Ellen Kampman

Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies

Objective To investigate the association between intake of dietary fibre and whole grains and risk of colorectal cancer. Design Systematic review and meta-analysis of prospective observational studies. Data sources PubMed and several other databases up to December 2010 and the reference lists of studies included in the analysis as well as those listed in published meta-analyses. Study selection Prospective cohort and nested case-control studies of dietary fibre or whole grain intake and incidence of colorectal cancer. Results 25 prospective studies were included in the analysis. The summary relative risk of developing colorectal cancer for 10 g daily of total dietary fibre (16 studies) was 0.90 (95% confidence interval 0.86 to 0.94, I2=0%), for fruit fibre (n=9) was 0.93 (0.82 to 1.05, I2=23%), for vegetable fibre (n=9) was 0.98 (0.91 to 1.06, I2=0%), for legume fibre (n=4) was 0.62 (0.27 to 1.42, I2=58%), and for cereal fibre (n=8) was 0.90 (0.83 to 0.97, I2=0%). The summary relative risk for an increment of three servings daily of whole grains (n=6) was 0.83 (0.78 to 0.89, I2=18%). Conclusion A high intake of dietary fibre, in particular cereal fibre and whole grains, was associated with a reduced risk of colorectal cancer. Further studies should report more detailed results, including those for subtypes of fibre and be stratified by other risk factors to rule out residual confounding. Further assessment of the impact of measurement errors on the risk estimates is also warranted.

Red and Processed Meat and Colorectal Cancer Incidence: Meta-Analysis of Prospective Studies

Background The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from prospective studies and explore whether there is a non-linear association of red and processed meats with colorectal cancer risk. Methods and Findings Relevant prospective studies were identified in PubMed until March 2011. For each study, relative risks and 95% confidence intervals (CI) were extracted and pooled with a random-effects model, weighting for the inverse of the variance, in highest versus lowest intake comparison, and dose-response meta-analyses. Red and processed meats intake was associated with increased colorectal cancer risk. The summary relative risk (RR) of colorectal cancer for the highest versus the lowest intake was 1.22 (95% CI  = 1.11−1.34) and the RR for every 100 g/day increase was 1.14 (95% CI  = 1.04−1.24). Non-linear dose-response meta-analyses revealed that colorectal cancer risk increases approximately linearly with increasing intake of red and processed meats up to approximately 140 g/day, where the curve approaches its plateau. The associations were similar for colon and rectal cancer risk. When analyzed separately, colorectal cancer risk was related to intake of fresh red meat (RR for 100 g/day increase  = 1.17, 95% CI  = 1.05−1.31) and processed meat (RR for 50 g/day increase  = 1.18, 95% CI  = 1.10−1.28). Similar results were observed for colon cancer, but for rectal cancer, no significant associations were observed. Conclusions High intake of red and processed meat is associated with significant increased risk of colorectal, colon and rectal cancers. The overall evidence of prospective studies supports limiting red and processed meat consumption as one of the dietary recommendations for the prevention of colorectal cancer.

Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States

Objective To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences. Design Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US. Setting General population. Participants 26 018 men and women aged 50-79 years Main outcome measures All-cause, cardiovascular, and cancer mortality. Results 25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses. Conclusions Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.

Dairy products and colorectal cancer risk: a systematic review and meta-analysis of cohort studies

