Occupational Exposures and Lung Cancer

Despite decreases in the incidence of certain cancers and associated mortality, cancer remains highly lethal and very common. About 41% of Americans will develop some form of cancer (including nonmelanoma skin cancer) in their lifetimes. One-fifth of Americans will die of cancer. Notwithstanding important progress made in the reduction of lung cancer in the United States with antismoking campaigns, it still tops the list for the most common cause of cancer death in the United States, as well as the world. Lung cancer is a global public health problem. There were an estimated 2.1 million lung cancer cases and 1.8 million deaths in 2018 worldwide. Incidence and mortality rates vary 20-fold between regions, mainly because of variation in carcinogen exposure such as tobacco smoking. However, if tobacco smoking were removed altogether, lung cancer would still be in the top 10 cancers worldwide (1). There are a number of well-known lung carcinogens to which exposure occurs mainly in the workplace. But studies of lung cancer in occupational populations are often hampered by small sample size and inability to control for, or assess interactions with, tobacco smoking. It is critical to understand the risks posed by exposures to occupational lung carcinogens to develop effective control programs for this deadly disease.

In this issue of the Journal, two papers by Ge and colleagues (pp. 402–411 and pp. 412–421) address major issues related to occupational lung cancer (2, 3). One critical feature in this published work is the large sample sizes garnered by pooling multiple case–control studies in their respective assessments of occupational diesel exhaust and crystalline silica exposure while adjusting for and examining interactions with tobacco smoking. Both papers leverage a large pooled sample of 14 case–control studies in Europe and Canada, numbering a total of 37,866 cases (16,901 lung cancer and 20,965 controls).

The first paper showed that diesel exhaust exposure caused increased lung cancer risk even in the lowest category of cumulative exposure using a job-exposure matrix. Moreover, lung cancer risk was increased in nonsmoking workers and there were superadditive joint effects of diesel and smoking in males for all four lung cancer subtypes. Finally, there was evidence for cell subtype differential risk, with the highest frequency of squamous cell and small cell and lowest of adenocarcinoma. Although diesel was classified by the International Agency for Research on Cancer as a class 1 human carcinogen based on prior studies, including a large cohort study performed by the U.S. National Cancer Institute and National Institute for Occupational Safety and Health (4), the added power of the current study aids our understanding of exposure–response at relatively low levels of cumulative exposure, smoking interactions, and cell type distribution. The public health consequences of the results are significant, as there are an estimated 1 million U.S. workers, 3.6 million European workers, and millions more in Asia who are exposed to diesel exhaust.

The second paper examined the risk of occupational exposure to crystalline silica and lung cancer using the same large pooled data. Although silica is also classified as a class 1 human carcinogen by the International Agency for Research on Cancer, the results addressed key knowledge gaps. There was an increased risk of lung cancer with cumulative occupational exposure in workers both with and without silicosis as well as in current, former, and never-smokers. Moreover, there was increased risk for all major histologic subtypes of lung cancer. Finally, there was a supermultiplicative risk with smoking and silica exposure for overall lung cancer risk. This paper has great significance at the current time because in addition to the nearly 2 million silica-exposed workers in the United States, 11.5 million in India, and millions in China, Turkey, Australia, and elsewhere, there has been an uptick in the number of workers exposed to crystalline silica while manufacturing and installing stone countertop materials for household use and sandblasting of denim for fashionwear (5).

For decades, research has been focused on the mechanisms of carcinogenesis, the genetics of cancer initiation and progression, and the epidemiology of cancer as a complex chronic disease. Researchers have aimed to identify avoidable causes of cancer, increase early detection, and develop treatments to improve outcomes in patients with cancer. The relative contributions of genetic and nongenetic (i.e., “environmental,” broadly speaking) factors to the development of common cancers have been studied and debated for decades. Relative contributions are expressed in terms of the “population attributable fraction”—the proportion of disease incidence that would be eliminated if a given risk factor, such as smoking or asbestos exposure, was removed. Toxic exposures in the environment, including workplace exposures, are responsible for a substantial percentage of all cancers (6). Precise apportionment is not possible because of gaps in the exposure data, interactions between environmental and lifestyle carcinogens, and differences from country to country in exposure patterns (7) However, credible estimates from the World Health Organization and the International Agency for Research on Cancer (8–10) suggest that the fraction of global cancer currently attributable to toxic environmental exposures is between 7% and 19%.

Efforts at reducing mortality from lung cancer have included early detection and precision therapies. Although more effective therapies and better early detection and screening methods are indispensable, the most valuable approaches to reducing cancer morbidity and mortality lie in primary prevention—avoiding introducing carcinogenic agents into the environment and eliminating existing exposures to carcinogenic agents. The first approach would be most effective if carcinogenic substances were identified before they could be introduced, although it is impossible to quantify the success of this approach. The value of the second approach has been demonstrated by the disappearance or reduced incidence of particular types of cancers following the elimination of specific occupational exposures. For example, occupational-related small cell lung cancer was eliminated after exposure to Bis-chloromethyl ether (used in producing bulletproof glass) was banned in most countries, and mesothelioma incidence was decreased after restrictions or bans were placed on asbestos use. Furthermore, risk has been reduced through greater regulatory control over compounds that remain in use—for instance, the U.S. Occupational Safety and Health Administration restrictions on exposure to asbestos fibers, coke oven emissions, crystalline silica, and other carcinogens.

A sobering realization about occupational lung cancer is that despite significant advances in reducing occupational carcinogen exposures in North America and Western Europe, the number of workers exposed globally to agents such as crystalline silica and diesel continues to rise. It is time for all stakeholders to work together to reduce the burden of occupational lung cancer by developing effective prevention measures to identify, control, and eliminate exposures to carcinogenic agents.