Systematic review with meta-analysis of the epidemiological evidence in the 1900s relating smoking to lung cancer

Abstract

BackgroundSmoking is a known lung cancer cause, but no detailed quantitative systematic review exists. We summarize evidence for various indices.MethodsPapers published before 2000 describing epidemiological studies involving 100+ lung cancer cases were obtained from Medline and other sources. Studies were classified as principal, or subsidiary where cases overlapped with principal studies. Data were extracted on design, exposures, histological types and confounder adjustment. RRs/ORs and 95% CIs were extracted for ever, current and ex smoking of cigarettes, pipes and cigars and indices of cigarette type and dose–response. Meta-analyses and meta-regressions investigated how relationships varied by study and RR characteristics, mainly for outcomes exactly or closely equivalent to all lung cancer, squamous cell carcinoma (“squamous”) and adenocarcinoma (“adeno”).Results287 studies (20 subsidiary) were identified. Although RR estimates were markedly heterogeneous, the meta-analyses demonstrated a relationship of smoking with lung cancer risk, clearly seen for ever smoking (random-effects RR 5.50, CI 5.07-5.96) current smoking (8.43, 7.63-9.31), ex smoking (4.30, 3.93-4.71) and pipe/cigar only smoking (2.92, 2.38-3.57). It was stronger for squamous (current smoking RR 16.91, 13.14-21.76) than adeno (4.21, 3.32-5.34), and evident in both sexes (RRs somewhat higher in males), all continents (RRs highest for North America and lowest for Asia, particularly China), and both study types (RRs higher for prospective studies). Relationships were somewhat stronger in later starting and larger studies. RR estimates were similar in cigarette only and mixed smokers, and similar in smokers of pipes/cigars only, pipes only and cigars only. Exceptionally no increase in adeno risk was seen for pipe/cigar only smokers (0.93, 0.62-1.40). RRs were unrelated to mentholation, and higher for non-filter and handrolled cigarettes. RRs increased with amount smoked, duration, earlier starting age, tar level and fraction smoked and decreased with time quit. Relationships were strongest for small and squamous cell, intermediate for large cell and weakest for adenocarcinoma. Covariate-adjustment little affected RR estimates.ConclusionsThe association of lung cancer with smoking is strong, evident for all lung cancer types, dose-related and insensitive to covariate-adjustment. This emphasises the causal nature of the relationship. Our results quantify the relationships more precisely than previously.

A 2-year retrospective review of the effect of cigarette smoking status on the histological cell types of lung carcinoma in the Western Cape

“…Other studies have also found this trend, demonstrating that SCC (more centrally located) tends to have an overall stronger relationship with cigarette smoking than does ADC (more peripherally located). [6,8,9,37,38] Our data found that on average patients with SCC smoked more than patients with ADC and this is further supported in the literature, where there appears, in general, to be a stronger dose-response relationship between centrally located tumours like SCC and cigarette smoking than with tumours situated more peripherally such as ADC. [9] One possible explanation for the closer association between SCC and smoking is nicotine.…”

Biological interaction of cigarette smoking on the association between genetic polymorphisms involved in inflammation and the risk of lung cancer: A case-control study in Japan

“…Smokers with the T allele may, therefore, be more sensitive to the effects of tobacco carcinogens such as quinones and benzene, and thus more susceptible to tobacco-associated lung cancer. The association between tobacco smoking and lung cancer has previously been revealed to be stronger for SCC and SCLC compared with adenocarcinoma (37), and may induce the association between rs1800566 and SCC. In the present study, no significant association between rs1800566 and lung cancer was demonstrated in the subgroup with SCLC; however, precise evaluation is difficult to obtain due to the small number of patients with SCLC.…”

A Case of Lung Cancer Originating from CavitaryMycobacterium xenopiInfection

“…Cavitary lesions are common in patients with squamous cell carcinoma. 3 Cigarette smoking certainly contributed to her risk of subsequent squamous cell carcinoma, 6 but it is unlikely that she had pre-existing cancer at the time of her initial presentation, as her initial biopsy did not show any evidence of malignancy, and it is unlikely that a poorly differentiated squamous cell carcinoma would remain radiographically inapparent for 18 months. Of the non-small cell lung cancer subtypes, several studies have shown squamous cell carcinoma to be one of the more rapidly growing tumor subtypes.…”