Masato Mitsuhashi¹, David Peel², Argyrios Ziogas² and Hoda Anton-Culver²

¹Hitachi Chemical Research Center, Inc., Irvine, CA, USA. ²Department of Epidemiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.

Abstract

This study was designed to discover blood biomarkers of cancer susceptibility using invasive multiple (n = 21), single primary breast cancer (n = 21), and control subjects (n = 20). Heparinized whole blood was incubated at 37 °C for 2 hours after 0–10 Gy of radiation, then cell cycle arrest marker CDKN1A and apoptosis marker BBC3 mRNA were quantified. This epidemiological study was practically feasible because radiation-induced mRNA was preserved for at least 1 day whenever blood was stored at 4 °C (r² = 0.901). Moreover, blood could be stored frozen after radiation treatment (r² = 0.797). Radiation- induced CDKN1A and BBC3 mRNA were dose dependent, and the degree of induction of CDKN1A was correlated with that of BBC3 (r² = 0.679). Interestingly, multiple primary cases showed higher induction of CDKN1A mRNA than single primary and control groups, whereas BBC3 did not show such differences. The results suggested that cancer susceptibility represented by the multiple primary breast cancer cases was related to over-reaction of CDKN1A mRNA, not BBC3. The study also suggests that ex vivo gene expression analysis could potentially be used as a new tool in epidemiological studies for cancer and radiation sensitivity research.