Premature ovarian aging in BRCA carriers: a prototype of systemic precocious aging?
| Autor: | Ronit Abir, Rinat Yerushalmi, Shlomit Perry, Ana Tobar, Irit Ben-Aharon, Shulamith Rizel, Noa Hasky, Salomon M. Stemmer, Benny Fisch, Ruth Shalgi, Mattan Levi, Eran Sharon, David Margel |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Infertility
Oncology medicine.medical_specialty endocrine system diseases BRCA Ovary Prophylactic Oophorectomy 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine Medicine Ovarian reserve skin and connective tissue diseases Klotho 030219 obstetrics & reproductive medicine business.industry BRCA mutation systemic precocious aging medicine.disease female genital diseases and pregnancy complications ovarian aging medicine.anatomical_structure 030220 oncology & carcinogenesis Cohort business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Irit Ben-Aharon 1, 5, * , Mattan Levi 2, * , David Margel 1, 5 , Rinat Yerushalmi 1, 5 , Shulamith Rizel 1 , Shlomit Perry 1, 5 , Eran Sharon 3, 5 , Noa Hasky 2 , Ronit Abir 4, 5 , Benny Fisch 4, 5 , Ana Tobar 6 , Ruth Shalgi 2 and Salomon Marcello Stemmer 1, 5 1 Institute of Oncology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel 2 Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel-Aviv, Israel 3 Department of Surgery, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel 4 IVF and Infertility Unit, Schneider Women Hospital, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel 5 Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel-Aviv, Israel 6 Department of Pathology, Rabin Medical Center, Petach Tikva, Israel * These authors have contributed equally to this work Correspondence to: Irit Ben-Aharon, email: iritbenaharon@gmail.com Keywords: BRCA; ovarian aging; systemic precocious aging Received: December 01, 2017 Accepted: February 27, 2018 Published: March 23, 2018 ABSTRACT Purpose: Though former evidence implies a correlation of breast cancer susceptibility gene ( BRCA ) mutation with reduced ovarian reserve, the data is yet inconsistent. Our aim was to investigate biomarkers of ovarian aging in a cohort of young healthy carriers of the BRCA mutation. We hypothesized that the role played by BRCA genes in aging pathways is not exclusive to the ovary. Experimental Design: Healthy female BRCA carriers, 40 years or younger and healthy male BRCA carriers, 50 years or younger, were enrolled in the study. Serum anti-mullerian Hormone (AMH), fibroblast growth factor-23 (FGF-23), Klotho and IL-1 were measured by enzyme-linked immunosorbent assay (ELISA). Ovarian AMH and protein kinase B (AKT) mRNA from BRCA carriers who underwent prophylactic oophorectomy and from age-matched, healthy, non-carriers who underwent partial oophorectomy due to benign conditions were analyzed by qPCR. Results: Thirty-three female (median age 35y) and 20 male (44y) BRCA carriers were enrolled into the study and matched to control non-carriers (34y and 43y, respectively). Serum AMH level was significantly lower in BRCA female carriers than in both non-carrier controls and age-matched nomograms. The levels of ovarian AMH and AKT mRNA were significantly lower in carriers than in controls. The systemic aging cytokines FGF-23, klotho and IL-1 displayed a differential expression in carriers of both genders. FGF-23 level was higher in carriers (P=0.06). Conclusions: Our results suggest a link between BRCA mutation, accelerated ovarian aging and systemic aging-related pathophysiology. |
| Databáze: | OpenAIRE |
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