Coffee and health outcomes: a systematic review of Mendelian randomisation studies.

Association between zinc intake and risk of digestive tract cancers: A systematic review and meta-analysis

Coffee and Tea Consumption Are Associated With a Lower Incidence of Chronic Liver Disease in the United States

BackgroundInverse associations have been observed between coffee consumption and liver cancer, but associations for other digestive cancers are unclear. Few previous studies have investigated coffee type (specifically instant or ground coffee) or a range of digestive cancer types within one cohort. We therefore investigated coffee consumption by type and digestive cancer risks in a population-based cohort.MethodsThe UK Biobank captured self-reported coffee consumption and cancer-registry recorded incident digestive cancers. Hazard ratios (HRs) and 95% CIs were calculated using Cox regression. The risk of every type of digestive cancer was investigated in association with coffee consumption by dose–response and by coffee type (decaffeinated, instant and ground).ResultsOver 7.5 years of follow-up, 3567 developed digestive cancer among 471,779 participants. There were 88 cases of hepatocellular carcinoma and a marked association was observed for hepatocellular carcinoma in coffee drinkers (HR 0.50, 95% CI 0.29, 0.87), which was similar for instant (HR 0.51, 95% CI 0.28, 0.93) and ground coffee (HR 0.47, 95% CI 0.20, 1.08). We did not observe significant consistently reduced risks of other individual digestive cancers amongst coffee drinkers.ConclusionsWe found some evidence that coffee consumption was inversely associated with hepatocellular carcinoma which was similar by coffee type.

Recent evidence suggests that common functional polymorphisms in the hypoxia inducible factor-1α (HIF-1α) gene may play an important role in the development and progression of digestive cancer, but individually published results are inconclusive. Our meta-analysis is aimed to derive a more precise estimation of the relationships between HIF-1α gene polymorphisms and digestive cancer risk. An extensive literature search for relevant studies was conducted on Pubmed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude odds ratios (OR) with 95% confidence interval (CI) were calculated. Eight case-control studies were included with a total of 1276 digestive cancer patients and 3392 healthy controls. Our meta-analysis revealed that the A variant of HIF-1α G1790A polymorphism might be associated with increased risk of colorectal, esophageal, gastric, and liver cancers, especially among Asian populations. However, no statistically significant associations were found between HIF-1α C1772T polymorphism and susceptibility to digestive cancer. No publication bias was detected in this meta-analysis. The current meta-analysis suggests that the HIF-1α G1790A polymorphism may increase the risk of colorectal, esophageal, gastric, and liver cancers, especially among Asian populations.

The conclusions on the association between the rs2736100 polymorphisms of telomerase reverse transcriptase (TERT) gene polymorphism and digestive cancers risk are still debated. This meta-analysis was conducted to update the association between the TERT rs2736100 polymorphisms and the risk of digestive cancers. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using the meta-analysis method. Eight case-control studies were included in this meta-analysis for associating TERT rs2736100 gene polymorphism and digestive cancer susceptibility. Pooled odds ratio with 95% confidence interval was calculated using a fixed or random-effects model. Overall, no evidence has shown that the TERT rs2736100 polymorphism was associated with the susceptibility to digestive cancers. Besides, stratified analysis with ethnicity also indicated no significant association between TRET rs2736100 and the risk of digestive cancers under all genetic models in both Asian and Caucasian populations were observed. According to the meta-analysis, TERT rs2736100 polymorphism might be unrelated to digestive cancer susceptibility. Evidence with adequate sample size is still needed.

Metabolic gene variants, smoking, and alcohol consumption are important upper digestive tract cancer (UDTC) risk factors. However, the gene-gene and gene-environment interactions remain unclear. A case-control study in a high incidence area for upper digestive tract cancer was conducted in China. DNA was extracted from buffy coat samples for PCR or PCR-restriction fragment length polymorphism. Smoking and alcohol drinking status was determined by questionnaires. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the associations. After adjusting for confounding factors, smoking increased esophageal cancer (EC), gastric cardia cancer (GCC) and gastric antral carcinoma (GAC) risk by 3.594, 4.658, and 3.999-fold, respectively. Alcohol consumption increased EC, GCC and GAC risk by 1.953, 2.442 and 1.765-fold, respectively. The cytochrome P4501A1 (CYP1A1) rs4646903 T>C polymorphism increased GCC risk, the cytochrome P4502E1 (CYP2E1) rs2031920 C>T polymorphism increased EC risk, while the GSTM1 null genotype decreased EC risk. An association existed between the following: CYP1A1 rs4646903 and smoking in EC, GCC and GAC; CYP1A1 rs4646903 and alcohol consumption in EC and GCC; CYP2E1 rs2031920 and smoking in EC, GCC and GAC and CYP2E1 rs2031920 and alcohol consumption in EC and GCC. No association was observed between CYP1A1 and CYP2E1. The glutathione S-transferase mu 1 (GSTM1) null genotype decreased EC risk (OR=0.510). Smoking/drinking are upper digestive tract cancer risk factors. The CYP1A1 rs4646903 and CYP2E1 rs2031920 polymorphisms were risk factors of GCC or EC, and the GSTM1 null genotype may serve a protective role against EC. The results of the present study indicated that gene-environment interactions increase the risk of UDTC.

