whereRU: Aresty Poster 41 - Melatonin SNPs in BRCA by Aresty Posters 2009

SNPs in Melatonin Receptor 1A and 1B Have Associations with Breast Cancer Phenotypes
Breast cancer is an extremely important disease to study. According to the American Cancer Society, the average woman in the United States has a lifetime risk of one in eight of developing breast cancer. After lung cancer, this disease is the second largest cause of cancer death in women. With continuing research, great strides have been made in understanding, detecting, and treating breast cancer. In fact, death rates from breast cancer have been declining since about 1990, with larger decreases in women younger than 50 (American Cancer Society, 2007). Nonetheless, a projected 40,480 women will die from breast cancer in the United States in 2008 (American Cancer Society, 2007). Currently, only 5 ? 10% of breast cancers have known genetic factors, primarily associated with mutations in the BRCA1 and BRCA2 genes. Due to the complexity of breast cancer, a great effort is focused on evaluating other genetic factors that may account for the remaining 90 ? 95% of cases. It is crucial to continue research, especially in risk assessment, in order to screen patients and decrease the likelihood of a woman dying of breast cancer.
Melatonin is a naturally occurring hormone found in a wide variety of organisms. It is produced in the pineal gland, usually at night, as it is regulated by the light/dark cycle. This molecule functions in numerous physiological processes as an antioxidant, anti-apoptotic signaler, and immunomodulator. Most importantly, melatonin has been implicated in the risk of developing breast cancer in shift workers in epidemiologic studies due to disrupted circadian rhythms. It exerts its action through melatonin receptors controlling the hormonal axis and ovarian estrogen production and through direct effects on the receptors Melatonin Receptor 1A (MTNR1A) and Melatonin Receptor 1B (MTNR1B) in breast tissue. Melatonin is known to suppress growth and proliferation of both estrogen receptor positive (ER+) and estrogen receptor negative (ER-) breast cancer cells in vitro. We hypothesized that single nucleotide polymorphisms (SNPs) in MTNR genes could affect risk of breast cancer and breast cancer outcomes due to its direct effect on breast tissue and that those effects could be modified by other host and hormonal factors.
TaqMan allelic discrimination assays for MTNR1A and MTNR1B melatonin receptors were performed on genomic DNA from breast cancer patients using the ABI Prism 7900HT (Applied Biosystems). Genotypes were linked to clinical information, then limited to Caucasians to reduce heterogeneity.
MTNR1A and 1B genotypes are in Hardy-Weinberg equilibrium in the Caucasian population. The frequency of the MTNR1A genotypes are 11.7% CC, 44.7% CT, and 43.6% TT and MTNR1B are 55.2% CC, 38.1% CG, and 6.7% GG. No genotype was more likely to be associated with ER- over ER+ breast cancer or vice versa. Polymorphic variants in MTNR1B resulted in measurable phenotypes for hormone receptor-negative, but not hormone receptor-positive breast cancers.
Jamie Kostialik1, Diptee Kulkarni2, DL Toppmeyer2, K Hirshfield2.
1Rutgers University, 2UMDNJ/Robert Wood Johnson Medical School, New Brunswick, New Jersey, CINJ, New Brunswick, New Jersey.
jamiekos@eden.rutgers.edu