Sara Hallum1, Marianne Antonius Jakobsen2, Thomas Alexander Gerds3, Anja Pinborg4, Anne Tjønneland1,5, Mads Kamper-Jørgensen1. 1. Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. 2. Department of Clinical Immunology, Odense University Hospital, Odense, Denmark. 3. Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. 4. Fertility Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 5. Danish Cancer Society Research Center, Institute of Cancer Epidemiology, Copenhagen, Denmark.
Abstract
BACKGROUND: Reduced risk of ovarian cancer is commonly ascribed to reduced exposure to endogenous hormones during pregnancy, using oral contraceptives or not using hormone replacement therapy. However, exposure to hormones alone account for less than half of all cases. Many women carry small amounts of male cells-known as male origin microchimerism-in their circulation and remarkable impacts of these cells on women's health are being published. Here, we pursue the possibility that male origin microchimerism has a role in reducing ovarian cancer risk. METHODS: We conducted a prospective case-cohort study using blood samples and questionnaire data from 700 women participating in the Danish Diet, Cancer, and Health cohort. Blood samples were analysed for Y chromosome presence as a marker of male microchimerism. We evaluated the association between male microchimerism and ovarian cancer, using weighted Cox regression models reporting hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). RESULTS: Male microchimerism was detected in 46% of cases and 65.9% of controls. Women testing positive for male microchimerism had a reduced hazard rate of ovarian cancer compared with women testing negative (HR = 0.44, 95% CI: 0.29-0.68). We found no evidence of interaction with measures of hormonal exposures (P = 0.50). CONCLUSIONS: For the first time we report that women who test positive for male microchimerism in their circulation have reduced rates of ovarian cancer compared with women who test negative. Although the underlying mechanisms are presently unknown, we believe male microchimerism is potent in preventing ovarian cancer.
BACKGROUND: Reduced risk of ovarian cancer is commonly ascribed to reduced exposure to endogenous hormones during pregnancy, using oral contraceptives or not using hormone replacement therapy. However, exposure to hormones alone account for less than half of all cases. Many women carry small amounts of male cells-known as male origin microchimerism-in their circulation and remarkable impacts of these cells on women's health are being published. Here, we pursue the possibility that male origin microchimerism has a role in reducing ovarian cancer risk. METHODS: We conducted a prospective case-cohort study using blood samples and questionnaire data from 700 women participating in the Danish Diet, Cancer, and Health cohort. Blood samples were analysed for Y chromosome presence as a marker of male microchimerism. We evaluated the association between male microchimerism and ovarian cancer, using weighted Cox regression models reporting hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). RESULTS: Male microchimerism was detected in 46% of cases and 65.9% of controls. Women testing positive for male microchimerism had a reduced hazard rate of ovarian cancer compared with women testing negative (HR = 0.44, 95% CI: 0.29-0.68). We found no evidence of interaction with measures of hormonal exposures (P = 0.50). CONCLUSIONS: For the first time we report that women who test positive for male microchimerism in their circulation have reduced rates of ovarian cancer compared with women who test negative. Although the underlying mechanisms are presently unknown, we believe male microchimerism is potent in preventing ovarian cancer.
Authors: Francesmary Modugno; Zhuxuan Fu; Susan J Jordan; Aocs Group; Jenny Chang-Claude; Renée T Fortner; Marc T Goodman; Kirsten B Moysich; Joellen M Schildkraut; Andrew Berchuck; Elisa V Bandera; Bo Qin; Rebecca Sutphen; John R McLaughlin; Usha Menon; Susan J Ramus; Simon A Gayther; Aleksandra Gentry-Maharaj; Chloe Karpinskyj; Celeste L Pearce; Anna H Wu; Harvey A Risch; Penelope M Webb Journal: Eur J Epidemiol Date: 2020-09-21 Impact factor: 8.082
Authors: Blanca Cómitre-Mariano; Magdalena Martínez-García; Bárbara García-Gálvez; María Paternina-Die; Manuel Desco; Susanna Carmona; María Victoria Gómez-Gaviro Journal: iScience Date: 2021-12-29