Genome-wide association studies provide a powerful approach to identify common genetic variants associated with disease risk. More than twenty genetic loci have been associated with prostate cancer, but these explain less than one quarter of the familial aggregation of the disease, indicating that many further loci remain to be found. In this project, we plan to combine data from 8 GWAS, including more than 14,000 cases and 19,000 controls of European, African-American, Japanese and Latino ancestry. This combined analysis will be used to select 3,000 SNPs for further genotyping in a second stage, involving 10,000 cases and 10,000 controls of European ancestry, and further 3,000 SNPs in 4,000 cases and 4,000 controls of African-American ancestry. Associations identified at this stage will then be characterised in >45,000 prostate cancer cases and 53,000 controls. In addition to associations with prostate cancer, we will look specifically for loci associated with eariy onset disease, and with aggressive disease. For susceptibility loci that are identified, we will attempt to define the likely causative variants, utilising the catalog of variants from the 1000 Genome Project data, together with dense genotyping in 14,000 cases and 14,000 controls for European and African-American ancestry. Genetic loci that are characterised in this project are likely to provide new insights into the underiying biology of the disease (to be pursued in the companion Project 2). In addition, the characterisation of susceptibility variants, in combination with other risk factors, will improve the ability to define individual risk profiles for prostate cancer, and hence inform strategies for disease prevention and management (to be pursued in Project 3).

Public Health Relevance

This project will utilize existing GWAS from multiple populations to reveal novel common risk alleles for prostate cancer. We expect findings from this work to guide the development of future preventive, eariy detection and prognostic strategies.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZCA1-SRLB-4)
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University of Southern California
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Han, Ying; Signorello, Lisa B; Strom, Sara S et al. (2015) Generalizability of established prostate cancer risk variants in men of African ancestry. Int J Cancer 136:1210-7
Agarwal, D; Pineda, S; Michailidou, K et al. (2014) FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium. Br J Cancer 110:1088-100
Al Olama, Ali Amin; Kote-Jarai, Zsofia; Berndt, Sonja I et al. (2014) A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat Genet 46:1103-9
Lindström, Sara; Thompson, Deborah J; Paterson, Andrew D et al. (2014) Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk. Nat Commun 5:5303
Pooley, Karen A; McGuffog, Lesley; Barrowdale, Daniel et al. (2014) Lymphocyte telomere length is long in BRCA1 and BRCA2 mutation carriers regardless of cancer-affected status. Cancer Epidemiol Biomarkers Prev 23:1018-24
Hazelett, Dennis J; Rhie, Suhn Kyong; Gaddis, Malaina et al. (2014) Comprehensive functional annotation of 77 prostate cancer risk loci. PLoS Genet 10:e1004102
Andreassen, Ole A; Zuber, Verena; Thompson, Wesley K et al. (2014) Shared common variants in prostate cancer and blood lipids. Int J Epidemiol 43:1205-14
Eeles, Rosalind; Goh, Chee; Castro, Elena et al. (2014) The genetic epidemiology of prostate cancer and its clinical implications. Nat Rev Urol 11:18-31
Milne, Roger L; Burwinkel, Barbara; Michailidou, Kyriaki et al. (2014) Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium. Hum Mol Genet 23:6096-111
Li, Jingmei; Lindström, Linda S; Foo, Jia N et al. (2014) 2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy. Nat Commun 5:4051

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