Elsevier

Lung Cancer

Volume 31, Issues 2–3, March 2001, Pages 139-148
Lung Cancer

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

https://doi.org/10.1016/S0169-5002(00)00181-1Get rights and content

Abstract

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.

Introduction

Lung cancer is one of the most common cancers worldwide and has the highest mortality rate among all cancer [1]. In the US, the incidence of the disease is gradually decreasing in men but is continuing to rise in women [2].

The dominant role of cigarette smoking in the etiology of lung cancer is well established throughout numerous epidemiological studies. Cigarette smoking is associated with all histologic types of lung cancer but the strength of the association varies with different histologic types of the disease.

Over the past two decades, the distribution of histologic types of lung cancer has changed. The incidence of squamous cell carcinoma (SQC), small cell cancer (SCLC) and large cell cancer (LGC) has decreased while the incidence of adenocarcinoma (ADC) has been moderately increasing in the US [3]. Numerous epidemiological studies on smoking and lung cancer have been conducted over the past 50 years. However, only limited number of these studies have examined the data according to histologic type and gender. Moreover, many studies examined the relative frequency of histologic types among cigarette smokers without providing meaningful estimates for relative risk.

While early studies of lung cancer reported much higher odds ratio (OR) for men than for women, later studies have indicated that the difference is narrowing. Several recent studies suggest that female smokers may have a higher relative risk for lung cancer than male smokers.

The association between histological types and smoking was reviewed by an IACR working group [4] and concluded that SQC, SCLC and ADC were probably caused by smoking, although the relative risk was weaker with ADC. The association of smoking and LGC was not included in this IACR review and only recent studies provided data on this histologic type of lung cancer.

This meta-analysis of peer-reviewed studies was conducted to assess the effect of cigarette smoking on major histologic types of lung cancer. The strength of the association between cigarette smoking and lung cancer was examined separately for men and women.

Section snippets

Materials and methods

The MEDLINE and CANCERLIT databases were searched using key words pertaining to smoking and histology. In addition, the reference lists of identified studies as well as review papers were examined to identify additional studies. This search strategy identified over 500 articles on smoking and lung cancer. The search was repeated until no additional articles were found prior to January 2000. Articles were examined and studies were excluded from further review for any one of the following

Results

Forty-eight studies evaluating the association between smoking and major histologic types of lung cancer were reviewed. These studies were published between 1970 and 1999. Fourteen studies [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22] were excluded because insufficient information was provided on estimator of relative risk or standard error. Four studies [23], [24], [25], [26] were excluded because the histologic types were identified only as Kreyberg I and

Discussion

The findings of this study suggest that all histologic types of lung cancer are significantly associated with cigarette smoking. The strength of the association varies among the four major histologic types of lung cancer. The dose response analyses show that the estimator of relative risk increases linearly with the number of cigarettes smoked per day or duration of smoking for all histologic types. SCLC displayed the strongest overall relationship followed by squamous cell carcinoma. ADC

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