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dc.creatorFusco, J.P. (Juan Pablo)-
dc.creatorPita, G. (Guillermo)-
dc.creatorPajares, M.J. (María José)-
dc.creatorAndueza, M.P. (Maria P.)-
dc.creatorPatiño-García, A. (Ana)-
dc.creatorTorres, J.P. (Juan P.) de-
dc.creatorGurpide, A. (Alfonso)-
dc.creatorZulueta, J. (Javier)-
dc.creatorAlonso, R. (Rosario)-
dc.creatorAlvarez, N. (Nuria)-
dc.creatorPio, R. (Rubén)-
dc.creatorMelero, I. (Ignacio)-
dc.creatorFernandez-Sanmamed, M. (Miguel)-
dc.creatorRodriguez-Ruiz, M. (María)-
dc.creatorGil-Bazo, I. (Ignacio)-
dc.creatorLopez-Picazo, J.M. (José M.)-
dc.creatorCasanova, C. (Ciro)-
dc.creatorBaz-Dávila, R. (Rebeca)-
dc.creatorAgudo, A. (Antonio)-
dc.creatorLozano, M.D. (María Dolores)-
dc.creatorGonzález, Á. (Álvaro)-
dc.creatorBou-i-Sala, N. (Núria)-
dc.creatorArdanaz, E. (Eva)-
dc.creatorBenitez, J. (Javier)-
dc.creatorMontuenga-Badia, L.M. (Luis M.)-
dc.creatorGonzalez-Neira, A. (Anna)-
dc.creatorPerez-Gracia, J.L. (Jose Luis)-
dc.date.accessioned2022-10-19T10:47:37Z-
dc.date.available2022-10-19T10:47:37Z-
dc.date.issued2018-
dc.identifier.citationNCBIes_ES
dc.identifier.issn2045-7634-
dc.identifier.urihttps://hdl.handle.net/10171/64523-
dc.description.abstractSingle nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC.es_ES
dc.description.sponsorshipSpanish Society of Medical Oncology, Fundación SEOM and Fundación Salud 2000, Government of Navarra.es_ES
dc.format.extentCANCER MEDICINEes_ES
dc.language.isoenges_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectATP10Des_ES
dc.subjectCancer riskes_ES
dc.subjectGenome-wide association studyes_ES
dc.subjectNon-small cell lung canceres_ES
dc.subjectPDE10Aes_ES
dc.subjectSingle nucleotide polymorphismes_ES
dc.subjectTobaccoes_ES
dc.titleGenomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung canceres_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.description.noteThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.es_ES
dc.identifier.doi10.1002/cam4.1500-
dadun.citation.endingPage3483es_ES
dadun.citation.number7es_ES
dadun.citation.startingPage3474es_ES
dadun.citation.volume7es_ES

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