The interaction of asbestos and smoking in lung cancer.

Both cigarette smoke and inhaled asbestos fibres can cause lung cancer, but the assessment of how these agents act in combination is a matter of great difficulty. In non-smokers, the condition is so rare that, in any cohort of asbestos workers, the standardised mortality ratio (SMR, that is the ratio of the numbers of deaths observed and expected) is quite imprecise. The SMR for smokers, with which it has to be compared, is also subject to sampling error, making the interaction even more unstable. This accounts for much of the variation that has bedevilled evaluation.The debate has been concentrated on two hypotheses: additive (asbestos and cigarette smoke act independently) and multiplicative (asbestos produces an effect proportional to the effect of smoking). The very few data available until 1977 failed to fit the former and fitted the latter only poorly. They would have fitted better a hypothesis of greater synergism, but the only one proposed was too convoluted. So the multiplicative model appeared the only alternative, and was deemed 'accepted'.The ratio of lung cancer SMRs for non-smokers and smokers was generalised into the relative asbestos effect, RAE, with all the advantages of a parametric statistic (Berry et al., 1985, British Journal of Industrial Medicine 42, 12). On the multiplicative hypothesis, RAE=1, while RAE>1 indicates less synergism. The RAEs for the three most recent of the six results then available were >1; for one, P<0.005. From the six results combined, it was concluded that 'overall non-smokers have a relative risk of lung cancer due to asbestos that is 1.8 times that of smokers'. Some admitted uncertainty about the figure 1.8 was seized upon and even the thrust of the conclusion has been very largely disregarded. So too has the RAE and all its benefits. As a result, all later reviewers have been led into error, much of it serious: in particular, they have failed to appreciate how much of the variation arises from the inevitable imprecision of all RAEs. This failure led reviewers in 1994 to discard, quite without justification, those interactions which were less than multiplicative and came from cohort studies. Although case-referent studies seemed to support the multiplicative hypothesis, the information from them is essentially unreliable. Thus it cannot weaken the conclusions from the cohort studies, that the multiplicative hypothesis is untenable and that the relative risk of lung cancer from asbestos exposure is about twice as high in non-smokers as in smokers; the best estimate of RAE is 2.04, with 95% confidence interval 1.28-3.25. This finding is not only of high statistical significance but of great social and scientific importance.     

Mining, lung cancer and smoking

Several studies have shown an increased lung cancer mortality among Swedish metal and iron ore miners, as probably caused by exposure to radon and its daughters. An earlier study of zinc-lead miners has been updated. The results show a 16-fold increase in lung cancer mortality. Surprisingly, nonsmokers were more apt to develop lung cancer than smokers, but the induction-latency time was about nine years shorter on the average for the smokers. An explanation for these findings might be that smoking increases the thickness of the mucus layer and therefore protects the bronchial epithelium from alpha radiation, but it also promotes the development of cancer once induced by the radiation.     

吸烟与饮酒对肺癌发病的影响及交互作用

目的探讨吸烟与饮酒及其交互作用对肺癌发病的影响。方法在肿瘤高发地区开展以人群为基础的病例对照研究,通过调查问卷收集主要人口学、吸烟和饮酒等相关信息,采用非条件logistic回归分析计算比值比(OR)及95%CI,并分析吸烟与饮酒在肺癌发病中的交互作用。结果调整相关因素(包括饮酒)后,与不吸烟者相比,吸烟者患肺癌的风险增加(P0.05),吸烟≥40年者患肺癌的风险是不吸烟者的4.79倍,每日吸烟≥20支者患肺癌的风险是不吸烟者的4.44倍,吸烟至肺部者患肺癌风险是不吸烟者的4.44倍(P值均0.001)。调整变量(包括吸烟)后,饮酒和饮酒年限与肺癌发病之间无统计学关联(P0.05)。吸烟和饮酒相乘交互作用的OR值(95%CI)为0.90(0.47~1.70)。吸烟和饮酒相加交互作用的超额相对危险度(RERI)值及其95%CI为0.36(-0.92~1.64),交互作用归因比(AP)值及95%CI为0.09(-0.22~0.40),交互作用指数(SI)值及95%CI为1.13(0.71~1.80)。结论吸烟是肺癌发病的主要危险因素,且该风险随吸烟年限、吸烟量、吸烟深度的增加而显著增加,现有证据并不支持饮酒与肺癌发病之间存在关联,吸烟和饮酒在肺癌发病中也未见交互作用。     

The interaction of asbestos and smoking in lung cancer: a modified measure of effect

