Influence of pre-diagnostic cigarette smoking on colorectal cancer survival: overall and by tumour molecular phenotype

Abstract

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.

Active Smoking and Mortality Among Colorectal Cancer Survivors: The Cancer Prevention Study II Nutrition Cohort

“…However, smoking was also positively associated with colorectal cancer-specific mortality, and the biologic mechanisms underlying this association are not well understood. 18, 38,39 Other mechanisms for the adverse impact of smoking on colorectal cancer-specific survival may include decreased efficacy of colorectal cancer treatment among smokers. [11][12][13] Although MSI-high tumors generally demonstrate higher survival, 33,34 BRAF mutation status is independently associated with higher risk of mortality, 35 and CIMP-high status in microsatellite-stable tumors is also associated with lower survival.…”

Prediagnostic Physical Activity and Colorectal Cancer Survival: Overall and Stratified by Tumor Characteristics

“…Thus, consideration of molecular markers that distinguish these pathways, such as BRAF , is important for better understanding the relationship between lifestyle factors and CRC risk and survival. We have previously identified differences in the relationship between smoking and CRC survival according to these markers (28, 29, 31). Additionally, in a previous paper from the S-CCFR, Coghill et al found that the inverse association between use of non-steroidal anti-inflammatory drugs and survival after CRC diagnosis was restricted to proximal colon cancers, which are more commonly MSI-H and BRAF -mutated than distal CRC (54).…”

“…Previous studies have also suggested some heterogeneity in the relationship of lifestyle factors with CRC risk and survival according to these tumor-markers (26–31). Thus, consideration of these tumor-markers may provide greater insight into the association between physical activity and CRC survival.…”

Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression

“…85–89 The MPE paradigm, which can encompass all human diseases, 148 is firmly established, 149–152 and has gained widespread recognition. 121, 153–176 …”