Misclassification of Smoking Status and Lung Cancer Risk from Environmental Tobacco Smoke in Never-Smokers

Abstract

Lung cancer risk estimates for exposure to environmental tobacco smoke remain controversial, a major unresolved issue being misclassification of smokers. We studied misclassification rates in two large cohorts using information on smoking obtained several years apart. Cohort I included Swedish twins born between 1886 and 1925 who answered questionnaires in 1961 and again in 1967 or 1970. Cohort II was a random stratified population sample of individuals born between 1894 and 1945 who responded to postal smoking surveys in 1963 and 1969. We considered those who stated that they had never smoked in the second questionnaire, but who reported smoking or former smoking in the first questionnaire, to be misclassified. In cohort I, 4.9% of male and 4.5% of female ever-smokers were misclassified, corresponding to 11.1% and 1.3% of reported never-smokers, respectively. Cohort II yielded similar results. A follow-up through 1992 of cohort I showed a relative risk for lung cancer among misclassified men of 1.9 [95% confidence interval (CI) = 0.4-9.1], as compared with 4.5 (95% CI = 2.0-9.9) and 13.3 (95% CI = 6.5-27.0) for former and current smokers, respectively. No case occurred among misclassified women. Although misclassification of smokers exists, our results indicate that it mainly concerns light smokers or long-time ex-smokers, who have only a very moderately elevated risk of lung cancer. It therefore appears unlikely that confounding by smoking explains the increased risk for lung cancer related to environmental tobacco smoke exposure.

Exposure Misclassification Bias in Studies of Environmental Tobacco Smoke and Lung Cancer

“…Several large, well-designed and well-conducted studies confirmed that the proportion of ever smokers reported as never smokers (10), the proportion of nonsmokers misclassified as ever smokers (based on cotinine measurements) (14,25), and the risk of lung cancer among misclassified smokers (10) are all low, in agreement with the conclusion of the NRC in 1986 that smoker misclassification cannot explain the ETS effect on lung cancer risk in never smokers (1). In addition, the risk of lung cancer associated with ETS exposure was essentially unaffected by misclassification bias in the only study that has directly evaluated its potential impact (26).…”

“…As shown in Table 2, the substantial variability in the percentage of nonsmokers misclassified as smokers (11-23% in males and 2-5% in females) contrasts with the relative stability of the proportion of ever smokers misclassified as never smokers (Table 1). Using the Swedish cohort mentioned previously, misclassifications of never smokers as smokers in cohort I and cohort II were 11.1 and 11.5%, respectively, for men and 1.3 and 2.2%, respectively, for women (10 (15), excluding the data from Britten (9), presented separately in this table. (10) no data.…”

“…Using the Swedish cohort mentioned previously, misclassifications of never smokers as smokers in cohort I and cohort II were 11.1 and 11.5%, respectively, for men and 1.3 and 2.2%, respectively, for women (10 (15), excluding the data from Britten (9), presented separately in this table. (10) no data. 'This represents an average of the percent misclassification found in cohort and cohort 11. as one of the determinants to determine smoker misclassification.…”

“…Conversely, the NRC report (1) and other investigators (2,4) concluded that the occurrence of smoker misclassification is relatively low (about 5%) and cannot account for the observed effect of ETS on lung cancer risk. Wald and co-workers (2) (3,5,9,10) (Table 1). This finding is generally comparable in men and women and in studies conducted in different countries.…”

“…An exception is the higher misclassification rate reported among male smokers in one study (3). In the largest study published to date on this topic, information on smoking habits was obtained on two occasions from approximately 18,000 Swedish twins born between 1886 and 1925 (cohort I) and approximately 22,000 Swedes born between 1914 and 1945 who were randomly selected from the general population (cohort II) (10). Smoker misclassifications in cohort I and cohort II were 4.9 and 5.0%, respectively, for men and 4.5 and 7.3%, respectively, for women (10).…”