Viola Walter

Meat subtypes and their association with colorectal cancer: Systematic review and meta-analysis

Associations between specific red meat subtypes and risk of colorectal cancer (CRC) have been investigated in a number of epidemiological studies. However, no publication to date has summarised the overall epidemiological evidence. We conducted a systematic review and meta‐analysis of prospective studies (cohort, nested case‐control or case‐cohort studies), which reported relative risk (RR) estimates and 95% confidence intervals (CI) for the association between intake of meat subtypes with colorectal, colon or rectal cancer or colorectal adenoma risk. PubMed and ISI Web of Science were searched up until August 1, 2014. Nineteen studies examined meat subtypes (5 beef, 5 pork, 2 lamb, 1 veal and 19 poultry) and associations with colorectal, colon or rectal cancer risk and 4 studies examined associations with adenoma risk (1 beef and 4 poultry). Comparing highest versus lowest intake, beef consumption was associated with an increased risk of CRC (RR = 1.11, 95% CI = 1.01 to 1.22) and colon cancer (RR = 1.24, 95% CI = 1.07 to 1.44), but no association was found with rectal cancer (RR = 0.95, 95% CI = 0.78 to 1.16). Higher consumption of lamb was also associated with increased risk of CRC (RR = 1.24, 95% CI = 1.08 to 1.44). No association was observed for pork (RR = 1.07, 95% CI = 0.90 to 1.27), but some between study heterogeneity was observed. No association was observed for poultry consumption and risk of colorectal adenomas or cancer. This meta‐analysis suggests that red meat subtypes differ in their association with CRC and its sub sites. Further analysis of data from prospective cohort studies is warranted, especially regarding the role of pork.

Smoking and survival of colorectal cancer patients: systematic review and meta-analysis

Smoking is a risk factor for colorectal cancer (CRC) incidence and mortality. However, little is known on smoking and its association with survival after CRC diagnosis. We conducted a systematic review and meta-analysis to summarize current evidence. A systematic literature search was carried out in MEDLINE and ISI Web of Science. We included studies that analyzed recurrence-free survival, disease-free survival, all-cause, and CRC-specific mortality according to smoking status. Data were extracted in duplicate. Standard methods of meta-analysis were applied. Sixteen studies from 11 countries were identified, comprising a total sample size of 62 278 CRC patients. Overall, in the 16 included studies, current smoking and, to a lesser extent, former smoking were rather consistently associated with a poorer prognosis compared with never smokers. Meta-analyses yielded random-effects hazard ratio estimates (95% confidence intervals) for all-cause mortality of 1.26 (1.15-1.37) and 1.11 (0.93-1.33) for current and former smokers, compared with never smokers, respectively. In particular, 30-day mortality was found to be increased by between 49% and 100% among current compared with never smokers. Our results support the existence of detrimental effects of smoking on survival also after CRC diagnosis. Perspectives for enhancing prognosis of CRC patients by smoking abstinence deserve increased attention in further research and clinical practice.

Smoking and survival of colorectal cancer patients: Population‐based study from Germany

Current evidence on the association between smoking and colorectal cancer (CRC) prognosis after diagnosis is heterogeneous and few have investigated dose‐response effects or outcomes other than overall survival. Therefore, the association of smoking status and intensity with several prognostic outcomes was evaluated in a large population‐based cohort of CRC patients; 3,130 patients with incident CRC, diagnosed between 2003 and 2010, were interviewed on sociodemographic factors, smoking behavior, medication and comorbidities. Tumor characteristics were collected from medical records. Vital status, recurrence and cause of death were documented for a median follow‐up time of 4.9 years. Using Cox proportional hazards regression, associations between smoking characteristics and overall, CRC‐specific, non‐CRC related, recurrence‐free and disease‐free survival were evaluated. Among stage I–III patients, being a smoker at diagnosis and smoking ≥15 cigarettes/day were associated with lower recurrence‐free (adjusted hazard ratios (aHR): 1.29; 95% confidence interval (CI): 0.93–1.79 and aHR: 1.31; 95%‐CI: 0.92–1.87) and disease‐free survival (aHR: 1.26; 95%‐CI: 0.95–1.67 and aHR: 1.29; 95%‐CI: 0.94–1.77). Smoking was associated with decreased survival in stage I–III smokers with pack years ≥20 (Overall survival: aHR: 1.40; 95%‐CI: 1.01–1.95), in colon cancer cases (Overall survival: aHR: 1.51; 95%‐CI: 1.05–2.17) and men (Recurrence‐free survival: aHR: 1.51; 95%‐CI: 1.09–2.10; disease‐free survival: aHR: 1.49; 95%‐CI: 1.12–1.97), whereas no associations were seen among women, stage IV or rectal cancer patients. The observed patterns support the existence of adverse effects of smoking on CRC prognosis among nonmetastatic CRC patients. The potential to enhance prognosis of CRC patients by promotion of smoking cessation, embedded in tertiary prevention programs warrants careful evaluation in future investigations.

