Genetic Evidence for a Causal Relationship Between Innate Leukocytes and the Risk of Digestive System Cancers in East Asians and Europeans.

IF 2.1 Q3 ONCOLOGY

World Journal of Oncology Pub Date : 2024-06-01 Epub Date: 2024-05-07 DOI:10.14740/wjon1860

Jia Hao Zhu, Ben Jie Xu, Xiang Yi Pang, Jie Lian, Ke Gu, Sheng Jun Ji, Hai Bo Lu

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引用次数: 0

Abstract

Background: Peripheral traditional immune cell disorder plays an important role in cancer onset and development. The causal relationships between leukocytes prior to cancer and the risk of digestive system cancer remain unknown. This study assesses the causal correlations between leukocytes and digestive system cancer risk in East Asians and Europeans.

Methods: Summary-level data on leukocyte-related genetic variation were extracted from Biobank Japan (107,964 participants) and a recent large-scale meta-analysis (563,946 participants). Summary-level data for the cancers were obtained from Biobank Japan (212,978 individuals) and the FinnGen consortium (178,802 participants). Univariable and multivariable Mendelian randomization (MR) analyses were performed on East Asians and Europeans separately.

Results: Univariable MR analysis demonstrated the significant association between circulating eosinophil counts and risk of colorectal cancer (CRC) in East Asians (odds ratio (OR) = 0.80, 95% confidence interval (CI): 0.69 - 0.92, P = 0.002) and a suggestive relationship in the European population (OR = 0.86, 95% CI: 0.77 - 0.97, P = 0.013). An inverse suggestive association was observed between levels of basophils and the risk of gastric cancer (GC) in East Asians (OR = 0.83, 95% CI: 0.72 - 0.97, P = 0.019). The multivariable MR analysis showed the independent causal effect of eosinophil count on CRC risk in East Asians (OR = 0.72, 95% CI: 0.57 - 0.92, P = 0.009) and Europeans (OR = 0.80, 95% CI: 0.70 - 0.92, P = 0.002). Circulating basophils served as the negative causal factor in GC risk in East Asians (OR = 0.80, 95% CI: 0.67 - 0.94, P = 0.007).

Conclusions: Our MR analyses revealed a genetic causal relationship between reduced blood eosinophils and an increased CRC risk in both Europeans and East Asians. Furthermore, our results suggested a causal association between decreased basophils and an elevated GC risk specifically in East Asians.

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先天性白细胞与东亚人和欧洲人罹患消化系统癌症风险之间因果关系的遗传学证据》（Genetic Evidence for a Causal Relationship Between Innate Leukocytes and Risk of Digestive System Cancers in East Asians and Europeans）。

背景：外周传统免疫细胞紊乱在癌症的发生和发展中起着重要作用。癌症前白细胞与消化系统癌症风险之间的因果关系仍然未知。本研究评估了东亚人和欧洲人的白细胞与消化系统癌症风险之间的因果关系：从日本生物库（107964 名参与者）和最近的大规模荟萃分析（563946 名参与者）中提取了白细胞相关遗传变异的汇总数据。癌症的汇总数据来自日本生物库（212 978 人）和芬兰基因联盟（178 802 人）。对东亚人和欧洲人分别进行了单变量和多变量孟德尔随机化（MR）分析：单变量 MR 分析表明，在东亚人中，循环嗜酸性粒细胞计数与结直肠癌（CRC）风险之间存在显著关联（比值比 (OR) = 0.80，95% 置信区间 (CI)：0.69 - 0.92，P = 0.002），而在欧洲人群中，两者之间存在提示关系（OR = 0.86，95% CI：0.77 - 0.97，P = 0.013）。在东亚人中，嗜碱性粒细胞水平与胃癌（GC）风险之间呈反向提示关系（OR = 0.83，95% CI：0.72 - 0.97，P = 0.019）。多变量 MR 分析显示，嗜酸性粒细胞数量对东亚人（OR = 0.72，95% CI：0.57 - 0.92，P = 0.009）和欧洲人（OR = 0.80，95% CI：0.70 - 0.92，P = 0.002）的 CRC 风险具有独立的因果效应。在东亚人中，循环中的嗜碱性粒细胞是GC风险的负因果因素（OR = 0.80，95% CI：0.67 - 0.94，P = 0.007）：我们的磁共振分析表明，在欧洲人和东亚人中，血液中嗜酸性粒细胞减少与 CRC 风险增加之间存在遗传因果关系。此外，我们的结果还表明，嗜碱性粒细胞减少与东亚人的 GC 风险升高之间存在因果关系。

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来源期刊

World Journal of Oncology ONCOLOGY-

CiteScore

6.10

自引率

15.40%

发文量

期刊介绍： World Journal of Oncology, bimonthly, publishes original contributions describing basic research and clinical investigation of cancer, on the cellular, molecular, prevention, diagnosis, therapy and prognosis aspects. The submissions can be basic research or clinical investigation oriented. This journal welcomes those submissions focused on the clinical trials of new treatment modalities for cancer, and those submissions focused on molecular or cellular research of the oncology pathogenesis. Case reports submitted for consideration of publication should explore either a novel genomic event/description or a new safety signal from an oncolytic agent. The areas of interested manuscripts are these disciplines: tumor immunology and immunotherapy; cancer molecular pharmacology and chemotherapy; drug sensitivity and resistance; cancer epidemiology; clinical trials; cancer pathology; radiobiology and radiation oncology; solid tumor oncology; hematological malignancies; surgical oncology; pediatric oncology; molecular oncology and cancer genes; gene therapy; cancer endocrinology; cancer metastasis; prevention and diagnosis of cancer; other cancer related subjects. The types of manuscripts accepted are original article, review, editorial, short communication, case report, letter to the editor, book review.