The aim of this meta-analysis was to evaluate the correlation between the Asp299Gly and Thr399Ile polymorphisms in the toll-like receptor 4 (TLR4) gene and the risk of digestive cancer. A comprehensive search in PubMed, Web of Science (ISI), the China National Knowledge Infrastructure (CNKI), the Database of Chinese Scientific and Technical Periodicals (VIP) and the China Biology Medical (CBM) literature databases, including all the studies until May 25 2012, was conducted in order to investigate the abovementioned correlation. Statistical analysis was performed using STATA version 10.1. A total of 12 case-control studies were identified comprising 1,877 cancer patients and 3,181 controls for Asp299Gly polymorphism, and 8 case-control studies with 1,062 cancer patients and 1,867 controls for Thr399Ile polymorphism. Following sensitivity analysis and excluding studies that deviated from the Hardy-Weinberg equilibrium (HWE) in the controls, this meta-analysis demonstrated a significant correlation between the G allele of the Asp299Gly polymorphism and increased risk of gastric cancer in dominant [fixed-effect model (FEM): odds ratio (OR), 1.772; 95% confidence interval (CI), 1.340-2.343] and codominant (FEM: OR, 1.761, CI, 1.347-2.301) models. However, no significant correlation was detected for overall digestive and colorectal cancer. Furthermore, following the sensitivity analysis and exclusion of studies deviating from HWE in controls, no significant effect of the T allele of Thr399Ile polymorphism on overall digestive, gastric and colorectal cancer risk was demonstrated. This study suggests that the G allele of the TLR4 Asp299Gly polymorphism might be correlated with an increased risk of gastric cancer. However, this result needs to be further investigated by future studies.

ObjectiveDespite several observational studies attempting to investigate the potential association between type 1 diabetes mellitus (T1DM) and the risk of digestive cancers, the results remain controversial. The purpose of this study is to examine whether there is a causal relationship between T1DM and the risk of digestive cancers.MethodsWe conducted a Mendelian randomisation (MR) study to systematically investigate the effect of T1DM on six most prevalent types of digestive cancers (oesophageal cancer, stomach cancer, hepatocellular carcinoma, biliary tract cancer, pancreatic cancer, and colorectal cancer). A total of 1,588,872 individuals were enrolled in this analysis, with 372,756 being the highest number for oesophageal cancer and 3,835 being the lowest for pancreatic cancer. Multiple MR methods were performed to evaluate the causal association of T1DM with the risk of six site-specific cancers using genome-wide association study summary data. Sensitivity analyses were also conducted to assess the robustness of the observed associations.ResultsWe selected 35 single nucleotide polymorphisms associated with T1DM as instrumental variables. Our findings indicate no significant effect of T1DM on the overall risk of oesophageal cancer (OR= 0.99992, 95% CI: 0.99979-1.00006, P= 0.2866), stomach cancer (OR=0.9298,95% CI: 0.92065-1.09466, P= 0.9298), hepatocellular carcinoma (OR= 0.99994,95% CI: 0.99987-1.00001, P= 0.1125), biliary tract cancer (OR=0.97348,95% CI: 0.8079-1.1729, P= 0.7775)), or pancreatic cancer (OR =1.01258, 95% CI: 0.96243-1.06533, P= 0.6294). However, we observed a causal association between T1DM and colorectal cancer (OR=1.000, 95% CI: 1.00045-1.0012, P<0.001), indicating that T1DM increases the risk of colorectal cancer. We also performed sensitivity analyses, which showed no heterogeneity or horizontal pleiotropy. For the reverse MR from T1DM to six digestive cancers, no significant causal relationships were identified.ConclusionsIn this MR study with a large number of digestive cancer cases, we found no evidence to support the causal role of T1DM in the risk of oesophageal cancer, stomach cancer, hepatocellular carcinoma, biliary tract cancer, or pancreatic cancer. However, we found a causal positive association between T1DM and colorectal cancer. Further large-scale prospective studies are necessary to replicate our findings.

