Genetic component of lung cancer: cohort study of twins

• Published in: The Lancet (British edition) Vol. 344; no. 8920; pp. 440 - 443
• Main Authors: Braun, M.M, Caporaso, N.E, Hoover, R.N, Page, W.F
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 13.08.1994; Lancet; Elsevier Limited
• Subjects: Adult; Age Factors; Biological and medical sciences; Causality; Diseases in Twins - epidemiology; Diseases in Twins - genetics; Follow-Up Studies; Genetic factors; Genetics; Health risks; Humans; Lung cancer; Lung Diseases - genetics; Lung Diseases - mortality; Male; Mass Screening; Medical research; Medical sciences; Middle Aged; Military; Military Personnel; Mortality; Pneumology; Population Surveillance; Predictive Value of Tests; Registries; Smoking; Smoking - adverse effects; Smoking - epidemiology; Survival Rate; Tumors of the respiratory system and mediastinum; Twins; Twins, Dizygotic; Twins, Monozygotic; United States - epidemiology; United States; Human; Lung disease; Respiratory disease; Cohort study; Risk factor; Tobacco smoking; Bronchus disease; Malignant tumor; Epidemiology; Monozygotic twin; Bronchopulmonary
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(94)91770-1

Summary Epidemiological and molecular epidemiological findings suggest that inherited predisposition may be a component of lung cancer risk and an important modulator of the carcinogenic effects of cigarette smoke. We have carried out a genetic analysis of lung cancer mortality on the National Academy of Sciences/National Research Council Twin Registry. The registry is composed of 15 924 male twin pairs who were born in the USA between 1917 and 1927 and who served in the armed forces during World War II. As evidence for a genetic effect on lung cancer, we required concordance for lung cancer death to be greater among monozygotic than among dizygotic twin pairs. No genetic effect on lung cancer mortality was observed. The ratio of observed to expected concordance among monozygotic twins did not exceed that among dizygotic twins (overall rate ratio 0·75 [95% Cl 0·35-1·6]), even though monozygotic twin pairs are more likely to be concordant for smoking than dizygotic twin pairs in this population. A cohort analysis (accounting for age, sex, race, and smoking intensity) of lung cancer mortality found no lung cancer deaths during 300 person-years of follow-up (observed to expected ratio 0 [0-4·09]) among 47 monozygotic twin smokers whose smoking twins had died of lung cancer, even though smoking histories were very similar within twin pairs. In our study, there is little if any effect of inherited predisposition on development of lung cancer. Genetic factors are not likely to be strongly predictive of lung cancer risk in most male smokers older than 50, the age group in which the vast majority of cases occur.