Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.
Int J Epidemiol. 2021 Mar 3;50(1):87-94. doi: 10.1093/ije/dyaa019.
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.
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).
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).
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.
人们普遍认为,怀孕时减少内源性激素暴露(使用口服避孕药或不使用激素替代疗法)会降低卵巢癌的风险。然而,荷尔蒙暴露本身仅占所有病例的不到一半。许多女性的循环中携带少量男性细胞——被称为男性来源的微嵌合体——这些细胞对女性健康的显著影响正在被发表。在这里,我们探讨了男性来源的微嵌合体在降低卵巢癌风险中的作用的可能性。
我们使用来自参加丹麦饮食、癌症和健康队列的 700 名女性的血液样本和问卷调查数据进行了一项前瞻性病例对照研究。血液样本被分析是否存在 Y 染色体,作为男性微嵌合体的标志物。我们使用加权 Cox 回归模型报告风险比(HR)和相应的 95%置信区间(CI),评估了男性微嵌合体与卵巢癌之间的关联。
46%的病例和 65.9%的对照者检测到了男性微嵌合体。与检测为阴性的女性相比,检测为阳性的女性患卵巢癌的风险率降低(HR=0.44,95%CI:0.29-0.68)。我们没有发现与激素暴露测量存在交互作用的证据(P=0.50)。
我们首次报告称,循环中检测到男性微嵌合体的女性与检测为阴性的女性相比,卵巢癌的发生率降低。尽管目前尚不清楚潜在机制,但我们认为男性微嵌合体在预防卵巢癌方面具有强大作用。