| Title: |
Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco‐induced lung cancer |
| Authors: |
Juan Pablo Fusco, Guillermo Pita, María José Pajares, Maria Pilar Andueza, Ana Patiño‐García, Juan P. de‐Torres, Alfonso Gurpide, Javier Zulueta, Rosario Alonso, Nuria Alvarez, Ruben Pio, Ignacio Melero, Miguel F. Sanmamed, Maria Rodriguez Ruiz, Ignacio Gil‐Bazo, Jose María Lopez‐Picazo, Ciro Casanova, Rebeca Baz Davila, Antonio Agudo, Maria Dolores Lozano, Alvaro Gonzalez, Nuria Sala, Eva Ardanaz, Javier Benitez, Luis Montuenga, Anna Gonzalez‐Neira, Jose Luis Perez‐Gracia |
| Source: |
Cancer Medicine, Vol 7, Iss 7, Pp 3474-3483 (2018) |
| Publisher Information: |
Wiley, 2018. |
| Publication Year: |
2018 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
ATP10D, cancer risk, extreme phenotypes, genome‐wide association study, non‐small cell lung cancer, PDE10A, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
Abstract Single 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 (pcombined = 5.66 × 10−5; ORcombined = 2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (pcombined = 1.02 × 10−4; ORcombined = 2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early‐stage NSCLC. PDE10A and ATP10DmRNA expressions correlated with survival in 821 stage I–II NSCLC patients (p = 0.01 and p |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2045-7634 |
| Relation: |
https://doaj.org/toc/2045-7634 |
| DOI: |
10.1002/cam4.1500 |
| Access URL: |
https://doaj.org/article/c3b285810a764be5ae798d81e210d99b |
| Accession Number: |
edsdoj.3b285810a764be5ae798d81e210d99b |
| Database: |
Directory of Open Access Journals |
