Geographic variation of mutagenic exposures in kidney cancer genomes

International differences in kidney cancer incidence suggest unidentified carcinogenic exposures. This study sequenced 962 clear cell renal cell carcinomas (ccRCCs) from 11 countries. Somatic mutation profiles varied geographically; aristolochic acid signatures were prevalent in Romania, Serbia, and Thailand, while an unknown signature dominated in Japan. Another unknown signature showed higher mutation loads in high-incidence countries. Tobacco smoking signatures correlated with consumption, but no signatures linked to obesity or hypertension were found. This highlights geographically variable mutagenic exposures potentially affecting tens of millions.

Sergey Senkin, Sarah Moody, Marcos Díaz-Gay, Behnoush Abedi-Ardekani, Thomas Cattiaux, Aida Ferreiro-Iglesias, Jingwei Wang, Stephen Fitzgerald, Mariya Kazachkova, Raviteja Vangara, Anh Phuong Le, Erik N. Bergstrom, Azhar Khandekar, Burçak Otlu, Saamin Cheema, Calli Latimer, Emily Thomas, Joshua Ronald 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 Jarmalaite, Rasa Sabaliauskaite, Tatsuhiro Shibata, Akihiko Fukagawa, Dana Mates, Viorel Jinga, Stefan Rascu, Mirjana Mijuskovic, Slavisa Savic, Sasa Milosavljevic, John M. S. Bartlett, Monique Albert, Larry Phouthavongsy, Patricia Ashton-Prolla, Mariana R. Botton, Brasil Silva Neto, Stephania Martins Bezerra, Maria Paula Curado, Stênio de Cássio Zequi, Rui Manuel Reis, Eliney Ferreira Faria, Nei Soares de Menezes, Renata Spagnoli Ferrari, Rosamonde E. Banks, Naveen S. Vasudev, David Zaridze, Anush Mukeriya, Oxana Shangina, Vsevolod Matveev, Lenka Foretova, Marie Navratilova, Ivana Holcatova, Anna Hornakova, Vladimir Janout, Mark P. Purdue, Nathaniel Rothman, Stephen J. Chanock, Per Magne Ueland, Mattias Johansson, James McKay, Ghislaine Scelo, Estelle Chanudet, Laura Humphreys, Ana Carolina de Carvalho, Sandra Perdomo, Ludmil B. Alexandrov, Michael R. Stratton, Paul Brennan