期刊
CANCER PREVENTION RESEARCH
卷 3, 期 10, 页码 1235-1245出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1940-6207.CAPR-10-0035
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资金
- NIH [U01 CA 127615, R01 CA 74880, P50 CA 91846, R01 CA 131335]
Sonic hedgehog (Shh) pathway genetic variations may affect bladder cancer risk and clinical outcomes. Therefore, we genotyped 177 single-nucleotide polymorphisms (SNP) in 11 Shh pathway genes in a study including 803 bladder cancer cases and 803 controls. We assessed SNP associations with cancer risk and clinical outcomes in 419 cases of non-muscle-invasive bladder cancer (NMIBC) and 318 cases of muscle-invasive and metastatic bladder cancer (MiMBC). Only three SNPs (GLI3 rs3823720, rs3735361, and rs10951671) reached nominal significance in association with risk (P <= 0.05), which became nonsignificant after adjusting for multiple comparisons. Nine SNPs reached a nominally significant individual association with recurrence of NMIBC in patients who received transurethral resection (TUR) only (P <= 0.05), of which two (SHH rs1233560 and GLI2 rs11685068) were replicated independently in 356 TUR-only NMIBC patients, with P values of 1.0 x 10(-3) (SHH rs1233560) and 1.3 x 10(-3) (GLI2 rs11685068). Nine SNPs also reached a nominally significant individual association with clinical outcome of NMIBC patients who received Bacillus Calmette-Guerin (BCG; P <= 0.05), of which two, the independent GLI3 variants rs6463089 and rs3801192, remained significant after adjusting for multiple comparisons (P = 2 x 10(-4) and 9 x 10(-4), respectively). The wildtype genotype of either of these SNPs was associated with a lower recurrence rate and longer recurrence-free survival (versus the variants). Although three SNPs (GLI2 rs735557, GLI2 rs4848632, and SHH rs208684) showed nominal significance in association with overall survival in MiMBC patients (P <= 0.05), none remained significant after multiple-comparison adjustments. Germ-line genetic variations in the Shh pathway predicted clinical outcomes of TUR and BCG for NMIBC patients. Cancer Prev Res; 3(10); 1235-45. (c) 2010 AACR.
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