Differences in the risk association of TERT rs2736098 (C > T) with lung cancer between Caucasian and Asian populations: A meta-analysis

The T allele variant of TERT rs2736098 has been associated with an increased risk of lung cancer (LC), yet various studies have yielded inconsistent findings. The purpose of this study is to verify the association between the rs2736098 variant and LC risk, as well as to investigate the differences in this association across different ethnic groups (Caucasians and Asians), various LC subtypes, and distinct smoking statuses. A computer search was conducted for literatures published up to December 20, 2024, in PubMed, Embase, Web of Science, and MEDLINE databases. Data were analyzed using RevMan 5.3, while sensitivity analysis and publication bias were assessed using Stata 14.0. The stability of the results was evaluated with TSA software Registration number: CRD420251030755. The T allele variant of rs2736098 was associated with an increased risk of LC ([OR] = 1.22, 95%CI [1.18, 1.27]), and this association was observed in both Caucasians ([OR] = 1.17, 95%CI [1.14, 1.20]) and Asians ([OR] = 1.26, 95%CI [1.19, 1.34]), with a stronger association in Asians than in Caucasians (Subgroup differences: P = 0.03, I² = 79.7%). In specific LC subtypes, rs2736098[T] was linked to the risk of NSCLC and LUAD in both Caucasians and Asians (P < 0.05), and the strength of the association with NSCLC and LUAD was greater in Asians than in Caucasians (Subgroup differences: P < 0.05, I² > 50%). Additionally, rs2736098[T] was associated with the risk of SCLC and LUSC in Asians (P < 0.05), with a similar strength of association for NSCLC and SCLC (subgroup differences: P = 0.87, I² = 0%), but a stronger association for LUAD than for LUSC (subgroup differences: P = 0.01, I² = 84.7%). The rs2736098[T] variant was also associated with the risk of LC in both Caucasian smokers/non-smokers and Asian smokers/non-smokers (P < 0.05), and the strength of the association did not vary between Caucasian smokers/non-smokers and Asian smokers/non-smokers (P ≥ 0.05, Subgroup differences: I² < 50%). Within LC subtypes, rs2736098[T] was primarily associated with the risk of NSCLC in Asian smokers ([OR] = 1.59, 95%CI[1.19, 2.12]) and the risk of LUAD in Asian non-smokers ([OR] = 1.43, 95%CI[1.17, 1.75]). The T allele variant of rs2736098 is associated with LC risk, and Asians have a higher risk of LC, NSCLC and LUAD due to the rs2736098 variant compared to Caucasians. Therefore, there is a difference in the strength of the association between the two populations for LC risk due to the rs2736098 variant. Additionally, regardless of whether Caucasians or Asians are smokers, they are likely to be at risk for LC due to the variant in rs2736098.