2024-03-28T09:55:01Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/114232024-01-30T18:42:18Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
Repisalud
author
Pineda, Silvia
author
Milne, Roger L
author
Calle, M Luz
author
Rothman, Nathaniel
author
Herranz, Jesús
author
Kogevinas, Manolis
author
Chanock, Stephen J
author
Tardón, Adonina
author
Márquez, Mirari
author
Guey, Lin T
author
García-Closas, Montserrat
author
Lloreta, Josep
author
Baum, Erin
author
Carrato, Alfredo
author
Navarro, Arcadi
author
Silverman, Debra T
author
Lopez de Maturana, Evangelina
author
Malats, Nuria
author
Gonzalez Neira, Anna
author
Real Arribas, Francisco
funder
Instituto de Salud Carlos III
funder
Red Temática de Investigación Cooperativa en Cáncer (RTICC) (España)
funder
Fundación La Marató TV3
funder
Unión Europea
funder
United States Department of Health and Human Services
funder
Institució Catalana de Recerca i Estudis Avançats
2020-11-25T10:43:32Z
2020-11-25T10:43:32Z
2014-05-12
PLoS One. 2014;9(5):e89952
http://hdl.handle.net/20.500.12105/11423
24818791
10.1371/journal.pone.0089952
PloS one
Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro), still present controversial results. We carried out an in depth assessment of associations between common germline variants in the TP53 pathway and bladder cancer risk.
We investigated 184 tagSNPs from 18 genes in 1,058 cases and 1,138 controls from the Spanish Bladder Cancer/EPICURO Study. Cases were newly-diagnosed bladder cancer patients during 1998-2001. Hospital controls were age-gender, and area matched to cases. SNPs were genotyped in blood DNA using Illumina Golden Gate and TaqMan assays. Cases were subphenotyped according to stage/grade and tumor p53 expression. We applied classical tests to assess individual SNP associations and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized logistic regression analysis to assess multiple SNPs simultaneously.
Based on classical analyses, SNPs in BAK1 (1), IGF1R (5), P53AIP1 (1), PMAIP1 (2), SERINPB5 (3), TP63 (3), and TP73 (1) showed significant associations at p-value≤0.05. However, no evidence of association, either with overall risk or with specific disease subtypes, was observed after correction for multiple testing (p-value≥0.8). LASSO selected the SNP rs6567355 in SERPINB5 with 83% of reproducibility. This SNP provided an OR = 1.21, 95%CI 1.05-1.38, p-value = 0.006, and a corrected p-value = 0.5 when controlling for over-estimation.
We found no strong evidence that common variants in the TP53 pathway are associated with bladder cancer susceptibility. Our study suggests that it is unlikely that TP53 Arg72Pro is implicated in the UCB in white Europeans. SERPINB5 and TP63 variation deserve further exploration in extended studies.
eng
Genetic variation in the TP53 pathway and bladder cancer risk. a comprehensive analysis.
journal article
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