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个人放射史与乳腺癌风险:一项孟德尔随机研究。

Personal history of irradiation and risk of breast cancer: A Mendelian randomisation study.

出版信息

J Glob Health. 2024 Oct 11;14:04106. doi: 10.7189/jogh.14.04106.

DOI:10.7189/jogh.14.04106
PMID:39391896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11467774/
Abstract

BACKGROUND

Studies on the relationship between personal history of irradiation and breast cancer have been reported for a long time. Still, epidemiological studies have not been conclusive, and the causal relationship is unclear. To address this issue, we employed Mendelian randomisation (MR) analysis to examine the association between individual radiation exposure history and breast cancer.

METHODS

We used a series of quality control methods to select single nucleotide polymorphism (SNP) closely related to exposure. Meanwhile, several analysis methods were used to analyse the sample data to make the conclusion more reliable. To evaluate the horizontal pleiotropy, heterogeneity and stability of SNPs for breast cancer, the MR-Egger intercept test, Cochran's Q test and 'leave one' sensitivity analysis were used. Finally, the outlier variation determined by the Mendelian Randomisation Pleiotropy RESidual Sum and Outlier test is gradually eliminated to reduce the influence of heterogeneity and horizontal pleiotropy.

RESULTS

After implementing rigorous quality control procedures, we carefully chose 102 qualified instrumental variables closely associated with the selected exposure for sensitivity analysis. This was conducted to evaluate the heterogeneity, level multiplicity, and stability of SNPs in the context of personal radiation history and its correlation with breast cancer. The results of the inverse variance weighted method analysis revealed a positive correlation between personal radiation and a heightened risk of breast cancer (odds ratio (OR) = 1.52; 95% confidence interval (CI) = 1.30-1.77). We also validated on another data set; the results were similar (OR = 1.51; 95% CI = 1.27-1.81). Furthermore, the findings from the sensitivity analysis were consistent. At the genetic level, our research demonstrated that personal radiation exposure is associated with an elevated risk of breast cancer.

CONCLUSIONS

Using genetic data provides evidence and strengthens the causal link that personal radiation causes breast cancer.

摘要

背景

个人辐射史与乳腺癌之间的关系的研究已经有很长一段时间了。然而,流行病学研究仍没有定论,因果关系也不清楚。为了解决这个问题,我们采用孟德尔随机化(MR)分析来检验个体辐射暴露史与乳腺癌之间的关联。

方法

我们使用了一系列质量控制方法来选择与暴露密切相关的单核苷酸多态性(SNP)。同时,使用了几种分析方法来分析样本数据,以使其结论更加可靠。为了评估 SNPs 对乳腺癌的水平多效性、异质性和稳定性,我们使用了 MR-Egger 截距检验、Cochran's Q 检验和“leave one”敏感性分析。最后,通过 Mendelian Randomisation Pleiotropy RESidual Sum and Outlier 检验确定的异常值变异逐渐消除,以减少异质性和水平多效性的影响。

结果

在实施严格的质量控制程序后,我们仔细选择了 102 个与所选暴露密切相关的合格工具变量进行敏感性分析,以评估个人辐射史及其与乳腺癌相关性的 SNP 异质性、水平多重性和稳定性。逆方差加权法分析的结果显示,个人辐射与乳腺癌风险升高呈正相关(比值比(OR)=1.52;95%置信区间(CI)=1.30-1.77)。我们还在另一个数据集上进行了验证,结果相似(OR=1.51;95%CI=1.27-1.81)。此外,敏感性分析的结果也是一致的。在遗传水平上,我们的研究表明个人辐射暴露与乳腺癌风险升高有关。

结论

使用遗传数据提供了证据,并加强了个人辐射导致乳腺癌的因果关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d542/11467774/cfd4977c0f05/jogh-14-04106-F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d542/11467774/e4f679c7ee70/jogh-14-04106-F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d542/11467774/8e155bb029ea/jogh-14-04106-F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d542/11467774/211a99287aad/jogh-14-04106-F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d542/11467774/0b090b1df0d9/jogh-14-04106-F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d542/11467774/cfd4977c0f05/jogh-14-04106-F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d542/11467774/e4f679c7ee70/jogh-14-04106-F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d542/11467774/8e155bb029ea/jogh-14-04106-F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d542/11467774/211a99287aad/jogh-14-04106-F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d542/11467774/0b090b1df0d9/jogh-14-04106-F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d542/11467774/cfd4977c0f05/jogh-14-04106-F5.jpg

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