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Dietary intake of vitamin C and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.
Sassano, M, Seyyedsalehi, MS, Collatuzzo, G, Pelucchi, C, Bonzi, R, Ferraroni, M, Palli, D, Yu, GP, Zhang, ZF, López-Carrillo, L, et al
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2024;(3):461-472
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Abstract
BACKGROUND Previous studies suggest that dietary vitamin C is inversely associated with gastric cancer (GC), but most of them did not consider intake of fruit and vegetables. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project, a consortium of epidemiological studies on GC. METHODS Fourteen case-control studies were included in the analysis (5362 cases, 11,497 controls). We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the association between dietary intake of vitamin C and GC, adjusted for relevant confounders and for intake of fruit and vegetables. The dose-response relationship was evaluated using mixed-effects logistic models with second-order fractional polynomials. RESULTS Individuals in the highest quartile of dietary vitamin C intake had reduced odds of GC compared with those in the lowest quartile (OR: 0.64; 95% CI: 0.58, 0.72). Additional adjustment for fruit and vegetables intake led to an OR of 0.85 (95% CI: 0.73, 0.98). A significant inverse association was observed for noncardia GC, as well as for both intestinal and diffuse types of the disease. The results of the dose-response analysis showed decreasing ORs of GC up to 150-200 mg/day of vitamin C (OR: 0.54; 95% CI: 0.41, 0.71), whereas ORs for higher intakes were close to 1.0. CONCLUSIONS The findings of our pooled study suggest that vitamin C is inversely associated with GC, with a potentially beneficial effect also for intakes above the currently recommended daily intake (90 mg for men and 75 mg for women).
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Increase from low to moderate, but not high, caffeinated coffee consumption is associated with favorable changes in body fat.
Henn, M, Babio, N, Romaguera, D, Vázquez-Ruiz, Z, Konieczna, J, Vioque, J, Torres-Collado, L, Razquin, C, Buil-Cosiales, P, Fitó, M, et al
Clinical nutrition (Edinburgh, Scotland). 2023;(4):477-485
Abstract
BACKGROUND & AIMS Higher consumption of coffee and caffeine has been linked to less weight gain and lower body mass index in prospective cohort studies. The aim of the study was to longitudinally assess the association of changes in coffee and caffeine intake with changes in fat tissue, in particular, visceral adipose tissue (VAT) using dual x-ray absorptiometry (DXA). METHODS In the setting of a large, randomized trial of Mediterranean diet and physical activity intervention, we evaluated 1483 participants with metabolic syndrome (MetS). Repeated measurements of coffee consumption from validated food frequency questionnaires (FFQ) and DXA measurements of adipose tissue were collected at baseline, 6 months, 12 months and 3 years of follow-up. DXA-derived measurements of total and regional adipose tissue expressed as % of total body weight were transformed into sex-specific z-scores. Linear multilevel mixed-effect models were used to investigate the relationship between changes in coffee consumption and corresponding concurrent changes in fat tissue during a 3-year follow-up. RESULTS After adjustment for intervention group, and other potential confounders, an increase in caffeinated coffee consumption from no or infrequent consumption (≤3 cups/month) to moderate consumption (1-7 cups/week) was associated with reductions in total body fat (Δ z-score: -0.06; 95% CI: -0.11 to -0.02), trunk fat (Δ z-score: -0.07; 95% CI: -0.12 to -0.02), and VAT (Δ z-score: -0.07; 95% CI: -0.13 to -0.01). Neither changes from no or infrequent consumption to high levels of caffeinated coffee consumption (>1 cup/day) nor any changes in decaffeinated coffee consumption showed significant associations with changes in DXA measures. CONCLUSIONS Moderate changes in the consumption of caffeinated coffee, but not changes to high consumption, were associated with reductions in total body fat, trunk fat and VAT in a Mediterranean cohort with MetS. Decaffeinated coffee was not linked to adiposity indicators. Moderate consumption of caffeinated coffee may be part of a weight management strategy. TRIAL REGISTRATION The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.
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Contribution of cardio-vascular risk factors to depressive status in the PREDIMED-PLUS Trial. A cross-sectional and a 2-year longitudinal study.
