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.