Aristolochic acid exposure in Romania and implications for renal cell carcinoma

Robert J. Turesky; Byeong Hwa Yun; Paul Brennan; Dana Mates; Viorel Jinga; Patricia Harnden; Rosamonde E. Banks; Helene Blanche; Marie Therese Bihoreau; Priscilia Chopard; Louis Letourneau; G. Mark Lathrop; Ghislaine Scelo

doi:10.1038/bjc.2015.402

Aristolochic acid exposure in Romania and implications for renal cell carcinoma

Robert J. Turesky, Byeong Hwa Yun, Paul Brennan, Dana Mates, Viorel Jinga, Patricia Harnden, Rosamonde E. Banks, Helene Blanche, Marie Therese Bihoreau, Priscilia Chopard, Louis Letourneau, G. Mark Lathrop, Ghislaine Scelo

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

Abstract

Background:Aristolochic acid (AA) is a nephrotoxicant associated with AA nephropathy (AAN) and upper urothelial tract cancer (UUTC). Whole-genome sequences of 14 Romanian cases of renal cell carcinoma (RCC) recently exhibited mutational signatures consistent with AA exposure, although RCC had not been previously linked with AAN and AA exposure was previously reported only in localised rural areas.Methods:We performed mass spectrometric measurements of the aristolactam (AL) DNA adduct 7-(deoxyadenosin-N 6 -yl) aristolactam I (dA-AL-I) in nontumour renal tissues of the 14 Romanian RCC cases and 15 cases from 3 other countries.Results:We detected dA-AL-I in the 14 Romanian cases at levels ranging from 0.7 to 27 adducts per 10 8 DNA bases, in line with levels reported in Asian and Balkan populations exposed through herbal remedies or food contamination. The 15 cases from other countries were negative.Interpretation:Although the source of exposure is uncertain and likely different in AAN regions than elsewhere, our results demonstrate that AA exposure in Romania exists outside localised AAN regions and provide further evidence implicating AA in RCC.

Original language	English (US)
Pages (from-to)	76-80
Number of pages	5
Journal	British Journal of Cancer
Volume	114
Issue number	1
DOIs	https://doi.org/10.1038/bjc.2015.402
State	Published - Jan 12 2016

Bibliographical note

Funding Information:
We thank David Zaridze and Anush Moukeria (Russian NN Blokhin Cancer Research Centre, Moscow, Russian Federation), Ivana Holcatova (First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic) and Antonin Brisuda (University Hospital Motol, Prague, Czech Republic), Lenka Foretova and Marie Navratilova (Masaryk Memorial Cancer Institute and MF MU, Brno, Czech Republic) for the collection of biospecimens and data from the Russian Federation and the Czech Republic; Christine Carreira (International Agency for Research on Cancer, Lyon, France) for processing renal biosamples in preparation for pathological review and DNA extractions; Cyrille Cuenin (International Agency for Research on Cancer, Lyon, France) for his technical support in DNA extractions; David Muller (International Agency for Research on Cancer, Lyon, France) for statistical support; Members of the CAGEKID consortium (http://www.cng.fr/cagekid/; PMID: 25351205) for their contribution to generating DNA sequencing data and enlightening discussions on the initial results. This research was funded in part by the National Institute of Environmental Health Sciences R01ES019564 (to RJT); the National Cancer Institute Cancer Center Support Grant CA-77598 (to RJT); the European Union FP7 241669 (the CAGEKID project, to GML); and the National Cancer Institute U01CA155309 (to GS).

Funding Information:
We thank David Zaridze and Anush Moukeria (Russian NN Blokhin Cancer Research Centre, Moscow, Russian Federation), Ivana Holcatova (First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic) and Antonin Brisuda (University Hospital Motol, Prague, Czech Republic), Lenka Foretova and Marie Navratilova (Masaryk Memorial Cancer Institute and MF MU, Brno, Czech Republic) for the collection of biospecimens and data from the Russian Federation and the Czech Republic; Christine Carreira (International Agency for Research on Cancer, Lyon, France) for processing renal biosamples in preparation for pathological review and DNA extractions; Cyrille Cuenin (International Agency for Research on Cancer, Lyon, France) for his technical support in DNA extractions; David Muller (International Agency for Research on Cancer, Lyon, France) for statistical support; Members of the CAGEKID consortium (http:// www.cng.fr/cagekid/; PMID: 25351205) for their contribution to generating DNA sequencing data and enlightening discussions on the initial results. This research was funded in part by the National Institute of Environmental Health Sciences R01ES019564 (to RJT); the National Cancer Institute Cancer Center Support Grant CA-77598 (to RJT); the European Union FP7 241669 (the CAGEKID project, to GML); and the National Cancer Institute U01CA155309 (to GS).

Publisher Copyright:
© 2016 Cancer Research UK.

