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

Result code in 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>

Alternative codes found

RIV/00216208:11130/25:10500030

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

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

Name of the periodical

Carcinogenesis

ISSN

0143-3334

e-ISSN

1460-2180

Volume of the periodical

46

Issue of the periodical within the volume

2

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

bgaf031

UT code for WoS article

001541126100001

EID of the result in the Scopus database

2-s2.0-105013349082