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Impact of prediagnostic smoking and smoking cessation on colorectal cancer prognosis: a meta-analysis of individual patient data from cohorts within the CHANCES consortium.

ABSTRACT: Background:Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies and might also be associated with prognosis after CRC diagnosis. However, current evidence on smoking in association with CRC prognosis is limited. Patients and methods:For this individual patient data meta-analysis, sociodemographic and smoking behavior information of 12?414 incident CRC patients (median age at diagnosis: 64.3?years), recruited within 14 prospective cohort studies among previously cancer-free adults, was collected at baseline and harmonized across studies. Vital status and causes of death were collected for a mean follow-up time of 5.1?years following cancer diagnosis. Associations of smoking behavior with overall and CRC-specific survival were evaluated using Cox regression and standard meta-analysis methodology. Results:A total of 5229 participants died, 3194 from CRC. Cox regression revealed significant associations between former [hazard ratio (HR)?=?1.12; 95 % confidence interval (CI)?=?1.04-1.20] and current smoking (HR?=?1.29; 95% CI?=?1.04-1.60) and poorer overall survival compared with never smoking. Compared with current smoking, smoking cessation was associated with improved overall (HR<10?years?=?0.78; 95% CI?=?0.69-0.88; HR?10?years?=?0.78; 95% CI?=?0.63-0.97) and CRC-specific survival (HR?10?years?=?0.76; 95% CI?=?0.67-0.85). Conclusion:In this large meta-analysis including primary data of incident CRC patients from 14 prospective cohort studies on the association between smoking and CRC prognosis, former and current smoking were associated with poorer CRC prognosis compared with never smoking. Smoking cessation was associated with improved survival when compared with current smokers. Future studies should further quantify the benefits of nonsmoking, both for cancer prevention and for improving survival among CRC patients, in particular also in terms of treatment response.

SUBMITTER: Ordonez-Mena JM

PROVIDER: S-EPMC6075220 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Impact of prediagnostic smoking and smoking cessation on colorectal cancer prognosis: a meta-analysis of individual patient data from cohorts within the CHANCES consortium.

Ordóñez-Mena J M JM Walter V V Schöttker B B Jenab M M O'Doherty M G MG Kee F F Bueno-de-Mesquita B B Peeters P H M PHM Stricker B H BH Ruiter R R Hofman A A Söderberg S S Jousilahti P P Kuulasmaa K K Freedman N D ND Wilsgaard T T Wolk A A Nilsson L M LM Tjønneland A A Quirós J R JR van Duijnhoven F J B FJB Siersema P D PD Boffetta P P Trichopoulou A A Brenner H H

Annals of oncology : official journal of the European Society for Medical Oncology 20180201 2

<h4>Background</h4>Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies and might also be associated with prognosis after CRC diagnosis. However, current evidence on smoking in association with CRC prognosis is limited.<h4>Patients and methods</h4>For this individual patient data meta-analysis, sociodemographic and smoking behavior information of 12 414 incident CRC patients (median age at diagnosis: 64.3 years), recruited within 14 prospective coh ...[more]

PMID: 29244072

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Project description:BACKGROUND:Many studies have suggested that the regular use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, has a protective effect and survival benefit on colorectal cancer (CRC). However, recent data suggest that CRCs have different responses to NSAIDs depending on the timing of NSAID initiation, duration of NSAID use, and molecular characteristics of the tumor. The aim of this study was to evaluate the effect of long-term prediagnostic aspirin use on the prognosis of stage III CRC. METHODS:From 2007 to 2009, patients who were diagnosed with stage III CRC were recruited, and their medical records were retrospectively analyzed. Patients were divided into prediagnostic aspirin users (who used aspirin for more than three months continuously before CRC diagnosis) and non-users (who did not use of aspirin and NSAIDs). The two groups were compared in terms of recurrence, cancer-specific mortality, disease-free survival (DFS), and cancer-specific survival. In an experimental study, three CRC cell lines (Caco2, SW480, and DLD-1) were pretreated with aspirin (1 mM) for four days or 28 days to make aspirin-resistant cells, treated with 5-fluorouracil (5-FU; 2 µM), and apoptosis was measured with flow cytometry using Annexin-V and propidium iodide double staining. RESULTS:Compared with the aspirin non-users (N=565), the prediagnostic aspirin users (N=121) were not different in terms of baseline characteristics including tumor characteristics, except for comorbidities and diabetes medication and statin use, which were higher in the prediagnostic aspirin users. Recurrence and cancer-specific mortality in stage III CRC were significantly higher in prediagnostic aspirin users than non-users (46.7% vs. 32.3%, P=0.003 and 32.2% vs. 19.8%, P=0.003, respectively). Survival analysis using Cox proportional hazards modeling demonstrated that DFS was significantly worse in prediagnostic aspirin users than non-users (HR, 1.525 (1.018-2.286); P=0.041). In cell line experiments, long-term aspirin pretreatment induced an increase in 5-FU-induced apoptosis in SW480 cells compared with control treatment without aspirin pretreatment. However, Caco2 cells showed a significant decrease of apoptosis in the same experiments and no change in DLD1 cells. CONCLUSION:Prediagnostic long-term aspirin use in stage III CRC could be a negative prognostic factor depending on the characteristics of the CRC.

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Dataset Information

Impact of prediagnostic smoking and smoking cessation on colorectal cancer prognosis: a meta-analysis of individual patient data from cohorts within the CHANCES consortium.

Publications

Impact of prediagnostic smoking and smoking cessation on colorectal cancer prognosis: a meta-analysis of individual patient data from cohorts within the CHANCES consortium.

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