Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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The association between vitamin D status and parameters for bone density and quality is modified by Body Mass Index
Sohl, E. ; Jongh, R.T. de; Swart, K.M.A. ; Enneman, A.W. ; Wijngaarden, J.P. van; Dijk, S.C. van; Ham, A.C. ; Zwaluw, N.L. van der; Brouwer-Brolsma, E.M. ; Velde, N. van der; Groot, C.P.G.M. de; Velde, S.J. te; Lips, P. ; Schoor, N.M. van - \ 2015
Calcified Tissue International 96 (2015)2. - ISSN 0171-967X - p. 113 - 122.
quantitative ultrasound parameters - mineral density - postmenopausal women - d deficiency - physical performance - 25-hydroxyvitamin d - risk-assessment - older persons - population - metaanalysis
The association of vitamin D status with bone mineral density (BMD) and Quantitative Ultrasound measurements (QUS) has been inconsistent in previous studies, probably caused by moderating effects. This study explored (1) the association of vitamin D status with QUS and BMD, and (2) whether these associations were modified by body mass index (BMI), age, gender, or physical activity. Two-independent cohorts of the Longitudinal Aging Study Amsterdam (LASA-I, 1995/1996, aged =65; LASA-II, 2008/2009, aged 61–71) and baseline measurement of the B-vitamins for the prevention of osteoporotic fractures (B-PROOF) study (2008–2011, aged 65+) were used. QUS measurements [broadband ultrasound attenuation (BUA) and speed of sound (SOS)] were performed at the calcaneus in all three cohorts (N = 1,235, N = 365, N = 1319); BMD was measured by Dual X-ray absorptiometry (DXA) in B-PROOF (N = 1,162 and 1,192 for specific sites) and LASA-I (N = 492 and 503). The associations of vitamin D status with BUA and BMD were modified by BMI. Only in persons with low-to-normal BMI (
Effect of vitamin B12 and folic acid supplementation on bone mineral density and quantitative ultrasound parameters in older people with an elevated plasma homocysteine level: B-PROOF, a randomized controlled trial
Enneman, A.W. ; Swart, K.M.A. ; Wijngaarden, J.P. van; Dijk, S.C. van; Ham, A.C. ; Brouwer-Brolsma, E.M. ; Zwaluw, N.L. van der; Dhonukshe-Rutten, R.A.M. ; Cammen, T.J.M. van der; Groot, C.P.G.M. de; Meurs, J.B.J. van; Lips, P. ; Uitterlinden, A.G. ; Zillikens, M.C. ; Schoor, N.M. van; Velde, N. van der - \ 2015
Calcified Tissue International 96 (2015)5. - ISSN 0171-967X - p. 401 - 409.
placebo-controlled trial - postmenopausal women - fracture risk - turnover markers - elderly-women - metaanalysis - association - population - folate - bmd
High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged =65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12, 400 µg folic acid, and 600 IU vitamin D or placebo with 600 IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2 years, FN-BMD and BUA had significantly decreased, while LS-BMD significantly increased (all p <0.01) and SOS did not change in either treatment arm. No statistically significant differences between the intervention and placebo group were present for FN-BMD (p = 0.24), LS-BMD (p = 0.16), SOS (p = 0.67), and BUA (p = 0.96). However, exploratory subgroup analyses revealed a small positive effect of the intervention on BUA at follow-up among compliant persons >80 years (estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group, p = 0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80 years who were compliant in taking the supplement.
Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort
Dossus, L. ; Boutron-Ruault, M.C. ; Kaaks, R. ; Gram, I.T. ; Vilier, A. ; Fervers, B. ; Manjer, J. ; Tjonneland, A. ; Olsen, A. ; Overvad, K. ; Chang-Claude, J. ; Boeing, H. ; Steffen, A. ; Trichopoulou, A. ; Lagiou, P. ; Sarantopoulou, M. ; Palli, D. ; Berrino, F. ; Tumino, R. ; Vineis, P. ; Mattiello, A. ; Bueno-de-Mesquita, H.B. ; Duijnhoven, F.J.B. van - \ 2014
International Journal of Cancer 134 (2014)8. - ISSN 0020-7136 - p. 1871 - 1888.
environmental tobacco-smoke - postmenopausal women - california teachers - 1st childbirth - never smokers - exposure - metaanalysis - association - carcinogens - reanalysis
Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05–1.28], 1.14 [1.04–1.25] and 1.10 [1.01–1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29–2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34–0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious.
Nutritional aspects of metabolic inflammation in relation to health-insights from transcriptomic biomarkers in PBMC of fatty acids and polyphenols
Afman, L.A. ; Milenkovic, D. ; Roche, H. - \ 2014
Molecular Nutrition & Food Research 58 (2014)8. - ISSN 1613-4125 - p. 1708 - 1720.
blood mononuclear-cells - gene-expression profiles - fish-oil supplementation - improves insulin sensitivity - randomized controlled-trial - coronary-artery-disease - adipose-tissue - postmenopausal women - nlrp3 inflammasome - in-vivo
Recent research has highlighted potential important interaction between metabolism and inflammation, within the context of metabolic health and nutrition, with a view to preventing diet-related disease. In addition to this, there is a paucity of evidence in relation to accurate biomarkers that are capable of reflecting this important biological interplay or relationship between metabolism and inflammation, particularly in relation to diet and health. Therefore the objective of this review is to highlight the potential role of transcriptomic approaches as a tool to capture the mechanistic basis of metabolic inflammation. Within this context, this review has focused on the potential of peripheral blood mononuclear cells transcriptomic biomarkers, because they are an accessible tissue that may reflect metabolism and subacute chronic inflammation. Also these pathways are often dysregulated in the common diet-related diseases obesity, type 2 diabetes, and cardiovascular disease, thus may be used as markers of systemic health. The review focuses on fatty acids and polyphenols, two classes of nutrients/nonnutrient food components that modulate metabolism/inflammation, which we have used as an example of a proof-of-concept with a view to understanding the extent to which transcriptomic biomarkers are related to nutritional status and/or sensitive to dietary interventions. We show that both nutritional components modulate inflammatory markers at the transcriptomic level with the capability of profiling pro- and anti-inflammatory mechanisms in a bidirectional fashion; to this end transcriptomic biomarkers may have potential within the context of metabolic inflammation. This transcriptomic biomarker approach may be a sensitive indicator of nutritional status and metabolic health.
Identification of coregulators influenced by estrogen receptor subtype specific binding of the ER antagonists 4-hydroxytamoxifen and fulvestrant
Evers, N.M. ; Wang, S. ; Berg, J.H.J. van den; Houtman, J. ; Melchers, D. ; Haan, L.H.J. de; Ederveen, A.G.H. ; Groten, J.P. ; Rietjens, I. - \ 2014
Chemico-Biological Interactions 220 (2014). - ISSN 0009-2797 - p. 222 - 230.
breast-cancer-cells - postmenopausal women - endogenous estrogens - molecular-mechanisms - beta expression - in-vitro - alpha - tamoxifen - proliferation - progression
The aim of the present study was to investigate modulation of the interaction of ERa and ERß with coregulators in the ligand dependent responses induced by the ER antagonistic compounds 4OHT and fulvestrant. Comparison with the modulation index (MI) profiles for the ER agonist estradiol (E2) will elucidate whether differences in the (ant)agonist dependent interaction of ERa and ERß with coregulators expressed in MI profiles contribute to the differences in (ant)agonist responses. To this end, the selected ER antagonistic compounds were first characterized for intrinsic relative potency and efficacy towards ERa and ERß using ER selective U2OS reporter gene assays, and subsequently tested for ligand dependent modulation of the interaction of ERa and ERß with coregulators using the MARCoNI assay. Results obtained indicate a preference of 4OHT to antagonize ERß and find fulvestrant to be less ER specific. MARCoNI assay responses reveal that ERa and ERß mediated interaction with coregulators expressed in MI profiles are similar for 4OHT and fulvestrant and generally opposite to the MI profile of the ER agonist E2. Hierarchical clustering based on the MI profiles appeared able to clearly discriminate the two compounds with ER antagonistic properties from the ER agonist E2. Taken together the data reveal that modulation of the interaction of ERs with coregulators discriminates ER agonists from antagonists but does not discriminate between the less specific ER antagonist fulvestrant and the preferential ERß antagonistic compound 4OHT. It is concluded that differences in modulation of the interaction of ERa and ERß with coregulators contribute to the differences in ligand dependent responses induced by ER agonists and ER antagonists but the importance of the subtle differences in modulation of the interaction of ERs with coregulators between the ER antagonistic compounds 4OHT and fulvestrant for the ultimate biological effect remains to be established.
