed a similar trend with the proportion of nonsmokers at 60.1%.…”

CRE: a cost effective and rapid approach for PCR-mediated concatenation of KRAS and EGFR exons

“…While EGFR and KRAS mutations largely occur mutually exclusively in non-small cell lung cancer (NSCLC), and predict contrasting response rate to tyrosine-kinase inhibitors (TKI) ( Chougule et al , 2013; Fukuoka et al , 2011; Ihle et al , 2012; Lynch et al , 2004; Mao et al , 2010; Mok et al , 2009), some recent studies, including ours, suggest co-occurrence of EGFR and KRAS mutations in the same patients, albeit at low frequency ( Choughule et al , 2014; Li et al , 2014). While no direct evidence exists as yet, these studies may have implications for carrying out routine KRAS molecular testing along with EGFR mutations for precluding a patient with NSCLC from therapy with EGFR inhibitors, as approved for colorectal cancer ( Lievre et al , 2006).…”