Circadian Genes and Aggressive Prostate Cancer in Caucasians and African American

白种人和非裔美国人的昼夜节律基因与侵袭性前列腺癌

• 批准号: 8513028
• 负责人: Ann Hsing
• 金额: $ 7.45万
• 依托单位: CANCER PREVENTION INSTIT OF CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8513028
• 关键词: Affect; African; African American; Anabolism; Androgen Metabolism; Asians; Biological; Biological Process; Cancer Etiology; Carcinogens; Caucasians; Caucasoid Race; Circadian Rhythms; Clinical; Data; Data Set; Development; Ethnic group; Evaluation; Extraprostatic; Genes; Genetic; Genetic Variation; Genotype; Gleason Grade for Prostate Cancer; Gonadal Steroid Hormones; Haplotypes; Heterogeneity; High-Risk Cancer; Hour; Human; Incidence; International Agency for Research on Cancer; Length; Link; Logistic Regressions; Malignant neoplasm of prostate; Metabolism; Mutation; Pathway interactions; Pattern; Population Attributable Risks; Procedures; Prostate; Prostatic Neoplasms; Race; Regression Analysis; Reporting; Risk; Risk Estimate; Risk Factors; Role; Sampling; Single Nucleotide Polymorphism; Subgroup; Testing; Variant; base; cancer genetics; cancer risk; caucasian American; cohort; energy balance; epidemiologic data; high risk; immune function; improved; insight; male; malignant breast neoplasm; member; men; mortality; novel; prostate cancer prevention; public health relevance; shift work; statistics

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.

描述（由申请人提供）：非洲裔美国人的前列腺癌发病率和死亡率在世界上最高，死于前列腺癌的可能性是白人的两倍多。这种种族差异的原因尚不清楚。最近，国际癌症研究机构（IARC）根据流行病学数据将昼夜节律破坏归类为癌症的可能原因，这些数据表明，涉及昼夜节律破坏的轮班工作可能与癌症（包括前列腺癌）的较高风险相关。在人体内，昼夜节律由15个已知的昼夜节律相关基因控制。这些基因的变异已被证明会影响雄激素代谢和能量平衡，这被认为有助于前列腺癌的发展。研究还表明，非洲人和非非洲人之间的一个昼夜节律基因的单倍型模式存在显著差异。我们假设，在高加索人和非洲裔美国人中，昼夜节律基因的变异会影响前列腺癌的风险，特别是侵袭性前列腺癌，并且昼夜节律基因变异与侵袭性前列腺癌风险之间的关系可能在两个种族群体之间存在差异，从而导致这两个群体中侵袭性前列腺癌的差异。为了验证这些假设，我们正在与非洲裔美国人前列腺癌（AAPC）遗传联盟和乳腺癌和前列腺癌队列联盟（BPC 3）合作，使用来自这两个联盟研究（4，000例侵袭性前列腺癌病例和9，500例对照）的现有遗传数据（来自15个基因的2，700个单核苷酸多态性）进行全面的统计分析。在研究中纳入的13，500名受试者中，约1，200例病例和5，000名健康对照是来自AAPC研究的非洲裔美国男性，2，800例病例和4，500名健康对照是来自BPC 3研究的高加索男性。我们计划进行统计分析：1）确定昼夜节律基因的变异是否与高加索人和非洲裔美国人的侵袭性前列腺癌风险相关; 2）确定昼夜节律基因变异与前列腺癌风险之间的关联是否在高加索人和非洲裔美国人之间存在差异，以及这种差异是否解释了前列腺癌风险的部分种族差异。这是第一项研究，有大量的侵袭性前列腺癌病例，特别是来自非洲裔美国人，广泛的SNP覆盖昼夜节律基因。因此，这项研究能够深入了解昼夜节律基因在前列腺癌中的作用，以及这些基因是否有助于高加索人和非洲裔美国人之间前列腺癌发病率的种族差异。