Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, No. 195 Dongfeng Xi Road, Guangzhou, 510000, China.
J Cancer Res Clin Oncol. 2023 Aug;149(10):6999-7006. doi: 10.1007/s00432-023-04612-6. Epub 2023 Feb 28.
Observational studies showed associations between smoking, and airflow limitation, with lung squamous cell carcinoma (LUSC). However, the causal association of airflow limitation with LUSC and the modification by smoking status for the association remains unclear.
Genetic summary data were obtained from large genome-wide association studies (GWAS). One hundred two single nucleotide polymorphisms (SNPs) for airflow limitation (i.e., FEV1/FVC < 0.7) and 153 SNPs for smoking behavior were used as instrumental variables and the main MR analysis methods. The univariable and multivariable Mendelian Randomization (MR) in a two-sample setting were performed to assess the association of airflow limitation, and smoking behavior with LUSC.
In the univariable MR analysis, genetic predisposition towards airflow limitation [Inverse Variance-Weighted (IVW) method Odds Ratio (OR) = 4.83, 95% Confidence Interval (CI) 1.55 to 15.06, P = 0.006], age of smoking initiation (IVW method OR = 0.10, 95%CI 0.02 to 0.36, P < 0.001), cigarettes smoked per day (IVW method OR = 3.10, 95%CI 2.07 to 4.63, P < 0.001), ex-smoking (IVW method OR = 0.47, 95%CI 0.31 to 0.69, P < 0.001), current smoking status (IVW method OR = 13.08, 95%CI 2.53 to 67.84, P = 0.002), pack-years of smoking (Weighted median method OR = 11.49, 95%CI 3.71 to 35.63, P < 0.001) were associated with LUSC. In the multivariable MR analysis, the causal effect of airflow limitation was still observed on LUSC (IVW method OR = 2.97, 95% CI 1.09 to 8.04, P = 0.032 adjusted for age of smoking initiation and cigarettes smoked per day; IVW method OR = 3.24, 95% CI 1.09 to 9.58, P = 0.033 adjusted for ex-smoking, current smoking status, and pack years of smoking; IVW method OR = 2.91, 95% CI 1.01 to 8.41, P = 0.049 adjusted for 5 smoking behaviors mentioned above).
Our MR analysis demonstrated that airflow limitation is likely to be an independent predictor of LUSC.
观察性研究表明，吸烟与气流受限与肺鳞状细胞癌（LUSC）有关。然而，气流受限与 LUSC 的因果关系以及吸烟状况对这种关联的修饰作用仍不清楚。
遗传汇总数据来自大型全基因组关联研究（GWAS）。使用 102 个用于气流受限（即 FEV1/FVC<0.7）的单核苷酸多态性（SNP）和 153 个用于吸烟行为的 SNP 作为工具变量，并使用主要 MR 分析方法。在两样本设置中进行单变量和多变量孟德尔随机化（MR），以评估气流受限和吸烟行为与 LUSC 的关联。
在单变量 MR 分析中，气流受限的遗传易感性[逆方差加权（IVW）法比值比（OR）=4.83，95%置信区间（CI）1.55 至 15.06，P=0.006]、吸烟起始年龄（IVW 法 OR=0.10，95%CI 0.02 至 0.36，P<0.001）、每日吸烟量（IVW 法 OR=3.10，95%CI 2.07 至 4.63，P<0.001）、戒烟（IVW 法 OR=0.47，95%CI 0.31 至 0.69，P<0.001）、当前吸烟状况（IVW 法 OR=13.08，95%CI 2.53 至 67.84，P=0.002）、吸烟年限（加权中位数法 OR=11.49，95%CI 3.71 至 35.63，P<0.001）与 LUSC 相关。在多变量 MR 分析中，气流受限对 LUSC 的因果效应仍然存在（IVW 法 OR=2.97，95%CI 1.09 至 8.04，P=0.032，调整了吸烟起始年龄和每日吸烟量；IVW 法 OR=3.24，95%CI 1.09 至 9.58，P=0.033，调整了戒烟、当前吸烟状况和吸烟年限；IVW 法 OR=2.91，95%CI 1.01 至 8.41，P=0.049，调整了上述 5 种吸烟行为）。
我们的 MR 分析表明，气流受限可能是 LUSC 的一个独立预测因子。
