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3. Exposure–response relationships for select cancer and non-cancer health outcomes in a cohort of US firefighters from San Francisco, Chicago and Philadelphia (1950–2009)

Author

Daniels, Robert D, Bertke, Stephen, Dahm, Matthew M, Yiin, James H, Kubale, Travis L, Hales, Thomas R, Baris, Dalsu, Zahm, Shelia H, Beaumont, James J, Waters, Kathleen M, and Pinkerton, Lynne E

Subjects
Prevention, Aging, Lung Cancer, Cancer, Lung, Digestive Diseases, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Aetiology, Good Health and Well Being, Adult, Age Distribution, Aged, Cause of Death, Chicago, Cohort Studies, Firefighters, Humans, Incidence, Leukemia, Lung Neoplasms, Male, Middle Aged, Occupational Diseases, Occupational Exposure, Philadelphia, Prognosis, Proportional Hazards Models, Retrospective Studies, Risk Assessment, San Francisco, Survival Analysis, Clinical Sciences, Public Health and Health Services, Other Commerce, Management, Tourism and Services, Environmental & Occupational Health
Abstract

ObjectivesTo examine exposure-response relationships between surrogates of firefighting exposure and select outcomes among previously studied US career firefighters.MethodsEight cancer and four non-cancer outcomes were examined using conditional logistic regression. Incidence density sampling was used to match each case to 200 controls on attained age. Days accrued in firefighting assignments (exposed-days), run totals (fire-runs) and run times (fire-hours) were used as exposure surrogates. HRs comparing 75th and 25th centiles of lagged cumulative exposures were calculated using loglinear, linear, log-quadratic, power and restricted cubic spline general relative risk models. Piecewise constant models were used to examine risk differences by time since exposure, age at exposure and calendar period.ResultsAmong 19,309 male firefighters eligible for the study, there were 1333 cancer deaths and 2609 cancer incidence cases. Significant positive associations between fire-hours and lung cancer mortality and incidence were evident. A similar relation between leukaemia mortality and fire-runs was also found. The lung cancer associations were nearly linear in cumulative exposure, while the association with leukaemia mortality was attenuated at higher exposure levels and greater for recent exposures. Significant negative associations were evident for the exposure surrogates and colorectal and prostate cancers, suggesting a healthy worker survivor effect possibly enhanced by medical screening.ConclusionsLung cancer and leukaemia mortality risks were modestly increasing with firefighter exposures. These findings add to evidence of a causal association between firefighting and cancer. Nevertheless, small effects merit cautious interpretation. We plan to continue to follow the occurrence of disease and injury in this cohort.

Published
2015

4. Mortality and cancer incidence in a pooled cohort of US firefighters from San Francisco, Chicago and Philadelphia (1950–2009)

Author

Daniels, Robert D, Kubale, Travis L, Yiin, James H, Dahm, Matthew M, Hales, Thomas R, Baris, Dalsu, Zahm, Shelia H, Beaumont, James J, Waters, Kathleen M, and Pinkerton, Lynne E

Subjects
Epidemiology, Public Health, Health Sciences, Prevention, Cancer, Lung, Good Health and Well Being, Adult, Aged, Asbestos, Cause of Death, Chicago, Cohort Studies, Digestive System Neoplasms, Female, Firefighters, Humans, Incidence, Lung Neoplasms, Male, Mesothelioma, Mesothelioma, Malignant, Middle Aged, Neoplasms, Occupational Diseases, Occupational Exposure, Philadelphia, Respiratory Tract Neoplasms, San Francisco, Longitudinal studies < Methodology, speciality, Clinical Sciences, Public Health and Health Services, Other Commerce, Management, Tourism and Services, Environmental & Occupational Health, Human resources and industrial relations, Public health
Abstract

