Browsing by Author "Cook, M.B."
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Item A comprehensive resequence-analysis of 250 kb region of 8q24.21 in men of African ancestry(Prostate, 2014-05) Chung, C.C.; Hsing, A.W.; Yeboah, E.; Biritwum, R.; Tettey, Y.; Adjei, A.; Cook, M.B.; De Marzo, A.; Netto, G.; Tay, E.; Boland, J.F.; Yeager, M.; Chanock, S.J.BACKGROUND Genome-wide association studies (GWAS) have identified that a ∼1 M region centromeric to the MYC oncogene on chromosome 8q24.21 harbors at least five independent loci associated with prostate cancer risk and additional loci associated with cancers of breast, colon, bladder, and chronic lymphocytic leukemia (CLL). Because GWAS identify genetic markers that may be indirectly associated with disease, fine-mapping based on sequence analysis provides important insights into patterns of linkage disequilibrium (LD) and is critical in defining the optimal variants to nominate for biological follow-up. METHODS To catalog variation in individuals of African ancestry, we resequenced a region (250 kb; chr8:128,050,768-128,300,801, hg19) containing several prostate cancer susceptibility loci as well as a locus associated with CLL. Our samples included 78 individuals from Ghana and 47 of African-Americans from Johns Hopkins University. RESULTS After quality control metrics were applied to next-generation sequence data, 1,838 SNPs were identified. Of these, 285 were novel and not yet reported in any public database. Using genotypes derived from sequencing, we refined the LD and recombination hotspots within the region and determined a set of tag SNPs to be used in future fine-mapping studies. Based on LD, we annotated putative risk loci and their surrogates using ENCODE data, which should help guide laboratory studies. CONCLUSIONS In comparison to the 1000 Genome Project data, we have identified additional variants that could be important in establishing priorities for future functional work designed to explain the biological basis of associations between SNPs and both prostate cancer and CLL.© 2014 Wiley Periodicals, Inc.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 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.