Sequence variant on 3q28 and urinary bladder cancer risk: findings from the Los Angeles-Shanghai bladder case-control study.
Recently, the first genome-wide association study of bladder cancer identified an association of genome-wide significance between single nucleotide polymorphism (SNP) rs715021 and urinary bladder cancer risk among European individuals. This SNP is in a haplotype block in linkage disequilibrium with the TP63 gene. We investigated the role of this SNP among 1,042 cases and 1,123 controls among non-Latino whites in Los Angeles County, CA and among Chinese in Shanghai, China. We confirmed an association between the A allele and bladder cancer risk [log-additive per A allele odds ratios (OR), 1.24; and 95% confidence intervals (95% CI), 1.02-1.52; P = 0.032] in Los Angeles County and a similar association in Shanghai (log-additive per A allele OR, 1.21; 95% CI, 0.98-1.49; P = 0.080). These estimates did not differ by study site, smoking status, or gender. However, the effects were greater in older individuals. Analysis within non-Latino whites, for whom we had histologic results, revealed that this association was restricted to low-risk tumors (OR, 1.49; 95% CI, 1.17-1.92; P = 0.002) and absent among high-risk tumors (OR, 1.03; 95% CI, 0.80-1.33; P = 0.790; heterogeneity, P = 0.019). A positive association (OR, 1.56; 95% CI, 0.93-2.62; P = 0.089) was only observed among high-risk tumors from individuals older than 56 years old (interaction, P = 0.045). Our results suggest that a TP63 gene variant may increase susceptibility for the development of urinary bladder tumors with low risk of progression.
Department of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089, USA. stern_m@ccnt.usc.edu
Mariana C
MC
Stern
David
D
Van Den Berg
Jian-Min
JM
Yuan
David V
DV
Conti
Manuela
M
Gago-Dominguez
Malcolm C
MC
Pike
Yong-Bing
YB
Xiang
Yu-Tang
YT
Gao
Victoria K
VK
Cortessis
D000328:Adult; D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015141:Los Angeles / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm