A flexible modeling approach to estimating the component effects of smoking behavior on lung cancer.

OBJECTIVE Despite the established causal association between cigarette smoking and lung cancer, the relative contributions of age started, duration, years since quitting, and daily amount smoked have not been well characterized. We estimated the contribution of each of these aspects of smoking behavior. STUDY DESIGN AND SETTING A case-control study was conducted in Montreal on the etiology of lung cancer. There were 640 cases and 938 control subjects for whom lifetime smoking histories were collected. We used generalized additive models, incorporating cubic smoothing splines to model nonlinear effects of various smoking variables. We adopted a multistep approach to deal with the multicollinearity among time-related variables. RESULTS The main findings are that (1) risk increases independently by daily amount and by duration; (2) among current smokers, lung cancer risk doubles for every 10 cigarettes per day up to 30 to 40 cigarettes per day and tails off thereafter; (3) among ex-smokers, the odds ratio decreases with increasing time since quitting, the rate of decrease being sharper among heavy smokers than among light smokers; and (4) absolute risks demonstrate the dramatic public health benefits of long-term smoking cessation. CONCLUSION Our results reinforce some previous findings on this issue.

[1]  P. Armitage,et al.  Multistage models of carcinogenesis. , 1985, Environmental health perspectives.

[2]  M. Kogevinas,et al.  Lung cancer and smoking: a case-control study in Buenos Aires, Argentina. , 1998, Lung cancer.

[3]  S. Selvin,et al.  Comparison of biochemical and questionnaire estimates of tobacco exposure. , 1979, Preventive medicine.

[4]  F. Berrino,et al.  Modifying risk of developing lung cancer by changing habits of cigarette smoking. , 1984, British medical journal.

[5]  B. Gillespie,et al.  Patterns of absolute risk of lung cancer mortality in former smokers. , 1993, Journal of the National Cancer Institute.

[6]  J. Fraumeni,et al.  Lung cancer and smoking in Shanghai. , 1988, International journal of epidemiology.

[7]  P Royston,et al.  The use of fractional polynomials to model continuous risk variables in epidemiology. , 1999, International journal of epidemiology.

[8]  R. Tibshirani,et al.  Generalized additive models for medical research , 1986, Statistical methods in medical research.

[9]  J. Fraumeni,et al.  Smoking and cancer mortality among U.S. veterans: A 26‐year follow‐up , 2006, International journal of cancer.

[10]  S. Greenland.  Dose‐Response and Trend Analysis in Epidemiology: Alternatives to Categorical Analysis , 1995, Epidemiology.

[11]  C. Begg,et al.  Variations in lung cancer risk among smokers. , 2003, Journal of the National Cancer Institute.

[12]  J Siemiatycki,et al.  Discovering carcinogens in the occupational environment. Methods of data collection and analysis of a large case-referent monitoring system. , 1987, Scandinavian journal of work, environment & health.

[13]  L H Kuller,et al.  The relationship of smoking cessation to coronary heart disease and lung cancer in the Multiple Risk Factor Intervention Trial (MRFIT). , 1990, American journal of public health.

[14]  H. Wichmann,et al.  Risk factors for lung cancer in young adults. , 1998, American journal of epidemiology.

[15]  E. Wynder,et al.  Cigarette smoking and lung cancer cell types , 1991, Cancer.

[16]  R. Tibshirani,et al.  Generalized Additive Models: Some Applications , 1987 .

[17]  D. Freedman,et al.  Ex‐Smokers and the Multistage Model for Lung Cancer , 1990, Epidemiology.

[18]  M. Bovenzi,et al.  Cigarette smoking and histologic type of lung cancer in men. , 1997, Chest.

[19]  J. Neyman,et al.  Proceedings of the Fourth Berkeley Symposium on Mathematical Statistics and Probability , 1963 .

[20]  R du Berger,et al.  Flexible modeling of the effects of serum cholesterol on coronary heart disease mortality. , 1997, American journal of epidemiology.

[21]  M. Law,et al.  The dose-response relationship between cigarette consumption, biochemical markers and risk of lung cancer. , 1997, British Journal of Cancer.

[22]  R. Doll,et al.  Cigarette smoking and bronchial carcinoma: dose and time relationships among regular smokers and lifelong non-smokers. , 1978, Journal of epidemiology and community health.

[23]  D. Kleinbaum,et al.  Applied Regression Analysis and Other Multivariate Methods , 1978 .

[24]  E. Wynder,et al.  Lung cancer pathology in smokers, ex-smokers and never smokers. , 1995, Cancer letters.

[25]  Michal Abrahamowicz,et al.  Time-Dependent Hazard Ratio: Modeling and Hypothesis Testing with Application in Lupus Nephritis , 1996 .