BACKGROUND Previous studies of the association between intake of dairy products and colorectal cancer risk have indicated an inverse association with milk, however, the evidence for cheese or other dairy products is inconsistent. METHODS We conducted a systematic review and meta-analysis to clarify the shape of the dose-response relationship between dairy products and colorectal cancer risk. We searched the PubMed database for prospective studies published up to May 2010. Summary relative risks (RRs) were estimated using a random effects model. RESULTS Nineteen cohort studies were included. The summary RR was 0.83 (95% CI [confidence interval]: 0.78-0.88, I2=25%) per 400 g/day of total dairy products, 0.91 (95% CI: 0.85-0.94, I2=0%) per 200 g/day of milk intake and 0.96 (95% CI: 0.83-1.12, I2=28%) per 50 g/day of cheese. Inverse associations were observed in both men and women but were restricted to colon cancer. There was evidence of a nonlinear association between milk and total dairy products and colorectal cancer risk, P<0.001, and the inverse associations appeared to be the strongest at the higher range of intake. CONCLUSION This meta-analysis shows that milk and total dairy products, but not cheese or other dairy products, are associated with a reduction in colorectal cancer risk.BACKGROUND Previous studies of the association between intake of dairy products and colorectal cancer risk have indicated an inverse association with milk, however, the evidence for cheese or other dairy products is inconsistent. METHODS We conducted a systematic review and meta-analysis to clarify the shape of the dose-response relationship between dairy products and colorectal cancer risk. We searched the PubMed database for prospective studies published up to May 2010. Summary relative risks (RRs) were estimated using a random effects model. RESULTS Nineteen cohort studies were included. The summary RR was 0.83 (95% CI [confidence interval]: 0.78-0.88, I2 = 25%) per 400 g/day of total dairy products, 0.91 (95% CI: 0.85-0.94, I2 = 0%) per 200 g/day of milk intake and 0.96 (95% CI: 0.83-1.12, I2 = 28%) per 50 g/day of cheese. Inverse associations were observed in both men and women but were restricted to colon cancer. There was evidence of a nonlinear association between milk and total dairy products and colorectal cancer risk, P < 0.001, and the inverse associations appeared to be the strongest at the higher range of intake. CONCLUSIONS This meta-analysis shows that milk and total dairy products, but not cheese or other dairy products, are associated with a reduction in colorectal cancer risk.

Nonlinear Reduction in Risk for Colorectal Cancer by Fruit and Vegetable Intake Based on Meta-analysis of Prospective Studies

BACKGROUND & AIMS The association between fruit and vegetable intake and colorectal cancer risk has been investigated by many studies but is controversial because of inconsistent results and weak observed associations. We summarized the evidence from cohort studies in categorical, linear, and nonlinear, dose-response meta-analyses. METHODS We searched PubMed for studies of fruit and vegetable intake and colorectal cancer risk that were published until the end of May 2010. We included 19 prospective studies that reported relative risk estimates and 95% confidence intervals (CIs) of colorectal cancer-associated with fruit and vegetable intake. Random effects models were used to estimate summary relative risks. RESULTS The summary relative risk for the highest vs the lowest intake was 0.92 (95% CI: 0.86-0.99) for fruit and vegetables combined, 0.90 (95% CI: 0.83-0.98) for fruit, and 0.91 (95% CI: 0.86-0.96) for vegetables (P for heterogeneity=.24, .05, and .54, respectively). The inverse associations appeared to be restricted to colon cancer. In linear dose-response analysis, only intake of vegetables was significantly associated with colorectal cancer risk (summary relative risk=0.98; 95% CI: 0.97-0.99), per 100 g/d. However, significant inverse associations emerged in nonlinear models for fruits (Pnonlinearity<.001) and vegetables (Pnonlinearity=.001). The greatest risk reduction was observed when intake increased from very low levels of intake. There was generally little evidence of heterogeneity in the analyses and there was no evidence of small-study bias. CONCLUSIONS Based on meta-analysis of prospective studies, there is a weak but statistically significant nonlinear inverse association between fruit and vegetable intake and colorectal cancer risk.

Meta-analyses of vitamin D intake, 25-hydroxyvitamin D status, vitamin D receptor polymorphisms and colorectal cancer risk

