{"doi":"10.1093/carcin/bgaf031","title":"Genome-wide association study of early-stage non-small cell lung cancer prognosis: a pooled analysis in the International Lung Cancer Consortium","abstract":"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 ≤5 × 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 ≤1 × 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 × 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 × 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.","journal":"Carcinogenesis","year":2025,"id":571477,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5641,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1209250,"name":"Abhinav Thakral","orcid":null,"position":1,"is_corresponding":false},{"id":246453,"name":"Karl Smith-Byrne","orcid":"0000-0002-1932-7463","position":2,"is_corresponding":false},{"id":232200,"name":"Yohan Bossé","orcid":"0000-0002-3067-3711","position":3,"is_corresponding":false},{"id":53273,"name":"Hufeng Zhou","orcid":"0000-0001-9382-5674","position":4,"is_corresponding":false},{"id":414222,"name":"Yi Zhang","orcid":"0000-0002-7453-6188","position":5,"is_corresponding":false},{"id":78858,"name":"Joshua Atkins","orcid":"0000-0003-0821-1112","position":6,"is_corresponding":false},{"id":78832,"name":"Philip C Haycock","orcid":"0000-0001-5001-3350","position":7,"is_corresponding":false},{"id":878640,"name":"M. 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