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A genome-wide association study meta-analysis, published online April 26 in Nature Genetics, has identified 63 susceptibility regions containing 108 independent risk loci for kidney cancer.
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.
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, 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).
“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.
Several authors disclosed ties to the biopharmaceutical and medical technology industries.
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