{"doi":"10.1126/science.adi3808","title":"An immunogenetic basis for lung cancer risk","abstract":"Cancer risk is influenced by inherited mutations, DNA replication errors, and environmental factors. However, the influence of genetic variation in immunosurveillance on cancer risk is not well understood. Leveraging population-level data from the UK Biobank and FinnGen, we show that heterozygosity at the human leukocyte antigen (HLA) -II loci is associated with reduced lung cancer risk in smokers. Fine-mapping implicated amino acid heterozygosity in the HLA -II peptide binding groove in reduced lung cancer risk, and single-cell analyses showed that smoking drives enrichment of proinflammatory lung macrophages and HLA -II+ epithelial cells. In lung cancer, widespread loss of HLA -II heterozygosity (LOH) favored loss of alleles with larger neopeptide repertoires. Thus, our findings nominate genetic variation in immunosurveillance as a critical risk factor for lung cancer.","journal":"Science","year":2024,"id":419873,"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":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":984265,"name":"Anniina Tervi","orcid":"0000-0002-9857-2132","position":1,"is_corresponding":false},{"id":45001,"name":"Miriam Saffern","orcid":"0000-0003-0365-3704","position":2,"is_corresponding":false},{"id":1210607,"name":"E. A. Wilson","orcid":null,"position":3,"is_corresponding":false},{"id":620420,"name":"Seong‐Keun Yoo","orcid":"0000-0002-8749-7050","position":4,"is_corresponding":false},{"id":251612,"name":"Nina Mars","orcid":"0000-0002-7259-5993","position":5,"is_corresponding":false},{"id":86516,"name":"Vladimir Roudko","orcid":"0000-0002-3835-6737","position":6,"is_corresponding":false},{"id":733977,"name":"Byuri Angela Cho","orcid":"0000-0002-1802-7709","position":7,"is_corresponding":false},{"id":1210608,"name":"Samuel Edward Jones","orcid":null,"position":12,"is_corresponding":false},{"id":105281,"name":"Natalie Vaninov","orcid":"0000-0002-5133-6941","position":13,"is_corresponding":false},{"id":51766,"name":"Myvizhi Esai Selvan","orcid":"0000-0003-4640-5727","position":14,"is_corresponding":false},{"id":51787,"name":"Zeynep H. Gümüş","orcid":"0000-0002-7364-2202","position":15,"is_corresponding":false},{"id":621124,"name":"Francisco Martínez-Jiménez","orcid":"0000-0001-7804-1134","position":16,"is_corresponding":false},{"id":51379,"name":"Tobias L. Lenz","orcid":"0000-0002-7203-0044","position":17,"is_corresponding":false},{"id":44523,"name":"Miriam Mérad","orcid":"0000-0002-4481-7827","position":18,"is_corresponding":false},{"id":265963,"name":"Paolo Boffetta","orcid":"0000-0002-3811-2791","position":19,"is_corresponding":false},{"id":555476,"name":"Hanna M. Ollila","orcid":"0000-0002-5302-6429","position":21,"is_corresponding":false},{"id":13003,"name":"Robert Samstein","orcid":"0000-0001-6860-2401","position":22,"is_corresponding":false},{"id":267982,"name":"Diego Chowell","orcid":"0000-0002-1355-5545","position":23,"is_corresponding":false},{"id":56492,"name":"Chirag Krishna","orcid":"0000-0002-9166-4632","position":0,"is_corresponding":true}],"reference_count":122,"raw_metadata":null,"created_at":"2026-07-19T01:57:19.937291Z","pmid":"38386728","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}