Geographic variation of mutagenic exposures in kidney cancer genomes

Date

2024-01-01

Author

Senkin, Sergey
Moody, Sarah
Díaz-Gay, Marcos
Abedi-Ardekani, Behnoush
Cattiaux, Thomas
Ferreiro-Iglesias, Aida
Wang, Jingwei
Fitzgerald, Stephen
Kazachkova, Mariya
Vangara, Raviteja
Le, Anh Phuong
Bergstrom, Erik N.
Khandekar, Azhar
Otlu Sarıtaş, Burçak
Cheema, Saamin
Latimer, Calli
Thomas, Emily
Atkins, Joshua Ronald
Smith-Byrne, Karl
Cortez Cardoso Penha, Ricardo
Carreira, Christine
Chopard, Priscilia
Gaborieau, Valérie
Keski-Rahkonen, Pekka
Jones, David
Teague, Jon W.
Ferlicot, Sophie
Asgari, Mojgan
Sangkhathat, Surasak
Attawettayanon, Worapat
Świątkowska, 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.
Silva Neto, Brasil
Bezerra, Stephania Martins
Curado, Maria Paula
Zequi, Stênio de Cássio
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

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

20
views

2
downloads

Cite This

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 burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. 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 and 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.

URI

https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85192020403&origin=inward
https://hdl.handle.net/11511/109684

Collections

Graduate School of Informatics, Article