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1.
Eur J Nutr ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33768317

RESUMO

PURPOSE: The UK Biobank study collected detailed dietary data using a web-based self-administered 24 h assessment tool, the Oxford WebQ. We aimed to describe a comprehensive food grouping system for this questionnaire and to report dietary intakes and key sources of selected nutrients by sex and education. METHODS: Participants with at least one valid 24-h questionnaire were included (n = 208,200). Dietary data were grouped based on the presence of nutrients as well as culinary use, processing, and plant/animal origin. For each food group, we calculated the contribution to energy intake, key macronutrients, and micronutrients. We also identified the top contributors to energy intake, free sugars and saturated fat by sex and education. RESULTS: From the 93 food groups, the top five contributors to energy intake (in descending order) were: desserts/cakes/pastries; white bread; white pasta/rice; bananas/other fruit; semi-skimmed milk. Wine, beer, and fruit juices were the top beverage contributors to overall energy intake. Biscuits, and desserts/cakes/pastries were the highest contributors to free sugars, total fat, and saturated fat intakes, but also contributed to the calcium and iron intakes. Top contributors to energy, saturated fat, and free sugars were broadly similar by sex and education category, with small differences in average nutrient intakes across the population. CONCLUSION: This new food classification system will support the growing interest in the associations between food groups and health outcomes and the development of food-based dietary guidelines. Food group variables will be available to all users of the UK Biobank WebQ questionnaire.

2.
Carcinogenesis ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33780524

RESUMO

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the non-enzymatic reaction between amino-acids and reducing sugars, or dicarbonyls as intermediate compounds. Experimental studies suggest that AGEs may promote colorectal cancer, but prospective epidemiologic studies are inconclusive. We conducted a case-control study nested within a large European cohort. Plasma concentrations of three protein-bound AGEs: N ε-(carboxy-methyl)lysine (CML), N ε-(carboxy-ethyl)lysine (CEL) and N δ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were measured by ultra-performance liquid chromatography tandem mass-spectrometry in baseline samples collected from 1,378 incident primary colorectal cancer cases and 1,378 matched controls. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression for colorectal cancer risk associated with CML, CEL, MG-H1, total AGEs, and [CEL+MG-H1: CML] and [CEL:MG-H1] ratios. Inverse colorectal cancer risk associations were observed for CML (OR comparing highest to lowest quintile, ORQ5vs.Q1=0.40, 95%CI:0.27-0.59), MG-H1 (ORQ5vs.Q1=0.73, 95%CI:0.53 - 1.00) and total AGEs (OR Q5vs.Q1=0.52, 95%CI:0.37 - 0.73) whereas no association was observed for CEL. A higher [CEL+MG-H1: CML] ratio was associated with colorectal cancer risk (ORQ5vs.Q1=1.91, 95%CI:1.31-2.79). The associations observed did not differ by sex, or by tumour anatomical subsite. Although individual AGEs concentrations appear to be inversely associated with colorectal cancer risk, a higher ratio of methylglyoxal-derived AGEs versus those derived from glyoxal (calculated by [CEL+MG-H1: CML] ratio) showed a strong positive risk association. Further insight on the metabolism of AGEs and their dicarbonyls precursors, and their roles in colorectal cancer development is needed.

3.
Int J Cancer ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33720423

RESUMO

We investigated the associations of estimated free and total circulating testosterone and sex hormone-binding globulin (SHBG) with cancer risk in men and postmenopausal women, using a pan-cancer approach, including 19 cancers in UK Biobank. Risk was estimated using multivariable-adjusted Cox regression in up to 182 608 men and 122 112 postmenopausal women who were cancer-free at baseline. Participants diagnosed with cancer within 2 years of baseline were excluded. Hazard ratios (HRs) and confidence intervals (CIs) were corrected for regression dilution bias using repeat measurements. We accounted for multiple testing using the false discovery rate. In men, higher free testosterone was associated with higher risks of melanoma and prostate cancer (HR per 50 pmol/L increase = 1.35, 95% CI 1.14-1.61 and 1.10, 1.04-1.18, respectively). Higher total testosterone was associated with an elevated risk of liver cancer (HR per 5 nmol/L = 2.45, 1.56-3.84), and higher SHBG was associated with a higher risk of liver cancer (HR per 10 nmol/L = 1.56, 1.31-1.87) and a lower risk of prostate cancer (0.93, 0.91-0.96); the associations with liver cancer were partially attenuated after excluding men diagnosed within 4.7 years from baseline. In postmenopausal women, free and total testosterone and SHBG were associated with risks of endometrial (HR per 10 pmol/L = 1.59, 1.32-1.90; HR per 0.5 nmol/L = 1.34, 1.18-1.52 and HR per 25 nmol/L = 0.78, 0.67-0.91, respectively) and breast cancer (1.32, 1.22-1.43; 1.24, 1.17-1.31 and 0.88, 0.83-0.94, respectively). We report a novel association of free testosterone with malignant melanoma in men, and confirm known associations between testosterone and risks for prostate, breast and endometrial cancers. The association with liver cancer in men may be attributable to reverse causation.

