RAGE may act as a tumour suppressor to regulate lung cancer development.

Although the correlation of the RAGE rs2070600 polymorphism and cancer risk has been confirmed, detailed studies with functional and experimental evaluations are lacking. In this study, we first aimed to examine whether this polymorphism is associated with cancer risk based on the latest published data, and consistent with previous meta-analyses, a significant association between the rs2070600 polymorphism and cancer risk was observed (A versus G: OR = 1.25; 95% CI = 1.12-1.40). In additional stratified analyses based on cancer type, rs2070600 was significantly associated with an increased risk of lung cancer (A versus G: OR = 1.20; 95% CI = 1.09-1.33). Moreover, TCGA database showed that the expression level of RAGE was significantly lower in lung cancer tumour tissues than in adjacent non-tumour tissues, which was validated in the GEO database. Additionally, eQTL analysis indicated that the rs2070600 polymorphism may modify the expression level of RAGE in lung squamous cell carcinoma tissues (P = 0.09). Finally, we performed functional experiments in lung cancer cells and preliminarily demonstrated that RAGE may act as a tumour suppressor in lung cancer development. These findings provide evidence that the variant A allele of rs2070600 may decrease the expression of the tumour suppressor gene RAGE, thereby increasing lung cancer risk.