Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep 20;10(18):e38130.
doi: 10.1016/j.heliyon.2024.e38130. eCollection 2024 Sep 30.

A cause-effect relationship between uterine diseases and breast cancer: A bidirectional Mendelian randomization study

Zhipeng Liu  1 , Min Jiang  2 , Taiyu Wang  1 , Fang Li  1 , Yinxing Zhu  1
Affiliations

A cause-effect relationship between uterine diseases and breast cancer: A bidirectional Mendelian randomization study

Zhipeng Liu et al. Heliyon. .

Abstract

Objective: To explore the cause-effect relationship between uterine diseases (UDs) and breast cancer (BC) and underlying mechanism of the cause-effect relationship, enhance understanding of the association between BC and UDs.

Methods: A two-sample bidirectional Mendelian randomization (MR) analysis was conducted. We obtained summary statistics data from GWAS for BC, endometriosis, endometrial cancer (EC), uterine leiomyoma (UL), uterine polyps (UP), and cervical cancer (CC). Independent SNPs were selected as instrumental variables (IVs) for each disease. The inverse variance weighted (IVW) method was primary used for estimating the causal association between UDs and BC. To further evaluate the consistency and dependability of the results, we also utilized the weighted median, weighted mode, simple mode, and MR-Egger methods, along with sensitivity analyses. Furthermore, a supplementary analysis focusing on the variants linked to BC and UDs was conducted. This involved identifying corresponding genes and subsequently performing KEGG/GO analyses to investigate potential molecular mechanisms.

Results: The results indicated significant associations between genetic susceptibility to endometriosis, EC, and UL with BC risk. The odds ratios (ORs) were as follows: endometriosis at 0.963 (95 % CI, 0.942-0.984; p = 7.11e-5), EC at 1.056 (95 % CI, 1.033-1.081; p = 2.39e-6), and UL at 1.027 (95 % CI, 1.006-1.048; p = 0.010). Conversely, the predisposition to BC inferred from genetic factors was markedly correlated with an elevated risk of EC indicated by an OR of 1.066 (95 % CI, 1.019-1.116; p = 0.006), and was correlated with UP risk (OR, 1.001,95 % CI, 1.000-1.002; p = 0.001).Sensitivity analyses provided weak evidence for these effects, suggesting that the study's outcomes are consistent and trustworthy. Further analysis of the genetic variants associated with BC, and these related genes are enriched in Cellular senescence, GnRH secretion, Phosphatidylinositol signaling system, and so on.

Conclusion: This study corroborates the existence of a reciprocal causal relationship between BC and EC, as well as highlighting the substantial correlations between a genetic susceptibility to UL and endometriosis with BC. BC may exert their influence on EC and UP through Cellular senescence, GnRH secretion, and other pathways. These discoveries offer fresh perspectives on the genetic pathogenesis of BC and UDs, and can guide future experimental studies. Additionally, they lay down a groundwork for the development of tailored preventative and therapeutic strategies moving forward.

Keywords: Breast cancer; Causal association; Mendelian randomization; Uterine diseases.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Schematic representation of the MR procedure.
Fig. 2
Fig. 2
Associations of uterine diseases with risk of breast cancer.
Fig. 3
Fig. 3
Associations of breast cancer with risk of uterine diseases.
Fig. 4
Fig. 4
Enrichment analysis of BC-related genes (A)Venn diagram of common genes (B) GO/KEGG enrichment analysis.
Fig. 5
Fig. 5
Associations of ER-breast cancer and ER + breast cancer with risk of endometrial cancer.
Fig. 6
Fig. 6
The association between specific uterine diseases and breast cancer.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Siegel R.L., Miller K.D., Wagle N.S., Jemal A. Cancer statistics. Ca - Cancer J. Clin. 2023;73:17–48. 2023. - PubMed
    1. Larsson S.C., Kar S., Perry J., Carter P., Vithayathil M., Mason A.M., Easton D.F., Burgess S. Serum estradiol and 20 site-specific cancers in women: mendelian randomization study. J. Clin. Endocrinol. Metab. 2022;107:e467–e474. - PMC - PubMed
    1. Johansson A., Schmitz D., Hoglund J., Hadizadeh F., Karlsson T., Ek W.E. Investigating the effect of estradiol levels on the risk of breast, endometrial, and ovarian cancer. J Endocr Soc. 2022;6:bvac100. - PMC - PubMed
    1. Wu X., Zhang W., Zhao X., Zhang L., Xu M., Hao Y., Xiao J., Zhang B., Li J., Kraft P., Smoller J.W., Jiang X. Investigating the relationship between depression and breast cancer: observational and genetic analyses. BMC Med. 2023;21:170. - PMC - PubMed
    1. Hoffman S.R., Farland L.V., Doll K.M., Nicholson W.K., Wright M.A., Robinson W.R. The epidemiology of gynaecologic health: contemporary opportunities and challenges. J. Epidemiol. Community Health. 2020;75:398–401. - PMC - PubMed

LinkOut - more resources