Publications
635 results found
Watling CZ, Kelly RK, Murphy N, et al., 2023, Figure 4 from Prospective Analysis Reveals Associations between Carbohydrate Intakes, Genetic Predictors of Short-Chain Fatty Acid Synthesis, and Colorectal Cancer Risk
<jats:p><p>Multivariable-adjusted hazard ratios (95% CI) for intake of fiber from breads and cereals from the touchscreen questionnaire and colorectal cancer risk by genetically predicted host short-chain fatty acid production for butyrate (<b>A</b>) and propionate (<i>n</i> = 343,621; <b>B</b>). Models stratified for sex and age at recruitment, and further adjusted for region, first 10 principal components, height, physical activity, Townsend deprivation index, education, employment, smoking, alcohol consumption measured at recruitment, diabetes status, nonsteroidal anti-inflammatory drug use, body mass index, processed and red meat intake, and female-specific covariates: menopausal hormone therapy use and menopausal status. Analyses are restricted to white British participants. χ<sup>2</sup> and <i>P</i> value represents improvement of fit obtained from likelihood ratio tests for including an interaction term between butyrate or propionate polygenic score and fiber from breads and cereals (modeled as a 5 gram/day increment) into the model. g/day, grams per day; <i>N</i>, number of participants; Q, quintile; ref, reference group.</p></jats:p>
Watling CZ, Kelly RK, Murphy N, et al., 2023, Data from Prospective Analysis Reveals Associations between Carbohydrate Intakes, Genetic Predictors of Short-Chain Fatty Acid Synthesis, and Colorectal Cancer Risk
<jats:p><div>Abstract<p>Whole grain and fiber intakes may decrease the risk of colorectal cancer. The interplay between host genetic factors, colonization of specific bacteria, production of short-chain fatty acids (SCFA), and intake of whole grains and fiber could alter the protective role of carbohydrates against colorectal cancer. Here, we assessed intakes of types and sources of carbohydrates in 114,217 UK Biobank participants with detailed dietary data (2–5 24-hour dietary assessments), and a host polygenic score (PGS) was applied to categorize participants as high or low for intraluminal microbial SCFA production, namely, butyrate and propionate. Multivariable Cox proportional hazards models were used to determine the associations of carbohydrates and SCFA with colorectal cancer incidence. During a median follow-up of 9.4 years, 1,193 participants were diagnosed with colorectal cancer. Risk was inversely associated with intakes of non-free sugar and whole grain fiber. Evidence of heterogeneity was observed by the butyrate PGS; consuming higher amounts of whole grain starch was only associated with a lower risk of colorectal cancer in those with predicted high SCFA production. Similarly, in additional analyses utilizing the larger UK Biobank cohort (<i>N</i> = 343,621) with less detailed dietary assessment, only individuals with a high genetically predicted butyrate production had a lower risk of colorectal cancer per 5 g/day intake of bread and cereal fiber. This study suggests that colorectal cancer risk varies by intake of carbohydrate types and sources, and the impact of whole grain intake may be modified by SCFA production.</p>Significance:<p>Prospective population-level analyses provide evidence supporting the importance of butyrate production in reduction of colorectal cancer risk by whole grain consumption.</p></div></jats:p>
Watling CZ, Kelly RK, Murphy N, et al., 2023, Data from Prospective Analysis Reveals Associations between Carbohydrate Intakes, Genetic Predictors of Short-Chain Fatty Acid Synthesis, and Colorectal Cancer Risk
<jats:p><div>Abstract<p>Whole grain and fiber intakes may decrease the risk of colorectal cancer. The interplay between host genetic factors, colonization of specific bacteria, production of short-chain fatty acids (SCFA), and intake of whole grains and fiber could alter the protective role of carbohydrates against colorectal cancer. Here, we assessed intakes of types and sources of carbohydrates in 114,217 UK Biobank participants with detailed dietary data (2–5 24-hour dietary assessments), and a host polygenic score (PGS) was applied to categorize participants as high or low for intraluminal microbial SCFA production, namely, butyrate and propionate. Multivariable Cox proportional hazards models were used to