Martín-Peláez, S, Serra-Majem, L, Cano-Ibáñez, N, Martínez-González, MÁ, Salas-Salvadó, J, Corella, D, Lassale, C, Martínez, JA, Alonso-Gómez, ÁM, Wärnberg, J, et al
PloS one. 2022;(4):e0265079
Abstract
BACKGROUND Cardio-vascular disease and depression are thought to be closely related, due to shared risk factors. The aim of the study was to determine the association between cardio-vascular risk (CVR) factors and depressive status in a population (55-75 years) with metabolic syndrome (MetS) from the PREDIMED-Plus trial. METHODS AND FINDINGS Participants were classified into three groups of CVR according to the Framingham-based REGICOR function: (1) low (LR), (2) medium (MR) or (3) high/very high (HR). The Beck Depression Inventory-II (BDI-II) was used to assess depressive symptoms at baseline and after 2 years. The association between CVR and depressive status at baseline (n = 6545), and their changes after 2 years (n = 4566) were evaluated through multivariable regression models (logistic and linear models). HR women showed higher odds of depressive status than LR [OR (95% CI) = 1.78 (1.26, 2.50)]. MR and HR participants with total cholesterol <160 mg/mL showed higher odds of depression than LR [OR (95% CI) = 1.77 (1.13, 2.77) and 2.83 (1.25, 6.42) respectively)] but those with total cholesterol ≥280 mg/mL showed lower odds of depression than LR [OR (95% CI) = 0.26 (0.07, 0.98) and 0.23 (0.05, 0.95), respectively]. All participants decreased their BDI-II score after 2 years, being the decrease smaller in MR and HR diabetic compared to LR [adjusted mean±SE = -0.52±0.20, -0.41±0.27 and -1.25±0.31 respectively). MR and HR participants with total cholesterol between 240-279 mg/mL showed greater decreases in the BDI-II score compared to LR (adjusted mean±SE = -0.83±0.37, -0.77±0.64 and 0.97±0.52 respectively). CONCLUSIONS Improving cardiovascular health could prevent the onset of depression in the elderly. Diabetes and total cholesterol in individuals at high CVR, may play a specific role in the precise response. International Standard Randomized Controlled Trial (ISRCTN89898870).
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Longitudinal association of dietary carbohydrate quality with visceral fat deposition and other adiposity indicators.
Zamanillo-Campos, R, Chaplin, A, Romaguera, D, Abete, I, Salas-Salvadó, J, Martín, V, Estruch, R, Vidal, J, Ruiz-Canela, M, Babio, N, et al
Clinical nutrition (Edinburgh, Scotland). 2022;41(10):2264-2274
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Plain language summary
Abdominal obesity, measured by waist circumference, a proxy of visceral fat, is increasing at an even greater rate than overall obesity alone. Diet plays a key role in body fat accumulation; however, recent evidence also indicates that, beyond quantity, the quality of certain nutrients may have an independent effect. The aim of this study was to determine the dynamic association between changes in overall dietary carbohydrate quality and changes in objectively measured visceral and overall adiposity distribution This study is a prospective cohort study based on data collected during the first year of the PREDIMED-Plus (PREvencion con DIeta MEDiterranea Plus) randomised controlled trial. In the PREDIMED-Plus trial, a total of 6874 people were randomly allocated in a 1:1 ratio to either the intervention or control group. Results show that a carbohydrate quality index increase was associated with a decrease in regional and overall adiposity. The observed associations were mostly driven by fibre and the wholegrains/total grains ratio. Authors conclude that the promotion of fibre-rich foods, including fruits, vegetables, legumes and nuts, and the substitution of refined grains by wholegrains, may be important dietary recommendations to adopt in clinical practice to promote a healthier body composition.
Expert Review
Conflicts of interest:
None
Take Home Message:
This prospective cohort of older adults with overweight/obesity and MetS, found that improvements in dietary carbohydrate quality over one year was associated with positive changes in visceral and overall fat deposition, largely due to dietary fibre and the wholegrain/total grain ratio.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
Obesity prevalence is increasing worldwide and is associated with a range of metabolic and cardiovascular diseases. Excess visceral fat appears with increasing age but also with unhealthy dietary patterns and lifestyle behaviours, and it contributes to chronic diseases, particularly type 2 diabetes (T2D), insulin resistance, metabolic syndrome (MetS), and cardiovascular diseases (CVD).
