Genetic Contribution of Endometriosis to the Risk of Developing Hormone-Related Cancers

• Main Authors: Aintzane Rueda-Martínez, Aiara Garitazelaia, Ariadna Cilleros-Portet, Sergi Marí, Rebeca Arauzo, Jokin de Miguel, Bárbara P. González-García, Nora Fernandez-Jimenez, Jose Ramon Bilbao, Iraia García-Santisteban
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: International Journal of Molecular Sciences
• Subjects: endometriosis; hormone-related cancers; epithelial ovarian cancer; breast cancer; endometrial cancer; mendelian randomization
• Online Access: https://www.mdpi.com/1422-0067/22/11/6083

Endometriosis is a common gynecological disorder that has been associated with endometrial, breast and epithelial ovarian cancers in epidemiological studies. Since complex diseases are a result of multiple environmental and genetic factors, we hypothesized that the biological mechanism underlying their comorbidity might be explained, at least in part, by shared genetics. To assess their potential genetic relationship, we performed a two-sample mendelian randomization (2SMR) analysis on results from public genome-wide association studies (GWAS). This analysis confirmed previously reported genetic pleiotropy between endometriosis and endometrial cancer. We present robust evidence supporting a causal genetic association between endometriosis and ovarian cancer, particularly with the clear cell and endometrioid subtypes. Our study also identified genetic variants that could explain those associations, opening the door to further functional experiments. Overall, this work demonstrates the value of genomic analyses to support epidemiological data, and to identify targets of relevance in multiple disorders.