EGFR L858R mutation and polymorphisms of genes related to estrogen biosynthesis and metabolism in never-smoking female lung adenocarcinoma patients

Shi Yi Yang, Tsung Ying Yang, Kun Chieh Chen, Yao Jen Li, Kuo Hsuan Hsu, Chi Rne 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 Yang, Chien Jen Chen

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Abstract

Purpose: To assess whether polymorphisms of genes related to estrogen biosynthesis and metabolism are associated with EGFR mutations. Experimental Design: We studied 617 patients with lung adenocarcinoma, including 302 neversmoking women. On the basis of multiple candidate genes approach, the effects of polymorphisms of CYP17, CYP19A1, ERα, and COMT in association with the occurrence of EGFR mutations were evaluated using logistic regression analysis. Results: In female never-smokers, significant associations with EGFR L858R mutation were found for the tetranucleotide (TTTA)n repeats in CYP19A1 (odds ratio, 2.6; 95%CI, 1.2-5.7 for 1 or 2 alleles with (TTTA) n repeats >7 compared with both alleles with (TTTA)n repeats ≤7), and the rs2234693 in ERα (OR, 2.1; 95% CI, 1.1-4.0 for C/T and C/C genotypes compared with T/T genotype). The C/C genotype (vs. T/T genotype) of ERa was significantly associated with EGFR L858R mutation (OR, 3.0; 95% CI, 1.1-8.1), in-frame deletion (OR, 2.9; 95% CI, 1.1-7.6) and other mutations (OR, 4.3; 95% CI, 1.3-14.0). The genotype of COMT rs4680 was significantly associated with EGFR L858R mutation in female and male never-smokers showing OR's (95% CI) of 1.8 (1.0-3.2) and 3.6 (1.1-11.3), respectively, for genotypes G/A and G/G compared with genotype A/A. The number of risk alleles of CYP17, CYP19A1, ERα, and COMT was associated with an increasing OR of EGFR L858R mutation in female neversmokers (P = 0.0002 for trend). Conclusions: The L858R mutation of EGFR is associated with polymorphisms of genes related to estrogen biosynthesis and metabolism in never-smoking female lung adenocarcinoma patients.

Original languageEnglish
Pages (from-to)2149-2158
Number of pages10
JournalClinical Cancer Research
Volume17
Issue number8
DOIs
Publication statusPublished - 2011 Apr 15

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Yang, S. Y., Yang, T. Y., Chen, K. C., Li, Y. J., 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., Yang, P. C., & Chen, C. J. (2011). EGFR L858R mutation and polymorphisms of genes related to estrogen biosynthesis and metabolism in never-smoking female lung adenocarcinoma patients. Clinical Cancer Research, 17(8), 2149-2158. https://doi.org/10.1158/1078-0432.CCR-10-2045