Rui Vieira

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.

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.

Dietary fiber and breast cancer risk: a systematic review and meta-analysis of prospective studies

BACKGROUND Evidence from case-control studies suggest that dietary fiber may be inversely related to breast cancer risk, but it is unclear if this is supported by prospective data. We conducted a systematic review and meta-analysis of the evidence from prospective studies. METHODS PubMed was searched for prospective studies of fiber intake and breast cancer risk until 31st August 2011. Random effects models were used to estimate summary relative risks (RRs). RESULTS Sixteen prospective studies were included. The summary RR for the highest versus the lowest intake was 0.93 [95% confidence interval (CI) 0.89-0.98, I(2) = 0%] for dietary fiber, 0.95 (95% CI 0.86-1.06, I(2) = 4%) for fruit fiber, 0.99 (95% CI 0.92-1.07, I(2) = 1%) for vegetable fiber, 0.96 (95% CI 0.90-1.02, I(2) = 5%) for cereal fiber, 0.91 (95% CI 0.84-0.99, I(2) = 7%) for soluble fiber and 0.95 (95% CI 0.89-1.02, I(2) = 0%) for insoluble fiber. The summary RR per 10 g/day of dietary fiber was 0.95 (95% CI 0.91-0.98, I(2) = 0%, P(heterogeneity) = 0.82). In stratified analyses, the inverse association was only observed among studies with a large range (≥13 g/day) or high level of intake (≥25 g/day). CONCLUSION In this meta-analysis of prospective studies, there was an inverse association between dietary fiber intake and breast cancer risk.

Selenium and prostate cancer: systematic review and meta-analysis

BACKGROUND Prostate cancer is a growing public health problem. Several human studies have shown a potentially protective effect of selenium, but the conclusions from published reports are inconsistent. OBJECTIVE The objective was to examine the evidence for relations between selenium intake, selenium status, and prostate cancer risk. DESIGN This was a systematic review and meta-analysis of randomized controlled trials, case-control studies, and prospective cohort studies. The World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project database was searched up to September 2010. The studies included reported measurements of selenium intake or status (plasma, serum, or toenail selenium), assessments of prostate cancer cases (number of events), and the RR in the adult population. Meta-analyses were performed, and study quality, heterogeneity, and small study effects were assessed. Dose-response meta-analyses were used, with restricted cubic splines and fractional polynomials for nonlinear trends, to investigate the association between selenium status and prostate cancer risk. RESULTS Twelve studies with a total of 13,254 participants and 5007 cases of prostate cancer were included. The relation between plasma/serum selenium and prostate cancer in a nonlinear dose-response meta-analysis showed that the risk decreased with increasing plasma/serum selenium up to 170 ng/mL. Three high-quality studies included in the meta-analysis of toenail selenium and cancer risk indicated a reduction in prostate cancer risk (estimated RR: 0.29; 95% CI: 0.14, 0.61) with a toenail selenium concentration between 0.85 and 0.94 μg/g. CONCLUSION The relation between selenium status and decreased prostate cancer risk was examined over a relatively narrow range of selenium status; further studies in low-selenium populations are required.

Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies

BACKGROUND Dairy product and calcium intakes have been associated with increased prostate cancer risk, but whether specific dairy products or calcium sources are associated with risk is unclear. OBJECTIVE In the Continuous Update Project, we conducted a meta-analysis of prospective studies on intakes of dairy products and calcium and prostate cancer risk. DESIGN PubMed and several other databases were searched up to April 2013. Summary RRs were estimated by using a random-effects model. RESULTS Thirty-two studies were included. Intakes of total dairy products [summary RR: 1.07 (95% CI: 1.02, 1.12; n = 15) per 400 g/d], total milk [summary RR: 1.03 (95% CI: 1.00, 1.07; n = 14) per 200 g/d], low-fat milk [summary RR: 1.06 (95% CI: 1.01, 1.11; n = 6) per 200 g/d], cheese [summary RR: 1.09 (95% CI: 1.02, 1.18; n = 11) per 50 g/d], and dietary calcium [summary RR: 1.05 (95% CI: 1.02, 1.09; n = 15) per 400 mg/d] were associated with increased total prostate cancer risk. Total calcium and dairy calcium intakes, but not nondairy calcium or supplemental calcium intakes, were also positively associated with total prostate cancer risk. Supplemental calcium was associated with increased risk of fatal prostate cancer. CONCLUSIONS High intakes of dairy products, milk, low-fat milk, cheese, and total, dietary, and dairy calcium, but not supplemental or nondairy calcium, may increase total prostate cancer risk. The diverging results for types of dairy products and sources of calcium suggest that other components of dairy rather than fat and calcium may increase prostate cancer risk. Any additional studies should report detailed results for subtypes of prostate cancer.