Aim
This study determined the association between changes in overall dietary carbohydrate quality and changes in objectively-measured visceral and overall adiposity distribution. Three repeated measurements of diet and adiposity were conducted throughout a 1-year follow-up, using a dual-energy X-ray absorptiometry (DXA) scans for body composition assessment.
The study compared an intensive weight-loss (intervention group) using an energy-reduced Mediterranean Diet (MedDiet), with physical activity (PA), and behavioural support on the prevention of CVD events, compared to usual care and dietary counselling only.
This prospective cohort study analysed a subgroup of 1476 participants (men aged 55-75 years and women aged 60-75 years) enrolled in the PREDIMED-Plus randomized controlled trial. Participants were overweight or obese (BMI>27 kg/m2 and <40 kg/m2) with no previous cardiovascular events and at least three characteristics of metabolic syndrome (MetS): hypertension, hyper-triglyceridemia, lower high-density lipoprotein (HDL) cholesterol, hyperglycemia, or central obesity.
Dietary intake was measured at baseline, 6- and 12-months using a Spanish version of the validated 143-item semi-quantitative food-frequency questionnaire, via face-to-face interviews by trained dietitian-nutritionists. Carbohydrate quality index (CQI) was calculated using four criteria: total dietary fibre, glycemic index, wholegrain/total grain carbohydrate ratio, and solid/total carbohydrate ratio.
Results
Improvements in body composition and lifestyle factors were observed compared to baseline data (both study arms combined) (p < 0.05 for all). A higher Carbohydrate Quality Index CQI (p = 0.024) was observed at both the 6 and 12 month follow-up.
A 3-point increment in CQI over 12-month follow-up was associated with a decrease in visceral fat (β 0.067 z-score, 95% CI -0.088 to -0.046, p<0.001), android-to-gynoid fat ratio* (β -0.038, 95% CI -0.059 to -0.017, p<0.001) (*calculated by dividing the fat mass (g) from the specific regions), and total fat (β -0.064, 95% CI -0.080 to -0.047, p<0.001).
Fibre intake and the ratio of whole grain/total grain showed the strongest inverse associations with all adiposity indicators. Statistically significant differences were observed over time in all CQI components. The most relevant changes were the increase in consumption of carbohydrates from whole-grains and a decrease in refined grains, and an increase in dietary fibre intake. After evaluating each CQI component separately, the study found that fibre intake and the ratio of whole grain/total grain presented the strongest and statistically significant negative associations with all adiposity indicators (all p-values <0.01).
Limitations
Due to the observational nature of the study, causality cannot be inferred. The study population is based on older people with overweight/obesity and MetS from a Mediterranean area, which can limit the generalisability of findings to the general population.
The use of self-reported dietary data is subject to measurement error, where self-reports may be affected by a tendency to respond in a manner to avoid criticism or judgement and to seek social approval.
Clinical practice applications:
Evidence has shown that the quality of dietary carbohydrates, rather than the quantity, may have a greater impact on health and overall mortality.
While visceral fat constitutes only a small proportion of total fat, the available evidence indicates that it plays an important role in certain chronic diseases, such as T2D, MetS, CVD and cancer.
Findings from this study suggest a better CQI via the manipulation of carbohydrate quality may be associated with a decrease in visceral fat, which are independent of changes in total body fat.
Considerations for future research:
Future strategies to decrease visceral fat are warranted.
Robust reference ranges are needed for the interpretation of visceral fat in clinical practice and research settings.