The association between plasma homocysteine levels and bone quality and bone mineral density parameters in older persons
Enneman, A.W. ; Swart, K.M.A. ; Zillikens, M.C. ; Dijk, S.C. van; Wijngaarden, J.P. van; Brouwer-Brolsma, E.M. ; Dhonukshe-Rutten, R.A.M. ; Hofman, A. ; Rivadeneira, F. ; Cammen, T.J.M. van der; Lips, P. ; Groot, C.P.G.M. de; Uitterlinden, A.G. ; Meurs, J.B.J. van; Schoor, N.M. van; Velde, N. van der - \ 2014
Bone 63 (2014). - ISSN 8756-3282 - p. 141 - 146.
band ultrasound attenuation - quantitative ultrasound - postmenopausal women - fracture risk - osteoporotic fracture - elderly-people - vitamin-b-12 - homocystinuria - mortality - turnover
Introduction High plasma homocysteine levels have been associated with incident osteoporotic fractures, but the mechanisms underlying this association are still unknown. It has been hypothesized that homocysteine might interfere with collagen cross-linking in bone, thereby weakening bone structure. Therefore, we wanted to investigate whether plasma homocysteine levels are associated with bone quality parameters, rather than with bone mineral density. Methods Cross-sectional data of the B-PROOF study (n = 1227) and of two cohorts of the Rotterdam Study (RS-I (n = 2850) and RS-II (n = 2023)) were used. Data on bone mineral density of the femoral neck and lumbar spine were obtained in these participants using dual-energy X-ray assessment (DXA). In addition, participants of B-PROOF and RS-I underwent quantitative ultrasound measurement of the calcaneus, as a marker for bone quality. Multiple linear regression analysis was used to investigate the associations between natural-log transformed plasma levels of homocysteine and bone mineral density or ultrasound parameters. Results Natural-log transformed homocysteine levels were inversely associated with femoral neck bone mineral density in the two cohorts of the Rotterdam Study (B = - 0.025, p = 0.004 and B = - 0.024, p = 0.024). In B-PROOF, no association was found. Pooled data analysis showed significant associations between homocysteine and bone mineral density at both femoral neck (B = - 0.032, p = 0.010) and lumbar spine (B = - 0.098, p = 0.021). Higher natural-log transformed homocysteine levels associated significantly with lower bone ultrasound attenuation in B-PROOF (B = - 3.7, p = 0.009) and speed of sound in both B-PROOF (B = - 8.9, p = 0.001) and RS-I (B = - 14.5, p = 0.003), indicating lower bone quality. Pooled analysis confirmed the association between homocysteine and SOS (B = - 13.1, p = 0.016). Results from ANCOVA-analysis indicate that differences in SOS and BUA between participants having a plasma homocysteine level above or below median correspond to 0.14 and 0.09 SD, respectively. Discussion In this study, plasma levels of homocysteine were significantly inversely associated with both bone ultrasound parameters and with bone mineral density. However, the size of the associations seems to be of limited clinical relevance and may therefore not explain the previously observed association between plasma homocysteine and osteoporotic fracture incidence.
