| 1. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 6. |
- Guha, N, et al.
(författare)
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Lung cancer risk in painters: results from the SYNERGY pooled case-control study consortium
- 2021
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Ingår i: Occupational and environmental medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 78:4, s. 269-278
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project.MethodsData were pooled from 16 participating case–control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens.ResultsEver having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0).ConclusionsOur results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.
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| 7. |
- Heath, A. K., et al.
(författare)
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Nutrient-wide association study of 92 foods and nutrients and breast cancer risk
- 2020
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study. Methods Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS). Results Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS. Conclusions Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.
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| 8. |
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| 10. |
- Kliemann, Nathalie, et al.
(författare)
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Predicted basal metabolic rate and cancer risk in the European Prospective Investigation into Cancer and Nutrition
- 2020
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 147:3, s. 648-661
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of predicted BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (hazard ratio per 1-standard deviation change in BMR [HR1-SD]: 2.46; 95% CI 1.20; 5.03) and distal colon cancer (HR1-SD: 1.33; 95% CI 1.001; 1.77) among men and with proximal colon (HR1-SD: 1.16; 95% CI 1.01; 1.35), pancreatic (HR1-SD: 1.37; 95% CI 1.13; 1.66), thyroid (HR1-SD: 1.65; 95% CI 1.33; 2.05), postmenopausal breast (HR1-SD: 1.17; 95% CI 1.11; 1.22) and endometrial (HR1-SD: 1.20; 95% CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness.
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| 11. |
- Tsilidis, Konstantinos K., et al.
(författare)
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Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent : a Mendelian randomization study
- 2021
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Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 113:6, s. 1490-1502
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Tidskriftsartikel (refereegranskat)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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| 12. |
- Hanley-Cook, Giles T, et al.
(författare)
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Food biodiversity and total and cause-specific mortality in 9 European countries : An analysis of a prospective cohort study
- 2021
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 18:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Food biodiversity, encompassing the variety of plants, animals, and other organisms consumed as food and drink, has intrinsic potential to underpin diverse, nutritious diets and improve Earth system resilience. Dietary species richness (DSR), which is recommended as a crosscutting measure of food biodiversity, has been positively associated with the micronutrient adequacy of diets in women and young children in low- and middle-income countries (LMICs). However, the relationships between DSR and major health outcomes have yet to be assessed in any population.METHODS AND FINDINGS: We examined the associations between DSR and subsequent total and cause-specific mortality among 451,390 adults enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (1992 to 2014, median follow-up: 17 years), free of cancer, diabetes, heart attack, or stroke at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires (DQs). DSR of an individual's yearly diet was calculated based on the absolute number of unique biological species in each (composite) food and drink. Associations were assessed by fitting multivariable-adjusted Cox proportional hazards regression models. In the EPIC cohort, 2 crops (common wheat and potato) and 2 animal species (cow and pig) accounted for approximately 45% of self-reported total dietary energy intake [median (P10-P90): 68 (40 to 83) species consumed per year]. Overall, higher DSR was inversely associated with all-cause mortality rate. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing total mortality in the second, third, fourth, and fifth (highest) quintiles (Qs) of DSR to the first (lowest) Q indicate significant inverse associations, after stratification by sex, age, and study center and adjustment for smoking status, educational level, marital status, physical activity, alcohol intake, and total energy intake, Mediterranean diet score, red and processed meat intake, and fiber intake [HR (95% CI): 0.91 (0.88 to 0.94), 0.80 (0.76 to 0.83), 0.69 (0.66 to 0.72), and 0.63 (0.59 to 0.66), respectively; PWald < 0.001 for trend]. Absolute death rates among participants in the highest and lowest fifth of DSR were 65.4 and 69.3 cases/10,000 person-years, respectively. Significant inverse associations were also observed between DSR and deaths due to cancer, heart disease, digestive disease, and respiratory disease. An important study limitation is that our findings were based on an observational cohort using self-reported dietary data obtained through single baseline food frequency questionnaires (FFQs); thus, exposure misclassification and residual confounding cannot be ruled out.CONCLUSIONS: In this large Pan-European cohort, higher DSR was inversely associated with total and cause-specific mortality, independent of sociodemographic, lifestyle, and other known dietary risk factors. Our findings support the potential of food (species) biodiversity as a guiding principle of sustainable dietary recommendations and food-based dietary guidelines.
