Gene expression profiles in daily and shift-workers with and without breast cancer

Introduction: The International Agency for Research on Cancer (IARC) has classified shift-work, which involves circadian disruption, in group 2A of probable carcinogens. In humans, no conclusive relationship has been found between breast cancer (BC) and shift-work, which includes night work. Some prospective evidence shows that shift-work, even in the long term, could slightly affect breast cancer incidence. Therefore, the associ ation could be restricted to some women, more susceptible to the conse quences of staying awake during the biological night. However, the investigation on relationship between BC and shift-work deserves further studies. Here, we started a pilot study to investigate if gene expression changes in Peripheral Blood Mononuclear Cells (PBMCs) might explain the connection between shift-work and BC susceptibility. Materials and methods: At the moment, we have investigated 3 groups of women: daily healthy workers and shift-workers with and without breast cancer. The enrolled population is composed of 12 subjects (4 for each group), who underwent peripheral blood sampling. PBMCs were isolated and used for the analysis of the gene expression profile of 624 genes related to cancer, by Real-Time Open Array PCR.Daily sick workers (12 women) are still under evaluation. Results: Comparing the gene expression panels of workers diagnosed with BC with those not exposed to night work, 38 genes were significantly over expressed and 48 under-expressed were highlighted; in comparison with those of healthy workers exposed to night work, 45 genes that were significantly over-expressed and 48 under-expressed emerged. Comparing the panels of healthy female workers not exposed to night work with those of healthy female workers exposed to night work, 36 genes that were significantly over-expressed and 13 under-expresses were detected. From the cross analysis of these comparisons 2 significant genes were detected: CENPA, a gene sensitive to the effects of night work and commonly up regulated in cases of BC; CTSE, a gene sensitive to the effects of night work and commonly down-regulated in cases of BC. Conclusions: Preliminary data seem to support the hypothesis that changes in gene expression profiles in PBMCs may correlate with the presence of BC in workers exposed to night shifts.Furthermore, this approach, if confirmed on a larger sample, will allow to verify the rele vance of molecular genetic studies for determination of professional risk to BC. Acknowledgements: This work was supported by grant from LILT(Lega Italiana per la Lotta contro i Tumori).