Ann Oncol. Jul 2012; 23(7): 1880–1888.
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Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4)
1Department of Epidemiology, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
2Department of Complex Genetics, Cluster of Genetics and Cell Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands
3Department of Occupational Health, University of Milan, Milan
4Department of Preclinical and Clinical Pharmacology “Mario Aiazzi Mancini”, Università degli Studi di Firenze, Florence, Italy
5National Cancer Institute, Bethesda
6Mayo Clinic, Rochester
7University of California, San Francisco, San Francisco
8The University of Texas M. D. Anderson Cancer Center, Houston
9Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven
10Department of Epidemiology and Biostatistics, Memorial Sloan–Kettering Cancer Center, New York, USA
11Toronto General Hospital, Toronto
12Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
13National Institute for Public Health and the Environment (RIVM), Bilthoven
14Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
15Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico—National Cancer Institute, Aviano, Italy
16Epidemiology Research Unit, Research Centre (CRCHUM), Montréal, Canada
17Public Health, Women's and Children's Hospital, Adelaide, Australia
18Cancer Center and Institute of Oncology, Warsaw, Poland
19Louisiana State University School of Public Health, New Orleans, USA
20Shanghai Cancer Institute, Shanghai, China
21Department of Medicine, Memorial Sloan–Kettering Cancer Center, New York, USA
22Cancer Care Ontario, Toronto, Canada
23European Institute of Oncology, Milan, Italy
24Catalan Institute of Oncology, Barcelona, Spain
25The Tisch Cancer Institute and Institute for Translational Epidemiology, Mount Sinai School of Medicine, New York, USA
26International Prevention Research Institute, Lyon, France
Received April 5, 2011; Revised October 6, 2011; Accepted October 10, 2011.
Table shows the distribution of 6507 pancreatic cancer cases and 12 890 controls by sex, age, and other potential confounding factors. Cases and controls have a similar sex distribution; cases were somewhat older than controls, were more frequently non-Hispanic White, had a higher level of education, a higher BMI, and more frequently reported a history of diabetes and pancreatitis.
Distribution of 6507 cases of pancreatic cancer and 12 890 controls according to sex, age, race, and other selected covariates. International Pancreatic Cancer Case–Control Consortium (PanC4)
The pooled ORs for pancreatic cancer according to cigarette smoking habits are given in Table . Compared with never smokers, the OR was 1.40 (95% CI 1.24–1.55) for ever cigarette smokers, 1.17 (95% CI 1.02–1.34) for former cigarette smokers, and 2.20 (95% CI 1.71–2.83) for current cigarette smokers. A significant trend in risk was observed with increased number of cigarettes smoked (OR = 3.4, 95% CI 2.4–4.9 for ≥35 cigarettes per day, P for trend <0.0001). Among current smokers, the risk increased with increased duration of cigarette smoking for up to 40 years of smoking (OR = 2.43, 95% CI 1.91–3.09) but did not increase further after 40 years. No trend in risk was observed for age at starting cigarette smoking in current smokers, whereas a significant decreasing trend in risk was found with increased time since quitting cigarette smoking. After ~20 years, risk estimates were not different from nonsmokers (OR = 0.98). Sensitivity analyses showed that no single study unduly influenced the magnitude or the statistical significance of these summary estimates.
Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer according to cigarette smoking habits among 6507 cases and 12 890 controls. International Pancreatic Cancer Case–Control Consortium (PanC4)
The cumulative meta-analysis for pancreatic cancer risk in current cigarette smokers showed a trend of increasing risk according to the year of publication: the OR for current versus never smokers was 1.74 in the initial study published in 1994, 1.75 in the studies published up to 2007, and rose to 2.2 when studies published between 2007 and 2010 were added (Figure ).
Figure 1 Cumulative meta-analysis of pancreatic cancer risk in current cigarette smokers as compared with never smokers. International Pancreatic Cancer Case–Control Consortium (PanC4). OR, odds ratio; 95% CI, 95% confidence intervals. aIncluding the unpublished (more ...)
A forest plot of the study-specific and the pooled ORs for pancreatic cancer risk for ever versus never cigarette smokers is presented in Figure . The corresponding forest plots for numbers of cigarettes smoked per day among current smokers are given in Figure . The pooled estimate for ever cigarette smokers as compared with never smokers was 1.40, with significant heterogeneity in ORs across studies (P = 0.003). Similarly, for current smokers of <15 (Figure A), 15–24 (Figure B), and ≥25 (Figure C) cigarettes per day, pooled estimates were significantly elevated, although between-study heterogeneity was observed for each level of cigarette smoking.
Figure 2 Study-specific and pooled odds ratios (ORs)a for pancreatic cancer according to ever cigarette smokers as compared with never smokers. International Pancreatic Cancer Case–Control Consortium (PanC4). aStudy-specific ORs were adjusted for age, (more ...)
Figure 3 Study-specific and pooled odds ratios (ORs)a for pancreatic cancer according to level of cigarette smoking in current smokers as compared with never smokers. (A) <15 cigarettes per day, (B) 15–24 cigarettes per day, (C) ≥15 cigarettes (more ...)
The association between number of cigarettes smoked and pancreatic cancer risk was further assessed in analyses stratified by sex, age, alcohol drinking, race/ethnicity, study area, source of controls, and type of respondents (Table ). The association appeared somewhat stronger—though not significantly—in women, in participants <65 years, and in proxy respondents; no meaningful differences in risk estimates were observed across strata of other covariates considered.
Table 4. Pooled odds ratios (ORs)a and corresponding 95% confidence intervals (CIs) for pancreatic cancer according to cigarette smoking in strata of selected covariates among 6507 cases and 12 890 controls. International Pancreatic Cancer Case–Control (more ...)