Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights.
Koutros S., Kiemeney LA., Pal Choudhury P., Milne RL., Lopez de Maturana E., Ye Y., Joseph V., Florez-Vargas O., Dyrskjøt L., Figueroa J., Dutta D., Giles GG., Hildebrandt MAT., Offit K., Kogevinas M., Weiderpass E., McCullough ML., Freedman ND., Albanes D., Kooperberg C., Cortessis VK., Karagas MR., Johnson A., Schwenn MR., Baris D., Furberg H., Bajorin DF., Cussenot O., Cancel-Tassin G., Benhamou S., Kraft P., Porru S., Carta A., Bishop T., Southey MC., Matullo G., Fletcher T., Kumar R., Taylor JA., Lamy P., Prip F., Kalisz M., Weinstein SJ., Hengstler JG., Selinski S., Harland M., Teo M., Kiltie AE., Tardón A., Serra C., Carrato A., García-Closas R., Lloreta J., Schned A., Lenz P., Riboli E., Brennan P., Tjønneland A., Otto T., Ovsiannikov D., Volkert F., Vermeulen SH., Aben KK., Galesloot TE., Turman C., De Vivo I., Giovannucci E., Hunter DJ., Hohensee C., Hunt R., Patel AV., Huang W-Y., Thorleifsson G., Gago-Dominguez M., Amiano P., Golka K., Stern MC., UROMOL Consortium None., Yan W., Liu J., Li SA., Katta S., Hutchinson A., Hicks B., Wheeler WA., Purdue MP., McGlynn KA., Kitahara CM., Haiman CA., Greene MH., Rafnar T., Chatterjee N., Chanock SJ., Wu X., Real FX., Silverman DT., Garcia-Closas M., Stefansson K., Prokunina-Olsson L., Malats N., Rothman N.
BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. RESULTS AND LIMITATIONS: Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p