Publications by authors named "Timothy J Key"

376 Publications

Associations of circulating insulin-like growth factor-I with intake of dietary proteins and other macronutrients.

Clin Nutr 2021 07 20;40(7):4685-4693. Epub 2021 Apr 20.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Background & Aims: Circulating insulin-like growth factor-I (IGF-I) is associated with the risk of several cancers. Dietary protein intake, particularly dairy protein, may increase circulating IGF-I; however, associations with different protein sources, other macronutrients, and fibre are inconclusive. To investigate the associations between intake of protein, macronutrients and their sources, fibre, and alcohol with serum IGF-I concentrations.

Methods: A total of 11,815 participants from UK Biobank who completed ≥4 24-h dietary assessments and had serum IGF-I concentrations measured at baseline were included. Multivariable linear regression was used to assess the cross-sectional associations of macronutrient and fibre intake with circulating IGF-I concentrations.

Results: Circulating IGF-I concentrations were positively associated with intake of total protein (per 2.5% higher energy intake: 0.56 nmol/L (95% confidence interval: 0.47, 0.66)), milk protein: 1.20 nmol/L (0.90, 1.51), and yogurt protein: 1.33 nmol/L (0.79, 1.86), but not with cheese protein: -0.07 nmol/L (-0.40, 0.25). IGF-I concentrations were also positively associated with intake of fibre (per 5 g/day higher intake: 0.46 nmol/L (0.35, 0.57)) and starch from wholegrains (Q5 vs. Q1: 1.08 nmol/L (0.77, 1.39)), and inversely associated with alcohol consumption (>40 g/day vs <1 g/day: -1.36 nmol/L (-1.00, -1.71)).

Conclusions: These results show differing associations with IGF-I concentrations depending on the source of dairy protein, with positive associations with milk and yogurt protein intake but no association with cheese protein. The positive association of fibre and starch from wholegrains with IGF-I warrants further investigation.
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http://dx.doi.org/10.1016/j.clnu.2021.04.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345002PMC
July 2021

Physical activity in relation to circulating hormone concentrations in 117,100 men in UK Biobank.

Cancer Causes Control 2021 Jul 3. Epub 2021 Jul 3.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Oxford, OX3 7LF, UK.

Purpose: Physical activity may reduce the risk of some types of cancer in men. Biological mechanisms may involve changes in hormone concentrations; however, this relationship is not well established. Therefore, we aimed to investigate the associations of physical activity with circulating insulin-like growth factor-I (IGF-I), sex hormone-binding globulin (SHBG, which modifies sex hormone activity), and total and free testosterone concentrations, and the extent these associations might be mediated by body mass index (BMI).

Methods: Circulating concentrations of these hormones and anthropometric measurements and self-reported physical activity data were available for 117,100 healthy male UK Biobank participants at recruitment. Objectively measured accelerometer physical activity levels were also collected on average 5.7 years after recruitment in 28,000 men. Geometric means of hormone concentrations were estimated using multivariable-adjusted analysis of variance, with and without adjustment for BMI.

Results: The associations between physical activity and hormones were modest and similar for objectively measured (accelerometer) and self-reported physical activity. Compared to men with the lowest objectively measured physical activity, men with high physical activity levels had 14% and 8% higher concentrations of SHBG and total testosterone, respectively, and these differences were attenuated to 6% and 3% following adjustment for BMI.

Conclusion: Our results suggest that the associations of physical activity with the hormones investigated are, at most, modest; and following adjustment for BMI, the small associations with SHBG and total testosterone were largely attenuated. Therefore, it is unlikely that changes in these circulating hormones explain the associations of physical activity with risk of cancer either independently or via BMI.
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http://dx.doi.org/10.1007/s10552-021-01466-6DOI Listing
July 2021

Breast cancer risk factors and circulating anti-Müllerian hormone concentration in healthy premenopausal women.

J Clin Endocrinol Metab 2021 Jun 22. Epub 2021 Jun 22.

Department of Population Health, New York University School of Medicine, New York, NY.

