Diesel exhaust and bladder cancer risk by pathologic stage and grade subtypes

Stella Koutros¹, Manolis Kogevinas², Melissa C Friesen³, Patricia A Stewart⁴, Dalsu Baris³, Margaret R Karagas⁵, Molly Schwenn⁶, Alison Johnson⁷, G M Monawar Hosain⁸, Consol Serra⁹, Adonina Tardon¹⁰, Alfredo Carrato¹¹, Reina Garcia-Closas¹², Lee E Moore³, Michael L Nickerson¹³, Stephen M Hewitt¹⁴, Petra Lenz¹⁵, Alan R Schned¹⁶, Josep Lloreta¹⁷, Yves Allory¹⁸, Haoyu Zhang¹⁹, Nilanjan Chatterjee¹⁹, Montserrat Garcia-Closas²⁰, Nathaniel Rothman³, Núria Malats²¹, Debra T Silverman²²

Affiliations

¹ Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. Electronic address: koutross@mail.nih.gov.
² ISGlobal, Barcelona, Spain; CIBER Epidemiologia y Salud Pública (CIBERESP), Madrid, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
³ Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
⁴ Stewart Exposure Assessments, LLC, Arlington, VA, USA.
⁵ Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
⁶ Maine Cancer Registry, Augusta, ME, USA.
⁷ Vermont Department of Health, Burlington, VT, USA.
⁸ Bureau of Public Health Statistics and Informatics, Department of Health and Human Services, Concord, NH, USA.
⁹ Center for Research in Occupational Health (CiSAL), Universitat Pompeu Fabra, IMIM-Hospital del Mar Medical Research Institut, Barcelona, CIBERESP, Spain.
¹⁰ Department of Preventive Medicine, Universidad de Oviedo, CIBERESP, Spain.
¹¹ Medical Oncology Department, Ramón y Cajal University Hospital, Alcalá University, IRYCIS, CIBERONC, Madrid, Spain.
¹² Hospital Universitario de Canarias, La Laguna, Tenerife, Spain.
¹³ Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
¹⁴ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
¹⁵ Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory of Cancer Research, Frederick, MD, USA.
¹⁶ Department of Pathology, Dartmouth Medical School, Hanover, NH, USA.
¹⁷ Department of Pathology, Hospital del Mar, Barcelona, Spain; Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
¹⁸ Pathology Department, Institut Curie, Saint Cloud, France; Pathology Department, Hospital Foch, Suresnes, France.
¹⁹ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
²⁰ Office of the Director, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
²¹ Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, CIBERONC, Spain.
²² Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. Electronic address: silvermd@exchange.nih.gov.

PMID: 31864026
PMCID: PMC8237313
DOI: 10.1016/j.envint.2019.105346

Diesel exhaust and bladder cancer risk by pathologic stage and grade subtypes

Stella Koutros et al. Environ Int. 2020 Feb.

. 2020 Feb:135:105346.

doi: 10.1016/j.envint.2019.105346. Epub 2019 Dec 18.

Authors

Affiliations

¹ Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. Electronic address: koutross@mail.nih.gov.
² ISGlobal, Barcelona, Spain; CIBER Epidemiologia y Salud Pública (CIBERESP), Madrid, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
³ Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
⁴ Stewart Exposure Assessments, LLC, Arlington, VA, USA.
⁵ Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
⁶ Maine Cancer Registry, Augusta, ME, USA.
⁷ Vermont Department of Health, Burlington, VT, USA.
⁸ Bureau of Public Health Statistics and Informatics, Department of Health and Human Services, Concord, NH, USA.
⁹ Center for Research in Occupational Health (CiSAL), Universitat Pompeu Fabra, IMIM-Hospital del Mar Medical Research Institut, Barcelona, CIBERESP, Spain.
¹⁰ Department of Preventive Medicine, Universidad de Oviedo, CIBERESP, Spain.
¹¹ Medical Oncology Department, Ramón y Cajal University Hospital, Alcalá University, IRYCIS, CIBERONC, Madrid, Spain.
¹² Hospital Universitario de Canarias, La Laguna, Tenerife, Spain.
¹³ Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
¹⁴ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
¹⁵ Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research Inc., Frederick National Laboratory of Cancer Research, Frederick, MD, USA.
¹⁶ Department of Pathology, Dartmouth Medical School, Hanover, NH, USA.
¹⁷ Department of Pathology, Hospital del Mar, Barcelona, Spain; Department of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
¹⁸ Pathology Department, Institut Curie, Saint Cloud, France; Pathology Department, Hospital Foch, Suresnes, France.
¹⁹ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
²⁰ Office of the Director, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
²¹ Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, CIBERONC, Spain.
²² Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. Electronic address: silvermd@exchange.nih.gov.

PMID: 31864026
PMCID: PMC8237313
DOI: 10.1016/j.envint.2019.105346

Abstract

Background: The International Agency for Research on Cancer (IARC) classifies diesel engine exhaust as carcinogenic to humans based on sufficient evidence for lung cancer. IARC noted, however, an increased risk of bladder cancer (based on limited evidence).

Objective: To evaluate the association between quantitative, lifetime occupational diesel exhaust exposure and risk of urothelial cell carcinoma of the bladder (UBC) overall and according to pathological subtypes.

Methods: Data from personal interviews with 1944 UBC cases, as well as formalin-fixed paraffin-embedded tumor tissue blocks, and 2135 controls were pooled from two case-control studies conducted in the U.S. and Spain. Lifetime occupational histories combined with exposure-oriented questions were used to estimate cumulative exposure to respirable elemental carbon (REC), a primary surrogate for diesel exhaust. Unconditional logistic regression and two-stage polytomous logistic regression were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for smoking and other risk factors.

Results: Exposure to cumulative REC was associated with an increased risk of UBC; workers with cumulative REC >396 μg/m³-years had an OR of 1.61 (95% CI, 1.08-2.40). At this level of cumulative exposure, similar results were observed in the U.S. and Spain, OR = 1.75 (95% CI, 0.97-3.15) and OR = 1.54 (95% CI, 0.89-2.68), respectively. In lagged analysis, we also observed a consistent increased risk among workers with cumulative REC >396 μg/m³-years (range of ORs = 1.52-1.93) for all lag intervals evaluated (5-40 years). When we accounted for tumor subtypes defined by stage and grade, a significant association between diesel exhaust exposure and UBC was apparent (global test for association p = 0.0019).

Conclusions: Combining data from two large epidemiologic studies, our results provide further evidence that diesel exhaust exposure increases the risk of UBC.

Keywords: Bladder cancer; Diesel exhaust; Occupation.

Published by Elsevier Ltd.

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Conflict of interest statement

Declaration of Competing Interest

The authors declare no competing financial interests.

Figures

**Fig. 1.**
Odds ratios from polytomous logistic regression for categories of cumulative REC (μg/m³-years), ≤396 μg/m³-years and > 396 μg/m³-years compared to the unexposed, and risk of UBC by pathologic stage (Panel A) and grade (Panel B). Models are adjusted for age, race, study, smoking status, and non-diesel exposed high-risk occupations. See also Supplemental Table A.3 for point estimates.

See this image and copyright information in PMC

References

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Diesel exhaust and bladder cancer risk by pathologic stage and grade subtypes

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Diesel exhaust and bladder cancer risk by pathologic stage and grade subtypes

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Conflict of interest statement

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