A genome-wide association study of bladder cancer identifies a new susceptibility locus within SLC14A1, a urea transporter gene on chromosome 18q12.3

作者：Garcia Closas Montserrat^*; Ye Yuanqing; Rothman Nathaniel; Figueroa Jonine D; Malats Nuria; Dinney Colin P; Chatterjee Nilanjan; Prokunina Olsson Ludmila; Wang Zhaoming; Lin Jie; Real Francisco X; Jacobs Kevin B; Baris Dalsu; Thun Michael; De Vivo Immaculata; Albanes Demetrius; Purdue Mark P; Kogevinas Manolis; Kamat Ashish M; Lerner Seth P; Grossman H Barton; Gu Jian; Pu Xia; Hutchinson Amy; Fu Yi Ping; Burdett Laurie; Yeager Meredith; Tang Wei

来源：Human Molecular Genetics, 2011, 20(21): 4282-4289.

DOI：10.1093/hmg/ddr342

Genome-wide and candidate-gene association studies of bladder cancer have identified 10 susceptibility loci thus far. We conducted a meta-analysis of two previously published genome-wide scans (4501 cases and 6076 controls of European background) and followed up the most significant association signals [17 single nucleotide polymorphisms (SNPs) in 10 genomic regions] in 1382 cases and 2201 controls from four studies. A combined analysis adjusted for study center, age, sex, and smoking status identified a novel susceptibility locus that mapped to a region of 18q12.3, marked by rs7238033 (P = 8.7 x 10(-9); allelic odds ratio 1.20 with 95% CI: 1.13-1.28) and two highly correlated SNPs, rs10775480/rs10853535 (r(2) = 1.00; P = 8.9 x 10(-9); allelic odds ratio 1.16 with 95% CI: 1.10-1.22). The signal localizes to the solute carrier family 14 member 1 gene, SLC14A1, a urea transporter that regulates cellular osmotic pressure. In the kidney, SLC14A1 regulates urine volume and concentration whereas in erythrocytes it determines the Kidd blood groups. Our findings suggest that genetic variation in SLC14A1 could provide new etiological insights into bladder carcinogenesis.

• 出版日期2011-11-1