PDF(Pubmed)
Abstract：
UNASSIGNED: Gallbladder cancer (GBC) is a rare malignancy of the digestive tract, characterized by a remarkably poor prognosis. Currently, there is a controversy on the relationship between type 2 diabetes (T2D) and GBC. Additionally, no definitive conclusions were established regarding the causal relationships between alcohol intake frequency (AIF), age at menarche (AAM) and GBC. The objective of this study was to elucidate the causal association between T2D, AIF, AAM, and GBC.
UNASSIGNED: Single-nucleotide polymorphisms (SNPs) associated with exposures and outcomes were sourced from the Integrative Epidemiology Unit (IEU) Open Genome-Wide Association Study (GWAS) database. Specifically, the data of GBC comprised 907 East Asians (pathological results of all cases were registered into Biobank Japan) and 425,707 SNPs; T2D comprised 655,666 Europeans with 5,030,727 SNPs; AIF comprised 462,346 Europeans and 9,851,867 SNPs; AAM comprised 243,944 Europeans and 9,851,867 SNPs. The measurement of exposure traits is collected uniformly from the UK Biobank (UKB) database and presented in the form of standard deviation (SD) or the logarithmic form of the odds ratio (logOR). We employed a two-sample Mendelian randomization (MR) analysis to discern the causalities between T2D, AIF, AAM, and GBC. Sensitivity analyses were conducted to identify and address potential heterogeneity, horizontal pleiotropy, and outliers.
UNASSIGNED: Our findings indicated that T2D reduced GBC risk [odds ratio (OR) =0.044; 95% confidence interval (CI): 0.004-0.55; P=0.015, inverse variance-weighted (IVW)]. However, no causal relationship was observed between AIF (OR =0.158; 95% CI: 5.33E-05 to 466.84; P=0.65, IVW), AAM (OR =0.19; 95% CI: 0.0003-140.34; P=0.62, IVW), and GBC. Sensitivity analysis revealed no evidence of horizontal pleiotropy, heterogeneity, or outliers, suggesting the robustness and reliability of our conclusions.
UNASSIGNED: T2D emerged as a potentially protective factor against GBC, whereas neither AIF nor AAM demonstrated a causal relationship with GBC risk. Regulation of glucose metabolism may be one of the methods for preventing GBC.
UNASSIGNED: Single-nucleotide polymorphisms (SNPs) associated with exposures and outcomes were sourced from the Integrative Epidemiology Unit (IEU) Open Genome-Wide Association Study (GWAS) database. Specifically, the data of GBC comprised 907 East Asians (pathological results of all cases were registered into Biobank Japan) and 425,707 SNPs; T2D comprised 655,666 Europeans with 5,030,727 SNPs; AIF comprised 462,346 Europeans and 9,851,867 SNPs; AAM comprised 243,944 Europeans and 9,851,867 SNPs. The measurement of exposure traits is collected uniformly from the UK Biobank (UKB) database and presented in the form of standard deviation (SD) or the logarithmic form of the odds ratio (logOR). We employed a two-sample Mendelian randomization (MR) analysis to discern the causalities between T2D, AIF, AAM, and GBC. Sensitivity analyses were conducted to identify and address potential heterogeneity, horizontal pleiotropy, and outliers.
UNASSIGNED: Our findings indicated that T2D reduced GBC risk [odds ratio (OR) =0.044; 95% confidence interval (CI): 0.004-0.55; P=0.015, inverse variance-weighted (IVW)]. However, no causal relationship was observed between AIF (OR =0.158; 95% CI: 5.33E-05 to 466.84; P=0.65, IVW), AAM (OR =0.19; 95% CI: 0.0003-140.34; P=0.62, IVW), and GBC. Sensitivity analysis revealed no evidence of horizontal pleiotropy, heterogeneity, or outliers, suggesting the robustness and reliability of our conclusions.
UNASSIGNED: T2D emerged as a potentially protective factor against GBC, whereas neither AIF nor AAM demonstrated a causal relationship with GBC risk. Regulation of glucose metabolism may be one of the methods for preventing GBC.
摘要：
■胆囊癌（GBC）是一种罕见的消化道恶性肿瘤，以预后极差为特征。目前,2型糖尿病（T2D）与GBC之间的关系存在争议。此外,关于酒精摄入频率(AIF)之间的因果关系没有明确的结论，初潮年龄（AAM）和GBC。这项研究的目的是阐明T2D之间的因果关系，AIF,AAM,GBC。
■与暴露和结果相关的单核苷酸多态性（SNP）来自综合流行病学单位（IEU）开放全基因组关联研究（GWAS）数据库。具体来说,GBC的数据包括907名东亚人(所有病例的病理结果均登记在日本Biobank)和425,707个SNP;T2D包括655,666名欧洲人和5,030,727个SNP;AIF包括462,346名欧洲人和9,851,867个SNP;AAM包括243,944名欧洲人和9,851,867个SNP。从英国生物库（UKB）数据库中统一收集暴露性状的测量值，并以标准偏差（SD）或比值比（logOR）的对数形式呈现。我们采用了双样本孟德尔随机化(MR)分析来辨别T2D之间的因果关系，AIF,AAM,GBC。进行了敏感性分析，以识别和解决潜在的异质性，水平多效性，和异常值。
■我们的发现表明T2D降低了GBC风险[比值比（OR）=0.044；95％置信区间（CI）：0.004-0.55；P=0.015，方差加权倒数（IVW）]。然而,AIF之间没有因果关系(OR=0.158;95%CI:5.33E-05至466.84;P=0.65,IVW),AAM（OR=0.19；95%CI：0.0003-140.34；P=0.62，IVW），GBC。敏感性分析显示没有水平多效性的证据，异质性，或异常值，表明了我们结论的稳健性和可靠性。
■T2D成为GBC的潜在保护因素，而AIF和AAM均未显示与GBC风险存在因果关系。调节葡萄糖代谢可能是预防GBC的方法之一。
■与暴露和结果相关的单核苷酸多态性（SNP）来自综合流行病学单位（IEU）开放全基因组关联研究（GWAS）数据库。具体来说,GBC的数据包括907名东亚人(所有病例的病理结果均登记在日本Biobank)和425,707个SNP;T2D包括655,666名欧洲人和5,030,727个SNP;AIF包括462,346名欧洲人和9,851,867个SNP;AAM包括243,944名欧洲人和9,851,867个SNP。从英国生物库（UKB）数据库中统一收集暴露性状的测量值，并以标准偏差（SD）或比值比（logOR）的对数形式呈现。我们采用了双样本孟德尔随机化(MR)分析来辨别T2D之间的因果关系，AIF,AAM,GBC。进行了敏感性分析，以识别和解决潜在的异质性，水平多效性，和异常值。
■我们的发现表明T2D降低了GBC风险[比值比（OR）=0.044；95％置信区间（CI）：0.004-0.55；P=0.015，方差加权倒数（IVW）]。然而,AIF之间没有因果关系(OR=0.158;95%CI:5.33E-05至466.84;P=0.65,IVW),AAM（OR=0.19；95%CI：0.0003-140.34；P=0.62，IVW），GBC。敏感性分析显示没有水平多效性的证据，异质性，或异常值，表明了我们结论的稳健性和可靠性。
■T2D成为GBC的潜在保护因素，而AIF和AAM均未显示与GBC风险存在因果关系。调节葡萄糖代谢可能是预防GBC的方法之一。