determine the associations of carbohydrates and SCFA with colorectal cancer incidence. During a median follow-up of 9.4 years, 1,193 participants were diagnosed with colorectal cancer. Risk was inversely associated with intakes of non-free sugar and whole grain fiber. Evidence of heterogeneity was observed by the butyrate PGS; consuming higher amounts of whole grain starch was only associated with a lower risk of colorectal cancer in those with predicted high SCFA production. Similarly, in additional analyses utilizing the larger UK Biobank cohort (<i>N</i> = 343,621) with less detailed dietary assessment, only individuals with a high genetically predicted butyrate production had a lower risk of colorectal cancer per 5 g/day intake of bread and cereal fiber. This study suggests that colorectal cancer risk varies by intake of carbohydrate types and sources, and the impact of whole grain intake may be modified by SCFA production.</p>Significance:<p>Prospective population-level analyses provide evidence supporting the importance of butyrate production in reduction of colorectal cancer risk by whole grain consumption.</p></div></jats:p>
Fournier A, Cairat M, Severi G, et al., 2023, Use of menopausal hormone therapy and ovarian cancer risk in a French cohort study, JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, Vol: 115, Pages: 671-679, ISSN: 0027-8874
Watling CZ, Kelly RK, Murphy N, et al., 2023, Supplementary Material from Prospective Analysis Reveals Associations between Carbohydrate Intakes, Genetic Predictors of Short-Chain Fatty Acid Synthesis, and Colorectal Cancer Risk
<jats:p><p>Supplementary Material</p></jats:p>
Watling CZ, Kelly RK, Murphy N, et al., 2023, Data from Prospective Analysis Reveals Associations between Carbohydrate Intakes, Genetic Predictors of Short-Chain Fatty Acid Synthesis, and Colorectal Cancer Risk
<jats:p><div>Abstract<p>Whole grain and fiber intakes may decrease the risk of colorectal cancer. The interplay between host genetic factors, colonization of specific bacteria, production of short-chain fatty acids (SCFA), and intake of whole grains and fiber could alter the protective role of carbohydrates against colorectal cancer. Here, we assessed intakes of types and sources of carbohydrates in 114,217 UK Biobank participants with detailed dietary data (2–5 24-hour dietary assessments), and a host polygenic score (PGS) was applied to categorize participants as high or low for intraluminal microbial SCFA production, namely, butyrate and propionate. Multivariable Cox proportional hazards models were used to determine the associations of carbohydrates and SCFA with colorectal cancer incidence. During a median follow-up of 9.4 years, 1,193 participants were diagnosed with colorectal cancer. Risk was inversely associated with intakes of non-free sugar and whole grain fiber. Evidence of heterogeneity was observed by the butyrate PGS; consuming higher amounts of whole grain starch was only associated with a lower risk of colorectal cancer in those with predicted high SCFA production. Similarly, in additional analyses utilizing the larger UK Biobank cohort (<i>N</i> = 343,621) with less detailed dietary assessment, only individuals with a high genetically predicted butyrate production had a lower risk of colorectal cancer per 5 g/day intake of bread and cereal fiber. This study suggests that colorectal cancer risk varies by intake of carbohydrate types and sources, and the impact of whole grain intake may be modified by SCFA production.</p>Significance:<p>Prospective population-level analyses provide evidence supporting the importance of butyrate production in reduction of colorectal cancer risk by whole grain consumption.</p></div></jats:p>
Watling CZ, Kelly RK, Murphy N, et al., 2023, Supplementary Material from Prospective Analysis Reveals Associations between Carbohydrate Intakes, Genetic Predictors of Short-Chain Fatty Acid Synthesis, and Colorectal Cancer Risk
<jats:p><p>Supplementary Material</p></jats:p>
Mao Z, Baker JR, Takeuchi M, et al., 2023, Prediagnostic serum glyceraldehyde-derived advanced glycation end products and mortality among colorectal cancer patients, INTERNATIONAL JOURNAL OF CANCER, Vol: 152, Pages: 2257-2268, ISSN: 0020-7136
Mahamat-Saleh Y, Rinaldi S, Kaaks R, et al., 2023, Metabolically defined body size and body shape phenotypes and risk of postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition, Cancer Medicine, Vol: 12, Pages: 12668-12682, ISSN: 2045-7634