Smoking and survival of colorectal cancer patients

Current evidence on the association between smoking and colorectal cancer (CRC) prognosis after diagnosis is heterogeneous and few have investigated dose‐response effects or outcomes other than overall survival. Therefore, the association of smoking status and intensity with several prognostic outcomes was evaluated in a large population‐based cohort of CRC patients; 3,130 patients with incident CRC, diagnosed between 2003 and 2010, were interviewed on sociodemographic factors, smoking behavior, medication and comorbidities. Tumor characteristics were collected from medical records. Vital status, recurrence and cause of death were documented for a median follow‐up time of 4.9 years. Using Cox proportional hazards regression, associations between smoking characteristics and overall, CRC‐specific, non‐CRC related, recurrence‐free and disease‐free survival were evaluated. Among stage I–III patients, being a smoker at diagnosis and smoking ≥15 cigarettes/day were associated with lower recurrence‐free (adjusted hazard ratios (aHR): 1.29; 95% confidence interval (CI): 0.93–1.79 and aHR: 1.31; 95%‐CI: 0.92–1.87) and disease‐free survival (aHR: 1.26; 95%‐CI: 0.95–1.67 and aHR: 1.29; 95%‐CI: 0.94–1.77). Smoking was associated with decreased survival in stage I–III smokers with pack years ≥20 (Overall survival: aHR: 1.40; 95%‐CI: 1.01–1.95), in colon cancer cases (Overall survival: aHR: 1.51; 95%‐CI: 1.05–2.17) and men (Recurrence‐free survival: aHR: 1.51; 95%‐CI: 1.09–2.10; disease‐free survival: aHR: 1.49; 95%‐CI: 1.12–1.97), whereas no associations were seen among women, stage IV or rectal cancer patients. The observed patterns support the existence of adverse effects of smoking on CRC prognosis among nonmetastatic CRC patients. The potential to enhance prognosis of CRC patients by promotion of smoking cessation, embedded in tertiary prevention programs warrants careful evaluation in future investigations.

Alcohol consumption and survival of colorectal cancer patients: a population-based study from Germany

BACKGROUND Studies on the association between alcohol consumption and colorectal cancer (CRC) prognosis have yielded inconsistent results. OBJECTIVE The associations of lifetime and 1-y prediagnostic alcohol consumption with relevant prognostic outcomes were evaluated in a large population-based cohort of CRC patients. DESIGN In 2003-2010, 3121 patients diagnosed with CRC were interviewed on sociodemographic and lifestyle factors, medication, and comorbidities. Cancer recurrence, vital status, and cause of death were documented for a median follow-up time of 4.8 y. With the use of Cox proportional hazard regression, associations between lifetime and recent alcohol consumption and overall, CRC-specific, recurrence-free, and disease-free survival were analyzed. RESULTS In this patient cohort with a median age of 69 y at diagnosis, lifetime abstainers showed poorer overall [adjusted HR (aHR): 1.25; 95% CI: 1.03, 1.52] and CRC-specific (aHR: 1.37; 95% CI: 1.10, 1.70) survival than lifetime light drinkers (women: >0-12 g/d; men: >0-24 g/d). Lifetime heavy drinkers showed poorer overall (aHR: 1.37; 95% CI: 1.06, 1.78) and disease-free (aHR: 1.38; 95% CI: 1.09, 1.74) survival. Alcohol abstaining in the year before diagnosis was associated with poorer overall (aHR: 1.42; 95% CI: 1.20, 1.68), CRC-specific (aHR: 1.38; 95% CI: 1.13, 1.68), and disease-free (aHR: 1.23; 95% CI: 1.05, 1.44) survival. Lifetime abstainers with nonmetastatic disease showed poorer CRC-specific (aHR: 1.48; 95% CI: 1.10, 2.00) and recurrence-free (aHR: 1.32; 95% CI: 1.02, 1.70) survival. Wine abstaining but not beer or liquor abstaining was associated with poorer survival. Associations between alcohol consumption and prognosis varied according to presence of diabetes and age. CONCLUSIONS Prediagnostic alcohol abstaining and heavy drinking were associated with poorer survival after a CRC diagnosis than light drinking. The protective effects of light consumption might be restricted to wine, and associations might differ according to age and presence of diabetes mellitus.