4.
BMC Med ; 19(1): 53, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33648505

RESUMO

BACKGROUND: There is limited prospective evidence on the association between meat consumption and many common, non-cancerous health outcomes. We examined associations of meat intake with risk of 25 common conditions (other than cancer). METHODS: We used data from 474,985 middle-aged adults recruited into the UK Biobank study between 2006 and 2010 and followed up until 2017 (mean follow-up 8.0 years) with available information on meat intake at baseline (collected via touchscreen questionnaire), and linked hospital admissions and mortality data. For a large sub-sample (~ 69,000), dietary intakes were re-measured three or more times using an online, 24-h recall questionnaire. RESULTS: On average, participants who reported consuming meat regularly (three or more times per week) had more adverse health behaviours and characteristics than participants who consumed meat less regularly, and most of the positive associations observed for meat consumption and health risks were substantially attenuated after adjustment for body mass index (BMI). In multi-variable adjusted (including BMI) Cox regression models corrected for multiple testing, higher consumption of unprocessed red and processed meat combined was associated with higher risks of ischaemic heart disease (hazard ratio (HRs) per 70 g/day higher intake 1.15, 95% confidence intervals (CIs) 1.07-1.23), pneumonia (1.31, 1.18-1.44), diverticular disease (1.19, 1.11-1.28), colon polyps (1.10, 1.06-1.15), and diabetes (1.30, 1.20-1.42); results were similar for unprocessed red meat and processed meat intakes separately. Higher consumption of unprocessed red meat alone was associated with a lower risk of iron deficiency anaemia (IDA: HR per 50 g/day higher intake 0.80, 95% CIs 0.72-0.90). Higher poultry meat intake was associated with higher risks of gastro-oesophageal reflux disease (HR per 30 g/day higher intake 1.17, 95% CIs 1.09-1.26), gastritis and duodenitis (1.12, 1.05-1.18), diverticular disease (1.10, 1.04-1.17), gallbladder disease (1.11, 1.04-1.19), and diabetes (1.14, 1.07-1.21), and a lower IDA risk (0.83, 0.76-0.90). CONCLUSIONS: Higher unprocessed red meat, processed meat, and poultry meat consumption was associated with higher risks of several common conditions; higher BMI accounted for a substantial proportion of these increased risks suggesting that residual confounding or mediation by adiposity might account for some of these remaining associations. Higher unprocessed red meat and poultry meat consumption was associated with lower IDA risk.

5.
Am J Clin Nutr ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740060

RESUMO

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 (ß-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 ß-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.

6.
Gut ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632709

RESUMO

OBJECTIVE: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. DESIGN: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. RESULTS: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. CONCLUSION: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33619024

RESUMO

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 = 1.23; 95% CI = 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.

8.
Int J Cancer ; 148(4): 825-834, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33405276

RESUMO

We investigated the association between metabolic syndrome (MetS) and its components and risk of prostate cancer (PCa) in a cohort of men enrolled in the UK Biobank. Our study cohort included 220 622 PCa-free men with baseline measurements of triglycerides (TGs), HDL-cholesterol (HDL), glycated hemoglobin (HbA1c), blood pressure (BP), and waist circumference (WC). Multivariable Cox proportional hazards regression was used to analyze associations with PCa for: individual metabolic components (TG, HDL, HbA1c, BP, WC), combinations of two and three components, and MetS overall (three or more components). We conducted mediation analyses to examine potential hormonal and inflammatory pathways (total testosterone [TT], C-reactive protein [CRP], insulin-like growth factor 1 [IGF-1]) through which MetS components may influence PCa risk. A total of 5409 men in the study developed PCa during a median follow-up of 6.9 years. We found no significant association between MetS and PCa risk (hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.92-1.06). No associations were found with PCa risk and individual measurements of TG, HDL, BP, or WC. However, an inverse association was observed with elevated HbA1c (≥42 mmol/mol) (HR = 0.89, 95% CI = 0.79-0.98). Consistent inverse associations were observed between HbA1c and risk of PCa. Mediation analysis revealed TT, CRP, and IGF-1 as potential mediating factors for this association contributing 10.2%, 7.1%, and 7.9% to the total effect, respectively. Overall MetS had no association with PCa risk. However, a consistent inverse association with PCa risk was found for HbA1c. This association may be explained in part through hormonal and inflammatory pathways.

