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Background: Risk variants identified so far for colorectal cancer explain only a small proportion of familial risk of this cancer, particularly in Asians., Methods: We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, including 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 promising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls of European descent. To identify additional risk variants in known colorectal cancer loci, we performed conditional analyses in East Asians., Results: An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk at P = 3.9 × 10 -8 in Asians ( OR per allele deletion = 1.13, 95% confidence interval = 1.08-1.18). This association was replicated in European descendants using a variant (rs2938616) in complete linkage disequilibrium with rs67052019 ( P = 7.7 × 10 -3 ). Of the remaining 59 variants, 12 showed an association at P < 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at P < 5 × 10 -8 and two variants with an association near the genome-wide significance level (rs60911071, P = 5.8 × 10 -8 ; rs62558833, P = 7.5 × 10 -8 ) in the combined analyses of Asian- and European-ancestry data. In addition, using data from East Asians, we identified 13 new risk variants at 11 loci reported from previous GWAS., Conclusions: In this large GWAS, we identified three novel risk loci and two highly suggestive loci for colorectal cancer risk and provided evidence for potential roles of multiple genes and pathways in the etiology of colorectal cancer. In addition, we showed that additional risk variants exist in many colorectal cancer risk loci identified previously., Impact: Our study provides novel data to improve the understanding of the genetic basis for colorectal cancer risk., (©2019 American Association for Cancer Research.)

Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a complication that affects up to 5% of HTLV-1-infected individuals. Several host genetic and viral factors have been associated with the risk of HAM/TSP. The aim of this study was to evaluate the performance of a prognostic model for HAM/TSP developed in Japan in a Peruvian population of 71 HAM/TSP patients and 94 asymptomatic carriers (ACs). This model included age, proviral load (PVL), the presence of HLA-A*02 and HLA-Cw*08 alleles, SDF-1 +801, and TNF-alpha -863 polymorphisms, and viral subgroup. We describe frequencies for the four host genetic markers and demonstrate the presence of the HTLV-1 tax B subgroup in Peru. Using cross-validation, we show that the predictive ability of the prognostic model, as characterized by the area under the receiver-operating characteristic curve (AUC), does not differ from a model containing PVL only (both AUC = 0.74). We found some suggestive evidence of a protective effect of the HLA-A*02 allele but failed to replicate the associations with the other three genetic markers and with viral subgroup. A logistic model containing PVL, age, gender, and HLA-A*02 provided the best predictive ability in the Peruvian cohort (AUC = 0.79). J. Med. Virol. 82:460-466, 2010. (c) 2010 Wiley-Liss, Inc.