Phipps AI, Shi Q, Newcomb PA, Nelson GD, Sargent DJ, Alberts SR, Limburg PJAssociations between cigarette smoking status and colon cancer prognosis among participants in North Central Cancer Treatment Group Phase III Trial N0147. J Clin Oncol 31(16): 2016-2023
PURPOSEBy using data from North Central Cancer Treatment Group Phase III Trial N0147, a randomized adjuvant trial of patients with stage III colon cancer, we assessed the relationship between smoking and cancer outcomes, disease-free survival (DFS), and time to recurrence (TTR), accounting for heterogeneity by patient and tumor characteristics. PATIENTS AND METHODS
Before random assignment to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or FOLFOX plus cetuximab, 1,968 participants completed a questionnaire on smoking history and other risk factors. Cox models assessed the association between smoking history and the primary trial outcome of DFS (ie, time to recurrence or death), as well as TTR, adjusting for other clinical and patient factors. The median follow-up was 3.5 years among patients who did not experience events. RESULTS: 70% v 74%; hazard ratio [HR], 1.21; 95% CI, 1.02 to 1.42). This association persisted after multivariate adjustment (HR, 1.23; 95% CI, 1.02 to 1.49). There was significant interaction in this association by BRAF mutation status (P = .03): smoking was associated with shorter DFS in patients with BRAF wild-type (HR, 1.36; 95% CI, 1.11 to 1.66) but not BRAF mutated (HR, 0.80; 95% CI, 0.50 to 1.29) colon cancer. Smoking was more strongly associated with poorer DFS in those with KRAS mutated versus KRAS wild-type colon cancer (HR, 1.50 [95% CI, 1.12 to 2.00] v HR, 1.09 [95% CI, 0.85 to 1.39]), although interaction by KRAS mutation status was not statistically significant (P = .07). Associations were comparable in analyses of TTR. CONCLUSION
Overall, smoking was significantly associated with shorter DFS and TTR in patients with colon cancer. These adverse relationships were most evident in patients with BRAF wild-type or KRAS mutated colon cancer.
"Our finding of increased mortality in colorectal cancer patients who are current smokers is consistent with some (Munro et al, 2006; Phipps et al, 2011, 2013), but not all (Yu et al, 1997; Park et al, 2006; McCleary et al, 2010; Nordenvall et al, 2013), previous research on this topic. Two studies have found that colon/colorectal cancer patients who were current smokers had poorer survival than those who were non-smokers (Munro et al, 2006; Phipps et al, 2013), whereas another study found that colon cancer-specific mortality, but not rectal cancer-specific mortality, was higher in current smokers than in never or former smokers (Phipps et al, 2011). The remaining four studies found no association between current smoking and survival in colorectal cancer patients (Yu et al, 1997; Park et al, 2006; McCleary et al, 2010; Nordenvall et al, 2013). "
[Show abstract][Hide abstract] ABSTRACT: Background:
Aside from tumour stage and treatment, little is known about potential factors that may influence survival in colorectal cancer patients. The aim of this study was to investigate the associations between physical activity, obesity and smoking and disease-specific and overall mortality after a colorectal cancer diagnosis.
A cohort of 879 colorectal cancer patients, diagnosed in Western Australia between 2005 and 2007, were followed up to 30 June 2012. Cox's regression models were used to estimate the hazard ratios (HR) for colorectal cancer-specific and overall mortality associated with self-reported pre-diagnosis physical activity, body mass index (BMI) and smoking.
Significantly lower overall and colorectal cancer-specific mortality was seen in females who reported any level of recent physical activity than in females reporting no activity. The colorectal cancer-specific mortality HR for increasing levels of physical activity in females were 0.34 (95% CI=0.15, 0.75), 0.37 (95% CI=0.17, 0.81) and 0.41 (95% CI=0.18, 0.90). Overweight and obese women had almost twice the risk of dying from any cause or colorectal cancer compared with women of normal weight. Females who were current smokers had worse overall and colorectal cancer-specific mortality than never smokers (overall HR=2.64, 95% CI=1.18, 5.93; colorectal cancer-specific HR=2.70, 95% CI=1.16, 6.29). No significant associations were found in males.
