BRCA1 promoter methylation in peripheral blood is associated with the risk of triple-negative breast cancer.

Methylation of the promoter of the BRCA1 gene in DNA derived from peripheral blood cells is a possible risk factor for breast cancer. It is not clear if this association is restricted to certain types of breast cancer or is a general phenomenon. We evaluated BRCA1 methylation status in peripheral blood cells from 942 breast cancer patients and from 500 controls. We also assessed methylation status in 262 paraffin-embedded breast cancer tissues. Methylation status was assessed using methylation-sensitive high-resolution melting and was categorized as positive or negative. BRCA1 methylation in peripheral blood cells was strongly associated with the risk of triple-negative breast cancer (TNBC) (odds ratio [OR] 4.70; 95% confidence interval [CI]: 3.13-7.07; p < 0.001), but not of estrogen-receptor positive breast cancer (OR 0.80; 95% CI: 0.46-1.42; p = 0.46). Methylation was also overrepresented among patients with high-grade cancers (OR 4.53; 95% CI: 2.91-7.05; p < 0.001) and medullary cancers (OR 3.08; 95% CI: 1.38-6.88; p = 0.006). Moreover, we detected a significant concordance of BRCA1 promoter methylation in peripheral blood and paired tumor tissue (p < 0.001). We found that BRCA1 promoter methylation in peripheral blood cells is associated with approximately five times greater risk of TNBC. We propose that BRCA1 methylation in blood-derived DNA could be a novel biomarker of increased breast cancer susceptibility, in particular for triple-negative tumors.

Blood flow in the internal jugular veins during the spaceflight - Is it actually bidirectional?

Recently intriguing results of the research performed on astronauts of the International Space Station have been published. Unexpectedly, in some crew members a stagnant and bidirectional flow in the internal jugular vein was found, and in one of the astronauts this vein seemed to be totally thrombosed. If it actually were the case that in the settings of weightlessness there is a substantial risk of jugular vein thrombosis, any long-term human space missions would be extremely dangerous. Yet, we interpret these findings differently. In our opinion, what has been explained as bidirectional flow, actually represented the flow separation, and what has been described as occluded vein was rather the vein with recirculating and low-velocity flow. In this paper, basing on physical laws governing the flow of fluids, we describe how the flow separation and recirculation can develop in a dilated internal jugular vein, how it can affect cerebral outflow through this vein, why such a phenomenon is more likely in the settings of microgravity and how future research on this topic should be directed.