[26]  E. Wynder,et al.  Relation of bronchioloalveolar carcinoma to tobacco. , 1992, BMJ.

[27]  M. Fukuoka,et al.  Lung Cancer Incidence Rate for Male Ex‐smokers According to Age at Cessation of Smoking , 1993, Japanese journal of cancer research : Gann.

[28]  P Royston,et al.  A strategy for modelling the effect of a continuous covariate in medicine and epidemiology. , 2000, Statistics in medicine.

[29]  Alan D. Lopez,et al.  At least one in seven cases of cancer is caused by smoking. Global estimates for 1985 , 1994, International journal of cancer.

[30]  E. Wynder,et al.  Reduction in risk of lung cancer among ex‐smokers with particular reference to histologic type , 1988, Cancer.

[31]  A. Whittemore,et al.  Lung cancer incidence in cigarette smokers: further analysis of Doll and Hill's data for British physicians. , 1976, Biometrics.

[32]  A. Neugut,et al.  Cigarette smoking and large cell carcinoma of the lung. , 1997, Cancer Epidemiology, Biomarkers and Prevention.

[33]  H. Becher,et al.  Smoking cessation and nonsmoking intervals: effect of different smoking patterns on lung cancer risk , 1991, Cancer Causes & Control.

[34]  M. Dosemeci,et al.  Mortality among laboratory workers employed at the U.S. Department of Agriculture. , 1992, Epidemiology.

[35]  M. Alsedà,et al.  Cigarette smoking and male lung cancer risk with special regard to type of tobacco. , 1999, International journal of epidemiology.

[36]  J. Ramsay.  Monotone Regression Splines in Action , 1988 .

[37]  A. Ciampi,et al.  Information theoretic criteria in non-parametric density estimation , 1991 .

[38]  S. Benhamou,et al.  Lung cancer and women: results of a French case-control study. , 1987, British Journal of Cancer.

[39]  Enstrom Je.  Smoking cessation and mortality trends among two United States populations. , 1999 .

[40]  S. Greenland,et al.  Problems in the average-risk interpretation of categorical dose-response analyses. , 1995, Epidemiology.

[41]  J. Lubin,et al.  Lung cancer and smoking cessation: patterns of risk. , 1993, Journal of the National Cancer Institute.

[42]  K. Chu,et al.  Use of multistage models to infer stage affected by carcinogenic exposure: example of lung cancer and cigarette smoking. , 1987, Journal of chronic diseases.

[43]  E. Wynder,et al.  Cigarette smoking: carboxyhemoglobin, plasma nicotine, cotinine and thiocyanate vs self-reported smoking data and cardiovascular disease. , 1983, Journal of chronic diseases.

[44]  Kuller Lh.  Rebuttal to the paper by Enstrom. , 1999 .

[45]  C. Vesey,et al.  Blood carboxyhaemoglobin, plasma thiocyanate, and cigarette consumption: implications for epidemiological studies in smokers. , 1982, British medical journal.

[46]  A. Andersen,et al.  The impact of smoking habits on lung cancer risk: 28 years' observation of 26,000 Norwegian men and women , 1996, Cancer Causes & Control.

[47]  S H Moolgavkar,et al.  Cigarette smoking and lung cancer: reanalysis of the British doctors' data. , 1989, Journal of the National Cancer Institute.

[48]  Jack Siemiatycki,et al.  Risk Factors For Cancer In The Workplace , 1991 .

[49]  Richard Doll,et al.  Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies , 2000, BMJ : British Medical Journal.

[50]  Michal Abrahamowicz,et al.  Modeling smoking history: a comparison of different approaches. , 2002, American journal of epidemiology.

[51]  H. Akaike.  A new look at the statistical model identification , 1974 .

[52]  S. Benhamou,et al.  The effect of age at smoking initiation on lung cancer risk. , 1994, Epidemiology.

[53]  J. Willey,et al.  Effect of cigarette smoking on major histological types of lung cancer in men. , 1998, Lung cancer.

[54]  S. Khuder,et al.  Age at smoking onset and its effect on smoking cessation. , 1999, Addictive behaviors.

[55]  M. Spitz,et al.  Lung carcinoma in former smokers , 1996, Cancer.

[56]  H Brenner,et al.  Controlling for Continuous Confounders in Epidemiologic Research , 1997, Epidemiology.

[57]  S Greenland,et al.  Avoiding power loss associated with categorization and ordinal scores in dose-response and trend analysis. , 1995, Epidemiology.

[58]  J H Lubin,et al.  The use of sliding time windows for the exploratory analysis of temporal effects of smoking histories on lung cancer risk. , 2000, Statistics in medicine.