Lung Cancer: Epidemiology and Etiology

16 are carcinogenic agents with limited evidence in humans. The table n° 1 presents all carcinogenic agents which are causally related with lung cancer according to the last classification by IARC [6].

In this table, the list (a) Carcinogens with sufficient evidence means that a causal relationship has been established between the agent and the type of cancer studied (carcinogenic agent), and that chance or bias that may be involved in this relationship have been ruled out. These are certain carcinogens for humans (group1).

The list (b): Carcinogenic agents with limited evidence means that a causal relationship has been established between the agent and the type of cancer studied (carcinogenic agent), but that chance or bias cannot be totally ruled out to explain this relationship. These are probable or possible carcinogens for humans (group 2A and 2B). This list also includes some elements belonging to group 1, like benzene, but which are carcinogenic for other organs whereas the scientific evidence on their carcinogenic capacity for the lungs remains limited.

These carcinogens may be both well-identified substances than activities in which it has not been possible to identify a single substance.

Finally, the table does not include sectors not covered by IARC monographs; including genetic factors, reproductive status and some nutritional factors.

Discussion: 

The most important occupational risk factors for lung cancer are asbestos, diesel, and some metals: chromium, nickel, beryllium, cadmium, arsenic and silicon (in the form of crystalline silica) [7].

For asbestos, for example, which is the main occupational etiologic factor for lung cancer, occupational exposure sources are in its mining and usage in industry or manufacture especially thermal and electrical insulation in construction and shipyard work, brakes, textile industry, asbestos cement products and watertightness [8]. These diverse uses are explained by its qualities: asbestos has a high thermal, chemical and mechanical resistance.

Asbestos is responsible for more than half of occupational lung cancer [9] and a dose-response relationship is clearly demonstrated between lung cancer mortality attributable to asbestos in populations exposed to continuous occupational exposures, and the cumulative exposure which takes a linear progression model [10].

In the workplace, carcinogens are mixed with each other in the different materials and processes used in the activity in question, which poses the problem of polyexposure and coexposure. This makes it difficult sometimes to know the real part of each agent in the appearance of cancer. The typical example is construction work, where several pulmonary carcinogens are brought together at the same time [11]. The construction worker is exposed to asbestos during the demolition or renovation of old buildings (among others), crystalline silica during sanding and the use of disc molding machine or jackhammer and polycyclic aromatic hydrocarbons (PAHs) contained in the tars during watertightness work (in addition to asbestos) which are all certain carcinogens for the lung (group1). Finally he’s also exposed to solar radiation during external work (carcinogenic for the skin), lead contained in some flashings (carcinogenic to the stomach) and titanium dioxide present as pigment in some sealants [11].

For attributable risk fractions, percentages were reported between 16.5% (for IARC Group 1 carcinogens) and 21.6% (for certain and probable carcinogens: IARC Group 1 and 2A) among men in the United Kingdom [12], a little more than in France: 12% [13]. In industrialized countries, it was between 13 and 30% [14]. However, these fractions remain very variable in time and space, in this context; a study reports attributable risk fractions ranging from 0 to 40% about 32 international studies over the last 30 years [15].

Clinically, there is no specificity for lung cancer manifestations; however, there are some arguments that support the relationship between this neoplasm and occupational exposure [16].

First, literature data that characterize the certain or probable carcinogenicity of some agents or work processes are very important to consider. The IARC evaluations, which are regularly updated, are very valuable in this regard [17].

Other arguments may also be considered such as the duration of exposure to the occupational carcinogen, the parameters that characterize this exposure, the presence of benign pathologies or associated biological signs attributable to the suspected causal agent, and non-occupational risk factors. 

The latency of occupational lung cancer is quite long; it is 10 to 30 years [18]. So, a lung cancer with less than 10 years of exposure to the suspected carcinogen would be difficult to attribute to an occupational origin.

The intensity of exposure, its cumulative duration, and possible co-exposure to other carcinogens should be clarified as the credibility of a causal relationship increases with cumulative exposure. These data can only be obtained through a detailed occupational history interview, possibly supplemented by the use of a job-exposure matrix and/or metrological data. 

In the specific case of asbestos, the mineralogical analysis of a biological sample provides the physician with an objective estimator of cumulative exposure. It is sometimes the only reliable estimator, especially if there is an unclear description of previous jobs, the patient does not know about the presence of asbestos in some jobs, or forgets the oldest exposure periods. Values greater than 1 asbestos body (AB) per millilitre of bronchoalveolar lavage fluid (1 AB/ml) or greater than 1000 AB per gram of dry lung tissue (1 AB/g) indicate a high probability of significant exposure to asbestos. Above 5 AB/ml bronchoalveolar lavage fluid (BAL) or 5000 AB/g lung tissue, occupational exposure is almost certain [19].

Also, for some carcinogens, there are sometimes elements of indirect ethological orientation: pleural and/or parenchymal fibrosis for asbestos, radiological or anatomopathological silicosis for crystalline silica, a history of acute or chronic berylliosis for beryllium, nasal ulcerations for chromium, palmo-plantar dyskeratosis for arsenic, renal biological damage to cadmium, etc.

These elements do not prove the causal relationship, but are additional signs, that generally confirm excessive levels of exposure to the carcinogen considered. On the other hand, their absence does not make it possible to reject a causal association.

At the anatomopathological level, there is usually no histological specificity for occupational lung cancer, although some histological types are more common for some agents. Some authors have reported an increased representation of adenocarcinomas in patients exposed to asbestos, whether or not there is parenchymal fibrosis [20-22]. However, an excess of other histological types has also been observed [23] and currently most authors consider that the histological type cannot be used to argue a relationship with asbestos exposure [20]. Arsenic, nickel and chromium do not induce histological specificity [24]. On the other hand, exposure to bis-(chloromethyl)ether is related to a high incidence of small cell lung cancer: up to 60% in most series, occurring in young and frequently non-smoking patients. Also, radon exposure increases the incidence of small cell lung carcinoma in smokers and non-smokers [25].

The existence of non-occupational risk factors, smoking in particular, does not allow the exclusion of the occupational origin of a lung cancer, as has been clearly demonstrated with regard to asbestos [26]. Indeed, asbestos-tobacco interaction appears to follow an approximately multiplicative model, indicating that each of these two etiological factors exert an independent action in the carcinogenesis process [26, 27].

On the other hand, the absence of non-occupational risk factors considerably reinforces the hypothesis of a direct and essential causal relationship.

The hypothesis of a molecular specificity of carcinogenic agents on specific genes is currently the subject of much research. some studies have studied the role of some agents (ionizing radiations, chromium, asbestos) in the occurrence of genetic alterations (bearing in particular on the P53 and Ras genes) [28, 29]. However, no specific mutation to an occupational carcinogen is clearly identified, although it has recently been suggested that a mutation in the Ras gene could be associated with the carcinogenic process induced by the asbestos [28].

Conclusion:

Lung cancer is the most common occupational cancer. The numerous etiologies and occupational exposure situations to proven carcinogens for the lung justify a particular vigilance of all health actors who tend to focus most their efforts on tobacco as ethiological factor of this cancer. 

A perfect coordination between different physicians is required: the pulmonologist who makes the positive diagnosis of the illness, the physician in the occupational pathology department who makes the ethiological diagnosis and the occupational physician who organizes the adaptation of the patient to his work after the treatment. Another role of this practitioner particularly involved in the organization of the health and security prevention at the workplace is to prevent the occurrence of new cases by fighting against potential exposure situations.