Dietary compared with blood concentrations of carotenoids and breast cancer risk: a systematic review and meta-analysis of prospective studies

BACKGROUND Measurement errors in the dietary assessment of fruit and vegetable intake may attenuate associations with breast cancer risk and might explain the weak associations observed in epidemiologic studies. Carotenoid concentrations in blood are biomarkers of fruit and vegetable intake; however, no systematic assessment has compared dietary intake with blood concentrations of carotenoids and breast cancer risk. OBJECTIVE We conducted a systematic review and meta-analysis of prospective studies of dietary intake and blood concentrations of carotenoids and breast cancer risk. DESIGN We searched PubMed and several other databases for relevant studies up to 31 August 2011. Random-effects models were used to estimate summary estimates. RESULTS Of the 6 dietary carotenoids assessed, only intake of β-carotene was significantly associated with a reduced breast cancer risk (summary RR: 0.95; 95% CI: 0.91, 0.99; I(2): 0%) per 5000 μg/d (n = 10). In contrast, the summary RR for blood concentrations of carotenoids was 0.78 (95% CI: 0.61, 0.99; I(2): 53%) per 100 μg total carotenoids/dL (n = 7), 0.74 (95% CI: 0.57, 0.97; I(2): 43%) per 50 μg β-carotene/dL (n = 13), 0.82 (95% CI: 0.73, 0.92, I(2): 3%) per 10 μg α-carotene/dL (n = 12), and 0.68 (95% CI: 0.52, 0.89; I(2): 0%) per 25 μg lutein/dL (n = 6). CONCLUSIONS Blood concentrations of carotenoids are more strongly associated with reduced breast cancer risk than are carotenoids assessed by dietary questionnaires. Our results suggest that the use of certain biomarkers may clarify inconsistent and weak results between dietary intake and breast cancer risk.

Dietary carbohydrates, glycemic index, glycemic load and endometrial cancer risk: a systematic review and meta-analysis of prospective studies

Endometrial cancer is the 5 th most common cancer among women worldwide with 287 000 new cases diagnosed in 2008, accounting for 4.8% of all female cancer cases (1) . Insulin resistance may play a role in the etiology of endometrial cancer based on the observation that several risk factors for endometrial cancer including adiposity (2) , low physical activity (2) , elevated levels of blood glucose (3) and C-peptide (4) , and diabetes (5) are linked to insulin resistance. Carbohydrates are the main dietary component affecting an individual’s insulin secretion, therefore glycemic response is also relevant in this topic (6) . Both glycemic index (GI) and glycemic load (GL) are used to rank foods according to their effects on blood glucose concentration. High GI and GL have been associated with increased risk of type 2 diabetes, obesity, and metabolic syndrome in several studies (6) . The objective of this study was to review and quantitatively summarize in a meta-analysis the evidence for an association between GI, GL and carbohydrates intake with the incidence of endometrial cancer in prospective cohort studies. PubMed database was searched for prospective studies of carbohydrates intake, GI, and GL and endometrial cancer risk, up to December 2011. A pre-specified protocol, which includes details of the search terms used, for the review was followed (http:// www.dietandcancerreport.org/cancer_resource_center/cup_protocols.php). We computed 95 % Confidence Intervals (CIs) from the natural logs of the Relative Risks (RRs) and CIs across categories of carbohydrate, and GI and GL intake. Overall RRs were estimated by use of a random effects model. Six cohort studies met the eligibility criteria for inclusion in the meta-analysis of carbohydrates, GI, GL and endometrial cancer risk. The summary RR for high vs. low intake was 1.17 (95 % CI: 1.03‐1.34) for carbohydrate intake, 1.00 (95 % CI: 0.87‐1.14) for GI, and 1.22 (95 % CI: 1.09‐1.37) for GL. In the dose-response analysis the summary RR was 1.18 (95 % CI: 1.02‐1.37) per 100 grams of carbohydrates per day and 1.15 (95% CI: 1.06‐1.25) per 50 GL units. The summary RR was 1.21 (95 % CI: 1.05‐1.38) for high vs. low total sugar intake and 1.07 (95% CI: 1.01‐1.13) per 25 g/d. In this meta-analysis of prospective studies we found that a higher intake of carbohydrates, as well as a high GL were predictors of an increased risk of endometrial cancer. There was no evidence of an association between endometrial cancer and GI. Our results provide further support for the hypothesis that dietary carbohydrate, glycemic load and total sugars may increase the risk of endometrial cancer.