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1.
Int J Mol Sci ; 22(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199930

RESUMO

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.


Assuntos
Neoplasias do Endométrio/epidemiologia , Endometriose/epidemiologia , Endométrio/patologia , Predisposição Genética para Doença , Neoplasias Hormônio-Dependentes/epidemiologia , Neoplasias Ovarianas/epidemiologia , Polimorfismo de Nucleotídeo Único , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Endometriose/genética , Endometriose/patologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fatores de Risco , Espanha/epidemiologia
2.
Life (Basel) ; 11(1)2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33401535

RESUMO

Endometriosis, one of the most common gynecological disorders, is a complex disease characterized by the growth of endometrial-like tissue in extra-uterine locations and is a cause of pelvic pain and infertility. Evidence from observational studies indicate that endometriosis usually appears together with several other phenotypes. These include a list of autoimmune diseases, most of them more prevalent in women, anthropometric traits associated with leanness in the adulthood, as well as female reproductive traits, including altered hormone levels and those associated with a prolonged exposure to menstruation. However, the biological mechanisms underlying their co-morbidity remains unknown. To explore whether those phenotypes and endometriosis share a common genetic origin, we performed a systematic Two-Sample Mendelian Randomization (2SMR) analysis using public GWAS data. Our results suggest potential common genetic roots between endometriosis and female anthropometric and reproductive traits. Particularly, our data suggests that reduced weight and BMI might be mediating the genetic susceptibility to suffer endometriosis. Furthermore, data on female reproductive traits strongly suggest that genetic variants that predispose to a more frequent exposure to menstruation, through earlier age at menarche and shorter menstrual cycles, might also increase the risk to suffer from endometriosis.

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