Geographic variation of mutagenic exposures in kidney cancer genomes

• 成果类型: Article
• 署名作者: Senkin, Sergey; Moody, Sarah; Diaz-Gay, Marcos; Abedi-Ardekani, Behnoush; Cattiaux, Thomas; Ferreiro-Iglesias, Aida; Wang, Jingwei; Fitzgerald, Stephen; Kazachkova, Mariya; Vangara, Raviteja; Anh Phuong Le; Bergstrom, Erik N.; Khandekar, Azhar; Otlu, Burcak; Cheema, Saamin; Latimer, Calli; Thomas, Emily; Atkins, Joshua Ronald; Smith-Byrne, Karl; Cardoso Penha, Ricardo Cortez; Carreira, Christine; Chopard, Priscilia; Gaborieau, Valerie; Keski-Rahkonen, Pekka; Jones, David; Teague, Jon W.; Ferlicot, Sophie; Asgari, Mojgan; Sangkhathat, Surasak; Attawettayanon, Worapat; Swiatkowska, Beata; Jarmalaite, Sonata; Sabaliauskaite, Rasa; Shibata, Tatsuhiro; Fukagawa, Akihiko; Mates, Dana; Jinga, Viorel; Rascu, Stefan; Mijuskovic, Mirjana; Savic, Slavisa; Milosavljevic, Sasa; Bartlett, John M. S.; Albert, Monique; Phouthavongsy, Larry; Ashton-Prolla, Patricia; Botton, Mariana R.; Neto, Brasil Silva; Bezerra, Stephania Martins; Curado, Maria Paula; Zequi, Stenio de Cassio; Reis, Rui Manuel; Faria, Eliney Ferreira; de Menezes, Nei Soares; Ferrari, Renata Spagnoli; Banks, Rosamonde E.; Vasudev, Naveen S.; Zaridze, David; Mukeriya, Anush; Shangina, Oxana; Matveev, Vsevolod; Foretova, Lenka; Navratilova, Marie; Holcatova, Ivana; Hornakova, Anna; Janout, Vladimir; Purdue, Mark P.; Rothman, Nathaniel; Chanock, Stephen J.; Ueland, Per Magne; Johansson, Mattias; McKay, James; Scelo, Ghislaine; Chanudet, Estelle; Humphreys, Laura; de Carvalho, Ana Carolina; Perdomo, Sandra; Alexandrov, Ludmil B.; Stratton, Michael R.; Brennan, Paul
• 署名单位: World Health Organization; International Agency for Research on Cancer (IARC); Wellcome Trust Sanger Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Middle East Technical University; University of Oxford; World Health Organization; International Agency for Research on Cancer (IARC); World Health Organization; International Agency for Research on Cancer (IARC); Universite Paris Saclay; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Bicetre - APHP; Iran University of Medical Sciences; Iran University of Medical Sciences; Prince of Songkla University; Prince of Songkla University; Nofer Institute of Occupational Medicine; National Cancer Institute - Lithuania; Vilnius University; University of Tokyo; National Cancer Center - Japan; University of Tokyo; Carol Davila University of Medicine & Pharmacy; University of Belgrade; University of Edinburgh; University of Guelph; University of Toronto; Ontario Institute for Cancer Research; Hospital de Clinicas de Porto Alegre; Universidade Federal do Rio Grande do Sul; Hospital de Clinicas de Porto Alegre; Hospital de Clinicas de Porto Alegre; Universidade Federal do Rio Grande do Sul; A.C.Camargo Cancer Center; A.C.Camargo Cancer Center; A.C.Camargo Cancer Center; A.C.Camargo Cancer Center; Universidade Federal de Sao Paulo (UNIFESP); Hospital de Cancer de Barretos; Universidade do Minho; Hospital de Cancer de Barretos; Hospital de Cancer de Barretos; University of Leeds; Masaryk Memorial Cancer Institute; Charles University Prague; Motol University Hospital; Charles University Prague; Motol University Hospital; Motol University Hospital; Charles University Prague; Palacky University Olomouc; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics; Radboud University Nijmegen
• 刊物名称: Nature
• ISSN/ISSBN: 0028-5925
• DOI: 10.1038/s41586-024-07368-2
• 发表日期: 2024-05-23
• 页码: 910-+
• 关键词: mutational signatures; nephropathy

摘要

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden(1). In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence(2). Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.