Increasing detection of presymptomatic tumors by imaging procedures, such as ultrasonography, computed tomography, and magnetic resonance imaging, does not fully explain the upward incidence trends of renal cell carcinoma. Other factors may be contributing to the rapidly increasing incidence of renal cell cancer in the United States, particularly among blacks.

A proinflammatory cytokine genetic profile increases the risk of noncardia gastric adenocarcinoma but not other upper gastrointestinal cancers, possibly by inducing a hypochlorhydric and atrophic response to gastric H. pylori infection.

Patients hospitalized with a diagnosis of diabetes appear to be at higher risk of developing cancers of the liver, biliary tract, pancreas, endometrium, and kidney. The elevated risks of endometrial and kidney cancers, however, may be confounded by obesity.

Because of the long lag time before risk of these tumors is reduced among ex-smokers, smoking may affect early stage carcinogenesis. The increase in smoking prevalence during the first two thirds of this century may be reflected in the rising incidence of these tumors in the past few decades among older individuals. The recent decrease in smoking may not yet have had an impact.

contributed to the design and execution of the overall study. M.P.P., M.J., J.R.T., G.S., L.E.M., L.A.K., X.W., V.G., K.B.J., J.D.M., N.R., S.J.C., and P Brennan contributed to the statistical analysis. M.P.P., M.J., S.J.C. and P. Brennan wrote the first draft of the manuscript. D. Zeleniak, E.P., L.A.K., X.W., K.B.J., S.H.V., S.L.M., Y.Y., A.M.M., E.S.B., N.N.C., M.F., D.L., I.G., S.H., H. Blanche, A.H., G.T., Z.W., M.Y., K.G.S., S.J.C., and M.L. supervised or conducted the genotyping. The remaining authors conducted the epidemiologic studies and contributed samples to the GWAS and/or replication. All authors contributed to the writing of the manuscript. NIH Public Access Author ManuscriptNat Genet. Author manuscript; available in PMC 2012 January 1. AbstractWe conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 cases and 8,505 controls of European background from 11 studies, and followed up 6 SNPs in three replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r 2 = 0.99 in controls), rs11894252 (P = 1.8×10 −8 ) and rs7579899 (P = 2.3×10 −9 ), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13, contains no characterized genes (P = 7.8×10 −14 ). In addition, we observed a promising association on 12q24.31 for rs4765623 which maps to the scavenger receptor class B, member 1 (SCARB1) gene (P = 2.6×10 −8 ). Our study reports novel genomic regions associated with RCC risk that may lead to new etiological insights. Table 1, Online Methods and Supplementary note). All subjects from the IARC/CNG study were genotyped at the CNG with the exception of 305 cases and 323 controls from Russia that were genotyped at the Center "Bioengineering" and at the "Kurchatov Institute" in Moscow. All subjects from the NCI study were scanned at the NCI Core Genotyping Facility. In addition, 1,438 controls from the Wellcome Trust Case-Control Consortium were genotyped at the Sanger Institute, UK 10 . All RCC cases were defined on the basis of the International Classification of Diseases for Oncology, Second Edition (ICD-O-2), and included all cancers that were coded as C64.Comparable quality control metrics were applied to the two scanned data sets and following sample and SNP exclusions, genotype data for up to 577,547 SNPs were available for 2,461 cases and 5,081 controls in the IARC/CNG scan, while data for 585,576 SNPs were available for 1,311 cases and 3,424 controls in the NCI scan (Online Methods). Primary analyses were conducted using unconditional logistic regression models for genotype trend effects (1 degree of freedom) and adjusted for sex, country, eigenvectors, and study for the USA (Online Methods). In order to compute summary findings across both scans, a metaanalysis was performed using a fixed effects model with inverse variance wei...