Prudence R. Carr

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.

Beta blockers and cancer prognosis - The role of immortal time bias: A systematic review and meta-analysis.

BACKGROUND Findings from experimental and observational studies have suggested beneficial effects of beta blocker (BB) use on cancer survival. Nevertheless, results have been inconclusive and there have been concerns that the observed associations might have resulted from immortal time bias (ITB). We conducted a systematic review and meta-analysis to summarize existing evidence, paying particular attention to this potential source of bias. METHODS A systematic literature search was performed in PubMed and Web of Science. Studies investigating the association between BB use and overall or cancer-specific survival were included. Summary estimates were derived from meta-analyses using random effects models. The potential influence of ITB was investigated. RESULTS We identified 30 eligible studies including 88,026 cancer patients in total. We deemed 11 studies to be at high or unclear risk of ITB. Including all studies in the meta-analysis, BB users had a significantly better overall (hazard ratio (HR) 0.88, 95% CI 0.79-0.97) and cancer-specific (HR 0.75, 95% CI 0.64-0.88) survival. Excluding the studies deemed to be prone to ITB resulted in HRs (95% CIs) of 1.00 (0.93-1.07) and 0.90 (0.83-0.98), respectively. Analyses on cancer site and BB type did not show beneficial associations besides overall survival among melanoma patients. However, melanoma-specific survival was not improved. CONCLUSION We found no clinically meaningful evidence for an association between BB use and survival after excluding studies with a possible ITB. Our results support suggestions that the proposed beneficial effect of BBs on cancer survival might be based on ITB.

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.

Lifestyle factors and risk of sporadic colorectal cancer by microsatellite instability status: a systematic review and meta-analyses

Introduction The association of lifestyle factors with molecular pathological subtypes of colorectal cancer (CRC), such as microsatellite instability (MSI), could provide further knowledge about the colorectal carcinogenic process. The aim of this review was to evaluate possible associations between lifestyle factors and risk of sporadic CRC by MSI status. Methods PubMed and Web of Science were searched for studies investigating the association between alcohol, body mass index, dietary fiber, hormone replacement therapy (HRT), non-steroidal anti-inflammatory drugs, physical activity, red meat, smoking, or statin use, with MSI-high (MSI-H) and microsatellite stable (MSS) CRC. Meta-analyses were carried out to calculate summary relative risks (sRR). Results Overall, 31 studies reporting on the association between lifestyle factors and CRC according to MSI status were included in this review. Ever smoking was associated with MSI-H (sRR = 1.62; 95% CI: 1.40-1.88) and MSS/MSI-low CRC (sRR = 1.10; 95% CI: 1.01-1.20), but the association was significantly stronger for MSI-H CRC. The use of HRT was associated with a 20% decrease (sRR = 0.80; 95% CI: 0.73-0.89) in the risk of MSS CRC, but was not associated with MSI-H CRC. An increase in body mass index per 5 kg/m2 was equally associated with MSS and MSI-H CRC (sRR = 1.22, in both cases), but was statistically significant for MSS CRC only (95% CI: 1.11-1.34 and 0.94-1.58, respectively). Limited evidence for associations between other lifestyle factors and CRC by MSI status exists. Conclusions Lifestyle factors, such as HRT and smoking are differentially associated with the risk of MSI-H and MSS CRC. Further research on associations of lifestyle factors and CRC subtypes is necessary to provide a better understanding of the CRC disease pathway.

Authors' reply: Meat subtypes and their association with colorectal cancer: Systematic review and meta-analysis.

We thank Dr Aykan for his interest in our study and for his comments. The p-values in Table 1 are p-values for the I statistic and describe potential heterogeneity of studies included in the meta-analysis rather than heterogeneity of studies from Europe and Asia (see column header of Table 1). Apparently, the correspondent misinterpreted these p-values. In regards to potentially overlooking important details as suggested by the correspondent, we reported subgroup analyses restricted to colon and rectal cancer because most studies differentiated between these anatomical subsites. Of course, if more studies had been available with detailed subgroup analyses, more detailed meta-analyses would have been feasible further differentiating between proximal and distal colon or between molecular subtypes. The aim of this systematic review and meta-analysis was to summarize current and available evidence from observational studies. We are aware that the amounts in the highest versus lowest intake groups varied between the studies and discuss this issue in the strengths and limitations section. Also, we conducted regional analyses to address international variation of meat consumption. Finally, the correspondent addresses an important point. The confidence limits reported for the studies by Norat et al. and by Sato et al. were not transferred correctly into Figure 3. We sincerely apologize to the authors of the two studies for this unnecessary mistake. Regarding Norat’s study, confidence limits should be 0.95–1.48 instead of 0.95–1.47 (colorectal cancer). Regarding Sato’s study, confidence limits should be 0.79–1.74 instead of 0.76–1.68 for colorectal cancer, 0.81–2.62 instead of 0.81–2.63 for colon cancer, and 0.39–1.42 instead of 0.39–1.41 for rectal cancer. However, the analyses and results of our meta-analyses were not affected by these minor typographical errors.