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| 13. |
- Kliemann, Nathalie, et al.
(författare)
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Metabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European Prospective Investigation into Cancer and Nutrition
- 2021
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The mechanisms underlying the obesity-cancer relationship are incompletely understood. This study aimed to characterise metabolic signatures of greater body size and to investigate their association with two obesity-related malignancies, endometrial and colorectal cancers, and with weight loss within the context of an intervention study.Methods: Targeted mass spectrometry metabolomics data from 4326 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and 17 individuals from a single-arm pilot weight loss intervention (Intercept) were used in this analysis. Metabolic signatures of body size were first determined in discovery (N = 3029) and replication (N = 1297) sets among EPIC participants by testing the associations between 129 metabolites and body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) using linear regression models followed by partial least squares analyses. Conditional logistic regression models assessed the associations between the metabolic signatures with endometrial (N = 635 cases and 648 controls) and colorectal (N = 423 cases and 423 controls) cancer risk using nested case-control studies in EPIC. Pearson correlation between changes in the metabolic signatures and weight loss was tested among Intercept participants.Results: After adjustment for multiple comparisons, greater BMI, WC, and WHR were associated with higher levels of valine, isoleucine, glutamate, PC aa C38:3, and PC aa C38:4 and with lower levels of asparagine, glutamine, glycine, serine, lysoPC C17:0, lysoPC C18:1, lysoPC C18:2, PC aa C42:0, PC ae C34:3, PC ae C40:5, and PC ae C42:5. The metabolic signature of BMI (OR1-sd 1.50, 95% CI 1.30–1.74), WC (OR1-sd 1.46, 95% CI 1.27–1.69), and WHR (OR1-sd 1.54, 95% CI 1.33–1.79) were each associated with endometrial cancer risk. Risk of colorectal cancer was positively associated with the metabolic signature of WHR (OR1-sd: 1.26, 95% CI 1.07–1.49). In the Intercept study, a positive correlation was observed between weight loss and changes in the metabolic signatures of BMI (r = 0.5, 95% CI 0.06–0.94, p = 0.03), WC (r = 0.5, 95% CI 0.05–0.94, p = 0.03), and WHR (r = 0.6, 95% CI 0.32–0.87, p = 0.01).Conclusions: Obesity is associated with a distinct metabolic signature comprising changes in levels of specific amino acids and lipids which is positively associated with both colorectal and endometrial cancer and is potentially reversible following weight loss.
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| 14. |
- Linseisen, Jakob, et al.
(författare)
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Red blood cell fatty acids and risk of colorectal cancer in the European Prospective investigation into cancer and nutrition (EPIC)
- 2021
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 30:5, s. 874-885
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Tidskriftsartikel (refereegranskat)abstract
- Background: A growing body of evidence suggests that alterations of dietary fatty acid (FA) profiles are associated with colorectal cancer risk. However, data from large-scale epidemiologic studies using circulating FA measurements to objectively assess individual FA and FA categories are scarce.Methods: We investigate the association between red blood cell (RBC) membrane FAs and risk of colorectal cancer in a case–control study nested within a large prospective cohort. After a median follow-up of 6.4 years, 1,069 incident colorectal cancer cases were identified and matched to 1,069 controls among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). The FA composition of RBC phospholipids (in mol%) was analyzed by gas chromatography, and their association with risk of colorectal cancer was estimated by multivariable adjusted conditional logistic regression models.Results: After correction for multiple testing, subjects with higher concentrations of RBC stearic acid were at higher risk for colorectal cancer (OR ¼ 1.23; 95% CI ¼ 1.07–1.42, per 1 mol%). Conversely, colorectal cancer incidence decreased with increasing proportions of RBC n-3 PUFA, particularly eicosapentaenoic acid (0.75; 0.62–0.92, per 1 mol%). The findings for the n-6 PUFA arachidonic acid were inconsistent.Conclusions: The positive association between prediagnostic RBC stearic acid and colorectal cancer reflects putative differences in FA intake and metabolism between cancer cases and matched controls, which deserve further investigation. The inverse relationship between EPA and colorectal cancer is in line with the repeatedly reported protective effect of fish consumption on colorectal cancer risk.Impact: These findings add to the evidence on colorectal cancer prevention.