BACKGROUND: Excess body fatness and hyperinsulinemia are both associated with an increased risk of postmenopausal breast cancer. However, whether women with high body fatness but normal insulin levels or those with normal body fatness and high levels of insulin are at elevated risk of breast cancer is not known. We investigated the associations of metabolically defined body size and shape phenotypes with the risk of postmenopausal breast cancer in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. METHODS: Concentrations of C-peptide-a marker for insulin secretion-were measured at inclusion prior to cancer diagnosis in serum from 610 incident postmenopausal breast cancer cases and 1130 matched controls. C-peptide concentrations among the control participants were used to define metabolically healthy (MH; in first tertile) and metabolically unhealthy (MU; >1st tertile) status. We created four metabolic health/body size phenotype categories by combining the metabolic health definitions with normal weight (NW; BMI < 25 kg/m2 , or WC < 80 cm, or WHR < 0.8) and overweight or obese (OW/OB; BMI ≥ 25 kg/m2 , or WC ≥ 80 cm, or WHR ≥ 0.8) status for each of the three anthropometric measures separately: (1) MHNW, (2) MHOW/OB, (3) MUNW, and (4) MUOW/OB. Conditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Women classified as MUOW/OB were at higher risk of postmenopausal breast cancer compared to MHNW women considering BMI (OR = 1.58, 95% CI = 1.14-2.19) and WC (OR = 1.51, 95% CI = 1.09-2.08) cut points and there was also a suggestive increased risk for the WHR (OR = 1.29, 95% CI = 0.94-1.77) definition. Conversely, women with the MHOW/OB and MUNW were not
Haycock PC, Borges MC, Burrows K, et al., 2023, The association between genetically elevated polyunsaturated fatty acids and risk of cancer, EBIOMEDICINE, Vol: 91, ISSN: 2352-3964
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Aglago EK, Cross AJ, Riboli E, et al., 2023, Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study, British Journal of Cancer, Vol: 128, Pages: 1529-1540, ISSN: 0007-0920
BackgroundIron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.MethodsWe examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.ResultsOf 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HRQ5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HRQ5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HRQ5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HRQ5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HRQ5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HRQ5vs.Q1:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99).ConclusionsOur findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.
Blanco-Lopez J, Iguacel I, Pisanu S, et al., 2023, Role of Maternal Diet in the Risk of Childhood Acute Leukemia: A Systematic Review and Meta-Analysis., Int J Environ Res Public Health, Vol: 20
Many studies have investigated the etiology of acute leukemia, one of the most common types of cancer in children; however, there is a lack of clarity regarding preventable risk factors. This systematic review and meta-analysis aimed to summarize the current evidence regarding the role of maternal dietary factors in the development of childhood leukemia. All epidemiological studies published until July 2022 that evaluated maternal dietary risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science) without limits of publication year or language. A total of 38 studies (1 prospective cohort study, 34 case-control studies and 3 studies with pooled analysis) were included. The published risk estimates were combined into a meta-analysis, using the Generic Inverse Variance method. The maternal consumption of fruits (two or more daily servings vs. less) was inversely associated with acute lymphoblastic leukemia (odds ratio = 0.71; 95% CI, 0.59-0.86), whereas maternal coffee intake (higher than two cups per day vs. no consumption) was associated with an increased risk of acute lymphoblastic leukemia (odds ratio = 1.45; 95% CI, 1.12-1.89). Despite these findings, more high-quality research from cohort studies and the identification of causal factors are needed to develop evidence-based and cost-effective prevention strategies applicable at the population level. Review Registration: PROSPERO registration no. CRD42019128937.
