Correlation of TNF-α polymorphisms with susceptibility to lung cancer: evidence from a meta-analysis based on 29 studies

Abstract

Objective: This meta-analysis aims to clarify the association between the TNF-α -308G > A and - 238G > A polymorphisms and lung cancer risk.

Method: A comprehensive search was conducted for relevant articles across databases such as PubMed, Google Scholar, Web of Science, EMBASE, and CNKI, up to September 25, 2023. Lung cancer risk was assessed by calculating odds ratios (ORs) and their 95% confidence intervals (CIs). The Z-test was used to determine the significance of combined ORs, with P < 0.05 considered statistically significant. All analyses were performed using Comprehensive Meta-Analysis (CMA) 2.0 software.

Results: The analysis included 19 case-control studies with 3,838 cases and 5,306 controls for the TNF-α -308G > A polymorphism, along with 10 studies comprising 2,427 cases and 2,357 controls for the - 238G > A polymorphism. The - 308G > A polymorphism showed no significant overall relationships, though in the Asian subgroup, the A allele was significantly reduced compared to G (OR: 0.831, p = 0.028) and the AA genotype showed significant reductions versus GG (OR: 0.571, p = 0.021), with no significant correlation in Caucasians. In non-small cell lung cancer (NSCLC), the A allele was associated with increased risk compared to G (OR: 1.131, p = 0.049). For the - 238G > A polymorphism, the AA genotype significantly increased risk compared to GG (OR: 3.171, p = 0.014), while showing a protective effect in Caucasians (OR: 0.120, p = 0.024) and a heightened risk in Asians (OR: 7.990, p = 0.007). In small cell lung cancer (SCLC), the A allele conferred protective effects, whereas NSCLC showed increased risk for the AA genotype (OR: 11.375, p = 0.002).

Conclusion: The - 308G > A polymorphism has no significant overall relationships but suggests a protective role of the A allele in the Asian subgroup. Conversely, the - 238G > A polymorphism presents a complex risk profile, increasing lung cancer likelihood in Asians while protecting Caucasians. Notably, the AA genotype significantly raises risk for NSCLC, indicating its potential as a risk factor.

Keywords: Ethnicity; Lung cancer; Meta-analysis; Polymorphisms; Susceptibility; TNF-α.

Fig. 1

Flow diagram of study selection for the meta-analysis

Fig. 2

Forest plot depicting the correlation of TNF-α -308G > A and − 238G > A polymorphisms with lung cancer risk: (A) allele model (A vs. G); (B) dominant model (AA + AG vs. GG)

Fig. 3

Begg’s funnel plot assessing publication bias for the correlation between TNF-α -238G > A polymorphism and lung cancer risk: (A) homozygote model (AA vs. GG); (B) recessive model (AA vs. AG + GG)