Context: In a previous study we reported that anti-Müllerian hormone (AMH), a marker of ovarian reserve, is positively associated with breast cancer risk, consistent with other studies.

Objective: Assess whether risk factors for breast cancer are correlates of AMH concentration.

Design: Cross-sectional.

Participants: 3831 healthy premenopausal women (aged 21-57, 87% aged 35-49).

Setting: Ten cohort studies, general population.

Results: Adjusting for age and cohort, we observed positive associations of AMH with age at menarche (p<0.0001) and parity (p=0.0008), and an inverse association with hysterectomy/partial oophorectomy (p=0.0008). Compared to women of normal weight (BMI 18.5-24.9 kg/m 2, AMH was lower (relative geometric mean difference 27%, p<0.0001) among women who were obese (BMI>30). Current oral contraceptive use and current/former smoking were associated with lower AMH concentration than never use (40% and 12% lower, respectively, p<0.0001). We observed higher AMH concentrations among women who had had a benign breast biopsy (15% higher, p=0.03), a surrogate for benign breast disease, an association that has not been reported. In analyses stratified by age (<40/≥40), associations of AMH with BMI and oral contraceptives were similar in younger and older women, while associations with the other factors (menarche, parity, hysterectomy/partial oophorectomy, smoking, and benign breast biopsy) were limited to women ≥40 (p-interaction<0.05).

Conclusion: This is the largest study of AMH and breast cancer risk factors among women from the general population (not presenting with infertility), and suggests that most of the associations are limited to women over 40, who are approaching menopause and whose AMH concentration is declining.
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http://dx.doi.org/10.1210/clinem/dgab461DOI Listing
June 2021

Biomarker Concentrations in White and British Indian Vegetarians and Nonvegetarians in the UK Biobank.

J Nutr 2021 Jun 16. Epub 2021 Jun 16.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: Prospective studies have shown differences in some disease risks between vegetarians and nonvegetarians, but the potential biological pathways are not well understood.

Objectives: We aimed to assess differences in concentrations of biomarkers related to disease pathways in people with varying degrees of animal foods exclusion.

Methods: The UK Biobank recruited 500,000 participants aged 40-69 y (54.4% women) throughout the United Kingdom in 2006-2010. Blood and urine were collected at recruitment and assayed for more than 30 biomarkers related to cardiovascular diseases, bone and joint health, cancer, diabetes, renal disease, and liver health. In cross-sectional analyses, we estimated adjusted geometric means of these biomarkers by 6 diet groups (regular meat eaters, low meat eaters, poultry eaters, fish eaters, vegetarians, vegans) in 466,058 white British participants and 2 diet groups (meat eaters, vegetarians) in 5535 British Indian participants.

Results: We observed differences in the concentrations of most biomarkers, with many biomarkers showing a gradient effect from meat eaters to vegetarians/vegans. Of the largest differences, compared with white British regular meat eaters, white British vegans had lower C-reactive protein [adjusted geometric mean (95% CI): 1.13 (1.03, 1.25) compared with 1.43 (1.42, 1.43) mg/L], lower low-density lipoprotein cholesterol [3.13 (3.07, 3.20) compared with 3.65 (3.65, 3.65) mmol/L], lower vitamin D [34.4 (33.1, 35.9) compared with 44.5 (44.4, 44.5) nmol/L], lower serum urea [4.21 (4.11, 4.30) compared with 5.36 (5.36, 5.37) mmol/L], lower urinary creatinine [5440 (5120, 5770) compared with 7280 (7260, 7300) μmol/L], and lower γ-glutamyltransferase [23.5 (22.2, 24.8) compared with 29.6 (29.6, 29.7) U/L]. Patterns were mostly similar in British Indians, and results were consistent between women and men.

Conclusions: The observed differences in biomarker concentrations, including lower C-reactive protein, lower LDL cholesterol, lower vitamin D, lower creatinine, and lower γ-glutamyltransferase, in vegetarians and vegans may relate to differences in future disease risk.
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http://dx.doi.org/10.1093/jn/nxab192DOI Listing
June 2021

Associations Between Macronutrients From Different Dietary Sources and Serum Lipids in 24 639 UK Biobank Study Participants.

