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探讨类风湿关节炎与宫颈癌风险之间的因果关联:两样本孟德尔随机化研究。

Exploring the causal association between rheumatoid arthritis and the risk of cervical cancer: a two-sample Mendelian randomization study.

机构信息

Department of Oncology, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, People's Republic of China.

Department of Radiation Oncology, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, Hunan Province, People's Republic of China.

出版信息

Arthritis Res Ther. 2024 Jan 23;26(1):35. doi: 10.1186/s13075-023-03240-2.

Abstract

OBJECTIVE

Whether rheumatoid arthritis patients have an increased risk of cervical cancer remains controversial, and further research is needed on this clinical question. This study aims to investigate the association between rheumatoid arthritis and the susceptibility to cervical cancer by employing Mendelian randomization methodology, utilizing the extensive dataset from human genome-wide association data analysis.

METHODS

The publicly accessible MR base database was utilized to obtain the complete genome, relevant research findings, and summarized data pertaining to rheumatoid arthritis and cervical cancer. Genetic tool variables, specifically single-nucleotide polymorphisms closely linked to rheumatoid arthritis, were chosen for analysis. Four methods, namely inverse variance weighted analysis, weighted median analysis, weighted mode, and MR-Egger regression, were employed. Statistical analysis was conducted to explore the potential association between rheumatoid arthritis and susceptibility to cervical cancer.

RESULTS

The results of the inverse variance weighted analysis (OR = 1.096, 95% CI: 1.018-1.180, P = 0.015) indicate a significant causal relationship between rheumatoid arthritis and an increased risk of cervical cancer. Furthermore, the absence of horizontal pleiotropic effects (MR-Egger intercept = 0.00025, P = 0.574) and heterogeneity (QEgger = 2.239, I2Egger = 0.225, PEgger = 0.268, QIVW = 2.734, I2IVW = 0.220, PIVW = 0.999) suggests that the observed association is not influenced by confounding factors. Sensitivity analysis and other statistical methods also support the conclusion that genetic pleiotropy does not introduce bias to the findings.

CONCLUSION

There is a causal relationship between rheumatoid arthritis and the occurrence of cervical cancer. People with rheumatoid arthritis is one of the high-risk groups for early screening of cervical cancer. The IL-18 may play a significant role in elevating the risk of cervical cancer among rheumatoid arthritis patients.

摘要

目的

类风湿关节炎患者罹患宫颈癌的风险是否增加仍存在争议,针对这一临床问题还需要开展进一步的研究。本研究旨在利用人类全基因组关联数据分析的大型数据集,采用孟德尔随机化方法探讨类风湿关节炎与宫颈癌易感性之间的关联。

方法

利用公开的 MR 基础数据库获取全基因组范围内与类风湿关节炎和宫颈癌相关的研究发现和汇总数据,并选择与类风湿关节炎紧密连锁的单核苷酸多态性作为遗传工具变量进行分析。采用逆方差加权分析、加权中位数分析、加权模式分析和 MR-Egger 回归分析 4 种方法进行统计分析,以探讨类风湿关节炎与宫颈癌易感性之间的潜在关联。

结果

逆方差加权分析(OR=1.096,95%CI:1.018-1.180,P=0.015)的结果表明,类风湿关节炎与宫颈癌风险增加之间存在显著的因果关系。此外,不存在水平的异质性(MR-Egger 截距=0.00025,P=0.574)和偏倚(QEgger=2.239,I2Egger=0.225,PEgger=0.268,QIVW=2.734,I2IVW=0.220,PIVW=0.999),表明观察到的关联不受混杂因素的影响。敏感性分析和其他统计方法也支持遗传异质性不会给研究结果带来偏差的结论。

结论

类风湿关节炎与宫颈癌的发生之间存在因果关系。类风湿关节炎患者属于宫颈癌早期筛查的高危人群之一。白细胞介素-18 可能在升高类风湿关节炎患者宫颈癌风险方面发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60a7/10804645/379a9358ed8e/13075_2023_3240_Fig1_HTML.jpg

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