Alcohol, genome instability and breast cancer.

Background - Alcohol abuse is associated with an increase in risk for a variety of cancers. The specific association between alcohol consumption and increased risk of breast cancer has been a consistent finding in numerous studies to date however the biological mechanism remains unknown. Objective - One possibility is that alcohol induces genome instability including specific pathological events commonly seen in breast cancer, such as chromosome 17 aneuploidy and/or HER2-neu gene amplification. Design - The cytokinesis block micronucleus (CBMN) assay was used to assess the ability of alcohol to induce genome damage in two cell lines; one containing a mutation of the BRCA1 gene, treated chronically with alcohol for a period of 6 weeks. It was demonstrated that in these cell lines, chronic treatment with physiological concentrations of alcohol (0.36%, 1.36%) induces micronuclei, nucleoplasmic bridges and nuclear buds, indicative of the various genome damaging events of chromosome loss and breakage, chromosome rearrangement and gene amplification respectively. Outcomes - Using the technique of chromogenic in situ hybridisation (CISH), it was possible to assess the occurrence of the specific genome instability event of chromosome 17 aneuploidy in these cell lines. Results from this assay indicate chronic treatment of alcohol induces chromosome 17 aneuploidy in both cell lines. Conclusion - The results from this study support the hypothesis that alcohol induces genotoxic events that are relevant to cancer risk including breast cancer risk. [ABSTRACT FROM AUTHOR]