Abstract
BACKGROUND & AIMS The quality of dietary carbohydrates rather than total carbohydrate intake may determine the accumulation of visceral fat; however, to date, few studies have examined the impact of diet on adiposity using specific imaging techniques. Thus, the aim of this prospective study was to investigate the association between concurrent changes in carbohydrate quality index (CQI) and objectively-quantified adiposity distribution over a year. METHODS We analyzed a cohort of 1476 participants aged 55-75 years with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus randomized controlled trial. Dietary intake information was obtained at baseline, 6- and 12-months from a validated 143-item semi-quantitative food-frequency questionnaire, and CQI (range: 4 to 20) was calculated based on four dietary criteria: total dietary fibre, glycemic index, wholegrain/total grain carbohydrate ratio, and solid/total carbohydrate ratio. Overall and regional adiposity (total body fat, visceral fat and android-to-gynoid fat ratio) was quantified using dual-energy X-ray absorptiometry at all three time points. Multiple adjusted linear mixed-effects models were used to assess associations between concurrent changes in repeatedly measured CQI and adiposity over time. RESULTS After controlling for potential confounding factors, a 3-point increment in CQI over 12-month follow-up was associated with a decrease in visceral fat (β -0.067 z-score, 95% CI -0.088; -0.046, p < 0.001), android-to-gynoid fat ratio (-0.038, -0.059; -0.017, p < 0.001), and total fat (-0.064, -0.080; -0.047, p < 0.001). Fibre intake and the ratio of wholegrain/total grain showed the strongest inverse associations with all adiposity indicators. CONCLUSIONS In this prospective cohort of older adults with overweight/obesity and MetS, we found that improvements in dietary carbohydrate quality over a year were associated with concurrent favorable changes in visceral and overall fat deposition. These associations were mostly driven by dietary fibre and the wholegrain/total grain ratio. TRIAL REGISTRATION The trial was registered at the International Standard Randomized. CONTROLLED TRIAL (ISRCTN http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.
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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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Validity of the energy-restricted Mediterranean Diet Adherence Screener.
Schröder, H, Zomeño, MD, Martínez-González, MA, Salas-Salvadó, J, Corella, D, Vioque, J, Romaguera, D, Martínez, JA, Tinahones, FJ, Miranda, JL, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(8):4971-4979
Abstract
BACKGROUND Short dietary assessment tools can be useful to estimate food intake and diet quality in large-scale epidemiological studies with time constraints. OBJECTIVE To determine the concurrent validity of the 17-item energy-restricted Mediterranean Adherence Screener (er-MEDAS) used in the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial and to analyse its capacity to detect 1-year changes in diet and cardiometabolic risk factors. METHODS Validation study nested in the PREDIMED-Plus (n = 6760, 55-75 years). Dietary data were collected by the 17-item er-MEDAS and a 143-item validated semiquantitative food frequency questionnaire (FFQ) at baseline and after 1-year intervention. Cardiometabolic risk markers were measured at both time points. A Mediterranean diet (MedDiet) score was derived from both instruments. Concurrent validity was evaluated by Pearson and intra-class correlation coefficients (ICC) and Bland and Altman limits of agreement. Construct validity was evaluated by assessing 1-year changes in FFQ-reported dietary intake and cardiometabolic profile changes in relation to changes in er-MEDAS. RESULTS A moderate to good correlation between the MedDiet score calculated by both measurement instruments was found: r = 0.61 and ICC = 0.60 (both p < 0.001). Agreement of each of the er-MEDAS items ranged from 55.4% to 85.0% with a moderate mean concordance (kappa = 0.41). Between baseline and 1-year follow-up, energy intake measured by the FFQ decreased by 242 kcal, while Mediterranean food consumption increased in participants with the highest increase in the er-MEDAS MedDiet score. An increase in the er-MEDAS MedDiet score ratings was associated with a decrease in BMI, waist circumference, triglycerides, fasting glucose, diastolic blood pressure, and triglycerides/HDL-cholesterol ratio (p < 0.001 for all), and with an increase in HDL-cholesterol (p = 0.006). CONCLUSION The er-MEDAS shows a modest to good concurrent validity compared with FFQ data. It shows acceptable construct validity, as a greater er-MEDAS score was associated with more favourable dietary and cardiometabolic profiles over time. TRIAL REGISTRY ISRCTN89898870; registration date, 24 July 2014. https://www.isrctn.com/ISRCTN89898870.
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The Effect of Lifestyle Intervention on Health-Related Quality of Life in Adults with Metabolic Syndrome: A Meta-Analysis.
