Browsing by Author "Schumacher, F."
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Item Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21.(2011-05-22) Haiman, C. A.; Chen, G. K.; Tettey, Y.; Strom, S. S.; Berndt, S. I.; Kittles, R. A.; Isaacs, W.B.; Ingles, S.A.; Stanford, J.L.; Diver, W.R.; Witte, J.S.; Hsing, A.W.; Nemesure, B.; Rebbeck, T.R.; Cooney, K.A.; Xu, J.; Kibel, A.S.; Hu, J.J.; John, E.M.; Gueye, S.M.; Watya, S.; Signorello, L.B.; Hayes, R.B.; Wang, Z.; Yeboah, E.; Tettey, Y.; Cai, Q.; Kolb, S.; Ostrander, E.A.; Zeigler-Johnson, C.; Yamamura, Y.; Neslund-Dudas, C.; Haslag-Minoff, J.; Wu, W.; Thomas, V.; Allen, G.O.; Murphy, A.; Chang, B.L.; Zheng, S.L.; Leske, M.C.; Wu, S.Y.; Ray, A.M.; Hennis, A.J.; Thun, M.J.; Carpten, J.; Casey, G.; Carter, E.N.; Duarte, E.R.; Xia, L.Y.; Sheng, X.; Wan, P.; Pooler, L.C.; Cheng, I.; Monroe, K.R.; Schumacher, F.; Le Marchand, L.; Kolonel, L.N.; Van Den Berg, D.; Chanock, S.J.; Stram, D.O.; Henderson, B.E.;In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ∼5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations.Item A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer(Nature Genetics, 2014-09) Al Olama, A.A.; Kote-Jarai, Z.; Berndt, S.I.; Conti, D.V.; Schumacher, F.; Biritwum, R.B.; Yao, T.Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of >10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.Item Two susceptibility loci identified for prostate cancer aggressiveness.(Nature Communications, 2015-05) Berndt, S.I.; Wang, Z.; Yeager, M.; Alavanja, M.C.; Albanes, D.; Amundadottir, L.; Andriole, G.; Beane Freeman, L.; Campa, D.; Cancel-Tassin, G.; Canzian, F.; Cornu, J.-N.; Cussenot, O.; Diver, W.R.; Gapstur, S.M.; Grönberg, H.; Haiman, C.A.; Henderson, B.; Hutchinson, A.; Hunter, D.J.; Key, T.J.; Kolb, S.; Koutros, S.; Kraft, P.; Le Marchand, L.; Lindström, S.; Machiela, M.J.; Ostrander, E.A.; Riboli, E.; Schumacher, F.; Siddiq, A.; Stanford, J.L.; Stevens, V.L.; Travis, R.C.; Tsilidis, K.K.; Virtamo, J.; Weinstein, S.; Wilkund, F.; Xu, J.; Lilly Zheng, S.; Yu, K.; Wheeler, W.; Zhang, H.; Sampson, J.; Black, A.; Jacobs, K.; Hoover, R.N.; Tucker, M.; Chanock, S.J.Most men diagnosed with prostate cancer will experience indolent disease; hence, discovering genetic variants that distinguish aggressive from nonaggressive prostate cancer is of critical clinical importance for disease prevention and treatment. In a multistage, case-only genome-wide association study of 12,518 prostate cancer cases, we identify two loci associated with Gleason score, a pathological measure of disease aggressiveness: rs35148638 at 5q14.3 (RASA1, P=6.49 × 10(-9)) and rs78943174 at 3q26.31 (NAALADL2, P=4.18 × 10(-8)). In a stratified case-control analysis, the SNP at 5q14.3 appears specific for aggressive prostate cancer (P=8.85 × 10(-5)) with no association for nonaggressive prostate cancer compared with controls (P=0.57). The proximity of these loci to genes involved in vascular disease suggests potential biological mechanisms worthy of further investigation.