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NIOSH Respiratory Diseases Research Program

Evidence Package for the National Academies' Review 2006-2007

NIOSH Programs > Respiratory Diseases > Evidence Package > 5. Respiratory Malignancies

5.1 Determination of Occupational Etiologies of Lung Cancer

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Issue

Based on the documented associations between occupational exposures to specific agents and cancer, it is estimated that there are approximately 10,000 to 12,000 new cases of lung cancer each year attributable to workplace exposures in the U.S.134 While many occupational lung carcinogens have been identified, there continues to be a need to better understand how they cause lung cancer and to refine risk assessments. Also, it is likely that additional occupational lung carcinogens remain to be identified. 

 Approach

RDRP scientists participated in NIOSH’s strategic planning and priority-setting for occupational cancer (A5-2).136, 137  This planning process was based on several key elements, including: toxicological data (substantial evidence for carcinogenicity in animals but limited or no evidence in humans) and public health importance (number of workers exposed). Additional inputs into priority-setting were surveillance data and stakeholders (e.g. OSHA, CPWR, unions, and other parts of CDC/DHHS) (A5-3 WoRLD report).138 A separate document gives a historical perspective to priority-setting for lung cancer research among workers exposed to ionizing radiation at U.S. DOE facilities is also available (A5-4).

RDRP has conducted a variety of mortality, incidence, and biomarker studies relating to respiratory cancer. These studies are conducted to elucidate relationships between occupational exposure and respiratory cancer, and to examine associations between biomarkers (of exposure, susceptibility, and oncogene expression) and health effects. Many of these research efforts have focused on specific exposures.  Recently completed and ongoing projects include studies of workers exposed to cadmium, ethylene oxide (including studies of biomarkers of effects), chrysotile asbestos, beryllium, uranium- and radiation-exposed workers.

RDRP also has studied workers in specific industrial sectors where workers are exposed to many different occupational exposures. For example, in the past decade, RDRP has studied occupational respiratory diseases, including lung cancer, among construction workers, for which there was limited data suggesting occupational risk.139

Outputs and Transfer

RDRP scientists have published at least 200 reports (peer-review and book chapters) on occupationally-related lung cancer; a list of 127 published since 2001 can be found in the Appendix (A5-5). We have estimated the global occupationally attributable fraction for lung cancer at nine percent (i.e., an estimated nine percent of all lung cancers are attributable to occupational exposure), and this would account for 102,000 lung cancer deaths worldwide each year (1, A5-6).

RDRP authors drew upon their data as well as data from other sources to review the epidemiology of occupational lung cancer. Focusing on agents identified as pulmonary carcinogens by IARC, they estimated that 9,000 - 10,000 men and 900 - 1,900 women develop lung cancer annually in the U.S. due to past exposure to occupational carcinogens; and that this estimate is likely conservative because it restricted analysis to confirmed lung cancer cases (2, A5-7). This manuscript has been cited 60 times.

Beryllium: RDRP scientists studied the association between lung cancer mortality (142 cases, 710 controls) and occupational exposure characteristics in a beryllium alloy production facility. Our data indicated that beryllium is a human lung carcinogen, and a lack of evidence was found for confounding by cigarette smoking (3, A5-8).

Cadmium: RDRP scientists observed an excess of lung cancer mortality (SMR) in relation to cadmium exposure in a cohort of cadmium-exposed workers.

Chromium (chapter 5.2): RDRP scientists conducted a risk assessment for hexavalent chromium and found evidence that the then-current OSHA PEL (52 μg/m3) was not fully protective (4, A5-9).

Silica (chapter 5.3): RDRP investigators conducted a pooled exposure-response analysis in 10 silica-exposed cohorts to investigate lung cancer risk, with a total cohort of more than 65,000 workers. The results helped to support a decision by the IARC to classify inhaled silica in occupational settings as a carcinogen, and suggest that the current exposure limits in many countries may be inadequate. The data may represent the first quantitative exposure-response analysis and risk assessment for silica using data from multiple studies (5, A5-10)

Chest x-rays: RDRP scientists conducted a study to determine lung cancer risk from work-related chest x-rays relative to conventional workplace radiation sources. This was done using methods developed to estimate absorbed doses to the active (hematopoietic) bone marrow from x-ray examinations and workplace exposures using data extracted from radiation and non-radiation worker dosimetry records (8,468) and health records (2,453). We found that work-related chest x-rays accounted for a substantial proportion of the total radiation dose, even in radiation workers.  Omitting doses from work-related chest x-rays is a likely source of bias that can lead to dose category misclassification and may skew the epidemiologic dose-response assessment for cancers induced by workplace radiation (6, A5-11).