Arterioscler Thromb Vasc Biol 2021 07 27;41(7):2190-2200. Epub 2021 May 27.

Cancer Epidemiology Unit (R.K.K., C.Z.W., T.Y.N.T., K.P., T.J.K., A.P.-C.), University of Oxford, United Kingdom.

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.120.315628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216602PMC
July 2021

Description of the updated nutrition calculation of the Oxford WebQ questionnaire and comparison with the previous version among 207,144 participants in UK Biobank.

Eur J Nutr 2021 Oct 6;60(7):4019-4030. Epub 2021 May 6.

Department of Public Health & Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK.

Purpose: The Oxford WebQ is a web-based 24-h dietary assessment method which has been used in UK Biobank and other large prospective studies. The food composition table used to calculate nutrient intakes has recently been replaced with the UK Nutrient Databank, which has food composition data closer in time to when participants completed the questionnaire, and new dietary variables were incorporated. Here we describe the updated version of the Oxford WebQ questionnaire nutrient calculation, and compare nutrient intakes with the previous version used.

Methods: 207,144 UK Biobank participants completed ≥ 1 Oxford WebQs, and means and standard deviations of nutrient intakes were averaged for all completed 24-h dietary assessments. Spearman correlations and weighted kappa statistics were used to compare the re-classification and agreement of nutrient intakes between the two versions.

Results: 35 new nutrients were incorporated in the updated version. Compared to the previous version, most nutrients were very similar in the updated version except for a few nutrients which showed a difference of > 10%: lower with the new version for trans-fat (- 20%), and vitamin C (- 15%), but higher for retinol (+ 42%), vitamin D (+ 26%) and vitamin E (+ 20%). Most participants were in the same (> 60%) or adjacent (> 90%) quintile of intake for the two versions. Except for trans-fat (r = 0.58, κ = 0.42), very high correlations were found between the nutrients calculated using the two versions (r > 0.79 and κ > 0.60).

Conclusion: Small absolute differences in nutrient intakes were observed between the two versions, and the ranking of individuals was minimally affected, except for trans-fat.
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http://dx.doi.org/10.1007/s00394-021-02558-4DOI Listing
October 2021

Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women: findings from the UK Biobank.

Br J Cancer 2021 Jul 16;125(1):126-134. Epub 2021 Apr 16.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood.

Methods: UK Biobank was used. Hormone concentrations were measured in serum collected in 2006-2010, and in a repeat subsample (N ~ 5000) in 2012-13. Incident cancers were identified through data linkage. Cox regression models were used, and hazard ratios (HRs) corrected for regression dilution bias.

Results: Among 30,565 pre-menopausal and 133,294 post-menopausal women, 527 and 2,997, respectively, were diagnosed with invasive breast cancer during a median follow-up of 7.1 years. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in pre-menopausal women (p = 0.03), and with IGF-1 (insulin-like growth factor-1) (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); p = 0.2), and inversely associated with SHBG (sex hormone-binding globulin) (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); p = 0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone.

Conclusions: This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone.
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http://dx.doi.org/10.1038/s41416-021-01392-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257641PMC
July 2021

Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.

Am J Clin Nutr 2021 06;113(6):1490-1502

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

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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http://dx.doi.org/10.1093/ajcn/nqab003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168352PMC
June 2021

Prospective analyses of testosterone and sex hormone-binding globulin with the risk of 19 types of cancer in men and postmenopausal women in UK Biobank.

Int J Cancer 2021 08 31;149(3):573-584. Epub 2021 Mar 31.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

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.
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http://dx.doi.org/10.1002/ijc.33555DOI Listing
August 2021

NMR Metabolite Profiles in Male Meat-Eaters, Fish-Eaters, Vegetarians and Vegans, and Comparison with MS Metabolite Profiles.

Metabolites 2021 Feb 20;11(2). Epub 2021 Feb 20.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK.

