PDF(Pubmed)
Abstract：
BACKGROUND: Inflammatory bowel disease (IBD), which includes Crohn\'s disease (CD) and ulcerative colitis (UC), has been associated with several cancer risks in observational studies, but the observed associations have been inconsistent and may face the bias of confounding and reverse causality. The potential causal relationships between IBD and the risk of cancers remain largely unclear.
METHODS: We performed genome-wide linkage disequilibrium score regression (LDSC), standard two-sample Mendelian randomization (MR), and colocalization analyses using summary genome-wide association study (GWAS) data across East Asian and European populations to evaluate the causal relationships between IBD and cancers. Sensitivity analyses for the MR approach were additionally performed to explore the stability of the results.
RESULTS: There were no significant genetic correlations between IBD, CD, or UC and cancers (all P values > 0.05) in East Asian or European populations. According to the main MR analysis, no significant causal relationship was observed between IBD and cancers in the East Asian population. There were significant associations between CD and ovarian cancer (odds ratio [OR] = 0.898, 95% CI = 0.844-0.955) and between UC and nonmelanoma skin cancer (OR = 1.002, 95% CI = 1.000-1.004, P = 0.019) in the European population. The multivariable MR analysis did not find any of the above significant associations. There was no shared causal variant to prove the associations of IBD, CD, or UC with cancers in East Asian or European populations using colocalization analysis.
CONCLUSIONS: We did not provide robust genetic evidence of causal associations between IBD and cancer risk. Exposure to IBD might not independently contribute to the risk of cancers, and the increased risk of cancers observed in observational studies might be attributed to factors accompanying the diagnosis of IBD.
METHODS: We performed genome-wide linkage disequilibrium score regression (LDSC), standard two-sample Mendelian randomization (MR), and colocalization analyses using summary genome-wide association study (GWAS) data across East Asian and European populations to evaluate the causal relationships between IBD and cancers. Sensitivity analyses for the MR approach were additionally performed to explore the stability of the results.
RESULTS: There were no significant genetic correlations between IBD, CD, or UC and cancers (all P values > 0.05) in East Asian or European populations. According to the main MR analysis, no significant causal relationship was observed between IBD and cancers in the East Asian population. There were significant associations between CD and ovarian cancer (odds ratio [OR] = 0.898, 95% CI = 0.844-0.955) and between UC and nonmelanoma skin cancer (OR = 1.002, 95% CI = 1.000-1.004, P = 0.019) in the European population. The multivariable MR analysis did not find any of the above significant associations. There was no shared causal variant to prove the associations of IBD, CD, or UC with cancers in East Asian or European populations using colocalization analysis.
CONCLUSIONS: We did not provide robust genetic evidence of causal associations between IBD and cancer risk. Exposure to IBD might not independently contribute to the risk of cancers, and the increased risk of cancers observed in observational studies might be attributed to factors accompanying the diagnosis of IBD.
摘要：
背景：炎症性肠病（IBD），其中包括克罗恩病（CD）和溃疡性结肠炎（UC），在观察性研究中与几种癌症风险有关，但观察到的关联并不一致,可能面临混淆和反向因果关系的偏倚.IBD与癌症风险之间的潜在因果关系仍不清楚。
方法：我们进行了全基因组连锁不平衡评分回归(LDSC)，标准双样本孟德尔随机化(MR)，和共定位分析使用总结全基因组关联研究(GWAS)数据在东亚和欧洲人群中评估IBD和癌症之间的因果关系。还对MR方法进行了敏感性分析，以探索结果的稳定性。
结果：IBD、CD,或UC和癌症（所有P值>0.05）在东亚或欧洲人群。根据主要的MR分析，在东亚人群中,未观察到IBD与癌症之间存在显著的因果关系.在欧洲人群中，CD与卵巢癌（比值比[OR]=0.898，95％CI=0.844-0.955）以及UC与非黑色素瘤皮肤癌（OR=1.002，95％CI=1.000-1.004，P=0.019）之间存在显着关联。多变量MR分析未发现任何上述显著关联。没有共同的因果变异来证明IBD的关联，CD,或UC在东亚或欧洲人群的癌症使用共定位分析。
结论：我们没有提供IBD与癌症风险之间因果关系的可靠遗传证据。接触IBD可能不会独立地导致癌症的风险，观察性研究中观察到的癌症风险增加可能归因于IBD诊断的相关因素。
方法：我们进行了全基因组连锁不平衡评分回归(LDSC)，标准双样本孟德尔随机化(MR)，和共定位分析使用总结全基因组关联研究(GWAS)数据在东亚和欧洲人群中评估IBD和癌症之间的因果关系。还对MR方法进行了敏感性分析，以探索结果的稳定性。
结果：IBD、CD,或UC和癌症（所有P值>0.05）在东亚或欧洲人群。根据主要的MR分析，在东亚人群中,未观察到IBD与癌症之间存在显著的因果关系.在欧洲人群中，CD与卵巢癌（比值比[OR]=0.898，95％CI=0.844-0.955）以及UC与非黑色素瘤皮肤癌（OR=1.002，95％CI=1.000-1.004，P=0.019）之间存在显着关联。多变量MR分析未发现任何上述显著关联。没有共同的因果变异来证明IBD的关联，CD,或UC在东亚或欧洲人群的癌症使用共定位分析。
结论：我们没有提供IBD与癌症风险之间因果关系的可靠遗传证据。接触IBD可能不会独立地导致癌症的风险，观察性研究中观察到的癌症风险增加可能归因于IBD诊断的相关因素。