Associations of red and processed meat with survival after colorectal cancer and differences according to timing of dietary assessment

BACKGROUND Little is known about the prognostic impact of red and processed meat intake or about changes in consumption after a diagnosis of colorectal cancer (CRC). OBJECTIVES We investigated associations of baseline red and processed meat with survival outcomes and explored changes in intake among CRC survivors 5 y after diagnosis. DESIGN A total of 3122 patients diagnosed with CRC between 2003 and 2010 were followed for a median of 4.8 y [DACHS (Darmkrebs: Chancen der Verhütung durch Screening) study]. Patients provided information on diet and other factors in standardized questionnaires at baseline and at the 5-y follow-up. Cox proportional hazards regression models were used to estimate HRs and 95% CIs. RESULTS Among patients with stage I-III CRC, baseline red and processed meat intake was not associated with overall (>1 time/d compared with <1 time/d; HR: 0.85; 95% CI: 0.67, 1.09), CRC-specific (HR: 0.83; 95% CI: 0.61, 1.14), cardiovascular disease-specific (HR: 0.92; 95% CI: 0.51, 1.68), non-CRC-specific (HR: 0.88; 95% CI: 0.59, 1.30), and recurrence-free (HR: 1.03; 95% CI: 0.80, 1.33) survival; results among stage IV patients were comparable. An association with worse overall survival was found among patients with Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated CRC (HR: 1.99; 95% CI: 1.10, 3.56) but not with microsatellite instability or CpG island methylator phenotype (CIMP) positivity. A much lower proportion of survivors reported daily consumption of red and processed meat at the 5-y follow-up than at baseline (concordance rate: 39%; κ-value: 0.10; 95% CI: 0.07, 0.13). CONCLUSIONS Our findings suggest that baseline red and processed meat intake is not associated with poorer survival among patients with CRC. The potential interaction with KRAS mutation status warrants further evaluation. Major changes in consumption measured at the 5-y follow-up may have had an impact on our survival estimates.

No association of CpG island methylator phenotype and colorectal cancer survival: population-based study

Background:Previous studies have shown adverse effects of CpG island methylator phenotype (CIMP) on colorectal cancer (CRC) prognosis. However, sample sizes were often limited and only few studies were able to adjust for relevant molecular features associated with CIMP. The aim of this study was to investigate the impact of CIMP on CRC survival in a large population-based study with comprehensive adjustment.Methods:The CIMP status and other molecular tumour features were analysed in 1385 CRC patients diagnosed between 2003 and 2010. Detailed information were obtained from standardised personal interviews and medical records. During follow-up (median: 4.9 years), we assessed vital status, cause of death and therapy details. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of survival after CRC.Results:The CIMP-H occurred more frequently in patients with older age, female gender, cancer in the proximal colon, BRAF mutation and microsatellite instability-high (MSI-H). However, CIMP status was not associated with CRC prognosis in CRC patients (HR=1.00; 95% CI=0.72–1.40 for overall survival; HR=0.96; 95% CI=0.65–1.41 for disease-specific survival) or in any of the subgroups. Although CIMP status was associated with the presence of MSI-H and BRAF mutation, the prognostic effects of MSI-H (HR=0.49; 95% CI=0.27–0.90) and BRAF mutation (HR=1.78; 95% CI=1.10–2.84) were independent of CIMP status. Similar benefit of chemotherapy was found for CRC outcomes in both the CIMP-low/negative group and the CIMP-high group.Conclusions:CpG island methylator phenotype was not associated with CRC prognosis after adjusting for other important clinical factors and associated mutations.

Gestational Weight Gain and Fetal-Maternal Adiponectin, Leptin, and CRP: results of two birth cohorts studies

Gestational weight gain (GWG) is an important modifiable factor known to influence fetal outcomes including birth weight and adiposity. Unlike behaviors such as smoking and alcohol consumption, the effect of GWG throughout pregnancy on fetal development and other outcomes has not been extensively studied. The aim of this study was to investigate the relationship of GWG with endocrine factors such as adiponectin, leptin, and C-reactive protein which may be associated with inflammatory response, fetal growth, and adiposity later in life. Data were obtained from the Ulm Birth Cohort Study (UBCS) and the Ulm SPATZ Health Study, two methodologically similar birth cohort studies including newborns and their mothers recruited from 11/2000–11/2001 and 04/2012–05/2013. In the two included birth cohorts we consistently observed statistically significant positive associations between GWG beginning as early as the second trimester with fetal cord blood leptin and stronger association beginning as early as the first trimester with post-delivery maternal serum leptin. Total weight gain exceeding commonly accepted recommended guidelines was consistently associated with higher leptin levels in both cord blood and post-delivery maternal serum. These results suggest a potential pathomechanistic link between fetal environment and surrogate markers of long-term health.

