We propose to establish a multidisciplinary team of epidemiologists, statisticians, basic scientists and clinician scientists to promote and pursue thorough identification and characterization of genomic loci associated with prostate cancer. ELLIPSE (ELucidating Loci Involved in Prostate cancer SuscEptibility) is a translational grant comprised of three highly integrated projects. Project 1 aims to take advantage of existing and shortly to be completed GWAS of prostate cancer in European, African American, Latino and Japanese populations to discover novel risk loci, and to rigorously replicate these associations in large existing consortia of prostate cases and controls (PRACTICAL, BPC3, and MADCaP). A major focus of this expanded effort is to identify loci that may selectively be associated with advanced disease and variants that contribute to ethnic difference in disease risk. Selective fine mapping of risk loci will also be performed to comprehensively characterize the relevant allelic locus, utilizing all available data on common variants from Hapmap, selective sequencing efforts, and from the 1000 Genome Project. Project 2 is focused on understanding the gene(s) that the non-protein coding risk variants are acting through. Two hypotheses will be systematically explored using a wide variety of established and emerging techniques: the risk loci harbor as yet undetected transcripts (either coding or non-coding) and the risk loci are regulatory elements. Finally, in Project 3 we propose to investigate the potential of this new knowledge on the genetic basis of prostate cancer susceptibility to enhance risk assessment, through gene-gene and gene-environment interactions, and importantly, to provide the potential for novel clinical practices through impacts on cancer diagnosis and treatment, or newer cancer prevention strategies. The overarching goal is to discover the pathways that drive prostate cancer pathogenesis and to assess their role in clinical decision making.
The discovery of novel risk alleles for prostate cancer will provide new insights into biological pathways that are important in the development of prostate cancer, particularly aggressive disease. This insight into prostate cancer biology will disclose novel targets for chemopreventive and therapeutic interventions and may reveal approaches to primary prevention.
|Lindström, Sara; Finucane, Hilary; Bulik-Sullivan, Brendan et al. (2017) Quantifying the Genetic Correlation between Multiple Cancer Types. Cancer Epidemiol Biomarkers Prev 26:1427-1435|
|Park, Sungshim L; Cheng, Iona; Haiman, Christopher A (2017) Genome-wide association studies of cancer in diverse populations. Cancer Epidemiol Biomarkers Prev :|
|Glubb, Dylan M; Johnatty, Sharon E; Quinn, Michael C J et al. (2017) Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci. Oncotarget 8:64670-64684|
|Amos, Christopher I; Dennis, Joe; Wang, Zhaoming et al. (2017) The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers. Cancer Epidemiol Biomarkers Prev 26:126-135|
|Sud, Amit; Thomsen, Hauke; Law, Philip J et al. (2017) Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility. Nat Commun 8:1892|
|Feng, Yen-Chen Anne; Cho, Kelly; Lindstrom, Sara et al. (2017) Investigating the genetic relationship between Alzheimer's disease and cancer using GWAS summary statistics. Hum Genet 136:1341-1351|
|Zuber, Verena; Bettella, Francesco; Witoelar, Aree et al. (2017) Bromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer. BMC Genomics 18:270|
|Milne, Roger L (see original citation for additional authors) (2017) Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet 49:1767-1778|
|Shimelis, Hermela; Mesman, Romy L S; Von Nicolai, Catharina et al. (2017) BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer. Cancer Res 77:2789-2799|
|Muranen, Taru A; Greco, Dario; Blomqvist, Carl et al. (2017) Genetic modifiers of CHEK2*1100delC-associated breast cancer risk. Genet Med 19:599-603|
Showing the most recent 10 out of 131 publications