感染对上皮性卵巢癌风险的因果效应评估：一项两样本孟德尔随机化研究。
Appraisal of the causal effect of infection on epithelial ovarian cancer risk: a two-sample Mendelian randomisation study.
作者信息
Perrott Sarah L, Kar Siddhartha P
机构信息
Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom.
出版信息
medRxiv. 2024 Oct 14:2024.10.13.24315417. doi: 10.1101/2024.10.13.24315417.
BACKGROUND
History of infection has previously been associated with epithelial ovarian cancer (EOC) in observational studies. We conducted a two-sample univariable Mendelian randomisation (MR) study to examine whether genetically predicted seropositivity to the major outer membrane protein (momp) D is causally associated with EOC.
METHODS
MR analyses employed genetic associations derived from UK Biobank as proxies for momp D seropositivity in 25 509 EOC cases and 40 941 controls that participated in the Ovarian Cancer Association Consortium. Findings were replicated using a GWAS meta-analyses of global biobanks including the UK Biobank, FinnGen and BioBank Japan.
RESULTS
Genetically predicted momp D seropositivity was associated with overall and high-grade serous EOC risk in inverse-variance weighted (IVW) and MR-Egger univariable MR analysis (odds ratio (OR) 1.06; 95% confidence interval (CI) 1.02-1.10, and OR 1.08; 95%CI 1.01-1.16, respectively). Replication yielded similar results for overall EOC (OR 1.11; 95%CI 1.01-1.22).
CONCLUSION
This MR study supports a causative link between infection and overall and high-grade serous EOC.
背景
在观察性研究中，既往感染史与上皮性卵巢癌（EOC）有关。我们进行了一项两样本单变量孟德尔随机化（MR）研究，以检验基因预测的对主要外膜蛋白（momp）D的血清学阳性是否与EOC存在因果关系。
方法
MR分析采用来自英国生物银行的基因关联作为25509例EOC病例和40941例对照中momp D血清学阳性的替代指标，这些病例和对照参与了卵巢癌协会联盟。研究结果通过对包括英国生物银行、芬兰基因库和日本生物银行在内的全球生物银行的GWAS荟萃分析进行了重复验证。
结果
在逆方差加权（IVW）和MR-Egger单变量MR分析中，基因预测的momp D血清学阳性与总体和高级别浆液性EOC风险相关（优势比（OR）分别为1.06；95%置信区间（CI）为1.02-1.10，以及OR为1.08；95%CI为1.01-1.16）。对总体EOC的重复验证得到了相似的结果（OR为1.11；95%CI为1.01-1.22）。
结论
这项MR研究支持感染与总体和高级别浆液性EOC之间存在因果联系。
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