Male Origin Microchimerism and Brain Cancer: a Case-cohort Study

Abstract Background: Despite considerable research effort, causes of brain cancer are largely unknown. Male BC predominance and reduced brain cancer risk with increasing parity among women, however, support a favourable role of pregnancy. We set out to determine whether peripheral male origin microchimerism, namely the presence of circulating male origin cells, likely obtained via natural trafficking across the placenta during pregnancy, associates with reduced risk of brain cancer in women. Methods: Using a case-cohort design, we sampled 505 middle aged women randomly at baseline in the Diet, Cancer and Health cohort (controls), and 73 women with incident brain cancer diagnosed during follow-up in the Danish Cancer Registry (cases). Male origin microchimerism was determined by presence of Y chromosome sequences in female blood samples. Data was analysed using weighted proportional Hazards regression, yielding Hazard Ratios with 95% confidence intervals. Results: Compared with male origin microchimerism negative women, positive women had half the risk of developing brain cancer (Hazard Ratio=0.50 [0.33-0.77]). Sensitivity analyses support that our findings are unlikely due to bias or chance. Conclusion: Here, for the first time we demonstrate half the risk of brain cancer in male origin microchimerism positive compared with negative women. Our findings resemble those of previous studies of male origin microchimerism and other female cancers.