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血浆胃饥饿素与性别特异性、部位特异性及早发性结直肠癌风险：一项孟德尔随机化分析

Plasma Ghrelin and Risks of Sex-Specific, Site-Specific, and Early-Onset Colorectal Cancer: A Mendelian Randomization Analysis.

作者信息

Hazelwood Emma, Lopez Manzano Catalina, Vincent Emma E, Albanes Demetrius, Bishop David Timothy, Le Marchand Loïc, Ulrich Cornelia M, Peters Ulrike, Murphy Gwen, Samadder Niloy Jewel, Anderson Laura, Gunter Marc J, Murphy Neil, Van Guelpen Bethany, Papadimitriou Nikos

机构信息

MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.

出版信息

Cancer Epidemiol Biomarkers Prev. 2024 Dec 2;33(12):1727-1732. doi: 10.1158/1055-9965.EPI-24-0926.

DOI:10.1158/1055-9965.EPI-24-0926
PMID:39361354
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11609820/
Abstract

BACKGROUND

Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and colorectal cancer risk overall and by sex, cancer subsite, and age at diagnosis.

METHODS

Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for colorectal cancer risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied.

RESULTS

We found no evidence for an association of genetically predicted plasma total ghrelin levels and colorectal cancer risk (0.95, 95% confidence interval, 0.81-1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset colorectal cancer.

CONCLUSIONS

Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified colorectal cancer risk.

IMPACT

This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with colorectal cancer risk.

摘要

背景

基于流行病学和实验室的研究对于胃饥饿素在结直肠癌发生中的作用提供了相互矛盾的证据。我们进行了两样本孟德尔随机化（MR）分析，以评估循环胃饥饿素与总体结直肠癌风险以及按性别、癌症亚部位和诊断年龄分层的结直肠癌风险之间关联的证据。

方法

从最近一项对54219名参与者的全基因组关联研究中获得了代表血浆总胃饥饿素水平的遗传工具。结直肠癌风险的汇总数据来自最近对几个遗传联盟的荟萃分析（多达73673例病例和86854名对照）。应用了两样本MR方法和几种敏感性分析。

结果

我们没有发现遗传预测的血浆总胃饥饿素水平与结直肠癌风险之间存在关联的证据（比值比为0.95，95%置信区间为0.81 - 1.12；胃饥饿素遗传工具的R2为4.6%），按性别、解剖亚部位分层以及对早发性结直肠癌进行分析时也观察到类似的阴性结果。

结论

我们的研究表明，血浆胃饥饿素水平不太可能与总体、早发性以及按性别和癌症亚部位分层的结直肠癌风险存在因果关系。

影响

这项大规模分析进一步增加了越来越多的证据，即血浆总胃饥饿素水平与结直肠癌风险无关。