Metabolomics may help to elucidate mechanisms underlying diet-disease relationships and identify novel risk factors for disease. To inform the design and interpretation of such research, evidence on diet-metabolite associations and cross-assay comparisons is needed. We aimed to compare nuclear magnetic resonance (NMR) metabolite profiles between meat-eaters, fish-eaters, vegetarians and vegans, and to compare NMR measurements to those from mass spectrometry (MS), clinical chemistry and capillary gas-liquid chromatography (GC). We quantified 207 serum NMR metabolite measures in 286 male participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford cohort. Using univariate and multivariate analyses, we found that metabolite profiles varied by diet group, especially for vegans; the main differences compared to meat-eaters were lower levels of docosahexaenoic acid, total n-3 and saturated fatty acids, cholesterol and triglycerides in very-low-density lipoproteins, various lipid factions in high-density lipoprotein, sphingomyelins, tyrosine and creatinine, and higher levels of linoleic acid, total n-6, polyunsaturated fatty acids and alanine. Levels in fish-eaters and vegetarians differed by metabolite measure. Concentrations of 13 metabolites measured using both NMR and MS, clinical chemistry or GC were mostly similar. In summary, vegans' metabolite profiles were markedly different to those of men consuming animal products. The studied metabolomics platforms are complementary, with limited overlap between metabolite classes.
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http://dx.doi.org/10.3390/metabo11020121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923783PMC
February 2021

Meat consumption and risk of 25 common conditions: outcome-wide analyses in 475,000 men and women in the UK Biobank study.

BMC Med 2021 03 2;19(1):53. Epub 2021 Mar 2.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Oxford, OX3 7LF, UK.

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.
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http://dx.doi.org/10.1186/s12916-021-01922-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923515PMC
March 2021

Circulating insulin-like growth factor-I, total and free testosterone concentrations and prostate cancer risk in 200 000 men in UK Biobank.

Int J Cancer 2021 05 11;148(9):2274-2288. Epub 2020 Dec 11.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

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), and 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. Two-sample Mendelian randomisation (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. A total of 5402 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.
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http://dx.doi.org/10.1002/ijc.33416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048461PMC
May 2021

Plant foods, dietary fibre and risk of ischaemic heart disease in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Int J Epidemiol 2021 03;50(1):212-222

Department of Public Health and Clinical Medicine, Section of Sustainable Health/Nutritional Research, Umeå University, Umeå, Sweden.

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.
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http://dx.doi.org/10.1093/ije/dyaa155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938513PMC
March 2021

Vegetarian and vegan diets and risks of total and site-specific fractures: results from the prospective EPIC-Oxford study.

BMC Med 2020 11 23;18(1):353. Epub 2020 Nov 23.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Oxford, OX3 7LF, UK.

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.
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http://dx.doi.org/10.1186/s12916-020-01815-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682057PMC
November 2020

Urinary Melatonin in Relation to Breast Cancer Risk: Nested Case-Control Analysis in the DOM Study and Meta-analysis of Prospective Studies.

Cancer Epidemiol Biomarkers Prev 2021 01 3;30(1):97-103. Epub 2020 Nov 3.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, England, United Kingdom.

Background: Exposure to higher levels of melatonin may be associated with lower breast cancer risk, but epidemiologic evidence has been limited. We examined the relationship in a case-control study nested within the Diagnostisch Onderzoek Mammacarcinoom (DOM) study and conducted a meta-analysis of prospective studies.

Methods: Concentrations of 6-sulfatoxymelatonin (aMT6s) in prediagnostic first morning urine voids were measured in 274 postmenopausal women diagnosed with breast cancer and 274 matched controls from the DOM study. Conditional logistic regression models were used to estimate multivariable adjusted ORs of breast cancer for thirds of aMT6s. Meta-analysis of this and previous prospective studies of urinary melatonin with breast cancer risk estimated the inverse-variance weighted averages of study-specific log RRs of breast cancer for the highest versus lowest levels of aMT6s.

Results: In the DOM study, the ORs of breast cancer for the middle and highest versus lowest thirds of aMT6s were 0.70 [95% confidence interval (CI), 0.45-1.09] and 0.72 (95% CI, 0.44-1.19), respectively. In the meta-analysis of the DOM study with six previous studies (2,296 cases), RR of breast cancer for the highest versus lowest levels of aMT6s was 0.87 (95% CI, 0.76-1.01).