Background&AimsThe relation between various types of plant-based diets and cancer risk is still unclear. We examined the association of overall plant-based diet index (PDI), healthy (hPDI) and unhealthy plant-based diet indices (uPDI) with the risk of selected digestive cancers. MethodsWe used data from a network of hospital-based case-control studies including 942 oral/pharyngeal, 304 esophageal, 230 stomach, 1953 colorectal, and 326 pancreatic cancer cases. We calculated PDI, hPDI, and uPDI from a validated food frequency questionnaire. We used multivariable logistic regression models to estimate the odds ratios (OR) of selected digestive cancers across the three PDIs (in quintiles, Q, or tertiles, T, and in continuous). ResultsThe PDI was significantly inversely associated with oral/pharyngeal (ORQ5 vs Q1=0.63, 95% confidence interval, CI, 0.47-0.84) and esophageal cancer risk (ORT3 vs T1=0.47, 95% CI 0.31-0.72). The inverse associations appeared stronger for the hPDI (oral cavity/pharynx: ORQ5 vs Q1=0.52; 95% CI 0.39-0.70; esophagus: ORT3 vs T1=0.59, 95% CI 0.39-0.91; stomach: ORT3 vs T1=0.42, 95% CI 0.27-0.67; colorectum: ORQ5 vs Q1=0.69; 95% CI 0.57-0.84; pancreas: ORT3 vs T1=0.60; 95% CI 0.41-0.89). In contrast, the uPDI was directly associated with the risk of oral/pharyngeal (ORQ5 vs Q1=1.57, 95% CI 1.17-2.12), colorectal (ORQ5 vs Q1=2.28, 95% CI 1.86-2.81), and pancreatic cancer (ORT3 vs T1=1.74, 95% CI 1.14-2.65). Esophageal and stomach cancer risks were non-significantly increased respectively by 34% and 46% in the highest uPDI quantile. ConclusionA plant-based diet, especially a healthy one, may reduce the risk of various digestive cancers, whereas an unhealthy plant-based diet may increase the risk. The quality of plant-based diets is important for digestive cancer risk evaluation and prevention.

The risk of chronic kidney disease (CKD) in individuals who regularly drink coffee is controversial. The aim of this meta-analysis was to evaluate the association between coffee consumption and CKD. A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception until April 2016. We included studies that reported odd ratios or hazard ratios comparing the risk of CKD in individuals consuming significant amount of coffee vs. those who did not consume coffee. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Four observational studies with 14898 individuals were included in our analysis to assess the association between coffee consumption and CKD. Coffee consumption was defined as one cup of coffee per day or greater. The pooled RR of CKD in individuals consuming coffee was 0.71 (95% CI, 0.47-1.08). The subgroup analysis showed the pooled RRs of CKD of 1.10 (95% CI, 0.94-1.29) in males and 0.81 (95% CI, 0.58-1.13) in females, respectively. Our study demonstrates no significant association between coffee consumption and CKD in males. However, future studies are required to assess a potential inverse association between coffee consumption and risk for developing CKD in females.

Interleukin-17A (IL-17A) is a multifunctional cytokine which plays a crucial role in the initiation and progression of cancer. To date, several studies have investigated associations between IL-17A -197G>A (rs2275913) polymorphism and digestive cancer risk, but the results remain conflicting. We here aimed to confirm the role of this single nucleotide polymorphism (SNP) in susceptibility to digestive cancer through a systemic review and meta-analysis. Ten eligible case-control studies were identified by searching electronic databases, involving 3,087 cases and 3,815 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of the association. The results of overall analyses indicated that the variant A allele was associated with an increased risk of digestive cancer (AA vs GG: OR=1.51, 95%CI=1.18-1.93; AA vs GG+GA: OR=1.45, 95%CI=1.12-1.87; A vs G: OR=1.21, 95%CI=1.05-1.39). In subgroup analysis stratified by specific cancer type, elevated risk among studies of gastric cancer was found (AA vs GG: OR=1.68, 95%CI=1.24-2.28; AA vs GG+GA: OR=1.62, 95%CI=1.16-2.26; A vs G: OR=1.23, 95%CI=1.04-1.46). According to ethnicity, there was evidence in the Asian populations for an association between this polymorphism and cancer risk (GA vs GG: OR=1.19, 95%CI=1.05-1.36; AA vs GG: OR=1.56, 95%CI=1.15-2.12; AA+GA vs GG: OR=1.28, 95%CI=1.13- 1.44; AA vs GG+GA: OR=1.42, 95%CI=1.01-2.00; A vs G: OR=1.24, 95%CI=1.08-1.44), while in the Caucasian populations an association was found in the recessive model (AA vs GG+GA: OR=1.62, 95%CI=1.17-2.24). In conclusion, the results of this meta-analysis suggest that the IL-17A -197G>A polymorphism contributes to an increased risk of human digestive cancer, both in the Asian and Caucasian populations and especially for gastric cancer.

