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Role of Diet in Colorectal Cancer Incidence: Umbrella Review of Meta-analyses of Prospective Observational Studies.
Veettil, SK, Wong, TY, Loo, YS, Playdon, MC, Lai, NM, Giovannucci, EL, Chaiyakunapruk, N
JAMA network open. 2021;(2):e2037341
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Abstract
IMPORTANCE Several meta-analyses have summarized evidence for the association between dietary factors and the incidence of colorectal cancer (CRC). However, to date, there has been little synthesis of the strength, precision, and quality of this evidence in aggregate. OBJECTIVE To grade the evidence from published meta-analyses of prospective observational studies that assessed the association of dietary patterns, specific foods, food groups, beverages (including alcohol), macronutrients, and micronutrients with the incidence of CRC. DATA SOURCES MEDLINE, Embase, and the Cochrane Library were searched from database inception to September 2019. EVIDENCE REVIEW Only meta-analyses of prospective observational studies with a cohort study design were eligible. Evidence of association was graded according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant. RESULTS From 9954 publications, 222 full-text articles (2.2%) were evaluated for eligibility, and 45 meta-analyses (20.3%) that described 109 associations between dietary factors and CRC incidence were selected. Overall, 35 of the 109 associations (32.1%) were nominally statistically significant using random-effects meta-analysis models; 17 associations (15.6%) demonstrated large heterogeneity between studies (I2 > 50%), whereas small-study effects were found for 11 associations (10.1%). Excess significance bias was not detected for any association between diet and CRC. The primary analysis identified 5 (4.6%) convincing, 2 (1.8%) highly suggestive, 10 (9.2%) suggestive, and 18 (16.5%) weak associations between diet and CRC, while there was no evidence for 74 (67.9%) associations. There was convincing evidence of an association of intake of red meat (high vs low) and alcohol (≥4 drinks/d vs 0 or occasional drinks) with the incidence of CRC and an inverse association of higher vs lower intakes of dietary fiber, calcium, and yogurt with CRC risk. The evidence for convincing associations remained robust following sensitivity analyses. CONCLUSIONS AND RELEVANCE This umbrella review found convincing evidence of an association between lower CRC risk and higher intakes of dietary fiber, dietary calcium, and yogurt and lower intakes of alcohol and red meat. More research is needed on specific foods for which evidence remains suggestive, including other dairy products, whole grains, processed meat, and specific dietary patterns.
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Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.
Tsilidis, KK, Papadimitriou, N, Dimou, N, Gill, D, Lewis, SJ, Martin, RM, Murphy, N, Markozannes, G, Zuber, V, Cross, AJ, et al
The American journal of clinical nutrition. 2021;(6):1490-1502
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Abstract
BACKGROUND The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. OBJECTIVES To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). METHODS Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. RESULTS Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk. CONCLUSIONS These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
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Meta-analysis of 16 studies of the association of alcohol with colorectal cancer.
McNabb, S, Harrison, TA, Albanes, D, Berndt, SI, Brenner, H, Caan, BJ, Campbell, PT, Cao, Y, Chang-Claude, J, Chan, A, et al
International journal of cancer. 2020;(3):861-873
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Abstract
Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.
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Different dietary fibre sources and risks of colorectal cancer and adenoma: a dose-response meta-analysis of prospective studies.
Oh, H, Kim, H, Lee, DH, Lee, A, Giovannucci, EL, Kang, SS, Keum, N
The British journal of nutrition. 2019;(6):605-615
Abstract
Dietary fibre is believed to provide important health benefits including protection from colorectal cancer. However, the evidence on the relationships with different dietary fibre sources is mixed and little is known about which fibre source provides the greatest benefits. We conducted a dose-response meta-analysis of prospective cohorts to summarise the relationships of different fibre sources with colorectal cancer and adenoma risks. Analyses were restricted to publications that reported all fibre sources (cereals, vegetables, fruits, legumes) to increase comparability between results. PubMed and Embase were searched through August 2018 to identify relevant studies. The summary relative risks (RR) and 95 % CI were estimated using a random-effects model. This analysis included a total of ten prospective studies. The summary RR of colorectal cancer associated with each 10 g/d increase in fibre intake were 0·91 (95 % CI 0·82, 1·00; I2 = 0 %) for cereal fibre, 0·95 (95 % CI 0·87, 1·03, I2 = 0 %) for vegetable fibre, 0·91 (95 % CI 0·78, 1·06, I2 = 43 %) for fruit fibre and 0·84 (95 % CI 0·63, 1·13, I2 = 45 %) for legume fibre. For cereal fibre, the association with colorectal cancer risk remained statistically significant after adjustment for folate intake (RR 0·89, 95 % CI 0·80, 0·99, I2 = 2 %). For vegetable and fruit fibres, the dose-response curve suggested evidence of non-linearity. All fibre sources were inversely associated with incident adenoma (per 10 g/d increase: RR 0·81 (95 % CI 0·54, 1·21) cereals, 0·84 (95 % CI 0·71, 0·98) for vegetables, 0·78 (95 % CI 0·65, 0·93) for fruits) but not associated with recurrent adenoma. Our data suggest that, although all fibre sources may provide some benefits, the evidence for colorectal cancer prevention is strongest for fibre from cereals/grains.