Conclusions: Results from the DOM study, together with the published prospective data, do not support a strong association of melatonin with breast cancer risk.

Impact: This study adds to the relatively scarce prospective data on melatonin in relation to breast cancer risk. The totality of the prospective evidence does not clearly show an association between melatonin and breast cancer risk, but further data are needed to be able to exclude a modest association.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0822DOI Listing
January 2021

Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Int J Cancer 2021 04 9;148(7):1637-1651. Epub 2020 Nov 9.

Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.

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.
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http://dx.doi.org/10.1002/ijc.33339DOI Listing
April 2021

Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank.

Br J Cancer 2020 12 23;123(12):1808-1817. Epub 2020 Sep 23.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

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.
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http://dx.doi.org/10.1038/s41416-020-01081-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722733PMC
December 2020

Health impacts and environmental footprints of diets that meet the Eatwell Guide recommendations: analyses of multiple UK studies.

BMJ Open 2020 08 26;10(8):e037554. Epub 2020 Aug 26.

Centre on Climate Change & Planetary Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Objectives: To assess the health impacts and environmental consequences of adherence to national dietary recommendations (the Eatwell Guide (EWG)) in the UK.

Design And Setting: A secondary analysis of multiple observational studies in the UK.

Participants: Adults from the European Prospective Investigation into Cancer - Oxford(EPIC-Oxford), UK Biobank and Million Women Study, and adults and children aged 5 and over from the National Diet and Nutrition Survey (NDNS).Primary and secondary outcome measures risk of total mortality from Cox proportional hazards regression models, total greenhouse gas emissions (GHGe) and blue water footprint (WF) associated with 'very low' (0-2 recommendations), 'low' (3-4 recommendations) or 'intermediate-to-high' (5-9 recommendations) adherence to EWG recommendations.

Results: Less than 0.1% of the NDNS sample adhere to all nine EWG recommendations and 30.6% adhere to at least five recommendations. Compared with 'very low' adherence to EWG recommendations, 'intermediate-to-high adherence' was associated with a reduced risk of mortality (risk ratio (RR): 0.93; 99% CI: 0.90 to 0.97) and -1.6 kg COeq/day (95% CI: -1.5 to -1.8), or 30% lower dietary GHGe. Dietary WFs were similar across EWG adherence groups. Of the individual Eatwell guidelines, adherence to the recommendation on fruit and vegetable consumption was associated with the largest reduction in total mortality risk: an RR of 0.90 (99% CI: 0.88 to 0.93). Increased adherence to the recommendation on red and processed meat consumption was associated with the largest decrease in environmental footprints (-1.48 kg COeq/day, 95% CI: -1.79 to 1.18 for GHGe and -22.5 L/day, 95% CI: -22.7 to 22.3 for blue WF).

Conclusions: The health and environmental benefits of greater adherence to EWG recommendations support increased government efforts to encourage improved diets in the UK that are essential for the health of people and the planet in the Anthropocene.
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http://dx.doi.org/10.1136/bmjopen-2020-037554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451532PMC
August 2020

Meat intake and cancer risk: prospective analyses in UK Biobank.

Int J Epidemiol 2020 10;49(5):1540-1552

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

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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http://dx.doi.org/10.1093/ije/dyaa142DOI Listing
October 2020

Circulating Insulin-like Growth Factor-I Concentrations and Risk of 30 Cancers: Prospective Analyses in UK Biobank.

