Abstract B115: Parity alters responses to ionizing radiation in the human mammary gland

B115

Parity is associated with a significant reduction in breast cancer risk. Identification of key pathways, which are altered by parity, will provide important information for the development of chemoprotective agents against breast cancer. Radiation is a potent carcinogen in the mammary gland. It appears to have mutagenic effects through its ability to induce DNA damage, as well as through its ability to induce “bystander effects”. These effects have been shown to be tumor promoting in immortalized cells and involve modulation of various growth factor pathways for stem cell maintenance. We hypothesized that we would be able to obtain important information on parity-induced changes by examining gene expression responses to radiation exposure from the two types of tissue. Methods: Women undergoing elective breast reduction surgery were asked to enroll and donate their excised tissue. Portions of tissue were cultured and then either exposed or not to 5 Gy radiation. The tissue remained in culture for six hours to allow for changes in gene expression. Tissue was fixed for immunohistochemical analysis or RNA was isolated for microarray analysis. Results: A SAM analysis indicated a loose 200 gene signature, which responded to radiation differentially. The breast tissue from nulliparous women showed the most striking changes with increased expression of 80% genes in response to radiation whereas tissue from parous women illustrated no change or decreased expression of these same genes. The other 20% of the genes were strongly down regulated in tissue from nulliparous women in response to radiation, while they were up-regulated or not changed in parous tissue. The major pathways that appeared to be inversely affected in these tissues indicate parity-induced changes in signaling to tissue homeostasis and wound repair, as well as DNA replication and repair.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):B115.