Validated polygenic risk score generated, with area under the curve of 0.65 among European ancestry individuals<\/p>\n<\/h3>\n
By Elana Gotkine HealthDay Reporter<\/b><\/p>\n
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THURSDAY, May 2, 2024 (HealthDay News) — A genome-wide association study meta-analysis, published online April 26 in Nature Genetics<\/em>, has identified 63 susceptibility regions containing 108 independent risk loci for kidney cancer.<\/p>\n Mark P. Purdue, Ph.D., from the National Cancer Institute in Rockville, Maryland, and colleagues conducted a multi-ancestry genome-wide association study meta-analysis of kidney cancer involving 29,020 cases and 835,670 controls to identify susceptibility regions.<\/p>\n The researchers identified 63 susceptibility regions, of which 50 were novel, which included 108 independent risk loci. In subtype-stratified analyses, 52 regions with 78 loci were associated with clear cell renal cell carcinoma (RCC) and six regions with seven loci were associated with papillary RCC. A variant common in individuals of African ancestry, located in the 3′ untranslated region of VHL<\/em>, yielded a nearly threefold increased risk for clear cell RCC (odds ratio, 2.72). In analyses of cis-expression quantitative trait loci, 34 regions with 48 variants indicated 83 candidate genes. The importance of hypoxia-related mechanisms in kidney cancer was underscored by enrichment of hypoxia-induced factor-binding sites. These results enabled generation of a validated polygenic risk score, which had an estimated area under the curve of 0.65 among individuals of European ancestry (0.74 in a model including risk factors).<\/p>\n “Our study demonstrates genetic factors common to different histologic subtypes and at the same time, defines subtype-specific variants, which in turn could lead to new avenues for research,” the authors write.<\/p>\n Several authors disclosed ties to the biopharmaceutical and medical technology industries.<\/p>\n Abstract\/Full Text (subscription or payment may be required)<\/a><\/p>\n <\/i><\/p>\n