Causal relationships between body mass index, smoking and lung cancer: Univariable and multivariable Mendelian randomization.

At the time of cancer diagnosis, body mass index (BMI) is inversely correlated with lung cancer risk, which may reflect reverse causality and confounding due to smoking behavior. We used two-sample univariable and multivariable Mendelian randomization (MR) to estimate causal relationships of BMI and smoking behaviors on lung cancer and histological subtypes based on an aggregated genome-wide association studies (GWASs) analysis of lung cancer in 29 266 cases and 56 450 controls. We observed a positive causal effect for high BMI on occurrence of small-cell lung cancer (odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.24-2.06, P = 2.70 × 10-4 ). After adjustment of smoking behaviors using multivariable Mendelian randomization (MVMR), a direct causal effect on small cell lung cancer (ORMVMR = 1.28, 95% CI = 1.06-1.55, PMVMR = .011), and an inverse effect on lung adenocarcinoma (ORMVMR = 0.86, 95% CI = 0.77-0.96, PMVMR = .008) were observed. A weak increased risk of lung squamous cell carcinoma was observed for higher BMI in univariable Mendelian randomization (UVMR) analysis (ORUVMR = 1.19, 95% CI = 1.01-1.40, PUVMR = .036), but this effect disappeared after adjustment of smoking (ORMVMR = 1.02, 95% CI = 0.90-1.16, PMVMR = .746). These results highlight the histology-specific impact of BMI on lung carcinogenesis and imply mediator role of smoking behaviors in the association between BMI and lung cancer.

Zhou W ，Liu G ，Hung RJ ，Haycock PC ，Aldrich MC ，Andrew AS ，Arnold SM ，Bickeböller H ，Bojesen SE ，Brennan P ，Brunnström H ，Melander O ，Caporaso NE ，Landi MT ，Chen C ，Goodman GE ，Christiani DC ，Cox A ，Field JK ，Johansson M ，Kiemeney LA ，Lam S ，Lazarus P ，Le Marchand L ，Rennert G ，Risch A ，Schabath MB ，Shete SS ，Tardón A ，Zienolddiny S ，Shen H ，Amos CI ... -  《-》

Causal relationship between feelings and cognitive decline: An univariable and multivariable Mendelian randomization study.

Liu J ，Liu L ，Hu YX ，Li JH ，Zou X ，Zhang HY ，Fan L ... -  《World Journal of Psychiatry》

Causal relationship between gastro-esophageal reflux disease and risk of lung cancer: insights from multivariable Mendelian randomization and mediation analysis.

A recent study has reported that anti-reflux surgery reduced the risk of lung cancer. However, the exact causal association between gastro-esophageal reflux disease (GORD) and lung cancer remains obscure. Therefore, we conducted a multivariable and network Mendelian randomization (MR) study to explore this potential association and mediation effect. Independent single nucleotide polymorphisms (SNPs) strongly associated with GORD were selected as instrumental variables (IVs) from the corresponding genome-wide association studies (GWAS). The summary statistics were obtained from the largest GORD GWAS meta-analysis of 367 441 (78 707 cases) European individuals, and the summary statistics of lung cancer and pathological subtypes came from International Lung Cancer Consortium (ILCCO) and FinnGen databases. Univariable and multivariable MR analyses were performed to investigate and verify the causal relationship between genetically predicted GORD and lung cancer. Network MR analysis was conducted to reveal the mediating role of GORD between smoking initiation and lung cancer. The univariable MR analysis demonstrated that GORD was associated with an increased risk of total lung cancer in both ILCCO [inverse variance weighted (IVW): odds ratio (OR) = 1.37, 95% confidence interval (CI) 1.16-1.62, P = 1.70E-04] and FinnGen database (IVW: OR = 1.25, 95% confidence interval CI 1.03-1.52, P = 2.27E-02). The consistent results were observed after adjusting the potential confounders [smoking traits, body mass index (BMI) and type 2 diabetes] in multivariable MR analyses. In subtype analyses, GORD was associated with lung adenocarcinoma (IVW: OR = 1.27, 95% CI 1.02-1.59, P = 3.48E-02) and lung squamous cell carcinomas (IVW: OR = 1.50, 95% CI 1.22-1.86, P = 1.52E-04). Moreover, GORD mediated 32.43% (95% CI 14.18-49.82%) and 25.00% (95% CI 3.13-50.00%) of the smoking initiation effects on lung cancer risk in the ILCCO and FinnGen databases, respectively. This study provides credible evidence that genetically predicted GORD was significantly associated with an increased risk of total lung cancer, lung adenocarcinoma and lung squamous cell carcinomas. Furthermore, our results suggest GORD is involved in the mechanism of smoking initiation-induced lung cancer.

Liu Y ，Lai H ，Zhang R ，Xia L ，Liu L ... -  《-》

[Causal relationship between obesity and male infertility: A two-sample Mendelian randomization study].

Li ZC ，Teng ZH ，Han ZW ，Zhang YP ，Jin CG ，Wang YX ... -  《-》

Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study.

Carreras-Torres R ，Johansson M ，Haycock PC ，Wade KH ，Relton CL ，Martin RM ，Davey Smith G ，Albanes D ，Aldrich MC ，Andrew A ，Arnold SM ，Bickeböller H ，Bojesen SE ，Brunnström H ，Manjer J ，Brüske I ，Caporaso NE ，Chen C ，Christiani DC ，Christian WJ ，Doherty JA ，Duell EJ ，Field JK ，Davies MPA ，Marcus MW ，Goodman GE ，Grankvist K ，Haugen A ，Hong YC ，Kiemeney LA ，van der Heijden EHFM ，Kraft P ，Johansson MB ，Lam S ，Landi MT ，Lazarus P ，Le Marchand L ，Liu G ，Melander O ，Park SL ，Rennert G ，Risch A ，Haura EB ，Scelo G ，Zaridze D ，Mukeriya A ，Savić M ，Lissowska J ，Swiatkowska B ，Janout V ，Holcatova I ，Mates D ，Schabath MB ，Shen H ，Tardon A ，Teare MD ，Woll P ，Tsao MS ，Wu X ，Yuan JM ，Hung RJ ，Amos CI ，McKay J ，Brennan P ... -  《-》