Causal Relationship Between Endometrial Cancer and Risk of Breast Cancer: A 2-sample Mendelian Randomization Study

Overview

Journal Medicine (Baltimore)

Specialty General Medicine

Date 2024 Jun 28

PMID 38941373

Authors

Ye Liu

Lichao Zhu

Lei Guo

Jianhai Zhao

Jiang Li

Wenying Li

Ziyun Li

Shuai Chen

Jiapeng Zheng

Yating Zhao

Affiliations

Soon will be listed here.

Abstract

Several studies have confirmed the important role of endometrial cancer (EC) in the development and progression of breast cancer (BC), and this study will explore the causal relationship between EC and BC by 2-sample Mendelian randomization analysis. Pooled data from published genome-wide association studies were used to assess the association between EC and BC risk in women using 5 methods, namely, inverse variance weighting (IVW), MR-Egger, weighted median (WME), simple multimaximetry (SM) and weighted multimaximetry (WM) with the EC-associated genetic loci as the instrumental variables (IV) and sensitivity analyses were used to assess the robustness of the results. The statistical results showed a causal association between EC and BC (IVW: OR = 1.07, 95% CI = 1.01-1.32, P = .02; MR-Egger: OR = 1.21, 95% CI = 0.71-1.51, P = .11; weighted median: OR = 1.05, 95% CI = 0.97-1.31, P = .19; simple plurality method: OR = 0.98, 95% CI = 0.81-1.15, P = .78; weighted plurality method: OR = 0.98, 95% CI = 0.81-1.14, P = .75), and the results of the sensitivity analyses showed that there was no significant heterogeneity or multiplicity, and the results were stable. EC is associated with an increased risk of developing BC. The results of this MR analysis can be used as a guideline for screening for BC in women with EC and to help raise awareness of screening for early detection and treatment.

References

Shomali N, Kamrani A, Heris J, Shahabi P, Nasiri H, Sadeghvand S . Dysregulation of P53 in breast cancer: Causative factors and treatment strategies. Pathol Res Pract. 2023; 247:154539. DOI: 10.1016/j.prp.2023.154539. View

Kappes H, Goemann C, Bamberger A, Loning T, Milde-Langosch K . PTEN expression in breast and endometrial cancer: correlations with steroid hormone receptor status. Pathobiology. 2002; 69(3):136-42. DOI: 10.1159/000048768. View

Pierce B, Burgess S . Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am J Epidemiol. 2013; 178(7):1177-84. PMC: 3783091. DOI: 10.1093/aje/kwt084. View

Boyko E . Observational research--opportunities and limitations. J Diabetes Complications. 2013; 27(6):642-8. PMC: 3818421. DOI: 10.1016/j.jdiacomp.2013.07.007. View

Lawlor D, Harbord R, Sterne J, Timpson N, Davey Smith G . Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2007; 27(8):1133-63. DOI: 10.1002/sim.3034. View

Grose R, Dickson C . Fibroblast growth factor signaling in tumorigenesis. Cytokine Growth Factor Rev. 2005; 16(2):179-86. DOI: 10.1016/j.cytogfr.2005.01.003. View

Bulun S . Endometriosis. N Engl J Med. 2009; 360(3):268-79. DOI: 10.1056/NEJMra0804690. View

Anifantaki F, Boutas I, Kalampokas T, Kalampokas E, Sofoudis C, Salakos N . Association of endometriosis and breast cancer: mini review of the literature. Arch Gynecol Obstet. 2015; 293(1):5-10. DOI: 10.1007/s00404-015-3809-8. View

Davey Smith G, Ebrahim S . Epidemiology--is it time to call it a day?. Int J Epidemiol. 2001; 30(1):1-11. DOI: 10.1093/ije/30.1.1. View

10.

Wang X, Wang X, Wang H, Yang M, Dong W, Shao D . Association between psoriasis and lung cancer: two-sample Mendelian randomization analyses. BMC Pulm Med. 2023; 23(1):4. PMC: 9814449. DOI: 10.1186/s12890-022-02297-0. View

11.

Moller B, Rasmussen C, Lindblom B, Olovsson M . Expression of the angiogenic growth factors VEGF, FGF-2, EGF and their receptors in normal human endometrium during the menstrual cycle. Mol Hum Reprod. 2001; 7(1):65-72. DOI: 10.1093/molehr/7.1.65. View

12.

Davies N, Holmes M, Davey Smith G . Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018; 362:k601. PMC: 6041728. DOI: 10.1136/bmj.k601. View

13.

Francavilla C, OBrien C . Fibroblast growth factor receptor signalling dysregulation and targeting in breast cancer. Open Biol. 2022; 12(2):210373. PMC: 8864352. DOI: 10.1098/rsob.210373. View

14.

Chen L, Yang H, Li H, He C, Yang L, Lv G . Insights into modifiable risk factors of cholelithiasis: A Mendelian randomization study. Hepatology. 2021; 75(4):785-796. PMC: 9300195. DOI: 10.1002/hep.32183. View

15.

Hartwig F, Davies N, Hemani G, Davey Smith G . Two-sample Mendelian randomization: avoiding the downsides of a powerful, widely applicable but potentially fallible technique. Int J Epidemiol. 2017; 45(6):1717-1726. PMC: 5722032. DOI: 10.1093/ije/dyx028. View

16.

Huber D, Seitz S, Kast K, Emons G, Ortmann O . Hormone replacement therapy in BRCA mutation carriers and risk of ovarian, endometrial, and breast cancer: a systematic review. J Cancer Res Clin Oncol. 2021; 147(7):2035-2045. PMC: 8164576. DOI: 10.1007/s00432-021-03629-z. View

17.

Rizner T . Estrogen biosynthesis, phase I and phase II metabolism, and action in endometrial cancer. Mol Cell Endocrinol. 2013; 381(1-2):124-39. DOI: 10.1016/j.mce.2013.07.026. View

18.

Halle M, Tangen I, Berg H, Hoivik E, Mauland K, Kusonmano K . HER2 expression patterns in paired primary and metastatic endometrial cancer lesions. Br J Cancer. 2017; 118(3):378-387. PMC: 5808034. DOI: 10.1038/bjc.2017.422. View

19.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

20.

Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin J, Friedman E, Slingerland J . Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention. CA Cancer J Clin. 2017; 67(5):378-397. PMC: 5591063. DOI: 10.3322/caac.21405. View