Abstract 2361: SNP (-617G>A) in ARE-like loci of the NRF2 gene: a new biomarker for prognosis of lung adenocarcinoma.

Abstract

Abstract Purpose: Accumulating evidence suggests nuclear factor (erythroid-derived 2)-like 2 (NRF2) plays an important role as cellular defense, tumor suppression, and oncogenesis. However, little information is available as to the genetic polymorohisms of the NRF2 gene and their clinical relevance. We aimed to validate the NRF2 gene as a prognostic biomarker in lung cancer. Experimental Design: We prepared genomic DNA from 392 Japanese patients with primary lung cancer and detected a SNP (c.-617C>A) in the ARE-like loci of the human NRF2 gene by the rapid genetic testing method we developed in this study. We analyzed an association between the NRF2 gene and overall survival. Results: We detected homozygous (A/A) and heterozygous (C/A) alleles with the SNP (c.-617C>A) in 24 (6.2%) and 147 (38.0%) patients, respectively. The frequency of the homozygote (A/A) was four-fold higher in females than in males (11.0% versus 2.7%). Multivariate logistic regression models including standard lung cancer factors revealed that the homozygous alleles (c.-617A/A) were significantly related to gender. Interestingly, lung cancer patients carrying the homozygous alleles (c.-617A/A) exhibited remarkable survival over 1,700 days after surgical operation (log-rank p=0.021). Conclusion: The homozygous allele (c.-617A/A) in the NRF2 gene is considered to be a prognostic biomarker for assessing both the gender-related risk of lung adenocarcinoma in the non-smoking sub-population and their overall survival. Citation Format: Yasuko Okano, Yasushi Ichikawa, Yohei Miyagi, Yutaka Natsumeda, Toshihisa Ishikawa. SNP (-617G>A) in ARE-like loci of the NRF2 gene: a new biomarker for prognosis of lung adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2361. doi:10.1158/1538-7445.AM2013-2361