Background: Our objective was to conduct a systematic review and meta-analysis of prospective studies on colorectal cancer (CRC) and vitamin D intake and 25-hydroxyvitamin D status, as part of the World Cancer Research Fund Continuous Update Project. We also aimed at conducting meta-analysis of all studies on CRC and vitamin D receptor (VDR) single-nucleotide polymorphisms. Methods: Relevant studies were identified in PubMed (up to June 2010). Inclusion criteria were original and peer-reviewed publications with a prospective design (for studies on vitamin D intake or status). Random effects of dose-response meta-analyses were performed on cancer incidence. Results: We observed inverse associations of CRC risk with dietary vitamin D [summary relative risk (RR) per 100 IU/day = 0.95, 95% CI: 0.93–0.98; 10 studies; range of intake (midpoints) = 39–719 IU/day] and serum/plasma 25-hydroxyvitamin D (RR per 100 IU/L = 0.96, 0.94–0.97; 6 studies; range = 200–1,800 IU/L), but not with total vitamin D (5 studies). Supplemental (2 studies; range = 0–600 IU/day) and total (4 studies; range = 79–732 IU/day) vitamin D intake and 25-hydroxyvitamin D status (6 studies; range = 200–1,800 IU/L) were inversely associated with colon cancer risk. We did not observe statistically significant associations between FokI, PolyA, TaqI, Cdx2, and ApaI VDR polymorphisms and CRC risk. The BsmI polymorphism was associated with a lower CRC risk (RR = 0.57, 0.36–0.89 for BB versus bb, 8 studies). Conclusions: These meta-analyses support the evidence of an inverse association between vitamin D intake, 25-hydroxyvitamin D status, and the BsmI VDR polymorphism and CRC risk. Impact: Improving vitamin D status could be potentially beneficial against CRC incidence. Cancer Epidemiol Biomarkers Prev; 20(5); 1003–16. ©2011 AACR.

Meat consumption, cigarette smoking, and genetic susceptibility in the etiology of colorectal cancer: results from a Dutch prospective study

Objective: We evaluated the effect of meat consumption and cigarette smoking in combination with N-acetyltransferases 1 and 2 (NAT1 and NAT2), and glutathione S-transferase M1 (GSTM1) genotypes on colorectal cancer. Methods: From a Dutch prospective study, after 8.5 years of follow-up, data of 102 incident colorectal cancer cases and a random sample of 537 controls frequency-matched for gender and age were analyzed. Baseline information on dietary and smoking habits, as well as blood samples for DNA isolation and genotyping, were available. Results: Red meat intake increased colorectal cancer risk among men (OR 2.7; 95% CI 1.1–6.7 highest vs. lowest intake), whereas poultry and fish decreased risk among women (OR 0.5; 95% CI 0.2–1.07). Cigarette smoking for at least 16 years increased colorectal cancer risk among former smokers only (OR 2.7; 95% CI 1.0–7.4), compared to those having smoked for 15 years or less. NAT1 and NAT2 polymorphisms did not significantly modify these associations. High consumption of poultry and fish was inversely associated with colorectal cancer only in the presence of GSTM1. Conclusions: In this study meat consumption and former long-term smoking were associated with colorectal cancer. Associations of colorectal cancer with different types of meat were modified by gender and GSTM1 genotype.

Interplay between dietary inducers of GST and the GSTM-1 genotype in colon cancer

The purpose of this study is to determine if cruciferous vegetables and coffee, two dietary inducers of glutatione‐S‐transferases, interact with GSTM‐1 genotype to alter risk of colon cancer. Data were available on 1579 incident cases of adenocarcinoma of the colon and 1898 population‐based controls. Intake of cruciferous vegetables, specific types of cruciferous vegetable, and coffee were not associated with colon cancer; GSTM‐1 genotype did not modify these associations. However, age at diagnosis and cigarette smoking appeared to be important effect modifiers of the associations between GSTM‐1, cruciferous vegetables and colon cancer. Among GSTM‐1 null individuals, <55 years at diagnosis, we observed an inverse association between colon cancer and high levels of cruciferous vegetable intake relative to people who did not eat cruciferous vegetables (ORs 0.23 95% CI 0.10–0.54); broccoli was the cruciferous vegetable associated with the strongest inverse association (OR 0.30 95% CI 0.13–0.70). Among younger individuals who were GSTM‐1 present (relative to those with GSTM‐1 null), we observed an inverse association with colon cancer regardless of level of cruciferous vegetable intake (OR 0.74 95% CI 0.30–1.79 for no intake; OR 0.44 95% CI 0.21–0.92 for <4 servings/week; and OR 0.44 95% CI 0.19–0.99 for ≥4 servings/week). These associations were further modified by cigarette smoking. People <65 years of age who smoked had a greater reduction in risk of colon cancer from consumption of cruciferous vegetables than non‐smokers at the same age. In summary, although cruciferous vegetables do not appear to modify colon cancer risk in the total population, there are subgroups of the population for whom these vegetables may be important. These subgroups are defined mostly by age and smoking status. Int. J. Cancer 87:728–733, 2000.