Physical activity, BMI and smoking may influence survival after a diagnosis of colorectal cancer, with more pronounced results found for females than for males.
British Journal of Cancer 06/2013; 109(3). DOI:10.1038/bjc.2013.310 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Regular use of aspirin reduces incidence and mortality of various cancers, including colorectal cancer. Anticancer effect of aspirin represents one of the 'Provocative Questions' in cancer research. Experimental and clinical studies support a carcinogenic role for PTGS2 (cyclooxygenase-2), which is an important enzymatic mediator of inflammation, and a target of aspirin. Recent 'molecular pathological epidemiology' (MPE) research has shown that aspirin use is associated with better prognosis and clinical outcome in PIK3CA-mutated colorectal carcinoma, suggesting somatic PIK3CA mutation as a molecular biomarker that predicts response to aspirin therapy. The PI3K (phosphatidylinositol-4,5-bisphosphonate 3-kinase) enzyme has a pivotal role in the PI3K-AKT signaling pathway. Activating PIK3CA oncogene mutations are observed in various malignancies including breast cancer, ovarian cancer, brain tumor, hepatocellular carcinoma, lung cancer and colon cancer. The prevalence of PIK3CA mutations increases continuously from rectal to cecal cancers, supporting the 'colorectal continuum' paradigm, and an important interplay of gut microbiota and host immune/inflammatory reaction. MPE represents an interdisciplinary integrative science, conceptually defined as 'epidemiology of molecular heterogeneity of disease'. As exposome and interactome vary from person to person and influence disease process, each disease process is unique (the unique disease principle). Therefore, MPE concept and paradigm can extend to non-neoplastic diseases including diabetes mellitus, cardiovascular diseases, metabolic diseases, and so on. MPE research opportunities are currently limited by paucity of tumor molecular data in the existing large-scale population-based studies. However, genomic, epigenomic and molecular pathology testings (for example, analyses for microsatellite instability, MLH1 promoter CpG island methylation, and KRAS and BRAF mutations in colorectal tumors) are becoming routine clinical practices. In order for integrative molecular and population science to be routine practice, we must first reform education curricula by integrating both population and molecular biological sciences. As consequences, next-generation hybrid molecular biological and population scientists can advance science, moving closer to personalized precision medicine and health care.Oncogene advance online publication, 24 June 2013; doi:10.1038/onc.2013.244.
[Show abstract][Hide abstract] ABSTRACT: The aim of this research was to study prognostic parameters of CRC by analyzing clinical and pathological variables associated with cancer patients at a northeastern Brazilian Hospital. This was a retrospective study evaluating CRC-diagnosed patients across a 10-year period (1995-2005) at Dr. Luiz Antônio Hospital in Natal, RN, Brazil. Data were collected from patients' medical files. A total of 358 patients were included over the 10-year period. The average age at diagnosis was 58.8 years (S.D.=15.26), 48.3% of the patients were males and 51.7% were females. Alcohol consumption significantly increased the chance of dying (p<0.023) from colorectal cancer; this increased risk of death was approximately 71%, compared to 52.2% of the non-alcoholics. In addition, tobacco increased the chance of developing high TNM stage tumors (level III, IV; p<0.001). Another risk factor for increased mortality was a family history for colorectal cancer (p<0.002). Our analysis found that patients with an unhealthy lifestyle and/or family history of colorectal cancer were more likely to develop advanced stage colorectal cancer and to have a poor disease prognosis compared to patients with healthy lifestyle and/or sporadic colorectal cancer. These data suggest that a mass screening program should be implemented in northeastern Brazil in order to better prevent and treat colorectal cancer.
Pathology - Research and Practice 09/2013; 209(12). DOI:10.1016/j.prp.2013.08.007 · 1.40 Impact Factor
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