Ao Yiyuan, Wen Yaokai, Li Yutian, Peng Haoxin, Wu Xiangrong, Wang Zhufeng, Jiang Yu, Lin Yuechun, Li Shuben
Department of Thoracic Surgery and Oncology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou, China.
Nanshan School, Guangzhou Medical University, Guangzhou, China.
Front Genet. 2022 Jul 15;13:861984. doi: 10.3389/fgene.2022.861984. eCollection 2022.
It remains uncertain whether ankylosing spondylitis is associated with an increased risk of lung cancer. We conducted a meta-analysis to comprehensively evaluate the correlation between ankylosing spondylitis and lung cancer based on existing literature. Eligible studies were identified by searching the PubMed, Web of Science, Embase, and Cochrane Library before 26 March 2021. Subgroup analyses based on regions were also carried out. To further explore their causality, a two-sample Mendelian randomization analysis was performed, with 25 ankylosing spondylitis-related single nucleotide polymorphisms derived from the largest sample genome-wide association study of ankylosing spondylitis (ebi-a-GCST005529, 22,647 individuals). The inverse variance-weighted method was applied to estimate the causality, and the pleiotropy was assessed utilizing the Mendelian randomization-Egger regression approach. The meta-analysis including seven studies, with a total of 39,186 individuals, suggested no significant association between ankylosing spondylitis and lung cancer (relative risk, 1.10; 95% confidence interval, 0.89-1.36; I2, 61.8%). After excluding one study leading to high heterogeneity, we found that ankylosing spondylitis was associated with a 19% increased risk of lung cancer (relative risk, 1.19; 95% confidence interval, 1.01-1.40; I2, 0.0%). Subgroup analyses suggested that ankylosing spondylitis was not associated with increased risks of lung cancer in neither European (relative risk, 1.05; 95% confidence interval, 0.80-1.39; I2, 0.0%) nor non-European (relative risk, 1.14; 95% confidence interval, 0.84-1.55; I2, 79.6%) patients. Nevertheless, the Mendelian randomization results indicated that genetically determined ankylosing spondylitis was causally correlated with a remarkably increased risk of lung cancer among European populations (odds ratio, 1.26; 95% confidence interval, 1.07-1.48). Subgroup analyses further elucidated that genetically determined ankylosing spondylitis was causally associated with a notably higher risk of only squamous cell lung cancer (odds ratio, 1.39; 95% confidence interval, 1.05-1.83), rather than lung adenocarcinoma (odds ratio, 1.18; 95% confidence interval, 0.91-1.54). In addition, the results indicated the absence of pleiotropy. The results of both modified meta-analysis and Mendelian randomization analysis suggested that ankylosing spondylitis was likely to be correlated with the development of lung cancer. Further research is warranted to clarify the specific mechanism regarding the causality between the two diseases.
强直性脊柱炎是否与肺癌风险增加相关仍不确定。我们进行了一项荟萃分析，以根据现有文献全面评估强直性脊柱炎与肺癌之间的相关性。通过检索2021年3月26日前的PubMed、科学网、Embase和Cochrane图书馆来确定符合条件的研究。还进行了基于地区的亚组分析。为了进一步探究它们之间的因果关系，进行了两样本孟德尔随机化分析，使用了来自强直性脊柱炎最大样本全基因组关联研究（ebi-a-GCST005529，22647人）中的25个与强直性脊柱炎相关的单核苷酸多态性。采用逆方差加权法估计因果关系，并利用孟德尔随机化-埃格回归方法评估多效性。包括7项研究、共39186人的荟萃分析表明，强直性脊柱炎与肺癌之间无显著关联（相对风险，1.10；95%置信区间，0.89 - 1.36；I²，61.8%）。排除一项导致高异质性的研究后，我们发现强直性脊柱炎与肺癌风险增加19%相关（相对风险，1.19；95%置信区间，1.01 - 1.40；I²，0.0%）。亚组分析表明，在欧洲患者（相对风险，1.05；95%置信区间，0.80 - 1.39；I²，0.0%）和非欧洲患者（相对风险，1.14；95%置信区间，0.84 - 1.55；I²，79.6%）中，强直性脊柱炎均与肺癌风险增加无关。然而，孟德尔随机化结果表明，基因决定的强直性脊柱炎与欧洲人群中肺癌风险显著增加存在因果关联（优势比，1.26；95%置信区间，1.07 - 1.48）。亚组分析进一步阐明，基因决定的强直性脊柱炎仅与鳞状细胞肺癌风险显著升高存在因果关联（优势比，1.39；95%置信区间，1.05 - 1.83），而非肺腺癌（优势比，1.18；95%置信区间，0.91 - 1.54）。此外，结果表明不存在多效性。改良荟萃分析和孟德尔随机化分析的结果均表明，强直性脊柱炎可能与肺癌的发生相关。有必要进一步研究以阐明这两种疾病之间因果关系的具体机制。
