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Oncol Lett. 2015 Sep;10(3):1775-1782. Epub 2015 Jun 23.

Ethnicity affects EGFR and KRAS gene alterations of lung adenocarcinoma.

Author information

1
Department of Thoracic Surgery Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Okayama, Japan ; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
2
Department of Thoracic Surgery Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Okayama, Japan ; Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Okayama, Japan.
3
Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Fukuoka, Japan.
4
Department of Thoracic Surgery Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Okayama, Japan.
5
Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA ; Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
6
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
7
Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia.
8
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA ; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

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.

KEYWORDS:

EGFR; KRAS; copy number gain; ethnicity; lung adenocarcinoma; mutation

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