Marcos-Delgado, A, Hernández-Segura, N, Fernández-Villa, T, Molina, AJ, Martín, V
International journal of environmental research and public health. 2021;(3)
Abstract
The aim of this meta-analysis was to assess the effects of a lifestyle intervention through health education on nutrition, physical activity, and healthy habits on physical and mental health-related quality of life (HRQoL), in adults with metabolic syndrome (MetS). The databases used were PubMed, WOS, and Scopus. The inclusion criteria were: observational, longitudinal and randomized clinical trial (RCT) study designs, adults (both sexes), with at least two criteria of MetS, lifestyle intervention and comparison with a control group, and a measurement of HRQoL with a validated questionnaire. We analyzed the Hedges' g and SF-36 score. I2 statistics were calculated and possible publication and small study biases were assessed using Egger's test and funnel plots. Seven RCTs were selected for meta-analysis, based on 637 study participants. Significant improvements were found in the physical dimensions of the HRQoL scores for subjects in the active intervention compared to the group that received general lifestyle information (Hedges' g 0.61, 95% confidence interval (CI) = 0.31-0.91). Mental health-related quality of life was also significantly improved in the intervention group compared with the control group (Hedges' g 0.84, 95% CI = 0.64-1.03). In conclusion, our results suggest that, according to the RCTs selected for this meta-analysis, a lifestyle intervention significantly improves HRQoL in all its domains.
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Contribution of ultra-processed foods in visceral fat deposition and other adiposity indicators: Prospective analysis nested in the PREDIMED-Plus trial.
Konieczna, J, Morey, M, Abete, I, Bes-Rastrollo, M, Ruiz-Canela, M, Vioque, J, Gonzalez-Palacios, S, Daimiel, L, Salas-Salvadó, J, Fiol, M, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(6):4290-4300
Abstract
BACKGROUND & AIMS Ultra-processed food and drink products (UPF) consumption has been associated with obesity and its-related comorbidities. Excess of visceral fat, which appears with increasing age, has been considered as the culprit contributing to adiposity-associated adverse health outcomes. However, none of previous studies elucidated the link between UPF and directly quantified adiposity and its distribution. We aimed to prospectively investigate the association between concurrent changes in UPF consumption and objectively assessed adiposity distribution. METHODS A subsample of 1485 PREDIMED-Plus participants (Spanish men and women aged 55-75 years with overweight/obesity and metabolic syndrome) underwent body composition measurements. Consumption of UPF at baseline, 6 and 12 months was evaluated using a validated 143-item semi-quantitative Food Frequency Questionnaire. Food items (g/day) were categorized according to their degree of processing using NOVA system. Regional adiposity (visceral fat (in g) and android-to-gynoid fat ratio) and total fat mass (in g) at three time points were measured with dual-energy X-ray absorptiometry (DXA) and were normalized using sex-specific z-scores. The association of changes in UPF consumption, expressed as the percentage of total daily intake (daily g of UPF/total daily g of food and beverage intake∗100), with adiposity changes was evaluated using linear mixed-effects models. RESULTS On average, the consumption of UPF accounted for 8.11% (SD 7.41%) of total daily intake (in grams) at baseline. In multivariable-adjusted model, 10% daily increment in consumption of UPF was associated with significantly (all p-values <0.05) greater accumulation of visceral fat (β 0.09 z-scores, 95% CI 0.05; 0.13), android-to-gynoid fat ratio (0.05, 0.00; 0.09) and total fat (0.09, 0.06; 0.13). CONCLUSION A higher consumption of UPF was associated with greater age-related visceral and overall adiposity accumulation. Further studies are warranted to confirm these results in other populations and settings. TRIAL REGISTRATION The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.
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Response to Li and Hopper.
Thomas, M, Sakoda, LC, Hoffmeister, M, Rosenthal, EA, Lee, JK, van Duijnhoven, FJB, Platz, EA, Wu, AH, Dampier, CH, de la Chapelle, A, et al
American journal of human genetics. 2021;(3):527-529
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Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.
Archambault, AN, Su, YR, Jeon, J, Thomas, M, Lin, Y, Conti, DV, Win, AK, Sakoda, LC, Lansdorp-Vogelaar, I, Peterse, EFP, et al
Gastroenterology. 2020;(5):1274-1286.e12
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Abstract
BACKGROUND & AIMS Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.