RT Journal Article
T1 Genetic variation in the TP53 pathway and bladder cancer risk. a comprehensive analysis
A1 Pineda Sanjuan, Silvia
A1 Milne, Roger
A1 Calle, M Luz
A1 Rothman, Nathaniel
A1 López de Maturana, Evangelina
A1 Herranz, Jesús
A1 Kogevinas, Manolis
A1 Chanock, Stephen
A1 Tardón, Adonina
A1 Márquez, Mirari
A1 Guey, Lin T
A1 García-Closas, Montserrat
A1 Lloreta, Josep
A1 Baum, Erin
A1 González-Neira, Anna
A1 Carrato, Alfredo
A1 Navarro, Arcadi
A1 Silverman, Debra
A1 Real, Francisco
A1 Maltas, Núria
A2 Chenette, Emily
AB Introduction: 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.Material and Methods: 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.Results: 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.Discussion: 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.
PB Public Library of Science. San Francisco, CA.
SN 1932-6203
YR 2014
FD 2014
LK https://hdl.handle.net/20.500.14352/97109
UL https://hdl.handle.net/20.500.14352/97109
LA eng
NO Pineda S, Milne RL, Calle ML, Rothman N, Lo´ pez de Maturana E, et al. (2014) Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis. PLoS ONE 9(5): e89952.
NO Ministerio de Sanidad (España)
NO Marató TV3
NO European Commission
NO US National Institute of Health
NO Ministerio de Economía y Competitividad (España)
DS Docta Complutense
RD 8 ago 2024