Effect of cigarette smoking on major histological types of lung cancer: a meta-analysis

Although cigarette smoking is an established risk factor for lung cancer, the strength of association with different histologic types is not well understood. This meta-analyses of peer-reviewed studies was conducted to assess the effect of cigarette smoking on major histologic types of lung cancer. Studies were identified through MEDLINE and CANCERLIT searches. A total of 48 studies published between 1970 and 1999 were identified. Combined estimates of relative risks (OR) and 95% confidence intervals (CI) were calculated using fixed and random effect models. Separate analyses were conducted by study design and gender. A linear dose-response was fit to studies reporting data on intensity and duration of smoking. All histologic types of lung cancer were significantly associated with cigarette smoking. The association was stronger with squamous cell carcinoma (SQC) and small cell carcinoma (SCLC) than with large cell cancer (LGC) and adenocarcinoma (ADC). The combined OR for heaviest smoking intensity (30+ cigarettes per day) ranged from 4.10 (CI 3.16–5.31) for ADC to 18.3 (CI 9.26–36.4) for SCLC. The combined OR for longest duration of smoking (40+ years) ranged from 3.80 (CI 2.35–6.16) for ADC to 38.6 (CI 11.9–125) for SCLC. In women, the combined OR for SQC and SCLC were higher than those in men. The dose response curve for intensity of smoking was steeper in women. The findings of this study provide additional evidence for a causal relationship between smoking and all histologic types of lung cancer.