Soluble CD14 concentration in human breast milk and its potential role in child atopic dermatitis: Results of the Ulm Birth Cohort Studies

Soluble CD14 (sCD14) is one of many factors in human breast milk which may influence programming of the immune response in the breastfed child. Although previous studies have mostly found little association between sCD14 concentration in breast milk and atopic outcomes, recent evidence continues to support a role of sCD14 in immune‐related disease.

Association of Abnormal Serum Potassium Levels with Arrhythmias and Cardiovascular Mortality: a Systematic Review and Meta-Analysis of Observational Studies

PurposeTo provide the first systematic review and meta-analysis of observational studies on the association of abnormal serum potassium and cardiovascular outcomes.MethodsMedline and ISI Web of Knowledge were systematically searched from inception until November 24, 2017. Data synthesis of relevant studies was performed using random effects model meta-analyses.ResultsMeta-analyses included 310,825 participants from 24 studies. In the older general population, low serum potassium was associated with a 1.6-fold increased risk of supraventricular arrhythmias (risk ratio [95% confidence interval] 1.62 [1.02–2.55]). Contrarily, high serum potassium was associated with increased cardiovascular mortality (CVM) (1.38 [1.14–1.66]). In patients with acute myocardial infarction, the risk of ventricular arrhythmias was increased for high serum potassium (2.33 [1.60–3.38]). A U-shaped association was observed with a composite cardiovascular outcome in hypertensive patients (2.6-fold increased risk with hypokalemia and 1.7-fold increased risk with hyperkalemia), with CVM in dialysis patients (1.1-fold increased risk with hypokalemia and 1.4-fold increased risk with hyperkalemia) and with CVM in heart failure patients (albeit not statistically significant). Further, only hyperkalemia was associated with an increased risk of a composite cardiovascular outcome in both dialysis (1.12 [1.03–1.23]) and chronic kidney disease (1.34 [1.06–1.71]) patients.ConclusionsControlled clinical trials are needed to determine which populations may profit from more frequent potassium-monitoring and subsequent interventions, e.g., change or withdrawal of potassium-influencing drugs, in order to restore normal values and prevent cardiovascular outcomes.Registration DetailsRegistration in PROSPERO (Centre for Reviews and Dissemination University of York, York, UK): CRD42016048897 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=48897).

Meat intake and risk of colorectal polyps: results from a large population-based screening study in Germany

Background: Red and processed meats have been shown to be associated with colorectal adenomas in many, but not all, studies, and the association according to the type of colorectal adenoma or the location in the colorectum is unclear.Objectives: We investigated the association of meat intake in relation to colorectal polyps and further investigated the association according to histologic subtypes and subsites in a large population-based screening study in Germany.Design: In this cross-sectional study, 15,950 participants aged ≥55 y underwent a screening colonoscopy. We calculated prevalence ratios (PRs) and 95% CIs for associations between meat intake and the most-advanced findings from a colonoscopy with the use of log binomial regression.Results: Overall, 3340 participants (20.4%) had nonadvanced adenomas, 1643 participants (10.0%) had advanced adenomas, and 189 participants (1.2%) had colorectal cancer. We observed no statistically significant association between red or processed meat consumption and the prevalence of any adenomas or advanced adenomas [highest compared with lowest: red meat, PR: 1.07 (95% CI: 0.83, 1.37); processed meat, PR: 1.11 (95% CI: 0.91, 1.36)]. In site-specific analyses, although no dose-response relation was observed, processed meat was positively associated with the prevalence of advanced adenomas in the rectum only (multiple times per day compared with <1 time/wk, PR: 1.87; 95% CI: 1.19, 2.95). Poultry intake was not associated with any outcome.Conclusions: On the basis of this large colonoscopy-based study, there are no significant associations between red or processed meat intake and the prevalence of any adenomas or advanced adenomas. However, processed meat may be positively associated with the prevalence of advanced adenomas in the rectum, but prospective cohort studies are needed to further clarify this association. There is no association between poultry consumption and the prevalence of colorectal polyps in this study.