Host Factors

As you already know, the epidemiology of lung cancer is essentially the epidemiology of cigarette smoking. As with most illnesses, the development of disease depends on a complex interaction between the environment and the host.

Specifically with lung cancer, host factors play a relatively minor role. However, when dealing with a specific case implicating host factors in the epidemiology of lung carcinoma, it is beneficial to have a knowledge related to the development of lung cancer. We shall review those host factors now.

In a review of autopsy material, it has become apparent that a patient with one malignancy was at increased risk of developing a second primary.

Risk of Second Primary

The incidence of development of a second primary cancer in patients who already have one malignancy is 5-11 times greater than the patient who does not have another primary malignancy

Associated Malignancies

One out of four patients who had lung cancer plus a second primary in this series had carcinoma of the larynx. Lung and laryngeal cancers occur together in persons more often than expected by change, perhaps because of "field carcinogenesis", in which dysplasia from the effects of tobacco and other carcinogens develop over a general epithelial region. In this particular series, there were 18 synchronous and 42 metachronous larynx and lung cancers. Cytology through the tracheostomy established the diagnosis in 17 of 34 patients.

Tylosis

Tylosis is considered a hereditary cutaneous disorder which seems to be controlled by a single autosomal gene with high penetrance and heterozygous effect. The physical findings of tylosis (mainly thickening and fissuring of the palmar and plantar skin) have been statistically associated with the presence of intrathoracic malignancy. By the age of 65, 95% of all patients with tylosis can be expected to develop carcinoma of the esophagus. One could postulate that squamous cell carcinoma of the bronchus and tylosis could co-exist since the bronchus, like the esophagus, is a derivative of the foregut. It must also be kept in mind that acquired tylosis may represent an unusual paraneoplastic manifestation of intrathoracic neoplasm.

COPD

The incidence of lung carcinoma in patients with COPD is 11.6/1000 man years, which is four to five times greater than that reported for series of smokers or in subjects with bronchitis. The most frequent cell type was squamous.

Chronic Lymphatic Leukemia

191 patients with a diagnosis of CLL were seen at the Rosewell park memorial institute from 1951-1976. Of the 191; 14 (7%) were found to have bronchogenic carcinoma. In this series, the incidence of bronchogenic carcinoma in patients with CLL was 11 times higher than in the general population.

Patients with CLL are also known to have impaired immunity, which may contribute to a second primary cancer. It is unlikely that the agents used in treatment of CLL are epidemiologically related to the development of lung cancer. The overall survival was not significantly different from the non-leukemic patients.

Aryl-Hydrocarbon Hydroxylase

Among first degree relatives of lung cancer patients who smoke, their risk of developing lung cancer is 14 times greater than a non-smoker without a family history of lung cancer. Attempts have been made to correlate this genetic susceptibility with an increased inducibility of the enzyme aryl-hydrocarbon hydroxylase (AHH). However, results have been inconsistent.

Scar Carcinoma

Adenocarcinoma, particularly the bronchiole-alveolar type, is the most common histology found in scar carcinomas. These cancers often arise in areas of hyperplastic epithelium or pulmonary fibrosis. The incidence of bronchiole-alveolar carcinoma is increasing, perhaps because more people are now surviving infarcts, trauma and inflammatory lung disease. Areas of scarring or fibrosis may actually develop within adenocarcinomas during their growth. This may result in prolonged radiographic stability and the erroneous assumption that the lesion is benign. The prognosis of tumors with advanced collagen formation within these fibrotic areas is poorer than that of tumors with little or no collagenation.

Tuberculosis

The incidence of bronchogenic carcinoma at autopsy in tuberculosis patients has been reported to be 20 times that in the general population, comparable to that reported for heavy smokers. Steinitz evaluated a population in Israel with relatively few heavy smokers, and found that patients with previous tuberculosis had an increased risk of developing lung carcinoma, approximately five times greater than the general population males and ten times greater in females. Other series show that association of lung carcinoma superimposed on previous tuberculosis is frequent, with the incidence being approximately 5%. Interestingly, the distribution of various histopathologic cell types of bronchogenic carcinoma are not significantly different from the population with lung cancer and no prior history of tuberculosis. Finally, the often severe chronic radiographic changes in tuberculosis significantly delay recognition of radiographic abnormalities and ultimate diagnosis of lung carcinoma.