| Genetic variations in the sonic hedgehog pathway affect clinical outcomes in non-muscle-invasive bladder cancer. | |
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MedLine Citation:
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PMID: 20858759 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-09-21 |
Journal Detail:
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Title: Cancer prevention research (Philadelphia, Pa.) Volume: 3 ISSN: 1940-6215 ISO Abbreviation: Cancer Prev Res (Phila) Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-15 Completed Date: 2011-01-25 Revised Date: 2013-05-27 |
Medline Journal Info:
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Nlm Unique ID: 101479409 Medline TA: Cancer Prev Res (Phila) Country: United States |
Other Details:
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Languages: eng Pagination: 1235-45 Citation Subset: IM |
Copyright Information:
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©2010 AACR. |
Affiliation:
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Department of Epidemiology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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P50 CA 91846/CA/NCI NIH HHS; R01 CA 131335/CA/NCI NIH HHS; R01 CA 74880/CA/NCI NIH HHS; R01 CA074880-10/CA/NCI NIH HHS; R01 CA111922-05/CA/NCI NIH HHS; R01 CA131335-04/CA/NCI NIH HHS; U01 CA 127615/CA/NCI NIH HHS; U01 CA127615-02/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/BCG Vaccine; 0/Hedgehog Proteins |
| Comments/Corrections | |
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