Green tea drinking, high tea temperature and esophageal cancer in high- and low-risk areas of Jiangsu Province, China: a population-based case-control study.

Epidemiological studies suggested drinking green tea is inversely associated with esophageal cancer but results remain inconclusive. Moreover, inconsistent observations found high temperature drinks are associated with esophageal cancer. A population‐based case–control study was conducted in a high‐risk area (Dafeng) and a low‐risk area (Ganyu) of esophageal cancer in Jiangsu province China from 2003 to 2007. It aimed to explore green tea drinking and tea temperature with the risk of esophageal cancer, and to compare the difference between different risk regions. Using identical protocols, 1,520 cases and 3,879 healthy controls were recruited as study subjects in 2 regions. Detailed information was collected to assess green tea drinking habits. Unconditional logistic regression was used to obtain OR and 95% CI. Results showed that ever drinking green tea elevated OR in both counties (Dafeng OR = 1.2, 95% CI = 0.9–1.5; Ganyu: OR = 1.9, 95% CI = 1.4–2.4). Drinking tea at high temperature was found to increase cancer risk in both areas (Dafeng: OR = 1.9, 95% CI = 1.2–2.9; Ganyu OR = 3.1 95% CI = 2.2–4.3). However, after further adjustment for tea temperature, ever drinking tea was not related to cancer in either county (Dafeng: OR = 1.0, 95% CI = 0.7–1.3; Ganyu: OR = 1.3, 95% CI = 0.9–1.7). For dose‐response relationships, we observed positive relationship with monthly consumption of tea (p for trend = 0.067) and tea concentration (p for trend = 0.006) after further adjustment for tea temperature. In conclusion, green tea drinking was not inversely associated with esophageal cancer in this study. However, drinking tea at high temperatures significantly increased esophageal cancer risk. There was no obvious difference of green tea drinking between low‐ and high‐risk areas.

Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease

BACKGROUND The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CAD. OBJECTIVE We tested whether common genetic polymorphisms associated with variation in tHcy are also associated with CAD. DESIGN We conducted a meta-analysis of genome-wide association studies (GWAS) on tHcy concentrations in 44,147 individuals of European descent. Polymorphisms associated with tHcy (P < 10(⁻⁸) were tested for association with CAD in 31,400 cases and 92,927 controls. RESULTS Common variants at 13 loci, explaining 5.9% of the variation in tHcy, were associated with tHcy concentrations, including 6 novel loci in or near MMACHC (2.1 × 10⁻⁹), SLC17A3 (1.0 × 10⁻⁸), GTPB10 (1.7 × 10⁻⁸), CUBN (7.5 × 10⁻¹⁰), HNF1A (1.2 × 10⁻¹²)), and FUT2 (6.6 × 10⁻⁹), and variants previously reported at or near the MTHFR, MTR, CPS1, MUT, NOX4, DPEP1, and CBS genes. Individuals within the highest 10% of the genotype risk score (GRS) had 3-μmol/L higher mean tHcy concentrations than did those within the lowest 10% of the GRS (P = 1 × 10⁻³⁶). The GRS was not associated with risk of CAD (OR: 1.01; 95% CI: 0.98, 1.04; P = 0.49). CONCLUSIONS We identified several novel loci that influence plasma tHcy concentrations. Overall, common genetic variants that influence plasma tHcy concentrations are not associated with risk of CAD in white populations, which further refutes the causal relevance of moderately elevated tHcy concentrations and tHcy-related pathways for CAD.