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| 15. |
- Mao, Ziling, et al.
(författare)
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Dietary intake of advanced glycation end products (Ages) and mortality among individuals with colorectal cancer
- 2021
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Advanced glycation end-products (AGEs) may promote oxidative stress and inflammation and have been linked to multiple chronic diseases, including cancer. However, the association of AGEs with mortality after colorectal cancer (CRC) diagnosis has not been previously investigated. Multivariable Cox proportional hazards models were used to calculate hazard ratios and corresponding 95% confidence intervals for associations between dietary intake of AGEs with CRC-specific and all-cause mortality among 5801 participant cases diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition study between 1993 and 2013. Dietary intakes of AGEs were estimated using country-specific dietary questionnaires, linked to an AGE database, that accounted for food preparation and processing. During a median of 58 months of follow-up, 2421 cases died (1841 from CRC). Individually or combined, dietary intakes of AGEs were not associated with all-cause and CRC-specific mortality among cases. However, there was a suggestion for a positive association between AGEs and all-cause or CRC-specific mortality among CRC cases without type II diabetes (all-cause, Pinteraction = 0.05) and CRC cases with the longest follow-up between recruitment and cancer diagnosis (CRC-specific, Pinteraction = 0.003; all-cause, Pinteraction = 0.01). Our study suggests that pre-diagnostic dietary intakes of AGEs were not associated with CRC-specific or all-cause mortality among CRC patients. Further investigations using biomarkers of AGEs and stratifying by sex, diabetes status, and timing of exposure to AGEs are warranted.
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| 16. |
- Papadimitriou, Nikos, et al.
(författare)
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Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value=0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value=0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers. Physical activity has been linked to lower risks of colorectal and breast cancer. Here, the authors present a Mendelian randomisation analysis supporting a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer.
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| 17. |
- Seyed Khoei, Nazlisadat, et al.
(författare)
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Circulating bilirubin levels and risk of colorectal cancer : serological and Mendelian randomization analyses
- 2020
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Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2).CONCLUSIONS: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
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| 18. |
- Stepien, M., et al.
(författare)
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Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study
- 2021
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 148:3, s. 609-625
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed forN1-acetylspermidine, isatin,p-hydroxyphenyllactic acid, tyrosine, sphingosine,l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, gamma-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.
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| 19. |
- Aglago, Elom K., et al.