Campbell PT, Newton CC, Jacobs EJ, et al., 2023, Data from Prospective Associations of Hemoglobin A<sub>1c</sub> and c-peptide with Risk of Diabetes-related Cancers in the Cancer Prevention Study-II Nutrition Cohort
<jats:p><div><p>Self-reported type 2 diabetes mellitus (T2DM) is a risk factor for many cancers, suggesting its pathology relates to carcinogenesis. We conducted a case-cohort study to examine associations of hemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>) and c-peptide with cancers associated with self-reported T2DM. This study was drawn from a prospective cohort of 32,383 women and men who provided blood specimens at baseline: c-peptide and HbA<sub>1c</sub> were assessed in 3,000 randomly selected participants who were cancer-free-at-baseline and an additional 2,281 participants who were cancer-free-at-baseline and subsequently diagnosed with incident colorectal, liver, pancreatic, female breast, endometrial, ovarian, bladder, or kidney cancers. Weighted Cox regression models estimated HRs and 95% confidence intervals (CI), adjusted for covariates. c-peptide was associated with higher risk of liver cancer [per SD HR: 1.80; 95% CI: 1.32–2.46]. HbA<sub>1c</sub> was associated with higher risk of pancreatic cancer (per SD HR: 1.21; 95% CI: 1.05–1.40) and with some suggestion of higher risks for all-cancers-of-interest (per SD HR: 1.05; 95% CI: 0.99–1.11) and colorectal (per SD HR: 1.09; 95% CI: 0.98–1.20), ovarian (per SD HR: 1.18; 95% CI: 0.96–1.45) and bladder (per SD HR: 1.08; 95% CI: 0.96–1.21) cancers. Compared with no self-reported T2DM and HbA<sub>1c</sub> < 6.5% (reference group), self-reported T2DM and HbA<sub>1c</sub> < 6.5% (i.e., T2DM in good glycemic control) was not associated with risk of colorectal cancer, whereas it was associated with higher risks of all-cancers-of-interest combined (HR: 1.28; 95% CI: 1.01–1.62), especially for breast and endometrial cancers. Additional large, prospective studies ar
Campbell PT, Newton CC, Jacobs EJ, et al., 2023, Appendix 1 from Prospective Associations of Hemoglobin A<sub>1c</sub> and c-peptide with Risk of Diabetes-related Cancers in the Cancer Prevention Study-II Nutrition Cohort
<jats:p><p>lab methods and qc</p></jats:p>
Campbell PT, Newton CC, Jacobs EJ, et al., 2023, Data from Prospective Associations of Hemoglobin A<sub>1c</sub> and c-peptide with Risk of Diabetes-related Cancers in the Cancer Prevention Study-II Nutrition Cohort
<jats:p><div><p>Self-reported type 2 diabetes mellitus (T2DM) is a risk factor for many cancers, suggesting its pathology relates to carcinogenesis. We conducted a case-cohort study to examine associations of hemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>) and c-peptide with cancers associated with self-reported T2DM. This study was drawn from a prospective cohort of 32,383 women and men who provided blood specimens at baseline: c-peptide and HbA<sub>1c</sub> were assessed in 3,000 randomly selected participants who were cancer-free-at-baseline and an additional 2,281 participants who were cancer-free-at-baseline and subsequently diagnosed with incident colorectal, liver, pancreatic, female breast, endometrial, ovarian, bladder, or kidney cancers. Weighted Cox regression models estimated HRs and 95% confidence intervals (CI), adjusted for covariates. c-peptide was associated with higher risk of liver cancer [per SD HR: 1.80; 95% CI: 1.32–2.46]. HbA<sub>1c</sub> was associated with higher risk of pancreatic cancer (per SD HR: 1.21; 95% CI: 1.05–1.40) and with some suggestion of higher risks for all-cancers-of-interest (per SD HR: 1.05; 95% CI: 0.99–1.11) and colorectal (per SD HR: 1.09; 95% CI: 0.98–1.20), ovarian (per SD HR: 1.18; 95% CI: 0.96–1.45) and bladder (per SD HR: 1.08; 95% CI: 0.96–1.21) cancers. Compared with no self-reported T2DM and HbA<sub>1c</sub> < 6.5% (reference group), self-reported T2DM and HbA<sub>1c</sub> < 6.5% (i.e., T2DM in good glycemic control) was not associated with risk of colorectal cancer, whereas it was associated with higher risks of all-cancers-of-interest combined (HR: 1.28; 95% CI: 1.01–1.62), especially for breast and endometrial cancers. Additional large, prospective studies ar
