{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Krishna C"],"funding":["NIAID NIH HHS","NCI NIH HHS","NIH HHS"],"pagination":["eadi3808"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11998992"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["383(6685)"],"pubmed_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 <i>human leukocyte antigen (HLA)</i>-II loci is associated with reduced lung cancer risk in smokers. Fine-mapping implicated amino acid heterozygosity in the <i>HLA</i>-II peptide binding groove in reduced lung cancer risk, and single-cell analyses showed that smoking drives enrichment of proinflammatory lung macrophages and <i>HLA</i>-II+ epithelial cells. In lung cancer, widespread loss of <i>HLA</i>-II heterozygosity (LOH) favored loss of alleles with larger neopeptide repertoires. Thu"],"journal":["Science (New York, N.Y.)"],"pubmed_title":["An immunogenetic basis for lung cancer risk."],"pmcid":["PMC11998992"],"funding_grant_id":["DP5 OD028171","R33 CA263705","T32 AI078892","R01 CA283469"],"pubmed_authors":["Selvan ME","Gumus ZH","Krishna C","Merad M","Roudko V","Lenz TL","Wilson EA","Saffern M","Yoo SK","Mars N","Cho BA","Martinez-Jimenez F","Chowell D","Vaninov N","Tervi A","Jones SE","Boffetta P","Samstein RM","FinnGen§","Ollila HM"],"additional_accession":[]},"is_claimable":false,"name":"An immunogenetic basis for lung cancer risk.","description":"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 <i>human leukocyte antigen (HLA)</i>-II loci is associated with reduced lung cancer risk in smokers. Fine-mapping implicated amino acid heterozygosity in the <i>HLA</i>-II peptide binding groove in reduced lung cancer risk, and single-cell analyses showed that smoking drives enrichment of proinflammatory lung macrophages and <i>HLA</i>-II+ epithelial cells. In lung cancer, widespread loss of <i>HLA</i>-II heterozygosity (LOH) favored loss of alleles with larger neopeptide repertoires. Thu","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2025-07-03T03:06:53.797Z","creation":"2025-07-03T03:06:53.797Z"},"accession":"S-EPMC11998992","cross_references":{"pubmed":["38386728"],"doi":["10.1126/science.adi3808"]}}