Document Detail


Genetic variations in the sonic hedgehog pathway affect clinical outcomes in non-muscle-invasive bladder cancer.
MedLine Citation:
PMID:  20858759     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 × 10(-3) (SHH rs1233560) and 1.3 × 10(-3) (GLI2 rs11685068). Nine SNPs also reached a nominally significant individual association with clinical outcome of NMIBC patients who received Bacillus Calmette-Guérin (BCG; P ≤ 0.05), of which two, the independent GLI3 variants rs6463089 and rs3801192, remained significant after adjusting for multiple comparisons (P = 2 × 10(-4) and 9 × 10(-4), respectively). The wild-type 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.
Authors:
Meng Chen; Michelle A T Hildebrandt; Jessica Clague; Ashish M Kamat; Antoni Picornell; Joshua Chang; Xiaofan Zhang; Julie Izzo; Hushan Yang; Jie Lin; Jian Gu; Stephen Chanock; Manolis Kogevinas; Nathaniel Rothman; Debra T Silverman; Montserrat Garcia-Closas; H Barton Grossman; Colin P Dinney; Núria Malats; Xifeng Wu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-09-21
Journal Detail:
Title:  Cancer prevention research (Philadelphia, Pa.)     Volume:  3     ISSN:  1940-6215     ISO Abbreviation:  Cancer Prev Res (Phila)     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-15     Completed Date:  2011-01-25     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  101479409     Medline TA:  Cancer Prev Res (Phila)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1235-45     Citation Subset:  IM    
Copyright Information:
©2010 AACR.
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MeSH Terms
Descriptor/Qualifier:
Aged
Antineoplastic Agents / therapeutic use
BCG Vaccine / therapeutic use
Carcinoma, Transitional Cell / genetics*,  pathology,  therapy
Case-Control Studies
Drug Resistance, Neoplasm / genetics
Female
Genetic Predisposition to Disease*
Genotype
Hedgehog Proteins / genetics*
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Recurrence, Local / genetics,  pathology
Neoplasm Staging
Polymorphism, Single Nucleotide
Treatment Outcome
Urinary Bladder Neoplasms / genetics*,  pathology,  therapy
Grant Support
ID/Acronym/Agency:
P50 CA 91846/CA/NCI NIH HHS; R01 CA 131335/CA/NCI NIH HHS; R01 CA 74880/CA/NCI NIH HHS; R01 CA074880/CA/NCI NIH HHS; R01 CA111922/CA/NCI NIH HHS; R01 CA131335/CA/NCI NIH HHS; U01 CA 127615/CA/NCI NIH HHS; U01 CA127615/CA/NCI NIH HHS; U01 CA127615-02/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/BCG Vaccine; 0/Hedgehog Proteins
Comments/Corrections

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