Campbell PT, Newton CC, Jacobs EJ, et al., 2023, Appendix 1 from Prospective Associations of Hemoglobin A<sub>1c</sub> and c-peptide with Risk of Diabetes-related Cancers in the Cancer Prevention Study-II Nutrition Cohort
<jats:p><p>lab methods and qc</p></jats:p>
Campbell PT, Newton CC, Jacobs EJ, et al., 2023, Supplementary Tables S1-S4 from Prospective Associations of Hemoglobin A<sub>1c</sub> and c-peptide with Risk of Diabetes-related Cancers in the Cancer Prevention Study-II Nutrition Cohort
<jats:p><p>Supplemental Table 1 - Association of self-reported T2DM at blood draw with risk of all-cancers combined and separately in CPS-II LifeLink participants; Supplemental Table 2 - Association BMI per 5 kg/m2 at blood draw with risk of all-cancers combined and separately in CPS-II LifeLink participants. Excludes those with BMI <18.5 kg/m2; Supplementary Table 3 - Associations of c-peptide with risk of all cancers combined and for the specific cancers of interest by sex in the CPS-II LifeLink cohort; Supplementary Table 4 - Associations of HbA1c with risk of all cancers combined and for the specific cancers of interest by sex in the CPS-II LifeLink cohort.</p></jats:p>
Campbell PT, Newton CC, Jacobs EJ, et al., 2023, Supplementary Tables S1-S4 from Prospective Associations of Hemoglobin A<sub>1c</sub> and c-peptide with Risk of Diabetes-related Cancers in the Cancer Prevention Study-II Nutrition Cohort
<jats:p><p>Supplemental Table 1 - Association of self-reported T2DM at blood draw with risk of all-cancers combined and separately in CPS-II LifeLink participants; Supplemental Table 2 - Association BMI per 5 kg/m2 at blood draw with risk of all-cancers combined and separately in CPS-II LifeLink participants. Excludes those with BMI <18.5 kg/m2; Supplementary Table 3 - Associations of c-peptide with risk of all cancers combined and for the specific cancers of interest by sex in the CPS-II LifeLink cohort; Supplementary Table 4 - Associations of HbA1c with risk of all cancers combined and for the specific cancers of interest by sex in the CPS-II LifeLink cohort.</p></jats:p>
Ugai T, Haruki K, Harrison TA, et al., 2023, Molecular Characteristics of Early-Onset Colorectal Cancer According to Detailed Anatomical Locations: Comparison With Later-Onset Cases, AMERICAN JOURNAL OF GASTROENTEROLOGY, Vol: 118, Pages: 712-726, ISSN: 0002-9270
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Castro-Espin C, Bonet C, Crous-Bou M, et al., 2023, Dietary patterns related to biological mechanisms and survival after breast cancer diagnosis: results from a cohort study, British Journal of Cancer, Vol: 128, Pages: 1301-1310, ISSN: 0007-0920
BackgroundInflammatory, insulin and oestrogenic pathways have been linked to breast cancer (BC). We aimed to examine the relationship between pre-diagnostic dietary patterns related to these mechanisms and BC survival.MethodsThe diabetes risk reduction diet (DRRD), inflammatory score of diet (ISD) and oestrogen-related dietary pattern (ERDP) were calculated using dietary data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to assess associations between dietary patterns and overall mortality and competing risk models for associations with BC-specific mortality.ResultsWe included 13,270 BC cases with a mean follow-up after diagnosis of 8.6 years, representing 2340 total deaths, including 1475 BC deaths. Higher adherence to the DRRD score was associated with lower overall mortality (HR1–SD 0.92; 95%CI 0.87–0.96). Greater adherence to pro-inflammatory diets was borderline associated with 6% higher mortality HR1–SD 1.06; 95%CI 1.00–1.12. No significant association with the oestrogen-related dietary pattern was observed. None of the dietary patterns were associated with BC-specific mortality.ConclusionsGreater adherence to an anti-diabetic and anti-inflammatory diet prior to diagnosis is associated with lower overall mortality among BC survivors. Long-term adherence to these dietary patterns could be a means to improve the prognosis of BC survivors.