10.
Int J Cancer ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33252839

RESUMO

Insulin-like growth factor-I (IGF-I) and testosterone have been implicated in prostate cancer aetiology. Using data from a large prospective full-cohort with standardised assays and repeat blood measurements, and genetic data from an international consortium, we investigated the associations of circulating IGF-I, sex hormone-binding globulin (SHBG), total and calculated free testosterone concentrations with prostate cancer incidence and mortality. For prospective analyses, risk was estimated using multivariable-adjusted Cox regression in 199,698 male UK Biobank participants. Hazard ratios (HRs) were corrected for regression dilution bias using repeat hormone measurements from a subsample. 2-sample Mendelian randomization (MR) analysis of IGF-I and risk used genetic instruments identified from UK Biobank men and genetic outcome data from the PRACTICAL consortium (79,148 cases and 61,106 controls). We used cis- and all (cis and trans) SNP MR approaches. 5,402 men were diagnosed with and 295 died from prostate cancer (mean follow-up 6.9 years). Higher circulating IGF-I was associated with elevated prostate cancer diagnosis (HR per 5 nmol/L increment=1.09, 95% CI 1.05-1.12) and mortality (HR per 5 nmol/L increment=1.15,1.02-1.29). MR analyses also supported the role of IGF-I in prostate cancer diagnosis (cis-MR odds ratio per 5 nmol/L increment=1.34,1.07-1.68). In observational analyses, higher free testosterone was associated with a higher risk of prostate cancer (HR per 50 pmol/L increment=1.10,1.05-1.15). Higher SHBG was associated with a lower risk (HR per 10 nmol/L increment=0.95,0.94-0.97), neither was associated with prostate cancer mortality. Total testosterone was not associated with prostate cancer. These findings implicate IGF-I and free testosterone in prostate cancer development and/or progression. This article is protected by copyright. All rights reserved.

11.
BMC Med ; 18(1): 353, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33222682

RESUMO

BACKGROUND: There is limited prospective evidence on possible differences in fracture risks between vegetarians, vegans, and non-vegetarians. We aimed to study this in a prospective cohort with a large proportion of non-meat eaters. METHODS: In EPIC-Oxford, dietary information was collected at baseline (1993-2001) and at follow-up (≈ 2010). Participants were categorised into four diet groups at both time points (with 29,380 meat eaters, 8037 fish eaters, 15,499 vegetarians, and 1982 vegans at baseline in analyses of total fractures). Outcomes were identified through linkage to hospital records or death certificates until mid-2016. Using multivariable Cox regression, we estimated the risks of total (n = 3941) and site-specific fractures (arm, n = 566; wrist, n = 889; hip, n = 945; leg, n = 366; ankle, n = 520; other main sites, i.e. clavicle, rib, and vertebra, n = 467) by diet group over an average of 17.6 years of follow-up. RESULTS: Compared with meat eaters and after adjustment for socio-economic factors, lifestyle confounders, and body mass index (BMI), the risks of hip fracture were higher in fish eaters (hazard ratio 1.26; 95% CI 1.02-1.54), vegetarians (1.25; 1.04-1.50), and vegans (2.31; 1.66-3.22), equivalent to rate differences of 2.9 (0.6-5.7), 2.9 (0.9-5.2), and 14.9 (7.9-24.5) more cases for every 1000 people over 10 years, respectively. The vegans also had higher risks of total (1.43; 1.20-1.70), leg (2.05; 1.23-3.41), and other main site fractures (1.59; 1.02-2.50) than meat eaters. Overall, the significant associations appeared to be stronger without adjustment for BMI and were slightly attenuated but remained significant with additional adjustment for dietary calcium and/or total protein. No significant differences were observed in risks of wrist or ankle fractures by diet group with or without BMI adjustment, nor for arm fractures after BMI adjustment. CONCLUSIONS: Non-meat eaters, especially vegans, had higher risks of either total or some site-specific fractures, particularly hip fractures. This is the first prospective study of diet group with both total and multiple specific fracture sites in vegetarians and vegans, and the findings suggest that bone health in vegans requires further research.

