Per accedir als documents amb el text complet, si us plau, seguiu el següent enllaç:

Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis
Pineda, S.; Milne, R.L.; Calle, M. Luz; Rothman, Nathaniel; López de Maturana, Evangelina; Herranz, J.; Kogevinas, Manolis; Chanock, Stephen; Tardón, Adonina; Márquez, M.; Guey, Lin T.; García-Closas, Montserrat; Lloreta, Josep; Baum, E.; González-Neira, Anna; Carrato, Alfredo; Navarro, Arcadi; Silverman, Debra T.; Real, Francisco X.; Malats i Riera, Núria
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.
Aquest document està subjecte a una llicència Creative Commons
Public Library of Science

Text complet d'aquest document

Fitxers Mida Format
artconlli_a2014_calle_malu_genetic_variation.pdf 334.2 KB PDF

Mostra el registre complet del document

Documents relacionats

Altres documents del mateix autor/a

López de Maturana, Evangelina; Ye, Yuanging; Calle, M. Luz; Rothman, Nathaniel; Urrea Gales, Víctor; Kogevinas, Manolis; Petrus, Sandra; Chanock, Stephen; Tardón, Adonina; García-Closas, Montserrat; González-Neira, Anna; Vellalta, Gemma; Carrato, Alfredo; Navarro, Arcadi; Lorente-Galdós, Belén; Silverman, Debra T.; Real, Francisco X.; Wu, Xifeng; Malats i Riera, Núria
Vedder, M.M.; Márquez, M.; Bekker-Grob de, E.W.; Calle, M. Luz; Dyrskjot, L.; Kogevinas, Manolis; Segersten, U.; Malmström, P.U.; Algaba, F.; Beukers, W.; Orntoft, T.F.; Zwarthoff, E.; Real, Francisco X.; Malats i Riera, Núria; Steyerberg, E.W.
Villanueva, Cristina M.; Gracia-Lavedan, Esther; Bosetti, Cristina; Righi, Elena; Molina, Antonio José; Martín, Vicente; Boldo, Elena; Aragonés, Nuria; Pérez Gómez, Beatriz; Pollán, Marina; Gómez Acebo, Inés; Altzibar, Jone M.; Jiménez Zabala, Ana; Ardanaz, Eva; Peiró, Rosana; Tardón, Adonina; Chirlaque, María Dolores; Tavani, Alessandra; Polesel, Jerri; Serraino, Diego; Pisa, Federica E.; Castaño-Vinyals, Gemma; Espinosa, Anna; Espejo-Herrera, Nadia; Palau, Margarita; Moreno Aguado, Víctor; Vecchia, Carlo La; Aggazzotti, Gabriella; Nieuwenhuijsen, Mark J.; Kogevinas, Manolis
Ibánez Sanz, Gemma; Díez Villanueva, Anna; Henar Alonso, M.; Rodríguez Moranta, Francisco; Pérez Gómez, Beatriz; Bustamante Pineda, Mariona; Martin, Vicente; Llorca Díaz, Javier; Amiano, Pilar; Ardanaz, Eva; Tardón, Adonina; Jiménez Moleón, José J.; Peiró, Rosana; Alguacil, Juan; Navarro, Carmen; Guinó, Elisabet; Binefa, Gemma; Fernández Navarro, Pablo; Espinosa, Anna; Dávila Batista, Verónica; Molina, Antonio José; Palazuelos, Camilo; Castaño-Vinyals, Gemma; Aragonés, Nuria; Kogevinas, Manolis; Pollán, Marina; Moreno, Victor