Plasma ghrelin and risks of sex-specific, site-specific, and early-onset colorectal cancer: A Mendelian randomization analysis.

IF 3.7 3区医学 Q2 ONCOLOGY Cancer Epidemiology Biomarkers & Prevention Pub Date : 2024-10-03 DOI:10.1158/1055-9965.EPI-24-0926

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

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Abstract

Background: Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer (CRC) development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and CRC 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 CRC 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 CRC 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 CRC.

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 CRC risk.

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

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血浆胃泌素与性别特异性、部位特异性和早发性结直肠癌的风险：孟德尔随机分析

背景：关于胃泌素在结直肠癌（CRC）发病中的作用，流行病学和实验室研究提供了相互矛盾的证据。我们进行了双样本孟德尔随机化（MR）分析，以评估循环胃泌素与总体 CRC 风险以及与性别、癌症分部位和诊断年龄相关的证据：代理血浆总胃泌素水平的遗传工具来自最近一项对 54,219 名参与者进行的全基因组关联研究。有关 CRC 风险的汇总数据来自最近对几个基因联盟（多达 73,673 例病例和 86,854 例对照）的荟萃分析。我们采用了双样本 MR 方法和几种敏感性分析：结果：我们发现，没有证据表明基因预测的血浆总胃泌素水平与 CRC 风险有关（0.95，95% 置信区间：0.81-1.12；胃泌素基因工具的 R2：4.6%）：结论：我们的研究表明，血浆总胃泌素水平与癌症风险之间的关系是不确定的（0.95，95% 置信区间：0.81-1.12；胃泌素基因工具的 R2：4.6%）：我们的研究表明，血浆胃泌素水平不太可能与总体、早发、按性别和癌症亚部位分层的 CRC 风险有因果关系：这项大规模分析补充了越来越多的证据，即血浆总胃泌素水平与 CRC 风险无关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Epidemiology Biomarkers & Prevention 医学-公共卫生、环境卫生与职业卫生

CiteScore

6.50

自引率

2.60%

发文量

538

审稿时长

1.6 months

期刊介绍： Cancer Epidemiology, Biomarkers & Prevention publishes original peer-reviewed, population-based research on cancer etiology, prevention, surveillance, and survivorship. The following topics are of special interest: descriptive, analytical, and molecular epidemiology; biomarkers including assay development, validation, and application; chemoprevention and other types of prevention research in the context of descriptive and observational studies; the role of behavioral factors in cancer etiology and prevention; survivorship studies; risk factors; implementation science and cancer care delivery; and the science of cancer health disparities. Besides welcoming manuscripts that address individual subjects in any of the relevant disciplines, CEBP editors encourage the submission of manuscripts with a transdisciplinary approach.