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端粒长度与乳腺疾病之间的因果关系:一项两样本双向孟德尔随机化研究。

Causality between telomere length and breast diseases: a two-sample bidirectional Mendelian randomization study.

作者信息

Luo Simin, Chai Jie, Cai Yangyang, Ding Linxiaoxiao, Tang Song

机构信息

Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

The Second Department of General Surgery, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.

出版信息

Ann Med Surg (Lond). 2025 Jul 18;87(9):5551-5556. doi: 10.1097/MS9.0000000000003601. eCollection 2025 Sep.

Abstract

BACKGROUND

The relationship between telomere length and breast diseases remains unclear, with conflicting evidence for breast cancer. Using an innovative genetic approach, we were the first to comprehensively assess their bidirectional causal relationship.

METHODS

Telomere length, breast cancer, benign neoplasm of breast, and breast inflammation were extracted from the genome-wide Association study (GWAS) database as the basis for large-scale population studies. The interaction of telomere length and breast diseases as exposure and outcome factors was analyzed by Mendelian randomization (MR).

RESULTS

When telomere length was used as an exposure factor and breast diseases as an outcome, the value of MR was less than 0.05. Breast cancer (odds ratio (OR) = 1.130, 95% confidence interval (CI) = 1.047-1.219, = 0.0016), benign neoplasm of breast (OR = 1.002, 95%CI = 1.001-1.004, = 0.0007) and breast inflammation (OR = 1.487, 95%CI = 1.008-2.191, = 0.0453). When breast diseases were taken as an exposure factor and telomere length was taken as an outcome, the value of MR between breast cancer, benign neoplasm of breast, and telomere length was greater than 0.05, and breast inflammation could not be calculated by MR.

CONCLUSION

Telomere length is a risk factor for breast diseases, and longer telomeres increase the risk of breast cancer, benign neoplasm of breast, and breast inflammation. However, the reverse study showed no causal association between breast cancer, benign neoplasm of breast and telomere length, and the causal association between breast inflammation and telomere length was not clear. Moreover, further studies are needed to validate our findings in non-European populations.

摘要

背景

端粒长度与乳腺疾病之间的关系仍不明确,关于乳腺癌的证据相互矛盾。我们采用创新的遗传学方法,首次全面评估了它们之间的双向因果关系。

方法

从全基因组关联研究(GWAS)数据库中提取端粒长度、乳腺癌、乳腺良性肿瘤和乳腺炎症,作为大规模人群研究的基础。通过孟德尔随机化(MR)分析端粒长度与乳腺疾病作为暴露因素和结局因素之间的相互作用。

结果

以端粒长度作为暴露因素、乳腺疾病作为结局时,MR值小于0.05。乳腺癌(优势比(OR)=1.130,95%置信区间(CI)=1.047 - 1.219,P = 0.0016)、乳腺良性肿瘤(OR = 1.002,95%CI = 1.001 - 1.004,P = 0.0007)和乳腺炎症(OR = 1.487,95%CI = 1.008 - 2.191,P = 0.0453)。以乳腺疾病作为暴露因素、端粒长度作为结局时,乳腺癌、乳腺良性肿瘤与端粒长度之间的MR值大于0.05,乳腺炎症无法通过MR计算。

结论

端粒长度是乳腺疾病的危险因素,较长的端粒会增加患乳腺癌、乳腺良性肿瘤和乳腺炎症的风险。然而,反向研究表明乳腺癌、乳腺良性肿瘤与端粒长度之间无因果关联,乳腺炎症与端粒长度之间的因果关联不明确。此外,需要进一步研究在非欧洲人群中验证我们的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7253/12401384/b30f72d96430/ms9-87-5551-g001.jpg

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