Effect of Smoking Cessation on Major Histologic Types of Lung Cancer* Sadik A. Khuder, PhD; and Anand B. Mutgi, MD, MSc Study objectives: It is well-recognized that the risk of lung cancer declines after smoking cessation. However, the degree of decline in different histologic types of lung cancer is not well understood. We conducted a meta-analysis of peer-reviewed studies to assess the effect of smoking cessation on rates of major histologic types of lung cancer. Design: Studies published in English between 1970 and 1999 were identified through searches of computerized databases (ie, MEDLINE and CANCERLIT). Combined estimates of relative risk and 95% confidence intervals were calculated for 27 studies using fixed and random effects models. Separate analyses were conducted for men and women. Results: Smoking cessation was associated with a reduction in the risk of all the major histologic types of lung cancer. The highest reduction was in small cell lung carcinoma (SCLC) and squamous cell carcinoma (SQC), and the lowest reduction was seen in large cell cancer and adenocarcinoma. In women, the combined risks for SQC and SCLC were higher than those in men. The dose-response curve for intensity of smoking was steeper in women. Conclusion: The findings of this study suggest that smoking cessation results in the greatest reductions for SCLC and SQC. This effect is most marked in heavy smokers, particularly among women. (CHEST 2001; 120:1577–1583) Key words: case-control; cessation; histology; lung cancer; odds ratio; smoking Abbreviations: ADC = adenocarcinoma; CI = confidence interval; LGC = large cell carcinoma; ln OR = natural logarithm of the odds ratio; OR = odds ratio; SCLC = small cell lung carcinoma; SQC = squamous cell carcinoma; L ung cancer is the most common malignancy in the United States and is the leading cause of cancer deaths in men and women. 1 The lung cancer incidence is leveling off in men but is continuing to rise at a steady rate among women. The association between smoking and lung cancer has been studied extensively and is well-established. Eighty-seven to ninety percent of lung cancer cases are attributable to cigarette smoking, and smokers are 22 times more likely to die from lung cancer than nonsmokers. 2 It is well-recognized that the risk of lung cancer declines after smoking cessation. 3,4 However, it is not known whether this decline varies with the histologic type of lung cancer. Previous studies have shown that smoking is more often associated with squamous cell carcinoma (SQC) or small cell lung carcinoma (SCLC) than with adenocarcinoma (ADC). 5,6 Con- sequently, it is expected that greater reductions would be seen in cases of SQC and SCLC after smoking cessation. The effect of quitting smoking on the risk of large cell carcinoma (LGC) is not well- understood. In this study, we examined the effects of the cessation of smoking on the risk for the major histologic types of lung cancer. Materials and Methods The MEDLINE and CANCERLIT databases were searched using key words pertaining to smoking and to histologic type of lung cancer. In addition, the reference lists of identified studies as well as review articles were examined to identify additional studies. This search strategy identified over 600 articles on smoking and lung cancer. Only studies pertaining to lung histol- ogy and published in English were reviewed. We excluded case series studies from further review. The search was repeated until no additional articles were found prior to September 2000. Articles were examined, and studies were excluded from the meta-analysis for any one of the following reasons: (1) two or more histologic types were grouped together and no data were presented on the specific histologic type; (2) lack of measures for relative risk; (3) absence of risk comparison to nonsmokers; and (4) the group studied was included in another published study. Articles were stratified into subgroups based on study design and year of publication. Studies were reviewed and data pertain- ing to estimator of relative risk were abstracted. A series of meta-analyses were conducted and the results were evaluated in *From the Department of Medicine, Medical College of Ohio, Toledo, OH. Manuscript received October 2, 2000; revision accepted May 17, 2001. Correspondence to: Sadik A. Khuder, PhD, Department of Med- icine, Medical College of Ohio, 3120 Glendale Ave, Toledo, OH 43614-5809; e-mail: skhuder@mco.edu CHEST / 120 / 5 / NOVEMBER, 2001 1577 Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21969/ on 04/28/2017