Browsing by Author "Netto, G."
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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 Prevalence of BPH and lower urinary tract symptoms in West Africa(Prostate Canc and Prostatic Dis, 2011) Chokkalingam, A.P.; Yeboah, E.D.; DeMarzo, A.; Netto, G.; Yu, K; Biritwum, R.B.; Tettey, Y.BACKGROUND: BPH and lower urinary tract symptoms (LUTS) are very common among older men in Western countries. However, the prevalence of these two conditions in the developing countries is less clear. METHODS: We assessed the age-standardized prevalence of BPH and/or LUTS among West Africans in a probability sample of 950 men aged 50-74 in Accra, Ghana, with no evidence of biopsy-confirmed prostate cancer after screening with PSA and digital rectal examination (DRE). Information on LUTS was based on self-reports of the International Prostate Symptom Score (IPSS). BPH was estimated using DRE, PSA levels and imputed prostate volume. RESULTS: The prevalence of DRE-detected enlarged prostate was 62.3%, while that of PSA≥1.5 ng ml -1 (an estimate of prostate volume ≥ 30 cm 3) was 35.3%. The prevalence of moderate-to-severe LUTS (IPSS≥8) was 19.9%. The prevalence of IPSS≥8 and an enlarged prostate on DRE was 13.3%. Although there is no universally agreed-upon definition of BPH/LUTS, making comparisons across populations difficult, BPH and/or LUTS appear to be quite common among older Ghanaian men. CONCLUSIONS: We found that after age standardization, the prevalence of DRE-detected enlarged prostate in Ghanaian men is higher than previously reported for American men, but the prevalence of LUTS was lower than previously reported for African Americans. Further studies are needed to confirm these findings and identify the risk factors for BPH in both Africans and African Americans. © 2012 Macmillan Publishers Limited All rights reserved.