Produção Nacional
Revisado por pares
Geographic variation of mutagenic exposures in kidney cancer genomes
2024; Nature Portfolio; Volume: 629; Issue: 8013 Linguagem: Inglês
10.1038/s41586-024-07368-2
ISSN1476-4687
AutoresS. Senkin, Sarah Moody, Marcos Díaz‐Gay, Behnoush Abedi‐Ardekani, Thomas Cattiaux, Aida Ferreiro-Iglesias, Jingwei Wang, Stephen Fitzgerald, Mariya Kazachkova, Raviteja Vangara, Anh Le, Erik N. Bergstrom, Azhar Khandekar, Burçak Otlu, Saamin Cheema, Calli Latimer, Emily Thomas, Joshua Atkins, Karl Smith-Byrne, Ricardo Cortez Cardoso Penha, Christine Carreira, Priscilia Chopard, Valérie Gaborieau, Pekka Keski‐Rahkonen, David Jones, Jon W. Teague, Sophie Ferlicot, Mojgan Asgari, Surasak Sangkhathat, Worapat Attawettayanon, Beata Świątkowska, Sonata Jarmalaitė, Rasa Sabaliauskaitė, Tatsuhiro Shibata, Akihiko Fukagawa, Dana Mateș, Viorel Jinga, Ștefan Rașcu, Mirjana Mijušković, Slaviša Savić, Saša Milosavljević, John M.S. Bartlett, Monique Albert, Larry Phouthavongsy, Patrícia Ashton‐Prolla, Mariana Rodrigues Botton, Brasil Silva Neto, Stephania Martins Bezerra, María Paula Curado, Stênio de Cássio Zéqui, Rui Manuel Reis, Eliney Ferreira Faria, Nei Soares de Menezes, Renata Spagnoli Ferrari, Rosamonde E. Banks, Naveen Vasudev, Давид Заридзе, Anush Mukeriya, Oxana Shangina, В. Б. Матвеев, Lenka Foretová, Marie Navrátilová, Ivana Holcátová, Anna Horňáková, Vladimír Janout, Mark P. Purdue, Nathaniel Rothman, Stephen J. Chanock, Per Magne Ueland, Mattias Johansson, James McKay, Ghislaine Scélo, Estelle Chanudet, Laura Humphreys, Ana Carolina de Carvalho, Sandra Pérdomo, Ludmil B. Alexandrov, Michael R. Stratton, Paul Brennan,
Tópico(s)DNA Repair Mechanisms
ResumoAbstract 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.
Referência(s)