Ann Hsing

NCI, DCEG, HREB

PLCO (Learn more about this study)

2007-0034

Jun 12, 2007

Circadian Genes and Serum Levels of Sex Hormones and their Joint Effects on Prostate Cancer Risk

Epidemiologic data from occupational cohorts suggest that circadian rhythm disruptions increase the risk for prostate cancer (1-3) although no underlying molecular mechanism has been identified. Nine known genes control the endogenous circadian rhythm in cells and influence biological processes, such as androgen metabolism, which are thought to be important prostate tumorigenesis (4). We hypothesize that variants in circadian genes modulate the risk of prostate cancer and that this risk is modified by sex hormones and their related genes. To test these hypotheses, we propose to collaborate with the Cancer Genetic Markers of Susceptibility (CGEMS) Project and the PLCO Cancer Screening Trial to: 1) first use available genotyping data from CGEMS to determine associations of prostate cancer with each circadian gene-related tag single nucleotide polymorphisms (SNPs), each circadian gene, and the circadian pathway; 2) genotype additional putatively functional SNPs to more comprehensively assess the role of circadian genes; 3) explore potential interactions between circadian genes and serum sex hormone levels and/or sex hormone-related genes with respect to prostate cancer using available serum hormone measurements from PLCO; and 4) determine the relationship between circadian gene variants and serum hormone levels to provide biological insight into the link between sex hormones and circadian genes. Because circadian rhythms influence many biological processes and are themselves influenced by environmental factors, findings from our proposed study may have broad and significant impact on prostate cancer research.