Abstract 4336: Direct genotyping of CYP2A6 whole gene deletion: A new biomarker for prognosis of lung adenocarcinoma in Japanese smoking male

Abstract

Abstract Purpose: Cytochrome P450 (CYP2A6) is known as an enzyme responsible for the metabolism of activation of tobacco-specific nitrosamines to their ultimate carcinogenic forms and metabolism of nicotine. We here report that the genetic polymorphisms of human CYP2A6*4 is associated with primary lung cancer and their overall survival. Experimental Design: We prepared genomic DNA samples from 387 Japanese patients with primary lung cancer and the genetic polymorphisms of human CYP2A6*4 (whole gene deletion) by the rapid genetic testing method we developed in this study. We analyzed the association between the CYP2A6*4 gene, NRF2 gene and overall survival. Results: Patients harboring wild-type CYP2A6*1 and whole gene deletion CYP2A6*4/*4 numbered 380 (98.2%) and 7 (1.8%), respectively. Its frequency was four-fold higher in male patients than in female (P = 0.038).Multivariate logistic regression models revealed that the genetic polymorphisms of human CYP2A6*4 were significantly related to gender and smoking behavior. Interestingly, lung cancer patients carrying CYP2A6*4/*4 (whole gene deletion), the NRF2 SNP heterozygous (c.-617C/A) and wild-type homozygous (c.-617C/C) exhibited remarkable survival over 1,500 days after surgical operation. Conclusion: CYP2A6*4/*4 whole gene is considered to be a prognostic biomarker for assessing both the gender-related risk of lung adenocarcinoma in the smoking sub-population and their overall survival. Citation Format: Yasuko Okano, Yasushi Ichikawa, Yohei Miyagi, Takashi Chishima, Yutaka Natsumeda. Direct genotyping of CYP2A6 whole gene deletion: A new biomarker for prognosis of lung adenocarcinoma in Japanese smoking male. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4336. doi:10.1158/1538-7445.AM2015-4336