Six minor allele variants in the TERT-CLPTM1L region are associated with lung cancer risk: a meta-analysis based on different ethnicities and different lung cancer subtypes

Abstract Background: Although many genome-wide association studies(GWAS) have confirmed the associations between multiple sites in the TERT-CLPTM1L region and lung cancer(LC) susceptibility in different populations, some of them haven’t found the associations between these sites and LC. The purpose of this study is to clarify the associations between TERT-CLPTM1L polymorphism and LC, as well as the differences in these associations between patients of different ethnicities and different LC subtypes. Methods: Relevant literatures published before May 7, 2022 on ‘TERT-CLPTM1L polymorphisms and LC susceptibility’ in PubMed, EMbase,Web of Science, MEDLINE databases were searched through the Internet. Statistical analysis of data was performed in Revman5.3 software, including drawing forest plots, funnel plots and so on. Sensitivity and publication bias analysis were performed in Stata 14.0 software. TSA 0.9.5.10 software was performed for the Trial sequential analysis(TSA) tests to evaluate the stability of the results. Registration number: CRD42023407890. Results: A total of 51 literatures were included in this meta-analysis, including 6 TERT-CLPTM1L polymorphisms and a total of 54 studies (12 GWAS and 42 case-control studies), including 11 studies in Caucasians and 43 studies in Asians. The results showed that the minor allele variants of the 6 polymorphisms were positively or negatively associated with the risk of LC (rs2736098[T]: [OR]=1.24, 95% CI [1.18, 1.31]; rs2736100[C]: [OR]=1.25, 95% CI [1.20, 1.30]; rs31489[A]: [OR]=0.87, 95% CI [0.82, 0.92]; rs401681[T]: [OR]=0.87, 95% CI [0.84, 0.90]; rs402710[T]: [OR]=0.86, 95% CI [0.83, 0.88]; rs4975616[G]: [OR]=0.86, 95% CI [0.82, 0.91]). However, there were clear differences in these associations in LC with different pathological subtypes in Caucasian and Asian populations (Subgroup differences: I 2 ≥50%). Conclusions: Our results confirmed the clear associations between 6 TERT-CLPTM1L polymorphisms and the risk of LC, and there were significant differences in these associations among different ethnicities/pathological subtypes of LC.