DESCRIPTION (provided by applicant): African Americans have the highest incidence and mortality rates for prostate cancer in the world and are more than twice as likely to die of prostate cancer as their Caucasian counterparts. Reasons for this racial disparity are unknown. Recently, the International Agency for Research on Cancer (IARC) classified circadian rhythm disruption as a probable cause of cancer based on epidemiologic data suggesting that shift work involving circadian disruptions may be associated with higher risk of cancers, including that of the prostate. Within the body, circadian rhythms are controlled by 15 known circadian-related genes. Variations in these genes have been shown to influence androgen metabolism and energy balance, which are thought to contribute to the development of prostate cancer. It has also been shown that haplotype patterns in one of the circadian genes differ significantly between Africans and non-Africans. We hypothesize that variation in circadian genes affects the risk of prostate cancer, in particular aggressive prostate cancer, in both Caucasians and African Americans, and that the relationship between circadian gene variants and aggressive prostate cancer risk may differ between the two ethnic groups, thereby contributing to the disparity of aggressive prostate cancer in these two groups. To test these hypotheses, we are collaborating with the African American Prostate Cancer (AAPC) Genetic Consortium and the Breast and Prostate Cancer Cohort Consortium (BPC3) in using existing genetic data (2,700 single nucleotide polymorphisms from 15 genes) from these two consortium studies (4,000 aggressive prostate cancer cases and 9,500 controls) for a comprehensive statistical analysis. Of the 13,500 subjects included in the study, about 1,200 cases and 5,000 healthy controls are African American men from the AAPC study and 2,800 cases and 4,500 healthy controls are Caucasian men from the BPC3 study. We plan to conduct statistical analyses to: 1) determine if variation in circadian genes are associated with risk of aggressive prostate cancer in Caucasians and African Americans; and 2) determine whether the association between circadian gene variants and prostate cancer risk differs between Caucasians and African Americans and whether this difference explains part of the racial disparity in prostate cancer risk. This is the first study t have a large number of aggressive prostate cancer cases, especially from African Americans, with extensive SNP coverage of circadian genes. This study is therefore able to provide insight into the role of circadian genes in prostate cancer and whether these genes contribute to the racial disparity of prostate cancer rates between Caucasians and African Americans.
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