A new trajectory approach for investigating the association between an environmental or occupational exposure over lifetime and the risk of chronic disease: Application to smoking, asbestos, and lung cancer

Abstract

Quantifying the association between lifetime exposures and the risk of developing a chronic disease is a recurrent challenge in epidemiology. Individual exposure trajectories are often heterogeneous and studying their associations with the risk of disease is not straightforward. We propose to use a latent class mixed model (LCMM) to identify profiles (latent classes) of exposure trajectories and estimate their association with the risk of disease. The methodology is applied to study the association between lifetime trajectories of smoking or occupational exposure to asbestos and the risk of lung cancer in males of the ICARE population-based case-control study. Asbestos exposure was assessed using a job exposure matrix. The classes of exposure trajectories were identified using two separate LCMM for smoking and asbestos, and the association between the identified classes and the risk of lung cancer was estimated in a second stage using weighted logistic regression and all subjects. A total of 2026/2610 cases/controls had complete information on both smoking and asbestos exposure, including 1938/1837 cases/controls ever smokers, and 1417/1520 cases/controls ever exposed to asbestos. The LCMM identified four latent classes of smoking trajectories which had different risks of lung cancer, all much stronger than never smokers. The most frequent class had moderate constant intensity over lifetime while the three others had either long-term, distant or recent high intensity. The latter had the strongest risk of lung cancer. We identified five classes of asbestos exposure trajectories which all had higher risk of lung cancer compared to men never occupationally exposed to asbestos, whatever the dose and the timing of exposure. The proposed approach opens new perspectives for the analyses of dose-time-response relationships between protracted exposures and the risk of developing a chronic disease, by providing a complete picture of exposure history in terms of intensity, duration, and timing of exposure.

Fig 1. Selection of subjects for the statistical analysis, ICARE case-control study, 2001–2007, France.

Fig 2. Lifetime trajectories of smoking intensities, ICARE case-control study, 2001–2007, France.

The left panel shows the estimated mean trajectory of smoking intensity in the four latent classes. The right panel shows for each class, 20 randomly selected observed individual trajectories of subjects who had a high probability (close to 1) to belong to the class, with the bold line representing the estimated mean trajectory in the Class, with its 95% CI. The representation of each estimated mean trajectory is truncated at the 95^th percentile of the distribution of observed exposure times in subjects a posteriori classified in the class.

Fig 3. Lifetime trajectories of intensities of occupational exposure to asbestos, ICARE case-control study, 2001–2007, France.

The left panel shows the estimated mean trajectory of asbestos intensity in the class of low cumulative exposure to asbestos (Class 5 including all subjects with a CIE lower than 0.26 f/mL-years) and in the four latent classes identified with the LCMM on the remaining subjects ever exposed to asbestos (Classes 1 to 4). The right panel shows for each class, 20 randomly selected observed individual trajectories of subjects who had a high probability (close to 1) to belong to the class, with the bold line representing the estimated mean trajectory in the Class, with its 95% CI. The representation of each estimated mean trajectory is truncated at the 95^th percentile of the distribution of observed exposure times in subjects a posteriori classified in the class.