Genome-wide association study identifies multiple loci associated with bladder cancer risk.
Figueroa JD., Ye Y., Siddiq A., Garcia-Closas M., Chatterjee N., Prokunina-Olsson L., Cortessis VK., Kooperberg C., Cussenot O., Benhamou S., Prescott J., Porru S., Dinney CP., Malats N., Baris D., Purdue M., Jacobs EJ., Albanes D., Wang Z., Deng X., Chung CC., Tang W., Bas Bueno-de-Mesquita H., Trichopoulos D., Ljungberg B., Clavel-Chapelon F., Weiderpass E., Krogh V., Dorronsoro M., Travis R., Tjønneland A., Brenan P., Chang-Claude J., Riboli E., Conti D., Gago-Dominguez M., Stern MC., Pike MC., Van Den Berg D., Yuan J-M., Hohensee C., Rodabough R., Cancel-Tassin G., Roupret M., Comperat E., Chen C., De Vivo I., Giovannucci E., Hunter DJ., Kraft P., Lindstrom S., Carta A., Pavanello S., Arici C., Mastrangelo G., Kamat AM., Lerner SP., Barton Grossman H., Lin J., Gu J., Pu X., Hutchinson A., Burdette L., Wheeler W., Kogevinas M., Tardón A., Serra C., Carrato A., García-Closas R., Lloreta J., Schwenn M., Karagas MR., Johnson A., Schned A., Armenti KR., Hosain GM., Andriole G., Grubb R., Black A., Ryan Diver W., Gapstur SM., Weinstein SJ., Virtamo J., Haiman CA., Landi MT., Caporaso N., Fraumeni JF., Vineis P., Wu X., Silverman DT., Chanock S., Rothman N.
Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10(-9)) and rs907611 on 11p15.5 (P = 4.11 × 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 × 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.