Objective To qualitatively and quantitatively investigate the link between a low estimated glomerular filtration rate (eGFR) at baseline and risk of future stroke. Design Systematic review and meta-analysis of prospective studies. Data sources PubMed (1966-October 2009 and Embase (1947-October 2009. Selection criteria Inclusion criteria were studies that prospectively collected data within cohort studies or clinical trials, estimated glomerular filtration rate at baseline using the modification of diet in renal disease or Cockcroft-Gault equations, assessed incident stroke, had a follow-up of at least one year, and reported quantitative estimates of multivariate adjusted relative risk and 95% confidence interval for stroke associated with an eGFR of 60-90 ml/min/1.73 m 2 or <60 ml/min/1.73 m 2 . Data abstraction Two investigators independently abstracted data from eligible studies. Estimates were combined using a random effects model. Heterogeneity was assessed by P value of χ 2 statistics and I 2 . Publication bias was assessed by visual examination of funnel plots. Results 21 articles derived from 33 prospective studies: 14 articles assessed eGFR <60 ml/min/1.73 m 2 and seven assessed eGRF at both <60 ml/min/1.73 m 2 and 60-90 ml/min/1.73 m 2 for a total of 284 672 participants (follow-up 3.2-15 years) with 7863 stroke events. Incident stroke risk increased among participants with an eGFR <60 ml/min/1.73 m 2 (relative risk 1.43, 95% confidence interval 1.31 to 1.57; P<0.001) but not among those with an eGFR of 60-90 ml/min/1.73 m 2 (1.07, 0.98 to 1.17; P=0.15). Significant heterogeneity existed between estimates among patients with an eGFR <60 ml/min/1.73 m 2 (P<0.001). In subgroup analyses among participants with an eGFR <60 ml/min/1.73 m 2

We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated the top SNP in nine European populations. A missense variant (rs2294008) in the PSCA gene showed consistent association with bladder cancer in US and European populations. Combining all subjects (6,667 cases, 39,590 controls), the overall P-value was 2.14 × 10−10 and the allelic odds ratio was 1.15 (95% confidence interval 1.10–1.20). rs2294008 alters the start codon and is predicted to cause truncation of nine amino acids from the N-terminal signal sequence of the primary PSCA translation product. In vitro reporter gene assay showed that the variant allele significantly reduced promoter activity. Resequencing of the PSCA genomic region showed that rs2294008 is the only common missense SNP in PSCA. Our data identify rs2294008 as a new bladder cancer susceptibility locus.

In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.