Keywords

DNA adducts
aristolochic acid
environment
mutational signatures
renal cell carcinoma

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title = "Aristolochic acid exposure in Romania and implications for renal cell carcinoma",

abstract = "Background:Aristolochic acid (AA) is a nephrotoxicant associated with AA nephropathy (AAN) and upper urothelial tract cancer (UUTC). Whole-genome sequences of 14 Romanian cases of renal cell carcinoma (RCC) recently exhibited mutational signatures consistent with AA exposure, although RCC had not been previously linked with AAN and AA exposure was previously reported only in localised rural areas.Methods:We performed mass spectrometric measurements of the aristolactam (AL) DNA adduct 7-(deoxyadenosin-N 6 -yl) aristolactam I (dA-AL-I) in nontumour renal tissues of the 14 Romanian RCC cases and 15 cases from 3 other countries.Results:We detected dA-AL-I in the 14 Romanian cases at levels ranging from 0.7 to 27 adducts per 10 8 DNA bases, in line with levels reported in Asian and Balkan populations exposed through herbal remedies or food contamination. The 15 cases from other countries were negative.Interpretation:Although the source of exposure is uncertain and likely different in AAN regions than elsewhere, our results demonstrate that AA exposure in Romania exists outside localised AAN regions and provide further evidence implicating AA in RCC.",

keywords = "DNA adducts, aristolochic acid, environment, mutational signatures, renal cell carcinoma",

author = "Turesky, {Robert J.} and Yun, {Byeong Hwa} and Paul Brennan and Dana Mates and Viorel Jinga and Patricia Harnden and Banks, {Rosamonde E.} and Helene Blanche and Bihoreau, {Marie Therese} and Priscilia Chopard and Louis Letourneau and Lathrop, {G. Mark} and Ghislaine Scelo",

note = "Funding Information: We thank David Zaridze and Anush Moukeria (Russian NN Blokhin Cancer Research Centre, Moscow, Russian Federation), Ivana Holcatova (First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic) and Antonin Brisuda (University Hospital Motol, Prague, Czech Republic), Lenka Foretova and Marie Navratilova (Masaryk Memorial Cancer Institute and MF MU, Brno, Czech Republic) for the collection of biospecimens and data from the Russian Federation and the Czech Republic; Christine Carreira (International Agency for Research on Cancer, Lyon, France) for processing renal biosamples in preparation for pathological review and DNA extractions; Cyrille Cuenin (International Agency for Research on Cancer, Lyon, France) for his technical support in DNA extractions; David Muller (International Agency for Research on Cancer, Lyon, France) for statistical support; Members of the CAGEKID consortium (http://www.cng.fr/cagekid/; PMID: 25351205) for their contribution to generating DNA sequencing data and enlightening discussions on the initial results. This research was funded in part by the National Institute of Environmental Health Sciences R01ES019564 (to RJT); the National Cancer Institute Cancer Center Support Grant CA-77598 (to RJT); the European Union FP7 241669 (the CAGEKID project, to GML); and the National Cancer Institute U01CA155309 (to GS). Funding Information: We thank David Zaridze and Anush Moukeria (Russian NN Blokhin Cancer Research Centre, Moscow, Russian Federation), Ivana Holcatova (First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic) and Antonin Brisuda (University Hospital Motol, Prague, Czech Republic), Lenka Foretova and Marie Navratilova (Masaryk Memorial Cancer Institute and MF MU, Brno, Czech Republic) for the collection of biospecimens and data from the Russian Federation and the Czech Republic; Christine Carreira (International Agency for Research on Cancer, Lyon, France) for processing renal biosamples in preparation for pathological review and DNA extractions; Cyrille Cuenin (International Agency for Research on Cancer, Lyon, France) for his technical support in DNA extractions; David Muller (International Agency for Research on Cancer, Lyon, France) for statistical support; Members of the CAGEKID consortium (http:// www.cng.fr/cagekid/; PMID: 25351205) for their contribution to generating DNA sequencing data and enlightening discussions on the initial results. This research was funded in part by the National Institute of Environmental Health Sciences R01ES019564 (to RJT); the National Cancer Institute Cancer Center Support Grant CA-77598 (to RJT); the European Union FP7 241669 (the CAGEKID project, to GML); and the National Cancer Institute U01CA155309 (to GS). Publisher Copyright: {\textcopyright} 2016 Cancer Research UK.",

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T1 - Aristolochic acid exposure in Romania and implications for renal cell carcinoma

AU - Turesky, Robert J.

AU - Yun, Byeong Hwa

AU - Brennan, Paul

AU - Mates, Dana

AU - Jinga, Viorel

AU - Harnden, Patricia

AU - Banks, Rosamonde E.

