EGFR exon 19 in-frame deletion and polymorphisms of DNA repair genes in never-smoking female lung adenocarcinoma patients

Shi Yi Yang, Tsung Ying Yang, Yao Jen Li, Kun Chieh Chen, Kuo Meng Liao, Kuo Hsuan Hsu, Chi Ren Tsai, Chih Yi Chen, Chung Ping Hsu, Jiun Yi Hsia, Cheng Yen Chuang, Ying Huang Tsai, Kuan Yu Chen, Ming Shyan Huang, Wu Chou Su, Yuh Min Chen, Chao A. Hsiung, Chen Yang Shen, Gee Chen Chang, Pan Chyr YangChien Jen Chen

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10 Citations (Scopus)

Abstract

We explored potential associations between genetic polymorphisms in genes related to DNA repair and detoxification metabolism and epidermal growth factor receptor (EGFR) mutations in a cohort of 410 never-smoking patients with lung adenocarcinoma. Multivariate-adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CI) of EGFR mutation status in association with the genotypes of DNA repair and detoxification metabolism genes were evaluated using logistic regression analysis. We found an association between in-frame deletion in EGFR exon 19 and a single nucleotide polymorphism (SNP) rs1800566C/T located in NQO1 (aOR, 2.2 with 95% CI, 1.0-4.8) in female never-smokers. The SNP rs744154C/G in ERCC4 was also associated with the EGFR exon 19 in-frame deletion both in never-smokers (aOR, 1.7 with 95% CI, 1.0-3.0) and female never-smokers (aOR, 1.9 with 95% CI, 1.0-3.6). Although the association was marginally significant in multivariate logistic regression analysis, the A/A genotype of rs1047840 in EXO1 was associated with a 7.6-fold increase in the occurrence of the EGFR exon 19 in-frame deletion in female never-smokers. Moreover, risk alleles in NQO1, ERCC4 and EXO1 were associated with an increasing aOR of the EGFR exon 19 in-frame deletion both in never-smokers (p = 0.007 for trend) and female never-smokers (p = 0.002 for trend). Our findings suggest that the in-frame deletion in EGFR exon 19 is associated with polymorphisms in DNA repair and detoxification metabolism genes in never-smoking lung adenocarcinoma patients, especially in females.

Original languageEnglish
Pages (from-to)449-458
Number of pages10
JournalInternational Journal of Cancer
Volume132
Issue number2
DOIs
Publication statusPublished - 2013 Jan 15

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Yang, S. Y., Yang, T. Y., Li, Y. J., Chen, K. C., Liao, K. M., Hsu, K. H., Tsai, C. R., Chen, C. Y., Hsu, C. P., Hsia, J. Y., Chuang, C. Y., Tsai, Y. H., Chen, K. Y., Huang, M. S., Su, W. C., Chen, Y. M., Hsiung, C. A., Shen, C. Y., Chang, G. C., ... Chen, C. J. (2013). EGFR exon 19 in-frame deletion and polymorphisms of DNA repair genes in never-smoking female lung adenocarcinoma patients. International Journal of Cancer, 132(2), 449-458. https://doi.org/10.1002/ijc.27630