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DOI 10.1038/s41467-026-76157-4

Медицинская библиотека · Nature communications · 2026

Multi-population GWAS meta-analysis identifies bladder cancer susceptibility loci and highlights genetic regulation of smoking-related risk.

Prokunina-Olsson Ludmila, Florez-Vargas Oscar, Levin Michael G, Dutta Diptavo, Breeze Charles E, Hurwitz Lauren M, Yan Wusheng, Lamy Philippe, Papenberg Brenen W, Wang Kevin, Lee Chia-Han, Milne Roger L, Gu Jian, Um Caroline Y, Joseph Vijai, Furberg Helena, Le Calvez-Kelm Florence, Lori Adriana, Choudhury Parichoy Pal, Afshar Nina, Kogevinas Manolis, Offit Kenneth, Vermeulen Sita H, López de Maturana Evangelina, Albanes Demetrius, Purdue Mark P, Cortessis Victoria K, Karagas Margaret R, Kooperberg Charles, Bjurlin Marc, Tadesse Deborah A, Moore Steven C, Huang Wen-Yi, Haiman Christopher A, Stern Mariana C, Eliassen A Heather, Mucci Lorelei A, Aben Katja K, Galesloot Tessel E, UROMOL Consortium, Verma Anurag, Yoshino Soichiro, Hikino Keiko, Terao Chikashi, Rafnar Thorunn, Matsuda Koichi, Shuin Taro, Garcia-Closas Montserrat, Real Francisco X, Kiemeney Lambertus A, Chanock Stephen J, Malats Núria, Silverman Debra T, Dyrskjot Lars, Rothman Nathaniel, Damrauer Scott M, Koutros Stella, Damrauer Jeffrey S

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Аннотация

Bladder cancer is the ninth most common cancer worldwide, caused by genetic and environmental risk factors. Here, we report the findings of a multi-population meta-analysis of genome-wide association studies, including 32,470 individuals with and 1,753,462 without bladder cancer. We identify 70 independent risk loci, of which 43 are novel. Using a 70-marker polygenic risk score (HR = 1.63 per standard deviation), we increase the area under the curve from 0.71 (baseline risk model) to 0.75. Integrative analyses reveal the enrichment of the associated variants within accessible chromatin regions, and of the prioritized genes within pathways for xenobiotic metabolism and smoking behavior. Specifically, we show that the 15q25.1 variant rs71581744-ACCCC/A co-localizes with tissue-specific CHRNA3 expression, modulates mRNA stability, and associates with risk of muscle-invasive bladder cancer among current smokers. Together, these findings substantially expand the known genetic architecture of bladder cancer risk and highlight the germline regulation of smoking behavior as a mechanism driving bladder cancer susceptibility.

Для цитирования: Prokunina-Olsson Ludmila, Florez-Vargas Oscar, Levin Michael G, Dutta Diptavo, Breeze Charles E, Hurwitz Lauren M, Yan Wusheng, Lamy Philippe, Papenberg Brenen W, Wang Kevin, Lee Chia-Han, Milne Roger L, Gu Jian, Um Caroline Y, Joseph Vijai, Furberg Helena, Le Calvez-Kelm Florence, Lori Adriana, Choudhury Parichoy Pal, Afshar Nina, Kogevinas Manolis, Offit Kenneth, Vermeulen Sita H, López de Maturana Evangelina, Albanes Demetrius, Purdue Mark P, Cortessis Victoria K, Karagas Margaret R, Kooperberg Charles, Bjurlin Marc, Tadesse Deborah A, Moore Steven C, Huang Wen-Yi, Haiman Christopher A, Stern Mariana C, Eliassen A Heather, Mucci Lorelei A, Aben Katja K, Galesloot Tessel E, UROMOL Consortium, Verma Anurag, Yoshino Soichiro, Hikino Keiko, Terao Chikashi, Rafnar Thorunn, Matsuda Koichi, Shuin Taro, Garcia-Closas Montserrat, Real Francisco X, Kiemeney Lambertus A, Chanock Stephen J, Malats Núria, Silverman Debra T, Dyrskjot Lars, Rothman Nathaniel, Damrauer Scott M, Koutros Stella, Damrauer Jeffrey S. Multi-population GWAS meta-analysis identifies bladder cancer susceptibility loci and highlights genetic regulation of smoking-related risk.. Nature communications. 2026. DOI: 10.1038/s41467-026-76157-4.

Предметные рубрики MeSH

HumansUrinary Bladder NeoplasmsGenome-Wide Association StudyGenetic Predisposition to DiseaseSmokingPolymorphism, Single NucleotideGenetic Risk ScoreGene Expression Regulation, NeoplasticReceptors, NicotinicRisk FactorsChromosomes, Human, Pair 15Genetic Loci
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