(författare)
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Dietary intake and plasma phospholipid concentrations of saturated, monounsaturated and trans fatty acids and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort
- 2021
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 149:4, s. 865-882
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiologic studies examining the association between specific fatty acids and colorectal cancer (CRC) risk are inconclusive. We investigated the association between dietary estimates and plasma levels of individual and total saturated (SFA), monounsaturated (MUFA), industrial-processed trans (iTFA), and ruminant-sourced trans (rTFA) fatty acids, and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Baseline fatty acid intakes were estimated in 450 112 participants (6162 developed CRC, median follow-up = 15 years). In a nested case-control study, plasma phospholipid fatty acids were determined by gas chromatography in 433 colon cancer cases and 433 matched controls. Multivariable-adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed using Cox and conditional logistic regression, respectively. Dietary total SFA (highest vs lowest quintile, HRQ5vsQ1 = 0.80; 95%CI:0.69-0.92), myristic acid (HRQ5vsQ1 = 0.83, 95%CI:0.74-0.93) and palmitic acid (HRQ5vsQ1 = 0.81, 95%CI:0.70-0.93) were inversely associated with CRC risk. Plasma myristic acid was also inversely associated with colon cancer risk (highest vs lowest quartile, ORQ4vsQ1 = 0.51; 95%CI:0.32-0.83), whereas a borderline positive association was found for plasma stearic acid (ORQ4vsQ1 = 1.63; 95%CI:1.00-2.64). Dietary total MUFA was inversely associated with colon cancer (per 1-SD increment, HR1-SD = 0.92, 95%CI: 0.85-0.98), but not rectal cancer (HR1-SD = 1.04, 95%CI:0.95-1.15, Pheterogeneity = 0.027). Dietary iTFA, and particularly elaidic acid, was positively associated with rectal cancer (HR1-SD = 1.07, 95%CI:1.02-1.13). Our results suggest that total and individual saturated fatty acids and fatty acids of industrial origin may be relevant to the aetiology of CRC. Both dietary and plasma myristic acid levels were inversely associated with colon cancer risk, which warrants further investigation.
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| 20. |
- Aglago, Elom K., et al.
(författare)
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Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk : A Case-Control Study Nested within a European Prospective Cohort
- 2021
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 30:1, s. 182-192
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation.METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively.RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99).CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk.IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.
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| 21. |
- Aleksandrova, Krasimira, et al.
(författare)
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Development and validation of a lifestyle-based model for colorectal cancer risk prediction : the LiFeCRC score
- 2021
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.
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| 22. |
- Baker, Jacqueline Roshelli, et al.
(författare)
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Prediagnostic blood selenium status and mortality among patients with colorectal cancer in western european populations
- 2021
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Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- A higher selenium (Se) status has been shown to be associated with lower risk for colorectal cancer (CRC), but the importance of Se in survival after CRC diagnosis is not well studied. The associations of prediagnostic circulating Se status (as indicated by serum Se and selenoprotein P (SELENOP) measurements) with overall and CRC-specific mortality were estimated using multi-variable Cox proportional hazards regression among 995 CRC cases (515 deaths, 396 from CRC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Se and SELENOP serum concentrations were measured on average 46 months before CRC diagnosis. Median follow-up time was 113 months. Participants with Se concentrations in the highest quintile (≥100 µg/L) had a multivariable-adjusted hazard ratio (HR) of 0.73 (95% CI: 0.52–1.02; Ptrend = 0.06) for CRC-specific mortality and 0.77 (95% CI: 0.57–1.03; Ptrend = 0.04) for overall mortality, compared with the lowest quintile (≤67.5 µg/L). Similarly, participants with SELENOP concentrations in the highest (≥5.07 mg/L) compared with the lowest quintile (≤3.53 mg/L) had HRs of 0.89 (95% CI: 0.64–1.24; Ptrend = 0.39) for CRC-specific mortality and 0.83 (95% CI: 0.62–1.11; Ptrend = 0.17) for overall mortal-ity. Higher prediagnostic exposure to Se within an optimal concentration (100–150 µg/L) might be associated with improved survival among CRC patients, although our results were not statistically significant and additional studies are needed to confirm this potential association. Our findings may stimulate further research on selenium’s role in survival among CRC patients especially among those residing in geographic regions with suboptimal Se availability.
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| 23. |
- Watts, Eleanor L., et al.
(författare)
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Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer : a collaborative analysis of 20 prospective studies and Mendelian randomization analysis
- 2023
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 52:1, s. 71-86
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer.Methods: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium.Results: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I.Conclusions: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.
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