ObjectivesTo examine mortality patterns and cancer incidence in a pooled cohort of 29 993 US career firefighters employed since 1950 and followed through 2009.MethodsMortality and cancer incidence were evaluated by life table methods with the US population referent. Standardised mortality (SMR) and incidence (SIR) ratios were determined for 92 causes of death and 41 cancer incidence groupings. Analyses focused on 15 outcomes of a priori interest. Sensitivity analyses were conducted to examine the potential for significant bias.ResultsPerson-years at risk totalled 858 938 and 403 152 for mortality and incidence analyses, respectively. All-cause mortality was at expectation (SMR=0.99, 95% CI 0.97 to 1.01, n=12 028). There was excess cancer mortality (SMR=1.14, 95% CI 1.10 to 1.18, n=3285) and incidence (SIR=1.09, 95% CI 1.06 to 1.12, n=4461) comprised mainly of digestive (SMR=1.26, 95% CI 1.18 to 1.34, n=928; SIR=1.17, 95% CI 1.10 to 1.25, n=930) and respiratory (SMR=1.10, 95% CI 1.04 to 1.17, n=1096; SIR=1.16, 95% CI 1.08 to 1.24, n=813) cancers. Consistent with previous reports, modest elevations were observed in several solid cancers; however, evidence of excess lymphatic or haematopoietic cancers was lacking. This study is the first to report excess malignant mesothelioma (SMR=2.00, 95% CI 1.03 to 3.49, n=12; SIR=2.29, 95% CI 1.60 to 3.19, n=35) among US firefighters. Results appeared robust under differing assumptions and analytic techniques.ConclusionsOur results provide evidence of a relation between firefighting and cancer. The new finding of excess malignant mesothelioma is noteworthy, given that asbestos exposure is a known hazard of firefighting.

Published
2014

6. GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma.

Author

Smedby, Karin, Foo, Jia, Skibola, Christine, Darabi, Hatef, Conde, Lucia, Hjalgrim, Henrik, Kumar, Vikrant, Chang, Ellen, Rothman, Nathaniel, Cerhan, James, Brooks-Wilson, Angela, Rehnberg, Emil, Irwan, Ishak, Ryder, Lars, Brown, Peter, Bracci, Paige, Agana, Luz, Riby, Jacques, Cozen, Wendy, Davis, Scott, Hartge, Patricia, Morton, Lindsay, Severson, Richard, Wang, Sophia, Slager, Susan, Fredericksen, Zachary, Novak, Anne, Kay, Neil, Habermann, Thomas, Armstrong, Bruce, Kricker, Anne, Milliken, Sam, Purdue, Mark, Vajdic, Claire, Boyle, Peter, Lan, Qing, Zahm, Shelia, Zhang, Yawei, Zheng, Tongzhang, Leach, Stephen, Spinelli, John, Smith, Martyn T., Chanock, Stephen, Padyukov, Leonid, Alfredsson, Lars, Klareskog, Lars, Glimelius, Bengt, Melbye, Mads, Liu, Edison, Adami, Hans-Olov, Humphreys, Keith, and Liu, Jianjun

Subjects
Chromosomes, Human, Pair 6, Denmark, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Genome-Wide Association Study, Haplotypes, Histocompatibility Antigens Class II, Humans, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Polymorphism, Single Nucleotide, Risk Factors, Sweden
Abstract

Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (OR(combined)  = 0.64, P(combined)  = 2 × 10(-21)) located 962 bp away from rs10484561 (r(2)

Published
2011

7. Research Recommendations for Selected IARC-Classified Agents

Author

Ward, Elizabeth M, Schulte, Paul A, Straif, Kurt, Hopf, Nancy B, Caldwell, Jane C, Carreón, Tania, DeMarini, David M, Fowler, Bruce A, Goldstein, Bernard D, Hemminki, Kari, Hines, Cynthia J, Pursiainen, Kirsti Husgafvel, Kuempel, Eileen, Lewtas, Joellen, Lunn, Ruth M, Lynge, Elsebeth, McElvenny, Damien M, Muhle, Hartwig, Nakajima, Tamie, Robertson, Larry W, Rothman, Nathaniel, Ruder, Avima M, Schubauer-Berigan, Mary K, Siemiatycki, Jack, Silverman, Debra, Smith, Martyn T, Sorahan, Tom, Steenland, Kyle, Stevens, Richard G, Vineis, Paolo, Zahm, Shelia Hoar, Zeise, Lauren, and Cogliano, Vincent J

