Influence of pre-diagnostic cigarette smoking on colorectal cancer survival: overall and by tumour molecular phenotype.
BACKGROUND
Smoking is a risk factor for incident colorectal cancer (CRC); however, it is unclear about its influence on survival after CRC diagnosis.


METHODS
A cohort of 706 CRC patients diagnosed from 1999 to 2003 in Newfoundland and Labrador, Canada, was followed for mortality and recurrence until April 2010. Smoking and other relevant data were collected by questionnaire after cancer diagnosis, using a referent period of '2 years before diagnosis' to capture pre-diagnosis information. Molecular analyses of microsatellite instability (MSI) status and BRAF V600E mutation status were performed in tumour tissue using standard techniques. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazards regression, controlling for major prognostic factors.


RESULTS
Compared with never smokers, all-cause mortality (overall survival, OS) was higher for current (HR: 1.78; 95% CI: 1.04-3.06), but not for former (HR: 1.06; 95% CI: 0.71-1.59) smokers. The associations of cigarette smoking with the study outcomes were higher among patients with ≥40 pack-years of smoking (OS: HR: 1.72; 95% CI: 1.03-2.85; disease-free survival (DFS: HR: 1.99; 95% CI: 1.25-3.19), those who smoked ≥30 cigarettes per day (DFS: HR: 1.80; 95% CI: 1.22-2.67), and those with microsatellite stable (MSS) or MSI-low tumours (OS: HR: 1.38; 95% CI: 1.04-1.82 and DFS: HR: 1.32; 95% CI: 1.01-1.72). Potential heterogeneity was noted for sex (DFS HR: 1.68 for men and 1.01 for women: P for heterogeneity=0.04), and age at diagnosis (OS: HR: 1.11 for patients aged <60 and 1.69 for patients aged ≥60: P for heterogeneity=0.03).


CONCLUSIONS
Pre-diagnosis cigarette smoking is associated with worsened prognosis among patients with CRC.
1] Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada [2] Department of Epidemiology, School of Public Health, Tianjin Medical University, Tianjin, China.
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Zhu
Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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Yang
1] Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada [2] Department of Epidemiology, School of Public Health, Tianjin Medical University, Tianjin, China.
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Wang
1] Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada [2] Discipline of Oncology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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Savas
Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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Wish
Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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J
Zhao
Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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Green
Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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Woods
Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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Sun
Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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Roebothan
Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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J
Squires
Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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Buehler
Clinical Epidemiology Unit, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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Dicks
Division of Community Health and Humanities, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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Zhao
Prosserman Centre for Health Research, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
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JR
Mclaughlin
Clinical Epidemiology Unit, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
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Parfrey
Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
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Campbell
D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics / Q000401:mortality*; D011795:Surveys and Questionnaires
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf