A novel polymorphism in the promoter of the RAGE gene is associated with non-small cell lung cancer

The receptor for advanced glycosylation endproducts (RAGE) is abundant at b oth the transcriptional and translational level in normal lung but is not e xpressed in non-small cell lung cancer (NSCLC). In order to determine wheth er sequence variations might be responsible for the inactivation of RAGE in NSCLC, we investigated the RAGE gene in primary NSCLCs and in the correspo nding normal tissues of nine patients. Although sequence analysis revealed no somatic, tumor-associated mutations, six never sequence variants were id entified: T --> A in the promoter region 388 bp upstream of the start codon : T --> A in exon 1 (Ala2Ala), C --> G in exon 3 (Val89Val), C --> T in int ron 6, G --> C and C --> G in exon 10 (Arg365Ser and Arg369Gly). In additio n, we detected a 63 bp deletion in the promoter region (358-421 bp upstream of the start codon) in one NSCLC patient. The T --> A transversion in the promoter region was detected in three of nine patients. Further analysis of this polymorphic locus in 54 NSCLC patients and 59 non-cancer controls rev ealed a significant difference in the genotype distribution between NSCLC p atients and controls. Interestingly, the AA genotype was more common in NSC LC patients (20.8%) than in controls (3.5%). The cumulative occurrence of t he AA variant in NSCLC suggests that this genotype is a putative risk facto r for NSCLC development. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.