Influence Of Prediagnostic Cigarette Smoking And Dietary Patterns On Colorectal Cancer Survival

Objectives:Cigarette smoking and dietary patterns are associated with colorectal cancer (CRC) incidence; however, little is known about their influence on survival after CRC diagnosis. We aimed1. To examine the association of smoking with all-cause (overall survival; OS) and disease-free survival (DFS) among patients diagnosed with invasive CRC; to assess potential interactions of smoking with sex, age at diagnosis, tumor stage at diagnosis, microsatellite instability status (MSI), and BRAF mutation status on cancer mortality;2. To investigate the association between dietary patterns and CRC survival; to explore if the relationship between dietary pattern and CRC survival is modified by sex, physical activity and BRAF mutation.Methods:A cohort of more than700CRC patients diagnosed from1999to2003in the Canadian province of Newfoundland and Labrador was followed for mortality and recurrence until April2010. Participants reported their smoking history, dietary intake, and other relevant co-variable information using a personal history questionnaire, a food frequency questionnaire, and a family history questionnaire. Molecular analyses of MSI and BRAF mutation status were performed in tumor tissue using standard technique. Dietary patterns were identified with factor analysis. Each participant was assigned a factor score for each pattern (factor) by summing the intakes from each food group multiplied by optimal weights. Multivariate hazard ratios (HRs) and95%confidence intervals (CIs) were calculated with Cox proportional hazards regression, controlling for age and stage at diagnosis, tumor molecular phenotype, and other covariates. Statistical significance was accepted for two-sided P＜0.05.Results:1. Compared with never smoking, current (HR:1.78;95%CI:1.04-3.06), but not former (HR:1.06;95%CI:0.71-1.59), smoking was associated with adverse OS, although this association was limited to tumors in the colon. The associations of cigarette smoking with the study outcomes were higher among patients with＞40pack years (OS:HR:1.72;95%CI:1.03-2.85; DFS:HR:1.99;95%CI:1.25-3.19). Potential heterogeneity was noted for sex (DFS:P for heterogeneity=0.04, HR:1.68for men and1.01for women) and age at diagnosis (OS:P for heterogeneity=0.03, HR:1.11for patients aged<60and1.69for patients aged≥60) while the stratified results for tumor molecular phenotype were more equivocal.2. Disease-free survival among CRC patients was significantly worsened among patients with a high processed meat dietary pattern (the highest versus the lowest quartile HR:1.82,95%CI:1.07-3.09). No associations were observed with the prudent vegetable or the high sugar patterns and DFS. The association between the processed meat pattern and DFS was restricted to patients diagnosed with colon cancer (the highest versus the lowest quartile:HR:2.29,95%CI:1.19-4.40) while the relationship between OS and this pattern was observed among patients with colon cancer only (the highest versus the lowest quartile:HR:2.13,95%CI:1.03-4.43). Potential effect modification was noted for sex (P for interaction=0.04, HR:3.85for women and1.22for men).Conclusion:1. Pre-diagnosis cigarette smoking is associated with worsened prognosis among patients with CRC. The relationship between smoking and CRC survival is modified by sex and age at diagnosis.2. The processed meat dietary pattern prior to diagnosis is associated with higher risk of tumor recurrence, metastasis, and death from any cause among patients with CRC. The effect of processed meat pattern on cancer recurrence or death was modified by sex. Nevertheless, neither the prudent vegetable pattern nor the high sugar pattern was observed to be significantly associated with predefined patient outcomes (i.e., DFS and OS).