OBJECTIVES: The ratio of the relative risk of lung cancer due to asbestos exposure in non-smokers to that in smokers has been termed the relative asbestos effect (RAE). In a review, Liddell [Liddell FDK (2001) Ann Occup Hyg; 45: 341-56] estimated that the RAE was approximately 2. This measure is satisfactory when there is an appreciable relative risk due to asbestos but does not generalize to lower levels of exposure. A modified measure is proposed to overcome this difficulty. The modified measure, RAEm, is defined as the ratio of the excess relative risk (RR - 1) in non-smokers to that in smokers. METHODS: The cohort studies combined in Liddell's 2001 analysis have been used to give a combined estimate of the modified measure. RESULTS: The combined value of RAEm is 3.19 with 95% confidence interval 1.67-6.13. CONCLUSION: The excess relative risk of lung cancer from asbestos exposure is about three times higher in non-smokers than in smokers. The modified measure has been placed within a more versatile model of interaction. If interaction is present the relative risk from asbestos exposure changes only slightly between light and heavy smokers, but is higher in very light smokers and non-smokers. The relative risk estimated from epidemiological studies of a mixed population of non-smokers and smokers applies to smokers.     

吸烟、被动吸烟与肺癌发病风险的病例对照研究

目的 探讨吸烟、被动吸烟与肺癌的关联.方法 采用病例对照研究设计,面访肺癌新发病例1 303例和按性别、年龄(±2岁)频数匹配的健康对照1 303例.结果 吸烟是男性肺癌的重要危险因素(调整OR=4.974,95％ CI:3.933 ～6.291),随着开始吸烟年龄提前、吸烟年限延长、日吸烟量、吸烟包年以及吸烟深度的增加,患肺癌危险性增高,呈剂量反应关系(Ptrend＜0.001),戒烟≥10年患肺癌的危险性降低45.4％.男性吸烟患肺鳞癌的危险性比患肺腺癌大.被动吸烟是非吸烟者肺癌的危险因素(调整OR=1.912,95％CI:1.486～2.460),工作环境被动吸烟的男性非吸烟者患肺癌的调整OR为2.221(95％CI:1.361 ～3.625),家庭环境被动吸烟的女性非吸烟者患肺癌的调整OR为1.804(95％ CI:1.270～2.562).68.04％男性肺癌的发生可归因于吸烟,26.51％非吸烟者肺癌的发生可归因于被动吸烟.结论 吸烟是肺癌的重要危险因素,工作环境被动吸烟是男性非吸烟者肺癌的主要危险因素,家庭环境被动吸烟是女性肺癌的主要危险因素.戒烟具有重大的公共卫生学意义.     

Models of smoking and lung cancer risk: a means to an end

This commentary provides some historical context to the analysis of smoking and lung cancer risk by Lubin and colleagues in this issue of epidemiology. It also considers the potential utility of ongoing efforts to apply complex mathematical models to epidemiologic data on smoking and lung cancer risk. We conclude that the work of Lubin and colleagues adds to the models already developed and points to some potential complexities that models should incorporate.     

GSTM1, smoking and lung cancer: a case-control study

BACKGROUND: We conducted a case-control study to examine the risk of lung cancer in relation to GSTM1 polymorphism and cigarette smoking (primarily of black tobacco) in a French population. METHODS: The 611 subjects were 301 incident lung cancer cases and 310 hospital controls. We were able to constitute a DNA bank for 547 subjects (89.5%) and gather detailed information on smoking history for all of them. Results presented here concern 247 cases and 254 controls. RESULTS: Taking non- or light smokers as the reference category, we estimated odds ratios (OR) of 4.2 (95% CI: 2.6-6.7) and 5.2 (95% CI: 3.3-8.3) for the medium and heavy smokers respectively. On the other hand we estimated that the crude OR associating GSTM1 with lung cancer was 1.3 (95% CI: 0.9-1.8). Furthermore our data do not depart significantly from a multiplicative model of the combined effects of smoking and GSTM1 deficiency. CONCLUSIONS: We conclude that smoking and the GSTM1 gene are each a risk factor for lung cancer, and that their combined effect does not differ significantly from that of a multiplicative model.     

Perceptions of lung cancer and smoking in an ecomomically disadvantaged population

This study assessed low socioeconomic adults' perceptions of lung cancer and smoking utilizing the Health Belief Model. A random sample of 500 Ohio residents, with an annual household income of less than $18,000, responded to a 45-item telephone survey. Thirty-six percent of respondents were aware of the prevalence of lung cancer. The majority were aware that sidestream smoke and air pollution are lung cancer risk factors (72% and 79% respectively). Forty-one percent believed there was nothing people could do to decrease their risk of developing lung cancer. Thirteen percent perceived themselves as more susceptible to lung cancer than others of their same age and sex though one in five believed that low SES people were more likely to develop lung cancer than higher SES people. Twenty-five percent believed that almost everyone who develops lung cancer dies of it within five years of diagnosis. Benefits of quitting were identified as saving money (95%), feeling healthier (90%), living longer (80%), and eliminating hassles with smoking in pullic (79%). The most common barriers of quitting smoking were addiction (86%), habit (82%), and having friends who smoke (66%).Funded by grants from the Ohio Division, Inc. of the American Cancer Society and the Division of Chronic Diseases, Ohio Department of Health.     