AU - Blanche, Helene

AU - Bihoreau, Marie Therese

AU - Chopard, Priscilia

AU - Letourneau, Louis

AU - Lathrop, G. Mark

AU - Scelo, Ghislaine

N1 - Funding Information: We thank David Zaridze and Anush Moukeria (Russian NN Blokhin Cancer Research Centre, Moscow, Russian Federation), Ivana Holcatova (First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic) and Antonin Brisuda (University Hospital Motol, Prague, Czech Republic), Lenka Foretova and Marie Navratilova (Masaryk Memorial Cancer Institute and MF MU, Brno, Czech Republic) for the collection of biospecimens and data from the Russian Federation and the Czech Republic; Christine Carreira (International Agency for Research on Cancer, Lyon, France) for processing renal biosamples in preparation for pathological review and DNA extractions; Cyrille Cuenin (International Agency for Research on Cancer, Lyon, France) for his technical support in DNA extractions; David Muller (International Agency for Research on Cancer, Lyon, France) for statistical support; Members of the CAGEKID consortium (http://www.cng.fr/cagekid/; PMID: 25351205) for their contribution to generating DNA sequencing data and enlightening discussions on the initial results. This research was funded in part by the National Institute of Environmental Health Sciences R01ES019564 (to RJT); the National Cancer Institute Cancer Center Support Grant CA-77598 (to RJT); the European Union FP7 241669 (the CAGEKID project, to GML); and the National Cancer Institute U01CA155309 (to GS). Funding Information: We thank David Zaridze and Anush Moukeria (Russian NN Blokhin Cancer Research Centre, Moscow, Russian Federation), Ivana Holcatova (First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic) and Antonin Brisuda (University Hospital Motol, Prague, Czech Republic), Lenka Foretova and Marie Navratilova (Masaryk Memorial Cancer Institute and MF MU, Brno, Czech Republic) for the collection of biospecimens and data from the Russian Federation and the Czech Republic; Christine Carreira (International Agency for Research on Cancer, Lyon, France) for processing renal biosamples in preparation for pathological review and DNA extractions; Cyrille Cuenin (International Agency for Research on Cancer, Lyon, France) for his technical support in DNA extractions; David Muller (International Agency for Research on Cancer, Lyon, France) for statistical support; Members of the CAGEKID consortium (http:// www.cng.fr/cagekid/; PMID: 25351205) for their contribution to generating DNA sequencing data and enlightening discussions on the initial results. This research was funded in part by the National Institute of Environmental Health Sciences R01ES019564 (to RJT); the National Cancer Institute Cancer Center Support Grant CA-77598 (to RJT); the European Union FP7 241669 (the CAGEKID project, to GML); and the National Cancer Institute U01CA155309 (to GS). Publisher Copyright: © 2016 Cancer Research UK.

PY - 2016/1/12

Y1 - 2016/1/12

N2 - Background:Aristolochic acid (AA) is a nephrotoxicant associated with AA nephropathy (AAN) and upper urothelial tract cancer (UUTC). Whole-genome sequences of 14 Romanian cases of renal cell carcinoma (RCC) recently exhibited mutational signatures consistent with AA exposure, although RCC had not been previously linked with AAN and AA exposure was previously reported only in localised rural areas.Methods:We performed mass spectrometric measurements of the aristolactam (AL) DNA adduct 7-(deoxyadenosin-N 6 -yl) aristolactam I (dA-AL-I) in nontumour renal tissues of the 14 Romanian RCC cases and 15 cases from 3 other countries.Results:We detected dA-AL-I in the 14 Romanian cases at levels ranging from 0.7 to 27 adducts per 10 8 DNA bases, in line with levels reported in Asian and Balkan populations exposed through herbal remedies or food contamination. The 15 cases from other countries were negative.Interpretation:Although the source of exposure is uncertain and likely different in AAN regions than elsewhere, our results demonstrate that AA exposure in Romania exists outside localised AAN regions and provide further evidence implicating AA in RCC.

AB - Background:Aristolochic acid (AA) is a nephrotoxicant associated with AA nephropathy (AAN) and upper urothelial tract cancer (UUTC). Whole-genome sequences of 14 Romanian cases of renal cell carcinoma (RCC) recently exhibited mutational signatures consistent with AA exposure, although RCC had not been previously linked with AAN and AA exposure was previously reported only in localised rural areas.Methods:We performed mass spectrometric measurements of the aristolactam (AL) DNA adduct 7-(deoxyadenosin-N 6 -yl) aristolactam I (dA-AL-I) in nontumour renal tissues of the 14 Romanian RCC cases and 15 cases from 3 other countries.Results:We detected dA-AL-I in the 14 Romanian cases at levels ranging from 0.7 to 27 adducts per 10 8 DNA bases, in line with levels reported in Asian and Balkan populations exposed through herbal remedies or food contamination. The 15 cases from other countries were negative.Interpretation:Although the source of exposure is uncertain and likely different in AAN regions than elsewhere, our results demonstrate that AA exposure in Romania exists outside localised AAN regions and provide further evidence implicating AA in RCC.

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KW - environment

KW - mutational signatures

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Aristolochic acid exposure in Romania and implications for renal cell carcinoma

Abstract

Bibliographical note

Keywords

UN SDGs

Access

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