Defining high-risk individuals in a population-based molecular-epidemiological study of lung cancer

Abstract

Abstract. Within the framework of the Liverpool Lung Project (LLP), population-based case-control and prospective cohort studies are in progress to identify molecular and epidemiological risk factors and define populations and individuals most at risk of developing lung cancer. This report describes a strategy for selection of a high-risk population and further provides support for the inclusion of occupational and genetic risk factors in future models. Data from the case-control study (256 incident cases and 314 population controls) were analysed to define a high-risk population. Detailed lifestyle and occupational information were collected during structured interviews. Models were constructed using conditional logistic regression and included terms for age, tobacco consumption and previous respiratory disease. Smoking duration was chosen as the most important predictor of lung cancer risk [>50 years (OR 15.65, 95% CI 6.10-40.15)]. However, such a model would preclude younger individuals. Several combinations of previous respiratory disease were also considered, of which a history of bronchitis, emphysema or pneumonia (BEP) was the most significant (OR 1.86, 95% CI 1.28-2.69). A high-risk subset (based on combinations of smoking duration and BEP) was identified, which have a 4.5-fold greater risk of developing lung cancer (OR 4.5, 95% CI 2. 33-8.68). Future refinement of the risk model to include individuals occupationally exposed to asbestos and with the p21 genotypes is discussed. There is real potential for environmental and genetic factors to improve on risk prediction and targeting of susceptible individuals beyond the traditional models based only on smoking and age. The development of a molecular-epidemiological model will inform the development of effective surveillance, early detection and chemoprevention strategies.

Assessing the Relationship Between Lung Cancer Risk and Emphysema Detected on Low-Dose CT of the Chest

“…There is less information regarding the association between emphysema and lung cancer. [15][16][17] Emphysema has traditionally been a pathologic diagnosis, but the development of CT-based image analysis techniques has lead to accurate noninvasive in vivo detection and quantification of emphysema. 18 For example, CT has been shown to be useful in the selection of individuals with severe emphysema who are at a greater risk for a poor outcome after lung volume reduction surgery (ie, those with a homogenous distribution of emphysema).…”

The UK Lung Screen (UKLS): Demographic Profile of First 88,897 Approaches Provides Recommendations for Population Screening

“…In Europe, the Dutch Belgian randomised lung cancer screening trial (NELSON) is currently underway (6). Screening for lung cancer relies first upon defining a highrisk population; in the United Kingdom, criteria for this have been determined through the Liverpool Lung Project (LLP) (7,8). The LLP risk prediction model incorporates age, sex, family history of lung cancer, smoking, personal history of other cancer and non-malignant respiratory disease, and occupational exposure (7,8).…”

“…Screening for lung cancer relies first upon defining a highrisk population; in the United Kingdom, criteria for this have been determined through the Liverpool Lung Project (LLP) (7,8). The LLP risk prediction model incorporates age, sex, family history of lung cancer, smoking, personal history of other cancer and non-malignant respiratory disease, and occupational exposure (7,8). The LLP model is a robust algorithm that has been validated on two international case-control populations (Harvard and EULC) and one independent cohort (LLP 7500; ref.…”

The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer

“…However, as noted above, a number of more formal lung cancer risk prediction algorithms have been developed, 13 and these may have utility in selecting those people who are suitable for screening. 14 In the UK, the risk model of choice is the LLP algorithm, 20,21 and this model has been used as the basis for risk assessment in the UKLS.…”