12.
Int J Epidemiol ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33245137

RESUMO

BACKGROUND: Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD. RESULTS: There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95% confidence interval (CI): 0.90-0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95-1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82-0.98, P-trend = 0.020), total fibre (per 10 g/day 0.91, 0.85-0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91-0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95-1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk. CONCLUSIONS: In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear.

13.
J Natl Cancer Inst ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010161

RESUMO

BACKGROUND: In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research. METHODS: Among prostate cancer cases diagnosed in 2007 in the U.S. SEER-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV). RESULTS: In our case population (n = 55,900), 3,073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM stage and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of stage T4 or N1 or M1 or Gleason score ≥8 prostate cancer, as this definition had one of the higher PPVs (0.23, 95% confidence interval [CI] 0.22-0.24) and reasonable sensitivity (0.66, 95% CI 0.64-0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses. CONCLUSIONS: We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced stage (T4 or N1 or M1), high grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology.

14.
Int J Cancer ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038275

RESUMO

Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (±0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33082206

RESUMO

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; P heterogeneity 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.

16.
BMC Med ; 18(1): 229, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32878631

RESUMO

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.

17.
Nutrients ; 12(10)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977480

RESUMO

This study aimed to compare calculated nutrient intakes from two different food composition databases using data from the European prospective investigation into cancer and nutrition (EPIC) cohort. Dietary intake data of the EPIC cohort was recently matched to 150 food components from the U.S. nutrient database (USNDB). Twenty-eight of these nutrients were already included in the EPIC nutrient database (ENDB-based upon country specific food composition tables), and used for comparison. Paired sample t-tests, Pearson's correlations (r), weighted kappa's (κ) and Bland-Altman plots were used to compare the dietary intake of 28 nutrients estimated by the USNDB and the ENDB for 476,768 participants. Small but significant differences were shown between the USNDB and the ENDB for energy and macronutrient intakes. Moderate to very strong correlations (r = 0.60-1.00) were found for all macro- and micronutrients. A strong agreement (κ > 0.80) was found for energy, water, total fat, carbohydrates, sugar, alcohol, potassium and vitamin C, whereas a weak agreement (κ < 0.60) was found for starch, vitamin D and vitamin E. Dietary intakes estimated via the USNDB compare adequately with those obtained via the ENDB for most macro- and micronutrients, although the agreement was weak for starch, vitamin D and vitamin E. The USNDB will allow exposure assessments for 150 nutrients to investigate associations with disease outcomes within the EPIC cohort.

18.
Br J Cancer ; 123(12): 1808-1817, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32963348

RESUMO

BACKGROUND: Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank. METHODS: A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure. RESULTS: After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death. CONCLUSION: We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.

19.
Sci Rep ; 10(1): 13814, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796953

RESUMO

Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case-control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled > 9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve = 0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors.

20.
Int J Epidemiol ; 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32814947

RESUMO

BACKGROUND: Red and processed meat have been consistently associated with colorectal cancer risk, but evidence for other cancer sites and for poultry intake is limited. We therefore examined associations between total, red and processed meat and poultry intake and incidence for 20 common cancers. METHODS: We analyzed data from 474 996 participants (54% women) in UK Biobank. Participants were aged 37-73 years and cancer-free at baseline (2006-10). Multivariable-adjusted Cox proportional hazards models were used to determine associations between baseline meat intake and cancer incidence. Trends in risk across the baseline categories were calculated, assigning re-measured intakes from a subsample. RESULTS: During a mean follow-up of 6.9 years, 28 955 participants were diagnosed with malignant cancer. After correction for multiple testing, red and processed meat combined, and processed meat, were each positively associated with colorectal cancer risk [hazard ratio (HR) per 70 g/day higher intake of red and processed meat 1.32, 95% confidence interval 1.14-1.53; HR per 20 g/day higher intake of processed meat 1.18, 1.03-1.31] and red meat was associated with colon cancer risk (HR per 50 g/day higher intake of red meat 1.36, 1.13-1.64). Positive associations of red meat intake with colorectal and prostate cancer, processed meat intake with rectal cancer and poultry intake with cancers of the lymphatic and haematopoietic tissues did not survive multiple testing. CONCLUSIONS: Higher intake of red and processed meat was specifically associated with a higher risk of colorectal cancer; there was little evidence that meat intake was associated with risk of other cancers.

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