Epidemiologic evidence on coffee consumption reducing the risk of gallstone disease has been contradictory. To perform a meta-analysis of observational studies, to investigate an association and dose-response of coffee consumption with gallstone disease. We used PubMed and EMBASE databases to identify all published studies before June 2015. A random-effects model was used to compute a pooled relative risk (RR) and corresponding 95% confidence intervals (CIs). One case-control study and five prospective cohort studies (with seven cohorts) involving 227,749 participants and 11,477 gallstone disease cases were included. Coffee consumption was significantly associated with a reduced risk of gallstone disease (RR, 0.83; 95% CI, 0.76 to 0.89; I(2) = 35.9%), based on prospective studies; specifically, we observed an inverse relation in females, but not in males. The case-control study did not reveal any association between coffee and gallstone disease (OR, 0.99; 95% CI, 0.64 to 1.53). In a dose-response analysis, the RR of gallstone disease was 0.95 (95% CI, 0.91 to 1.00; P = 0.049) per 1 cup/day of coffee consumption. A significant nonlinear dose-response association was also identified (P for nonlinearity = 0.0106). For people who drank 2, 4 and 6 cups of coffee per day, the estimated RRs of gallstone disease were 0.89 (95% CI, 0.79 to 0.99), 0.81 (95% CI, 0.72 to 0.92) and 0.75 (95% CI, 0.64 to 0.88), respectively, compared with the lowest level drinkers. This study suggests that coffee consumption is related to a significantly decreased risk of gallstone disease.

Mendelian randomization study of coffee consumption and age at onset of Huntington's disease

Recent reports have suggested an association between consumption of coffee or decaffeinated coffee and the risk of rheumatoid arthritis (RA), although data are sparse and somewhat inconsistent. Furthermore, existing studies measured dietary exposures and potential confounders only at baseline and did not consider possible changes in diet or lifestyle over the followup period. We studied whether coffee, decaffeinated coffee, total coffee, tea, or overall caffeine consumption was associated with the risk of RA, using the Nurses' Health Study, a longitudinal cohort study of 121,701 women. Information on beverage consumption was assessed with a food frequency questionnaire (FFQ) that was completed every 4 years, from baseline in 1980 through 1998. Among the 83,124 women who completed the FFQ at baseline, the diagnosis of incident RA (between 1980 and 2000) was confirmed in 480 women by a connective tissue disease screening questionnaire and medical record review for American College of Rheumatology criteria. Relationships between intake of various beverages and the risk of RA were assessed in age-adjusted models and in multivariate Cox proportional hazards models including the cumulative average intake of each beverage during the followup period, adjusted for numerous potential confounders. In addition, for direct comparisons with prior reports, multivariate analyses were repeated using only baseline beverage information. We did not find a significant association between decaffeinated coffee consumption of >/=4 cups/day (compared with no decaffeinated coffee consumption) and subsequent risk of incident RA, in either an adjusted multivariate model (relative risk [RR] 1.1, 95% confidence interval [95% CI] 0.5-2.2) or a multivariate model using only baseline reports of decaffeinated coffee consumption (RR 1.0, 95% CI 0.6-1.7). Similarly, there was no relationship between cumulative caffeinated coffee consumption and RA risk (RR 1.1, 95% CI 0.8-1.6 for >/=4 cups per day versus none) or between tea consumption and RA risk (RR 1.1, 95% CI 0.7-1.8 for >3 cups/day versus none). Total coffee and total caffeine consumption were also not associated with the risk of RA. In this large, prospective study, we find little evidence of an association between coffee, decaffeinated coffee, or tea consumption and the risk of RA among women.

Epidemiological studies regarding the associations of tea and coffee consumption with esophageal cancer (EC) risk are still inconsistent and this meta-analysis was conducted to examine these associations. PubMed, ISI -Web of Science, China National Knowledge Infrastructure (CNKI), and Chinese VIP database up to October 2011 were searched and manual search for reference lists of relevant studies were conducted. Random effects model was used to pool the odds ratios (OR). Twenty-four case-control and cohort studies with 7376 EC cases were included in this meta-analysis. The pooled OR of EC was 0.77 [95% confidence intervals (95% CI): 0.57, 1.04] for highest vs. non/lowest green tea consumption; but it was statistically significant for case-control studies (OR = 0.70; 95% CI: 0.51, 0.96) and for studies conducted in China (OR = 0.64; 95% CI: 0.44, 0.95). No significant association was observed for the highest vs. non/lowest black tea consumption against EC risk (OR = 1.35; 95% CI: 0.86, 2.11). A borderline significantly inverse association of highest vs. non/lowest coffee consumption against EC risk was found (OR = 0.88; 95% CI: 0.76, 1.01). In conclusion, our data showed that both green tea and coffee consumption, but not black tea consumption, have protective effects on EC.