Genome-wide association study of early-stage non-small cell lung cancer prognosis: a pooled analysis in the International Lung Cancer Consortium

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F25%3A10500030" target="_blank" >RIV/00064203:_____/25:10500030 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/25:10500030

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=b4upuIim.R" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=b4upuIim.R</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/carcin/bgaf031" target="_blank" >10.1093/carcin/bgaf031</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Genome-wide association study of early-stage non-small cell lung cancer prognosis: a pooled analysis in the International Lung Cancer Consortium

Popis výsledku v původním jazyce

Lung cancer is the leading cause of cancer mortality. To investigate genetic determinants for prognosis among patients diagnosed with early-stage non-small cell lung cancer (NSCLC), we conducted the first large-scale genome-wide association prognostic study using data from the International Lung Cancer Consortium (ILCCO) through a two-phase analysis. Phase 1 includes the discovery of genome-wide association studies analysis using a multivariable Cox PH model on 3428 NSCLC patients of European ancestry from 10 ILCCO participating studies to identify genetic variants associated with overall survival and validation analysis for genome-wide significant variants (P-value &lt;=5 x 10-8) using the Cancer Genome Atlas (TCGA). Phase 2 aims to identify causal variants using functional analyses of genome-wide significant and suggestive variants (P-value &lt;=1 x 10-5), including variant-epigenetic functional annotation (FAVOR), CHIP-seq data, variant-gene expression association, and colocalization analysis. We identified two significant variants; of those, a locus at 9q21.31 (rs117979484) was significant at the genome-wide level (P = 3.67 x 10-8) and validated in TCGA (P = 0.03). Three suggestive variants were found to have a putative epigenetic function: intronic variants rs149281784 (BCL7B gene) and rs148031766 (POM121 gene) both located at 7q11.23 and in moderate linkage disequilibrium with each other; and variant rs2471630 (SRCIN1 gene; 17q12). Specifically, variants rs149281784 and rs148031766 have potential regulatory roles in the transcriptional activation of the BCL7B gene and POM121 gene. Exploratory survival analyses in the squamous cell carcinomas subgroup also identified a significant variant, rs138467404 (GRHL-2 gene; 8q22.3) at a genome-wide level (P = 4.75 x 10-8) and validated by TCGA (P = 0.02). These new findings indicate potential novel pathways associated with early-stage NSCLC prognosis. Future research may validate additional genome-wide suggestive variants as being relevant for lung cancer outcomes.

Název v anglickém jazyce

Genome-wide association study of early-stage non-small cell lung cancer prognosis: a pooled analysis in the International Lung Cancer Consortium

Popis výsledku anglicky

Lung cancer is the leading cause of cancer mortality. To investigate genetic determinants for prognosis among patients diagnosed with early-stage non-small cell lung cancer (NSCLC), we conducted the first large-scale genome-wide association prognostic study using data from the International Lung Cancer Consortium (ILCCO) through a two-phase analysis. Phase 1 includes the discovery of genome-wide association studies analysis using a multivariable Cox PH model on 3428 NSCLC patients of European ancestry from 10 ILCCO participating studies to identify genetic variants associated with overall survival and validation analysis for genome-wide significant variants (P-value &lt;=5 x 10-8) using the Cancer Genome Atlas (TCGA). Phase 2 aims to identify causal variants using functional analyses of genome-wide significant and suggestive variants (P-value &lt;=1 x 10-5), including variant-epigenetic functional annotation (FAVOR), CHIP-seq data, variant-gene expression association, and colocalization analysis. We identified two significant variants; of those, a locus at 9q21.31 (rs117979484) was significant at the genome-wide level (P = 3.67 x 10-8) and validated in TCGA (P = 0.03). Three suggestive variants were found to have a putative epigenetic function: intronic variants rs149281784 (BCL7B gene) and rs148031766 (POM121 gene) both located at 7q11.23 and in moderate linkage disequilibrium with each other; and variant rs2471630 (SRCIN1 gene; 17q12). Specifically, variants rs149281784 and rs148031766 have potential regulatory roles in the transcriptional activation of the BCL7B gene and POM121 gene. Exploratory survival analyses in the squamous cell carcinomas subgroup also identified a significant variant, rs138467404 (GRHL-2 gene; 8q22.3) at a genome-wide level (P = 4.75 x 10-8) and validated by TCGA (P = 0.02). These new findings indicate potential novel pathways associated with early-stage NSCLC prognosis. Future research may validate additional genome-wide suggestive variants as being relevant for lung cancer outcomes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Carcinogenesis

ISSN

0143-3334

e-ISSN

1460-2180

Svazek periodika

46

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

bgaf031

Kód UT WoS článku

001541126100001

EID výsledku v databázi Scopus

2-s2.0-105013349082