Cancer Res 2020 09 24;80(18):4014-4021. Epub 2020 Jul 24.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Circulating insulin-like growth factor I (IGF-I) is positively associated with the risks of colorectal, breast, and prostate cancer, but evidence for other less common cancers is limited. In this study, we investigated associations between serum IGF-I concentrations and incidence of less common cancers in the UK Biobank study. To enable comparison of effect estimates, and as positive controls, both common and less common cancer sites (total 30) were included in an outcome-wide analysis. Data from 394,388 cancer-free participants in the UK Biobank study were analyzed. Multivariable adjusted Cox proportional hazards models were used to determine associations between baseline serum IGF-I concentrations and cancer incidence, using repeated IGF-I measurements from up to 14,149 participants to correct for regression dilution bias. Higher IGF-I concentration was associated with increased risks of thyroid cancer [HR per 5 nmol/L higher concentration 1.18; 95% confidence interval (CI), 1.01-1.37] in addition to colorectal (HR, 1.08; 95% CI, 1.03-1.13), breast (HR, 1.11; 95% CI, 1.07-1.15), and prostate cancer (HR, 1.08; 95% CI, 1.05-1.12), and reduced risks of ovarian and liver cancer. Mean follow-up was 6.9 years and the possibility that the observed associations may be influenced by reverse causality bias cannot be excluded. Additional nominally significant associations with malignant melanoma, multiple myeloma, oral cancer, and esophageal squamous cell carcinoma did not survive correction for multiple testing. Studies with longer follow-up and pooled analyses are needed to further assess how broad the role of IGF-I is in cancer development. SIGNIFICANCE: The results from this outcome-wide analysis are consistent with a positive association of IGF-I with cancers at several sites.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-1281DOI Listing
September 2020

Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction.

J Med Genet 2021 Jun 26;58(6):369-377. Epub 2020 Jun 26.

Cancer Center Amsterdam, Amsterdam, The Netherlands.

Background: Most cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection.

Objective: We generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score.

Methods: We tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I-III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes.

Results: The scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54×10 highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64×10, highest vs lowest quintile of the weighted multifactorial score).

Conclusion: We found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.
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http://dx.doi.org/10.1136/jmedgenet-2020-106961DOI Listing
June 2021

A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data.

Cancer Epidemiol Biomarkers Prev 2020 09 24;29(9):1731-1738. Epub 2020 Jun 24.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Background: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening.

Methods: United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score ≥7, stage T3-T4, PSA ≥10, or nodal/distant metastases). Using HRs estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age, when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-year-standard risk), was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups.

Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-year-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age.

Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS.

Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483627PMC
September 2020

Hematologic Markers and Prostate Cancer Risk: A Prospective Analysis in UK Biobank.

Cancer Epidemiol Biomarkers Prev 2020 08 26;29(8):1615-1626. Epub 2020 May 26.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Background: Risk factors for prostate cancer are not well understood. Red blood cell, platelet, and white blood cell indices may be markers of a range of exposures that might be related to prostate cancer risk. Therefore, we examined the associations of hematologic parameters with prostate cancer risk.

Methods: Complete blood count data from 209,686 male UK Biobank participants who were free from cancer at study baseline were analyzed. Participants were followed up via data linkage. After a mean follow-up of 6.8 years, 5,723 men were diagnosed with prostate cancer and 323 men died from prostate cancer. Multivariable-adjusted Cox regression was used to estimate adjusted HRs and 95% confidence intervals (CI) for prostate cancer incidence and mortality by hematologic parameters, and corrected for regression dilution bias.

Results: Higher red blood cell (HR per 1 SD increase = 1.09, 95% CI, 1.05-1.13) and platelet counts (HR = 1.07, 1.04-1.11) were associated with an increased risk of prostate cancer. Higher mean corpuscular volume (HR = 0.90, 0.87-0.93), mean corpuscular hemoglobin (HR = 0.90, 0.87-0.93), mean corpuscular hemoglobin concentration (HR = 0.87, 0.77-0.97), and mean sphered cell volume (HR = 0.91, 0.87-0.94) were associated with a lower prostate cancer risk. Higher white blood cell (HR = 1.14, 1.05-1.24) and neutrophil count (HR = 1.27, 1.09-1.48) were associated with prostate cancer mortality.

Conclusions: These associations of blood indices of prostate cancer risk and mortality may implicate shared common causes, including testosterone, nutrition, and inflammation/infection among several others in prostate cancer development and/or progression.

Impact: These associations provide insights into prostate cancer development and progression.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611250PMC
August 2020

Alcohol Consumption and Risk of Parkinson's Disease: Data From a Large Prospective European Cohort.

