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甲状腺癌对第二原发恶性肿瘤的因果效应：来自英国生物银行和芬兰基因队列的研究结果。

Causal effect of thyroid cancer on secondary primary malignancies: findings from the UK Biobank and FinnGen cohorts.

机构信息

Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Shanghai Center of Thyroid Diseases, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

出版信息

Front Immunol. 2024 Sep 26;15:1434737. doi: 10.3389/fimmu.2024.1434737. eCollection 2024.

DOI:10.3389/fimmu.2024.1434737
PMID:39391305
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11464368/
Abstract

BACKGROUND

Existing epidemiological data indicated a correlation between thyroid cancer (THCA) and the risk of secondary primary malignancies (SPMs). However, the correlation does not always imply causality.

METHODS

The Mendelian randomization (MR) analyses were performed to investigate the causal relationships between THCA and SPMs based on international multicenter data. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. The Cancer Genome Atlas (TCGA) was used to explore potential mechanisms shared by THCA and bladder cancer (BLCA).

RESULTS

Summary datasets of genome-wide association studies (GWAS) on 30 types of cancers were obtained from the United Kingdom Biobank (UKB) and FinnGen database. Meta-analysis of the UKB and FinnGen results revealed that THCA was significantly positively correlated with BLCA (OR = 1.140; 95% CI, 1.072-1.212; P < 0.001). Four genes, including WNT3, FAM171A2, MLLT11, and ULBP1, were identified as key genes shared by both TCHA and BLCA. Correlation analysis indicated that THCA may increase the risk of secondary BLCA through augmentation of N2 neutrophil infiltration.

CONCLUSIONS

This study showed that THCA was causally related to BLCA. It is recommended to conduct more rigorous screenings for BLCA during the follow-up of THCA patients.

摘要

背景

现有流行病学数据表明甲状腺癌 (THCA) 与第二原发恶性肿瘤 (SPM) 的风险之间存在相关性。然而，相关性并不总是意味着因果关系。

方法

基于国际多中心数据，采用孟德尔随机化 (MR) 分析来研究 THCA 和 SPM 之间的因果关系。计算了比值比 (OR) 及其 95%置信区间 (95%CI)。采用癌症基因组图谱 (TCGA) 来探讨 THCA 和膀胱癌 (BLCA) 之间可能存在的共同机制。

结果

从英国生物库 (UKB) 和芬兰遗传 (FinnGen) 数据库中获得了 30 种癌症的全基因组关联研究 (GWAS) 的汇总数据集。UKB 和 FinnGen 结果的荟萃分析表明，THCA 与 BLCA 显著正相关 (OR = 1.140; 95%CI，1.072-1.212; P < 0.001)。鉴定出 WNT3、FAM171A2、MLLT11 和 ULBP1 等 4 个关键基因在 THCA 和 BLCA 中共享。相关性分析表明，THCA 可能通过增加 N2 中性粒细胞浸润来增加发生继发性 BLCA 的风险。

结论

本研究表明 THCA 与 BLCA 之间存在因果关系。建议在 THCA 患者的随访过程中对 BLCA 进行更严格的筛查。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cec/11464368/93ad6194d485/fimmu-15-1434737-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cec/11464368/d12b18fcd3b2/fimmu-15-1434737-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cec/11464368/ccde01f8876a/fimmu-15-1434737-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cec/11464368/93cbf99e3c86/fimmu-15-1434737-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cec/11464368/81d800df5251/fimmu-15-1434737-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cec/11464368/47b81f7f82bf/fimmu-15-1434737-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cec/11464368/93ad6194d485/fimmu-15-1434737-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cec/11464368/d12b18fcd3b2/fimmu-15-1434737-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cec/11464368/ccde01f8876a/fimmu-15-1434737-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cec/11464368/93cbf99e3c86/fimmu-15-1434737-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cec/11464368/81d800df5251/fimmu-15-1434737-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cec/11464368/47b81f7f82bf/fimmu-15-1434737-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cec/11464368/93ad6194d485/fimmu-15-1434737-g006.jpg

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