Ethnicity affects EGFR and KRAS gene alterations of lung adenocarcinoma

Abstract

Abstract. Mutations or copy number gains (CNGs) of the EGFR and KRAS genes are representative alterations in lung adenocarcinomas that are individually associated with patient characteristics such as ethnicity, smoking status and gender. However, the effects of combinations of these genetic alterations have not been statistically examined. The present study analyzed previously examined lung adenocarcinoma cases in Asian (n=166) and non-Asian (n=136) individuals in whom all four EGFR and KRAS alterations had been studied. The polynomial logistic regression models were used following adjustment for gender and smoking status, and using patients without any type of EGFR/KRAS alterations as a reference. Between the two ethnic groups, EGFR CNGs (gEGFR) occurred more frequently than EGFR mutations (mEGFR) (46 vs. 38% in Asians; 21 vs. 10% in non-Asians), whereas KRAS mutations (mKRAS) were more frequent than KRAS CNGs (gKRAS) (13 vs. 7% and 35 vs. 4%, respectively). Additionally, gEGFR and gKRAS occurred significantly more frequently in respective mutant cases, and all EGFR alterations were almost exclusive of all KRAS alterations. The polynomial logistic regression models confirmed that all types of EGFR alterations were significantly more frequent among Asian individuals than among non-Asian individuals, independent of gender and smoking status (odds ratios, 2.36-6.67). KRAS alterations occurred less frequently among Asian individuals than among non-Asian individuals, although a significant difference was not detected. The present study results indicated that the EGFR and KRAS profiles, including mutations and CNGs, differ between Asian and non-Asian individuals with lung adenocarcinoma, suggesting that ethnicity strongly affects the molecular characteristics of lung adenocarcinoma. IntroductionActivating mutations of EGFR and KRAS genes are characteristic mutations, or so-called 'driver mutations', of lung adenocarcinomas (1-3). Approximately 80% of patients with EGFR mutations (mEGFR) respond efficiently to treatment with EGFR-tyrosine kinase inhibitors (TKIs) (1,2), but KRAS mutations (mKRAS) are considered to predict resistance to EGFR-TKI therapy (4). Over the past decade, other 'driver mutations' in ALK (5), HER2 (6), and BRAF (7) have been found in lung adenocarcinomas, although mEGFR and mKRAS remain the most frequent 'driver mutations' in lung adenocarcinomas (8). Significantly, mEGFR and mKRAS are mutually exclusive and exhibit a characteristic association with clinical factors, particularly ethnicity; mEGFR are frequently observed in Asian individuals, women and never-smokers, but mKRAS are frequently observed in Caucasian individuals, men and smokers (9,10).A copy number gain (CNG) is another mechanism of oncogenic activation (11). A large-scale project to characterize copy number alterations in primary lung adenocarcinomas confirmed that EGFR and KRAS loci were significantly recurrent events when using a high-resolution genome-wide

Geographic Variation in EGFR Mutation Frequency in Lung Adenocarcinoma May Be Explained by Interethnic Genetic Variation

“…5 It has been proposed that ethnicity may explain these differences. 6,7 To investigate the potential role of interethnic genetic variation in the etiology of EGFR-mutant lung cancer, we analyzed the relationship between two genetic biomarkers of East Asian ancestry and the frequency of EGFR mutations in patients with lung adenocarcinoma in a range of countries.…”

Somatic Mutations and Ancestry Markers in Hispanic Lung Cancer Patients

“…2 Since precision medicine is driven by data that primarily represents non-Hispanic white (NHW) patients, there is a significant potential health disparity for under-represented groups. 3–6 Non-small cell lung cancer (NSCLC), is the leading cause of cancer death among H/L men and second only to breast cancer in H/L women. 3 In NHW individuals, half of NSCLC cases have been shown to possess at least one of several known driver mutations, including alterations in KRAS, EGFR, MET, HER2, BRAF, PIK3CA, AKT1, MAP2K1, ALK, and MEK.…”

Prognostic model for brain metastases from lung adenocarcinoma identified with epidermal growth factor receptor mutation status

“…All of the patients in this study were from Chinese populations, and the rate of EGFR mutation in lung adenocarcinoma is different between ethnic groups. It has been reported that EGFR mutation rates in Asian patients are higher than in Westerners, at rates of 50% and 20%, respectively . As such, our prognostic model may be more suitable to Asian patients.…”

“…It has been reported that EGFR mutation rates in Asian patients are higher than in Westerners, at rates of 50% and 20%, respectively. 27,28 As such, our prognostic model may be more suitable to Asian patients. Finally, we used two kinds of test methods that might have different positive detectable rates of EGFR mutations.…”