Professional driving, smoking, and lung cancer: a case referent study

In a case referent study of about 600 cases of male lung cancer in northern Sweden the risk in professional drivers was specifically studied. Data concerning occupations, time and type of employment, and smoking habits were collected by questionnaires directed to close relatives. On average, professional drivers were heavier smokers and this was the chief cause of a slightly increased crude risk ratio in the study as a whole. Smoking drivers in an upper age group (70 and over) had a high relative risk of lung cancer, whereas in a lower age group (under 70) no significant increase was found. The relative risk in non-smoking drivers in the upper age group was moderately raised with borderline statistical significance. The high relative risk estimated for smoking drivers in the upper age group suggests a synergistic effect between smoking and occupational exposure.     

Cigarette smoking, genetic variants in carcinogen-metabolizing enzymes, and colorectal cancer risk

The risk of colorectal cancer associated with smoking is unclear and may be influenced by genetic variation in enzymes that metabolize cigarette carcinogens. The authors examined the colorectal cancer risk associated with smoking and 26 variants in carcinogen metabolism genes in 1,174 colorectal cancer cases and 1,293 population-based controls recruited in Canada by the Ontario Familial Colorectal Cancer Registry from 1997 to 2001. Adjusted odds ratios were calculated by multivariable logistic regression. Smoking for >27 years was associated with a statistically significant increased colorectal cancer risk (adjusted odds ratio (AOR) = 1.25, 95% confidence interval (CI): 1.02, 1.53) in all subjects. Colorectal cancer risk associated with smoking was higher in males for smoking status, duration, and intensity. The CYP1A1-3801-CC (AOR = 0.47, 95% CI: 0.23, 0.94) and CYP2C9-430-CT (AOR = 0.82, 95% CI: 0.68, 0.99) genotypes were associated with decreased risk, and the GSTM1-K173N-CG (AOR = 1.99, 95% CI: 1.21, 3.25) genotype was associated with an increased risk of colorectal cancer. Statistical interactions between smoking and genetic variants were assessed by comparing logistic regression models with and without a multiplicative interaction term. Significant interactions were observed between smoking status and SULT1A1-638 (P = 0.02), NAT2-857 (P = 0.01), and CYP1B1-4390 (P = 0.04) variants and between smoking duration and NAT1-1088 (P = 0.02), SULT1A1-638 (P = 0.04), and NAT1-acetylator (P = 0.03) status. These findings support the hypothesis that prolonged cigarette smoking is associated with increased risk of colorectal cancer and that this risk may be modified by variation in carcinogen metabolism genes.     

Attributed risk to smoking for lung cancer,laryngeal cancer and esophageal cancer

OBJECTIVE: Lung, laryngeal and esophageal cancers have smoking as one of their main risk factors. The objective of this study was to evaluate the population attributed risk (PAR) of smoking for these forms of cancer. METHODS: The study was based in three case-control studies conducted in medium size cities in Brazil. Incident cases of lung cancer, laryngeal cancer and esophageal cancer seen at a hospital setting and diagnosed through biopsy were analyzed; controls were hospitalized patients with another diagnoses. Smoking was the exposure factor measured at three levels: non-smokers, former smokers and smokers, which were defined using a questionnaire applied by trained interviewers. For effect measure, odds ratio was used and the populational attributed risk for smoking was then calculated for a 95% CI. RESULTS: A total of 122 lung cancer cases and 244 controls, 50 cases of laryngeal cancer and 48 cases of esophageal cancer, and 96 controls for both of them were studied. The prevalence of smoking exposure was 34%, which is the overall prevalence of smoking in this city's adult population. Odds ratios (OR) for the PAR analysis were the adjusted OR for confounding variables from each study. Lung cancer PAR was 63% (95% IC, 0.58-0.68) for former smokers and 71% (95%IC, 0.65-0.77) for smokers. Larynx cancer PAR was 74% (95% IC, 0.70-0.78) and 86% (95%IC, 0.81-0.85) for former smokers and smokers, respectively. Esophageal cancer PAR was 54% (95%IC, 0.46-0.62) for smokers. CONCLUSION: Smoking is an avoidable risk factor and smoking cessation could be responsible for significant reductions in the incidence of these three forms of cancer.     