Construction workers: RDRP scientists conducted a series of studies to characterize mortality patterns of construction workers with the aim of providing information for development of interventions to reduce both mortality and morbidity. These studies, in collaboration with the CPWR, the Laborer's International Union of North America, and other construction-related organizations, examined the cause-specific mortality experiences of workers from 11 of the 15 Building and Construction Trades Departments of the AFL-CIO, primarily using proportionate mortality ratio analyses. Manuscripts describing 10 of the 11 studies have been published to date (A5-12). RDRP scientists found significantly elevated lung cancer mortality in all 10 published studies (7, A5-13).

RDRP presented its strategic planning and priority setting concerning occupational cancer before the Executive Branch of the federal government in 1994 (A5-14). NIOSH presented a wide-range of issues relevant to occupational and environmental cancer in a meeting of the Role of Government Agencies in the Research Mission of the National Cancer Program.

Recently, RDRP scientists were solicited for comment on the June 2006 “Surgeon General’s Report on the Health Consequences of Secondhand Smoke.” The same scientists also helped to craft approximately 17 Fact Sheets based on the content of the report for dissemination by the Surgeon General to a wide variety of stakeholders and customers: legislators, employers, unions, physicians, parents, and others.

RDRP notifies workers of the results of its studies according to policies of the NIOSH  Worker Notification Program http://www.cdc.gov/niosh/pgms/worknotify (A5-15). RDRP worker notifications involving lung cancer that have taken place since 1996 include a wide variety of hazards, and we estimate from our records that more than 48,900 workers have received notifications for lung cancer hazards (A5-16 shows breakdown by industry).

Intermediate Outcomes

Most RDRP studies that gained prominence in occupational lung cancer epidemiology were initiated prior to 1985 (e.g. uranium miners, beryllium, ethylene oxide, formaldehyde, and cadmium). Many of them provided direct support for OSHA exposure standards. OSHA has not issued many new substance-specific standards in the past 10 years. Among the more recent OSHA standards are those for hexavalent chromium and cadmium. In 2006, OSHA enacted a final rule on hexavalent chromium, reducing the PEL to five μg/m3,based in part on RDRP data (chapter 5.2). In 1992, the cadmium standard (29 CFR 1910.1027) became effective; RDRP findings were cited in the preamble to the Final Rule on cadmium140 (http://www.osha.gov/pls/oshaWeb/owasrch.search_form?p_doc_type=PREAMBLES&p_toc_level=1&p_keyvalue=Cadmium [External link]).

IARC has used evidence from RDRP studies along with other data for evaluation of more than 26 agents (chemical and physical agents, and processes) for carcinogenic risk to humans. Of these 14 were classified as Group 1 “carcinogenic” (e.g., cadmium, beryllium, chromium and asbestos), four were classified as Group 2A “probably carcinogenic” (e.g., diesel engine exhaust), seven were classified as Group 2B “possibly carcinogenic” (e.g., antimony trioxide [Sb2O3], and one, talc, was classified as Group 3 “not carcinogenic.” For a more complete list see appendix A5-16s.

What’s Ahead

 RDRP scientists are conducting a lung cancer case-control study among former workers at the Portsmouth Naval Shipyard. The results of the study are anticipated to be disseminated in 2006 and will consist of worker notifications and peer-reviewed publications.

RDRP scientists are conducting a series of studies of flight crew members. Workplace exposures which may potentially contribute to adverse health outcomes for that occupational group include ionizing cosmic radiation. Several studies are underway, including cohort mortality studies of former Pan Am flight attendants and pilots and a cytogenetic study of markers of cosmic radiation exposure and possible effects among pilots. Results from these studies will be of relevance to the nearly 200,000 current U.S. flight crew members, as well as frequent fliers, and workers exposed to ionizing radiation. This health information will be in the form of direct worker notifications and peer-reviewed publications. The Flight Crew Research Program page is currently available on the NIOSH Web site (http://www.cdc.gov/niosh/topics/flightcrew) to disseminate information about RDRP and other research in this area (A5-17).

 

136. Ward E [1995]. Overview of preventable industrial causes of occupational cancer. Environ Health Perspect 103(Suppl 8):197-203.

137. Ward E, Ruder A, Mills C [1993]. Assessment of cancer priority setting in IWSB. Working draft NIOSH report.

138. Ward EM, Schulte PA, Bayard S, Blair A, Brandt-Rauf P, Butler MA, Dankovic D, Hubbs AF, Jones C, Karstadt M, Kedderis GL, Melnick R, Redlich CA, Rothman N, Savage RE, Sprinker M, Toraason M, Weston A [2003]. Priorities for development of research methods in occupational cancer. Environ Health Perspect 111:2-12.

139. Steenland K, Palu S. Cohort mortality study of 57,000 painters and other union members: A 15 year update. Occup Environ Med. 56:315-321, 1999.

140. U.S. DOL [1993]. Regulations [Preambles to Final Rules] Occupational Exposure to Cadmium Section 5 - V. Health Effects 57 FR 42102, Sept. 14, 1992; 58 FR 21778.