Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.

• MeSH
• adenokarcinom genetika   MeSH
• běloši genetika   MeSH
• celogenomová asociační studie * MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• homeostáza telomer genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• kouření epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokus kvantitativního znaku MeSH
• mapování chromozomů MeSH
• nádory plic epidemiologie   etnologie   genetika   MeSH
• senioři MeSH
• zdraví rodiny MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.

• MeSH
• alfa receptor estrogenů genetika   metabolismus   MeSH
• exprese genu MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• lidské chromozomy, pár 6 genetika   MeSH
• nádory prsu genetika   metabolismus   MeSH
• proteiny buněčného cyklu genetika   metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• rizikové faktory MeSH
• sekvence nukleotidů MeSH
• transportní proteiny genetika   metabolismus   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH