title: Common variation at 1q24.1 (ALDH9A1) is a potential risk factor for renal cancer.
abstract: So far six susceptibility loci for renal cell carcinoma (RCC) have been discovered by genome-wide association studies (GWAS). To identify additional RCC common risk loci, we performed a meta-analysis of published GWAS (totalling 2,215 cases and 8,566 controls of Western-European background) with imputation using 1000 Genomes Project and UK10K Project data as reference panels and followed up the most significant association signals [22 single nucleotide polymorphisms (SNPs) and 3 indels in eight genomic regions] in 383 cases and 2,189 controls from The Cancer Genome Atlas (TCGA). A combined analysis identified a promising susceptibility locus mapping to 1q24.1 marked by the imputed SNP rs3845536 (Pcombined =2.30x10-8). Specifically, the signal maps to intron 4 of the ALDH9A1 gene (aldehyde dehydrogenase 9 family, member A1). We further evaluated this potential signal in 2,461 cases and 5,081 controls from the International Agency for Research on Cancer (IARC) GWAS of RCC cases and controls from multiple European regions. In contrast to earlier findings no association was shown in the IARC series (P=0.94; Pcombined =2.73x10-5). While variation at 1q24.1 represents a potential risk locus for RCC, future replication analyses are required to substantiate our observation.
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
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authors.affiliation: Division of Cancer Epidemiology and Genetics, Department Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
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authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
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authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
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authors.affiliation: International Agency for Research on Cancer, Lyon, France.
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authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Mattias
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authors.affiliation: McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada.
authors.forename: Mark
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authors.affiliation: Royal Marsden NHS Foundation Trust, London, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Larkin
authors.affiliation: Division of Cancer Epidemiology and Genetics, Department Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.affiliation: Division of Cancer Epidemiology and Genetics, Department Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America; Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Gaithersburg, Maryland, United States of America.
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Division of Cancer Epidemiology and Genetics, Department Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America; Division of Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America.
authors.forename: Victoria L
authors.initials: VL
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authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America.
authors.forename: W Ryan
authors.initials: WR
authors.lastname: Diver
authors.affiliation: Division of Cancer Epidemiology and Genetics, Department Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Demetrius
authors.initials: D
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authors.forename: Paul
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authors.lastname: Brennan
authors.affiliation: Cambridge University Health Partners, Cambridge, United Kingdom.
authors.forename: Timothy
authors.initials: T
authors.lastname: Eisen
authors.affiliation: Division of Cancer Epidemiology and Genetics, Department Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Stephen
authors.initials: S
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authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
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mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
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