The Association Between Mutations in BRAF and Colorectal Cancer–Specific Survival Depends on Microsatellite Status and Tumor Stage

Background & Aims Colorectal tumors with mutations in BRAF and microsatellite stability (MSS) have been associated with adverse outcomes of patients. Combined tests for microsatellite instability‐high (MSI‐H) and BRAF mutations might therefore be used in risk assessment, particularly for patients with stage II tumors. We investigate the stage‐specific prognostic value of combined testing for MSI‐H and BRAF for patients with colorectal cancer. Methods We performed a retrospective analysis of colorectal tumor samples collected from 1995 patients at 22 hospitals in Germany, between 2003 and 2010. Samples were analyzed for MSI‐H using an established mononucleotide marker panel; BRAF mutations (BRAFV600E) were detected by Sanger sequencing or in tissue microarray blocks using immunohistochemistry. Cancers were assigned to categories of having MSS without mutations in BRAF, MSS with mutant BRAF, MSI‐H without mutations in BRAF, and MSI‐H with mutant BRAF. We investigated the association between tumor categories with clinical and pathologic features and patient’s overall, disease‐specific, and recurrence‐free survival (median follow‐up time, 5.1 y). Results Tumors were stage I in 364 (18%), stage II in 678 (34%), stage III in 673 (34%), and stage IV (14%) in 280 patients. Sixty‐three percent of tumors were located in the colon and 37% in the rectum. Most tumors (85%) had MSS without mutations in BRAF, 3% had MSS with mutant BRAF, 7% had MSI‐H without mutations in BRAF, and 5% had MSI‐H with mutant BRAF. In patients whose tumors were MSI‐H, mutation of BRAF did not significantly affect survival time. Patients whose tumors had MSS with mutant BRAF had significantly reduced overall survival (hazard ratio [HR], 2.16; 95% CI, 1.54–3.04; P < .001), disease‐specific survival (HR, 2.59; 95% CI, 1.77–3.79; P < .001), and recurrence‐free survival (HR, 2.45; 95% CI, 1.70–3.52; P < .001) than patients whose tumors had MSS without BRAF mutation. Although BRAF mutations in tumors with MSS were associated with disease‐specific survival of patients with stage III or IV tumors (P < .001), these features did not affect survival of patients with stage II tumors (P = .639). Conclusions In an analysis of almost 2000 patients with colorectal cancer, we found BRAF mutations to reduce survival of patients in stage III or IV (but not stage II) tumors with MSS. These findings do not support testing stage I or II colorectal tumors for BRAF mutations, although additional large studies are needed.

Association of household cleaning agents and disinfectants with asthma in young German adults

Objectives We scrutinised the association of private use of household sprays and disinfectants with asthma incidence in young adults in the transition from school to working life. Methods Between 2007 and 2009,2051 young adults aged 19–24 years living in two major German cities took part in the Study on Occupational Allergy Risks II. Self-reported exposure to household sprays and disinfectants was characterised according to a composite score for frequency of use as no use (score=0), low use (score between 1 and the median), medium use (score between the median and the 90th percentile) and high use (score above the 90th percentile). Two outcome variables (current asthma and current wheezing) with four mutually exclusive categories (never, incident, persistent and remittent) were used for the risk analyses. Multinomial logistic regression models examined the association between the frequency of using household sprays and disinfectants with asthma and wheezing adjusting for potential confounders. Results Compared with no use, high use of disinfectants was associated with a more than twofold increased odds of incident asthma (OR 2.79, 95% CI 1.14 to 6.83). In addition, low/medium use of disinfectants was associated with remittent asthma (OR 2.39, 95% CI 1.29 to 4.47). The evidence for an association between high usage of household sprays and asthma incidence was weak (OR 2.79, 95% CI 0.84 to 9.20). Conclusion Our results support the hypothesis of an association between the use of cleaning products and elevated risks for asthma and wheezing in young adults at the start of working life.