Mov Disord 2020 07 1;35(7):1258-1263. Epub 2020 May 1.

Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.

Background: Parkinson's disease (PD) etiology is not well understood. Reported inverse associations with smoking and coffee consumption prompted the investigation of alcohol consumption as a risk factor, for which evidence is inconclusive.

Objective: To assess the associations between alcohol consumption and PD risk.

Methods: Within NeuroEPIC4PD, a prospective European population-based cohort, 694 incident PD cases were ascertained from 209,998 PD-free participants. Average alcohol consumption at different time points was self-reported at recruitment. Cox regression hazard ratios were estimated for alcohol consumption and PD occurrence.

Results: No associations between baseline or lifetime total alcohol consumption and PD risk were observed. Men with moderate lifetime consumption (5-29.9 g/day) were at ~50% higher risk compared with light consumption (0.1-4.9 g/day), but no linear exposure-response trend was observed. Analyses by beverage type also revealed no associations with PD.

Conclusion: Our data reinforce previous findings from prospective studies showing no association between alcohol consumption and PD risk. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496254PMC
July 2020

Body size and composition, physical activity and sedentary time in relation to endogenous hormones in premenopausal and postmenopausal women: Findings from the UK Biobank.

Int J Cancer 2020 10 24;147(8):2101-2115. Epub 2020 Apr 24.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Anthropometric and lifestyle factors may influence cancer risks through hormonal changes. We investigated cross-sectional associations between body size and composition, physical activity and sedentary time and serum concentrations of oestradiol (premenopausal women only), testosterone, sex hormone binding globulin (SHBG) and insulin-like growth factor-I (IGF-I) in 20 758 premenopausal and 71 101 postmenopausal women in UK Biobank. In premenopausal women, higher BMI (body mass index) was associated with a lower concentration of total oestradiol (15% difference in the highest vs lowest BMI group) and a higher concentration of calculated free oestradiol (22%). In both premenopausal and postmenopausal women, higher BMI was associated with higher concentrations of total and calculated free testosterone (premenopausal 29% and 113%, postmenopausal 39% and 126%, respectively) and lower concentrations of SHBG and IGF-I (premenopausal 51% and 14%, postmenopausal 51% and 12%, respectively). Similar associations were observed with waist to height ratio, waist to hip ratio and body or trunk fat mass. Self-reported physical activity was associated with somewhat lower concentrations of total and calculated free testosterone (premenopausal 10% difference [free testosterone], postmenopausal 5% and 11% difference respectively in the most vs least active group) and a higher concentration of SHBG (premenopausal 11%, postmenopausal 10%), and the opposite was true for self-reported sedentary time. The associations were slightly stronger with accelerometer-measured physical activity, but were attenuated after adjustment for BMI. Overall, our study confirms strong associations of hormones and SHBG with anthropometric factors. The associations with physical activity and sedentary time were at most modest.
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http://dx.doi.org/10.1002/ijc.33010DOI Listing
October 2020

The associations of major foods and fibre with risks of ischaemic and haemorrhagic stroke: a prospective study of 418 329 participants in the EPIC cohort across nine European countries.

Eur Heart J 2020 07;41(28):2632-2640

Department of Public Health and Clinical Medicine, Umeå University, 901 87 Umeå, Sweden.

Aim: To investigate the associations between major foods and dietary fibre with subtypes of stroke in a large prospective cohort.

