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不同性别欧洲人群中恶性淋巴瘤与乳腺癌的相关性研究:孟德尔随机化分析。

Correlation study of malignant lymphoma and breast Cancer in different gender European populations: mendelian randomization analysis.

机构信息

Department of General Surgery, Affiliated Changsha Hospital of Hunan Normal University, Changsha, 410000, China.

出版信息

BMC Genom Data. 2023 Oct 9;24(1):59. doi: 10.1186/s12863-023-01162-1.

Abstract

BACKGROUND

Previous research has already indicated an elevated risk of breast cancer (BC) among survivors of malignant lymphoma, but the underlying reasons remain unknown. Our objective is to elucidate the causal relationship between malignant lymphoma and BC through Mendelian randomization (MR). Genome-wide association studies (GWAS) data from 181,125 Hodgkin lymphoma (HL) patients and 181,289 non-Hodgkin lymphoma (NHL) patients from the FinnGen Consortium were utilized as exposure. We selected single nucleotide polymorphisms (SNPs) strongly associated with the exposure as instrumental variables to investigate their relationship with BC in a cohort of 107,722 participants. Subsequently, we obtained data from the UK Biobank containing gender-stratified information on HL, NHL, and BC. We validated the findings from our analysis and explored the impact of gender. The Inverse-Variance Weighted (IVW) method served as the primary reference for the two-sample MR, accompanied by tests for heterogeneity and pleiotropy.

RESULTS

The analysis results from the FinnGen consortium indicate that there is no causal relationship between HL and NHL with BC. HL (OR = 1.01, 95% CI = 0.98-1.04, p = 0.29), NHL (OR = 1.01, 95% CI = 0.96-1.05, p = 0.64). When utilizing GWAS data from the UK Biobank that includes different gender cohorts, the lack of association between HL, NHL, and BC remains consistent. HL (OR = 1.08, 95% CI = 0.74-1.56, p = 0.69), HL-Female (OR = 0.84, 95% CI = 0.59-1.19, p = 0.33), NHL (OR = 0.89, 95% CI = 0.66-1.19, p = 0.44), and NHL-Female (OR = 0.81, 95% CI = 0.58-1.11, p = 0.18).

CONCLUSIONS

The two-sample MR analysis indicates that there is no significant causal relationship between malignant lymphoma (HL and NHL) and BC. The association between malignant lymphoma and breast cancer requires further in-depth research and exploration.

摘要

背景

先前的研究已经表明恶性淋巴瘤幸存者患乳腺癌(BC)的风险增加,但潜在原因尚不清楚。我们的目的是通过孟德尔随机化(MR)阐明恶性淋巴瘤与 BC 之间的因果关系。利用 FinnGen 联盟中来自 181125 名霍奇金淋巴瘤(HL)患者和 181289 名非霍奇金淋巴瘤(NHL)患者的全基因组关联研究(GWAS)数据作为暴露因素。我们选择与暴露因素强烈相关的单核苷酸多态性(SNP)作为工具变量,以在一个包含 107722 名参与者的队列中研究它们与 BC 的关系。随后,我们从 UK Biobank 获得了包含 HL、NHL 和 BC 的性别分层信息的数据。我们验证了我们分析的结果并探讨了性别的影响。两样本 MR 的主要参考方法是逆方差加权(IVW)方法,同时还进行了异质性和多效性检验。

结果

FinnGen 联盟的分析结果表明,HL 和 NHL 与 BC 之间没有因果关系。HL(OR=1.01,95%CI=0.98-1.04,p=0.29),NHL(OR=1.01,95%CI=0.96-1.05,p=0.64)。当使用 UK Biobank 的 GWAS 数据时,该数据包含不同的性别队列,HL、NHL 和 BC 之间缺乏关联仍然一致。HL(OR=1.08,95%CI=0.74-1.56,p=0.69),HL-Female(OR=0.84,95%CI=0.59-1.19,p=0.33),NHL(OR=0.89,95%CI=0.66-1.19,p=0.44)和 NHL-Female(OR=0.81,95%CI=0.58-1.11,p=0.18)。

结论

两样本 MR 分析表明,恶性淋巴瘤(HL 和 NHL)与 BC 之间没有显著的因果关系。恶性淋巴瘤与乳腺癌之间的关联需要进一步深入研究和探讨。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c53/10561426/f1249e97e9dd/12863_2023_1162_Fig1_HTML.jpg

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