Passive smoking and lung cancer: a cumulative meta-analysis

OBJECTIVE: To review the epidemiological evidence for the association between passive smoking and lung cancer. METHOD: Primary studies and meta-analyses examining the relationship between passive smoking and lung cancer were identified through a computerised literature search of Medline and Embase, secondary references, and experts in the field of passive smoking. Primary studies meeting the inclusion criteria were meta-analysed. RESULTS: From 1981 to the end of 1999 there have been 76 primary epidemiological studies of passive smoking and lung cancer, and 20 meta-analyses. There were 43 primary studies that met the inclusion criteria for this meta-analysis; more studies than previous assessments. The pooled relative risk (RR) for never-smoking women exposed to environmental tobacco smoke (ETS) from spouses, compared with unexposed never-smoking women was 1.29 (95% CI 1.17-1.43). Sequential cumulative meta-analysed results for each year from 1981 were calculated: since 1992 the RR has been greater than 1.25. For Western industrialised countries the RR for never-smoking women exposed to ETS compared with unexposed never-smoking women, was 1.21 (95% CI 1.10-1.33). Previously published international spousal meta-analyses have all produced statistically significant RRs greater than 1.17. CONCLUSIONS: The abundance of evidence in this paper, and the consistency of findings across domestic and workplace primary studies, dosimetric extrapolations and meta-analyses, clearly indicates that non-smokers exposed to ETS are at increased risk of lung cancer. IMPLICATIONS: The recommended public health policy is for a total ban on smoking in enclosed public places and work sites.     

Professional driving, smoking, and lung cancer: a case referent study.

In a case referent study of about 600 cases of male lung cancer in northern Sweden the risk in professional drivers was specifically studied. Data concerning occupations, time and type of employment, and smoking habits were collected by questionnaires directed to close relatives. On average, professional drivers were heavier smokers and this was the chief cause of a slightly increased crude risk ratio in the study as a whole. Smoking drivers in an upper age group (70 and over) had a high relative risk of lung cancer, whereas in a lower age group (under 70) no significant increase was found. The relative risk in non-smoking drivers in the upper age group was moderately raised with borderline statistical significance. The high relative risk estimated for smoking drivers in the upper age group suggests a synergistic effect between smoking and occupational exposure.     

Insulation,asbestos, smoking habits,and lung cancer cell types

The association between occupational exposure to asbestos and histological type of lung cancer was analyzed in a multicenter hospital-based case-control study (2,871 male cases and 5,240 male controls) conducted from 1981-1991. Twenty-two percent of cases and 18% of controls were employed in asbestos-related occupations for at least 1 year. Most of these asbestos jobs were in the construction field. The odds ratio (OR) among current smokers was 1.0 [95% confidence intervals (CI) 0.9 to 1.3]; for ex-smokers, the OR was 1.4 (95% CI 1.1 to 1.6). In contrast, 10% of cases and 5% of controls self-reported that they were chronically exposed to asbestos for at least 1 year. Self-reported asbestos exposure was significantly related to all lung cancer cell types among smokers and ex-smokers, although a trend in the ORs with duration of self-reported exposure was not found for current smokers. Among 48 cases and 52 controls reporting distinct exposure to building insulation, the OR was 2.2 (95% CI 1.2 to 4.3) for current smokers, and 1.8 (95% CI 0.9 to 3.6) for ex-smokers, compared to subjects who were not exposed to building insulation and asbestos. A nonsignificant association with self-reported exposure to asbestos was observed for a small number of never smokers (eight of 83 nonsmoking cases, OR = 2.0, 95% CI 0.9 to 4.6). When examining these results and their causal implications, possible misclassification and reporting biases need to be considered.     

Family history, maternal smoking, and clubfoot: an indication of a gene-environment interaction

Although epidemiologic studies of some birth defects have suggested a gene-smoking interaction, the possibility of this interaction in clubfoot has not been examined. The authors analyzed risk factors among 346 infants with isolated clubfoot and 3,029 infants without defects from the Atlanta Birth Defects Case-Control Study. All infants were born during 1968-1980, and mothers were interviewed in 1982-1983. The authors examined the family history-smoking interaction as an indication of a gene-environment interaction. They defined "smoking" as smoking any time during the first 3 months of pregnancy and "family history" as having a first-degree relative with clubfoot. Conditional logistic regression (matching variables: race, birth hospital, and birth period) was used to obtain effect estimates. The adjusted odds ratios were 1.34 (95% confidence interval (CI): 1.04, 1.72) for smoking only, 6.52 (95% CI: 2.95, 14.41) for family history only, and 20.30 (95% CI: 7.90, 52.17) for a joint exposure of smoking and family history. The effect estimate for the joint exposure was higher than would be expected under either an additive or a multiplicative model of interaction and showed a statistically significant departure from additivity. This study confirms the importance of familial factors and smoking in the etiology of clubfoot and identifies a potentially important interaction.