Bonet C, Crous-Bou M, Tsilidis KK, et al., 2023, The association between body fatness and mortality among breast cancer survivors: results from a prospective cohort study, EUROPEAN JOURNAL OF EPIDEMIOLOGY, ISSN: 0393-2990
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Papadimitriou N, Kazmi N, Dimou N, et al., 2023, Leisure time sedentary behaviour and risks of breast, colorectal, and prostate cancer: A Mendelian randomization analysis., medRxiv
UNLABELLED: Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal. We examined potential causal associations between self-reported leisure television watching and computer use and risks of breast, colorectal, and prostate cancer using a two-sample Mendelian randomization framework. Genetic variants were identified from a recent genome-wide association study (GWAS). Cancer data were obtained from cancer GWAS consortia. Additional sensitivity analyses were applied to examine the robustness of the results. A 1-standard deviation increment in hours of television watching increased risk of breast (OR: 1.15, 95% confidence interval [CI]: 1.05,1.26) and colorectal cancer (OR: 1.32, 95%CI: 1.16,1.49) with little evidence of an association for prostate cancer risk. In multivariable models adjusted for years of education, the effect estimates for television watching were attenuated (breast cancer, OR: 1.08, 95%CI: 0.92,1.27; colorectal cancer, OR: 1.08, 95%CI: 0.90,1.31). Post-hoc analyses showed that years of education might have a possible confounding and mediating role in the association between television watching with breast and colorectal cancer. Consistent results were observed by sex (colorectal cancer), anatomical subsites, and cancer subtypes. There was little evidence of associations between computer use and cancer risk. We found evidence of positive associations between hours of television watching and risks of breast and colorectal cancer. However, these findings should be interpreted cautiously given the complex role of education. Future studies using objective measures of exposure can provide new insights into the possible role of sedentary behaviour in cancer development. NOVELTY AND IMPACT: Evidence from observational studies that examined associations between sedentary behaviours and common cancers is mixed and causality is uncertain. In our Me
Su Y-R, Sakoda LC, Jeon J, et al., 2023, Validation of a Genetic-Enhanced Risk Prediction Model for Colorectal Cancer in a Large Community-Based Cohort., Cancer Epidemiol Biomarkers Prev, Vol: 32, Pages: 353-362
BACKGROUND: Polygenic risk scores (PRS) which summarize individuals' genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance. METHODS: The model was developed using 20,338 individuals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and calibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group). RESULTS: In European-ancestral individuals, the predicted 5-year risk calibrated well [E/O = 1.01; 95% confidence interval (CI), 0.91-1.13] and had high discriminatory accuracy (AUC = 0.73; 95% CI, 0.71-0.76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (P < 0.001) and 0.14 (P = 0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P < 0.001) in the screening-eligible age group. In the younger-age group it improved the sensitivity by 27% (P = 0.04) with similar specificity. CONCLUSIONS: The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort. IMPACT: The proposed model has potential utility in risk-stratified colorectal cancer prevention.