Methods And Results: We analysed data on 418 329 men and women from nine European countries, with an average of 12.7 years of follow-up. Diet was assessed using validated country-specific questionnaires which asked about habitual intake over the past year, calibrated using 24-h recalls. Multivariable-adjusted Cox regressions were used to estimate hazard ratios (HRs) for ischaemic and haemorrhagic stroke associated with consumption of red and processed meat, poultry, fish, dairy foods, eggs, cereals, fruit and vegetables, legumes, nuts and seeds, and dietary fibre. For ischaemic stroke (4281 cases), lower risks were observed with higher consumption of fruit and vegetables combined (HR; 95% CI per 200 g/day higher intake, 0.87; 0.82-0.93, P-trend < 0.001), dietary fibre (per 10 g/day, 0.77; 0.69-0.86, P-trend < 0.001), milk (per 200 g/day, 0.95; 0.91-0.99, P-trend = 0.02), yogurt (per 100 g/day, 0.91; 0.85-0.97, P-trend = 0.004), and cheese (per 30 g/day, 0.88; 0.81-0.97, P-trend = 0.008), while higher risk was observed with higher red meat consumption which attenuated when adjusted for the other statistically significant foods (per 50 g/day, 1.07; 0.96-1.20, P-trend = 0.20). For haemorrhagic stroke (1430 cases), higher risk was associated with higher egg consumption (per 20 g/day, 1.25; 1.09-1.43, P-trend = 0.002).

Conclusion: Risk of ischaemic stroke was inversely associated with consumption of fruit and vegetables, dietary fibre, and dairy foods, while risk of haemorrhagic stroke was positively associated with egg consumption. The apparent differences in the associations highlight the importance of examining ischaemic and haemorrhagic stroke subtypes separately.
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http://dx.doi.org/10.1093/eurheartj/ehaa007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377582PMC
July 2020

Adult weight change and premenopausal breast cancer risk: A prospective pooled analysis of data from 628,463 women.

Int J Cancer 2020 09 15;147(5):1306-1314. Epub 2020 Feb 15.

Albert Einstein College of Medicine, Bronx, NY.

Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18-24 years and other breast cancer risk factors showed that weight gain from ages 18-24 to 35-44 or to 45-54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.95-0.98) and with oestrogen-receptor(ER)-positive breast cancer (HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.94-0.98). Weight gain from ages 25-34 was inversely associated with ER-positive breast cancer only and weight gain from ages 35-44 was not associated with risk. None of these weight gains were associated with ER-negative breast cancer. Weight loss was not consistently associated with overall or ER-specific risk after adjusting for initial weight. Weight increase from early-adulthood to ages 45-54 years is associated with a reduced premenopausal breast cancer risk independently of early-adulthood weight. Biological explanations are needed to account for these two separate factors.
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http://dx.doi.org/10.1002/ijc.32892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365745PMC
September 2020

This is not the EAT-Lancet Diet - Authors' reply.

Lancet 2020 01;395(10220):272

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.

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http://dx.doi.org/10.1016/S0140-6736(19)32542-5DOI Listing
January 2020

Physical activity and breast cancer risk: results from the UK Biobank prospective cohort.

Br J Cancer 2020 03 10;122(5):726-732. Epub 2020 Jan 10.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: Previous studies suggest a protective role of physical activity in breast cancer risk, largely based on self-reported activity. We aimed to clarify this association by examining breast cancer risk in relation to self-reported physical activity, informed by accelerometer-based measures in a large subset of participants.

Methods: We analysed data from 47,456 premenopausal and 126,704 postmenopausal women in UK Biobank followed from 2006 to 2014. Physical activity was self-reported at baseline, and at resurvey in a subsample of 6443 participants. Accelerometer data, measured from 2013 to 2015, were available in 20,785 women. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using multivariable-adjusted Cox regression.

Results: A total of 3189 cases were diagnosed during follow-up (mean = 5.7 years). Women in the top compared with the bottom quartile of self-reported physical activity had a reduced risk of both premenopausal (RR 0.75; 95% CI 0.60-0.93) and postmenopausal breast cancer (RR 0.87; 95% CI 0.78-0.98), after adjusting for adiposity. In analyses utilising physical activity values assigned from accelerometer measurements, an increase of 5 milli-gravity was associated with a 21% (RR 0.79; 95% CI 0.66-0.95) reduction in premenopausal and a 16% (RR 0.84; 95% CI 0.73-0.96) reduction in postmenopausal breast cancer risk.

Conclusions: Greater physical activity is associated with a reduction in breast cancer risk, which appears to be independent of any association it may have on risk through its effects on adiposity.
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http://dx.doi.org/10.1038/s41416-019-0700-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054300PMC
March 2020
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