Subjects
Biomedical and Clinical Sciences, Environmental Sciences, Oncology and Carcinogenesis, Cancer, Prevention, Animals, Carcinogenicity Tests, Evidence-Based Medicine, Humans, animal, carcinogen, carcinogenesis, epidemiology, human, IARC, mechanisms of carcinogenicity, occupational, Medical and Health Sciences, Toxicology, Biomedical and clinical sciences, Environmental sciences, Health sciences
Abstract

ObjectivesThere are some common occupational agents and exposure circumstances for which evidence of carcinogenicity is substantial but not yet conclusive for humans. Our objectives were to identify research gaps and needs for 20 agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans.Data sourcesFor each chemical agent (or category of agents), a systematic review was conducted of new data published since the most recent pertinent International Agency for Research on Cancer (IARC) Monograph meeting on that agent.Data extractionReviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches.Data synthesisSeveral overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress, and immuno- and hormonal modulation.ConclusionsStudies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes.

Published
2010

8. Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32

Author

Conde, Lucia, Halperin, Eran, Akers, Nicholas K, Brown, Kevin M, Smedby, Karin E, Rothman, Nathaniel, Nieters, Alexandra, Slager, Susan L, Brooks-Wilson, Angela, Agana, Luz, Riby, Jacques, Liu, Jianjun, Adami, Hans-Olov, Darabi, Hatef, Hjalgrim, Henrik, Low, Hui-Qi, Humphreys, Keith, Melbye, Mads, Chang, Ellen T, Glimelius, Bengt, Cozen, Wendy, Davis, Scott, Hartge, Patricia, Morton, Lindsay M, Schenk, Maryjean, Wang, Sophia S, Armstrong, Bruce, Kricker, Anne, Milliken, Sam, Purdue, Mark P, Vajdic, Claire M, Boyle, Peter, Lan, Qing, Zahm, Shelia H, Zhang, Yawei, Zheng, Tongzhang, Becker, Nikolaus, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Butterbach, Katja, Cocco, Pierluigi, Foretova, Lenka, Maynadié, Marc, de Sanjosé, Silvia, Staines, Anthony, Spinelli, John J, Achenbach, Sara J, Call, Timothy G, Camp, Nicola J, Glenn, Martha, Caporaso, Neil E, Cerhan, James R, Cunningham, Julie M, Goldin, Lynn R, Hanson, Curtis A, Kay, Neil E, Lanasa, Mark C, Leis, Jose F, Marti, Gerald E, Rabe, Kari G, Rassenti, Laura Z, Spector, Logan G, Strom, Sara S, Vachon, Celine M, Weinberg, J Brice, Holly, Elizabeth A, Chanock, Stephen, Smith, Martyn T, Bracci, Paige M, and Skibola, Christine F

Subjects
Lymphoma, Prevention, Cancer, Human Genome, Genetics, Rare Diseases, Hematology, Aetiology, 2.1 Biological and endogenous factors, Disease Susceptibility, Genetic Variation, Genome-Wide Association Study, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Follicular, Lymphoma, Non-Hodgkin, Major Histocompatibility Complex, Risk Factors, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).

Published
2010

21. Pesticides and Cancer

Author

Dich, Jan, Zahm, Shelia Hoar, Hanberg, Annika, and Adami, Hans-Olov

Published
1997

24. The Agricultural Health Study

Author

Sandler, Dale P., McMaster, Suzanne B., Zahm, Shelia Hoar, McDonnell, Cheryl J., Lynch, Charles F., Pennybacker, Margaret, Rothman, Nathaniel, Dosemeci, Mustafa, Bond, Andrew E., and Blair, Aaron

Published
1996
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