Kliemann N, Rauber F, Levy R, et al., 2023, Food processing and cancer risk in Europe: results from the prospective EPIC cohort study, The Lancet Planetary Health, Vol: 7, Pages: E219-E232, ISSN: 2542-5196
BackgroundFood processing has been hypothesised to play a role in cancer development; however, data from large-scale epidemiological studies are scarce. This study investigated the association between dietary intake according to amount of food processing and risk of cancer at 25 anatomical sites using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.MethodsThis study used data from the prospective EPIC cohort study, which recruited participants between March 18, 1991, and July 2, 2001, from 23 centres in ten European countries. Participant eligibility within each cohort was based on geographical or administrative boundaries. Participants were excluded if they had a cancer diagnosis before recruitment, had missing information for the NOVA food processing classification, or were within the top and bottom 1% for ratio of energy intake to energy requirement. Validated dietary questionnaires were used to obtain information on food and drink consumption. Participants with cancer were identified using cancer registries or during follow-up from a combination of sources, including cancer and pathology centres, health insurance records, and active follow-up of participants. We performed a substitution analysis to assess the effect of replacing 10% of processed foods and ultra-processed foods with 10% of minimally processed foods on cancer risk at 25 anatomical sites using Cox proportional hazard models.Findings521 324 participants were recruited into EPIC, and 450 111 were included in this analysis (318 686 [70·8%] participants were female individuals and 131 425 [29·2%] were male individuals). In a multivariate model adjusted for sex, smoking, education, physical activity, height, and diabetes, a substitution of 10% of processed foods with an equal amount of minimally processed foods was associated with reduced risk of overall cancer (hazard ratio 0·96, 95% CI 0·95–0·9
Fernandez-Rozadilla C, Timofeeva M, Chen Z, et al., 2023, Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries (vol 55, pg 89, 2023), NATURE GENETICS, Vol: 55, Pages: 519-520, ISSN: 1061-4036
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Carreras-Torres R, Kim AE, Lin Y, et al., 2023, Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 32, Pages: 315-328, ISSN: 1055-9965
Rothwell JA, Bešević J, Dimou N, et al., 2023, Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts, BMC Medicine, Vol: 21, Pages: 1-13, ISSN: 1741-7015
BACKGROUND: Amino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts. METHODS: Concentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases. RESULTS: Histidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69-0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87-0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75-0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89-1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded. CONCLUSIONS: Higher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted.
Yammine SG, Huybrechts I, Biessy C, et al., 2023, Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition., BMC Cancer, Vol: 23, Pages: 1-12, ISSN: 1471-2407
BACKGROUND: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. RESULTS: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5-Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. CONCLUSION: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer.
Sedlmeier AMM, Viallon V, Ferrari P, et al., 2023, Body shape phenotypes of multiple anthropometric traits and cancer risk: a multi-national cohort study, BRITISH JOURNAL OF CANCER, Vol: 128, Pages: 594-605, ISSN: 0007-0920
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Tsilidis KK, Cariolou M, Becerra-Tomas N, et al., 2023, Postdiagnosis body fatness, recreational physical activity, dietary factors and breast cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading, International Journal of Cancer, Vol: 152, Pages: 635-644, ISSN: 0020-7136
Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta-analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random-effects meta-analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all-cause mortality (RR per 5 kg/m2 in body mass index: 1.07, 95% CI: 1.05-1.10), breast cancer-specific mortality (RR: 1.10, 95% CI: 1.06-1.14) and second primary breast cancer (RR: 1.14, 95% CI: 1.04-1.26) was graded as strong (likelihood of causality: probable). The evidence for body fatness and breast cancer recurrence and other nonbreast cancer-related mortality was graded as limited (likelihood of causality: limited-suggestive). The evidence on recreational physical activity and lower risk of all-cause (RR per 10 metabolic equivalent of task-hour/week: 0.85, 95% CI: 0.78-0.92) and breast cancer-specific mortality (RR: 0.86, 95% CI: 0.77-0.96) was judged as limited-suggestive. Data on dietary factors was limited, and no conclusions could be reached except for healthy dietary patterns, isoflavone and dietary fibre intake and serum 25(OH)D concentrations that were graded with limited-suggestive evidence for lower risk of the examined outcomes. Our results encourage the development of lifestyle recommendations for breast cancer patients to avoid obesity and be physically active.
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