Browsing by Author "Hoover, R.N."
Now showing 1 - 7 of 7
Results Per Page
Sort Options
Item A genome-wide association study of prostate cancer in West African men(Human Genetics, 2014-05) Cook, M.B.; Wang, Z.; Yeboah, E.D.; Tettey, Y.; Biritwum, R.B.; Adjei, A.A.; Tay, E.; Truelove, A.; Niwa, S.; Chung, C.C.; Chokkalingam, A.P.; Chu, L.W.; Yeager, M.; Hutchinson, A.; Yu, K.; Rand, K.A.; Haiman, C.A.; Hoover, R.N.; Hsing, A.W.; Chanock, S.J.Age-adjusted mortality rates for prostate cancer are higher for African-American men compared with those of European ancestry. Recent data suggest that West African men also have elevated risk for prostate cancer relative to European men. Genetic susceptibility to prostate cancer could account for part of this difference. We conducted a genome-wide association study (GWAS) of prostate cancer in West African men in the Ghana Prostate Study. Association testing was performed using multivariable logistic regression adjusted for age and genetic ancestry for 474 prostate cancer cases and 458 population-based controls on the Illumina HumanOmni-5 Quad BeadChip. The most promising association was at 10p14 within an intron of a long non-coding RNA (lncRNA RP11-543F8.2) 360 kb centromeric of GATA3 (p = 1.29E-7). In sub-analyses, SNPs at 5q31.3 were associated with high Gleason score (≥7) cancers, the strongest of which was a missense SNP in PCDHA1 (rs34575154, p = 3.66E-8), and SNPs at Xq28 (rs985081, p = 8.66E-9) and 6q21 (rs2185710, p = 5.95E-8) were associated with low Gleason score (<7) cancers. We sought to validate our findings in silico in the African Ancestry Prostate Cancer GWAS Consortium, but only one SNP, at 10p14, replicated at p < 0.05. Of the 90 prostate cancer loci reported from studies of men of European, Asian or African-American ancestry, we were able to test 81 in the Ghana Prostate Study, and 10 of these replicated at p < 0.05. Further genetic studies of prostate cancer in West African men are needed to confirm our promising susceptibility loci. © 2013 Springer-Verlag Berlin Heidelberg (outside the USA).Item High prevalence of screen detected prostate cancer in West Africans: Implications for racial disparity of prostate cancer(Journal of Urology, 2014-04) Hsing, A.W.; Yeboah, E.; Biritwum, R.; Tettey, Y.; De Marzo, A.M.; Adjei, A.; Netto, G.J.; Yu, K.; Li, Y.; Chokkalingam, A.P.; Chu, L.W.; Chia, D.; Partin, A.; Thompson, I.M.; Quraishi, S.M.; Niwa, S.; Tarone, R.; Hoover, R.N.Purpose To our knowledge the reasons for the high rates of prostate cancer in black American men are unknown. Genetic and lifestyle factors have been implicated. Better understanding of prostate cancer rates in West African men would help clarify why black American men have such high rates since the groups share genetic ancestry and yet have different lifestyles and screening practices. To estimate the prostate cancer burden in West African men we performed a population based screening study with biopsy confirmation in Ghana. Materials and Methods We randomly selected 1,037 healthy men 50 to 74 years old from Accra, Ghana for prostate cancer screening with prostate specific antigen testing and digital rectal examination. Men with a positive screen result (positive digital rectal examination or prostate specific antigen greater than 2.5 ng/ml) underwent transrectal ultrasound guided biopsies. Results Of the 1,037 men 154 (14.9%) had a positive digital rectal examination and 272 (26.2%) had prostate specific antigen greater than 2.5 ng/ml, including 166 with prostate specific antigen greater than 4.0 ng/ml. A total of 352 men (33.9%) had a positive screen by prostate specific antigen or digital rectal examination and 307 (87%) underwent biopsy. Of these men 73 were confirmed to have prostate cancer, yielding a 7.0% screen detected prostate cancer prevalence (65 patients), including 5.8% with prostate specific antigen greater than 4.0 ng/ml. Conclusions In this relatively unscreened population in Africa the screen detected prostate cancer prevalence is high, suggesting a possible role of genetics in prostate cancer etiology and the disparity in prostate cancer risk between black and white American men. Further studies are needed to confirm the high prostate cancer burden in African men and the role of genetics in prostate cancer etiology. © 2014 by American Urological Association Education and Research, Inc.Item Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions(Human Molecular Genetics, 2015-07) Han, Y.; Hazelett, D.J.; Wiklund, F.; Schumacher, F.R.; Stram, D.O.; Berndt, S.I.; Wang, Z.; Rand, K.A.; Hoover, R.N.; Machiela, M.J.; Yeager, M.; Burdette, L.; Chung, C.C.; Hutchinson, A.; Yu, K.; Xu, J.; Travis, R.C.; Key, T.J.; Siddiq, A.; Canzian, F.; Takahashi, A.; Kubo, M.; Stanford, J.L.; Kolb, S.; Gapstur, S.M.; Ryan Diver, W.; Stevens, V.L.; Strom, S.S.; Pettaway, C.A.; Al Olama, A.A.Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genomeencoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry. Markers at 55 regions passed a region-specific significance threshold (P-value cutoff range: 3.9 × 10-4-5.6 × 10-3) and in 30 regions we identified markers thatwere more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (P < 5.0 × 10-6) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with P-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation. © The Author 2015. Published by Oxford University Press. All rights reserved.Item Overall and abdominal obesity and prostate cancer risk in a West African population: An analysis of the Ghana Prostate Study(International Journal of Cancer, 2020-03-11) Yeboah, E.D.; Hurwitz, L.M.; Biritwum, R.B.; Tettey, Y.; Adjei, A.A.; Mensah, J.E.; Tay, E.; Okyne, V.; Truelove, A.; Kelly, S.P.; Zhou, C.K.; Butler, E.N.; Hoover, R.N.; Hsing, A.W.; Cook, M.B.Obesity has been associated with an increased risk of advanced prostate cancer. However, most studies have been conducted among North American and European populations. Prostate cancer mortality appears elevated in West Africa, yet risk factors for prostate cancer in this region are unknown. We thus examined the relationship between obesity and prostate cancer using a case-control study conducted in Accra, Ghana in 2004 to 2012. Cases and controls were drawn from a populationbased sample of 1037 men screened for prostate cancer, yielding 73 cases and 964 controls. An additional 493 incident cases were recruited from the Korle-Bu Teaching Hospital. Anthropometric measurements were taken at enrollment. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR) and prostate cancer, adjusting for potential confounders. The mean BMI was 25.1 kg/m2 for cases and 24.3 kg/m2 for controls. After adjustment, men with BMI ≥ 30 kg/m2 had an increased risk of prostate cancer relative to men with BMI < 25 kg/m2 (OR 1.86, 95% CI 1.11-3.13). Elevated WC (OR 1.76, 95% CI 1.24-2.51) and WHR (OR 1.46, 95% CI 0.99-2.16) were also associated with prostate cancer. Associations were not modified by smoking status and were evident for low- and high-grade disease. These findings indicate that overall and abdominal obesity are positively associated with prostate cancer among men in Ghana, implicating obesity as a potentially modifiable risk factor for prostate cancer in this region.Item Serum proteomics links suppression of tumor immunity to ancestry and lethal prostate cancer(nature, 2022) Minas, T.Z.; Candia, J.; Dorsey, T.H.; Baker, F.; Tang, W.; Kiely, M.; Smith, C.J.; Zhang, A.L.; Jordan, S.V.; Obadi, O.M.; Ajao, A.; Tettey, Y.; Biritwum, R.B.; Adjei, A.A.; Mensah, J.E.; Hoover, R.N.; Jenkins, F.J.; Kittles, R.; Hsing, A.W.; Wang, X.W.; Loffredo, C.A.; Yates, C.; Cook, M.B.; Ambs, S.There is evidence that tumor immunobiology and immunotherapy response may differ between African American and European American prostate cancer patients. Here, we determine if men of African descent harbor a unique systemic immune-oncological signature and measure 82 circulating proteins in almost 3000 Ghanaian, African American, and European American men. Protein signatures for suppression of tumor immunity and chemotaxis are elevated in men of West African ancestry. Importantly, the suppression of tumor immunity protein signature associates with metastatic and lethal prostate cancer, pointing to clinical importance. Moreover, two markers, pleiotrophin and TNFRSF9, predict poor disease survival specifically among African American men. These findings indicate that immuneoncology marker profiles differ between men of African and European descent. These differences may contribute to the disproportionate burden of lethal prostate cancer in men of African ancestry. The elevated peripheral suppression of tumor immunity may have important implication for guidance of cancer therapy which could particularly benefit African American patients.Item TMPRSS2:ERG Gene Fusions in Prostate Cancer of West African Men and Ameta-Analysis of Racial Differences(American Journal of Epidemiology, 2017-06) Zhou, C.K.; Young, D.; Yeboah, E.D.; Coburn, S.B.; Tettey, Y.; Biritwum, R.B.; Adjei, A.A.; Tay, E.; Niwa, S.; Truelove, A.; Welsh, J.; Mensah, J.E.; Hoover, R.N.; Sesterhenn, I.A.; Hsing, A.W.; Srivastava, S.; Cook, M.B.The prevalence of TMPRSS2-ERG fusions in prostate cancer varies by race. However, such somatic aberration and its association with prognostic factors have neither been studied in a West African population nor been systematically reviewed in the context of racial differences. We used immunohistochemistry to assess ERG expression as the established surrogate of ERG fusion genes among 262 prostate cancer biopsies from the Ghana Prostate Study. Poisson regression with robust variance estimation provided prevalence ratios and 95% confidence intervals of ERG expression in relation to patients' characteristics. We found 47 of 262 (18%) prostate cancers were ERG-positive, and negative ERG staining was associated with higher Gleason score. We further conducted a systematic review and meta-analysis of TMPRSS2-ERG fusions in relation to race, Gleason score, and tumor stage, combining results from Ghana with 40 additional studies. Meta-analysis showed the prevalence of TMPRSS2-ERG fusions in prostate cancer to be highest in men of European descent (49%) followed by Asian (27%) and then African (25%). The lower prevalence of TMPRSS2-ERG fusions in men of African descent implies that alternative genomic mechanisms might explain the disproportionately high prostate cancer burden in such populations.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.