Estimating the mediating effect of different biomarkers on the relation of alcohol consumption with the risk of type 2 diabetes
Beulens, J.W.J. ; Schouw, Y.T. van der; Moons, K.G.M. ; Boshuizen, H.C. ; A, D.L. van der; Groenwold, R.H.H. - \ 2013
Annals of Epidemiology 23 (2013)4. - ISSN 1047-2797 - p. 193 - 197.
coronary-heart-disease - food frequency questionnaire - high-density-lipoprotein - myocardial-infarction - postmenopausal women - insulin sensitivity - epic-nl - moderate - metaanalysis - validity
Purpose Moderate alcohol consumption is associated with a reduced type 2 diabetes risk, but the biomarkers that explain this relation are unknown. The most commonly used method to estimate the proportion explained by a biomarker is the difference method. However, influence of alcohol–biomarker interaction on its results is unclear. G-estimation method is proposed to accurately assess proportion explained, but how this method compares with the difference method is unknown. Methods In a case–cohort study of 2498 controls and 919 incident diabetes cases, we estimated the proportion explained by different biomarkers on the relation between alcohol consumption and diabetes using the difference method and sequential G-estimation method. Results Using the difference method, high-density lipoprotein cholesterol explained the relation between alcohol and diabetes by 78% (95% confidence interval [CI], 41–243), whereas high-sensitivity C-reactive protein (-7.5%; -36.4 to 1.8) or blood pressure (-6.9; -26.3 to -0.6) did not explain the relation. Interaction between alcohol and liver enzymes led to bias in proportion explained with different outcomes for different levels of liver enzymes. G-estimation method showed comparable results, but proportions explained were lower. Conclusions The relation between alcohol consumption and diabetes may be largely explained by increased high-density lipoprotein cholesterol but not by other biomarkers. Ignoring exposure–mediator interactions may result in bias. The difference and G-estimation methods provide similar results.
Mechanisms underlying the dualistic mode of action of major soy isoflavones in relation to cell proliferation and cancer risks
Rietjens, I.M.C.M. ; Sotoca, A.M. ; Vervoort, J. ; Louisse, J. - \ 2013
Molecular Nutrition & Food Research 57 (2013)1. - ISSN 1613-4125 - p. 100 - 113.
estrogen-receptor-beta - randomized controlled-trial - health initiative memory - mediated gene-regulation - tumor-suppressor genes - breast-cancer - prostate-cancer - postmenopausal women - in-vitro - messenger-rna
Isoflavones are phytoestrogens that have been linked to both beneficial as well as adverse effects in relation to cell proliferation and cancer risks. The present article presents an overview of these seemingly contradicting health effects and of mechanisms that could be involved in this dualistic mode of action. One mechanism relates to the different ultimate cellular effects of activation of estrogen receptor (ER) a, promoting cell proliferation, and of ERß, promoting apoptosis, with the major soy isoflavones genistein and daidzein activating especially ERß. A second mode of action includes the role of epigenetics, including effects of isoflavones on DNA methylation, histone modification and miRNA expression patterns. The overview presented reveals that we are only at the start of unraveling the complex underlying mode of action for effects of isoflavones, both beneficial or adverse, on cell proliferation and cancer risks. It is evident that whatever model system will be applied, its relevance to human tissues with respect to ERa and ERß levels, co-repressor and co-activator characteristics as well as its relevance to human exposure regimens, needs to be considered and defined
Hormonal, Metabolic, and Inflammatory Profiles and Endometrial Cancer Risk Within the EPIC Cohort-A Factor Analysis
Dossus, L. ; Lukanova, A. ; Rinaldi, S. ; Allen, N. ; Cust, A.E. ; Becker, S. ; Tjonneland, A. ; Hansen, L. ; Overvad, K. ; Chabbert-Buffet, N. ; Mesrine, S. ; Clavel-Chapelon, F. ; Teucher, B. ; Duijnhoven, F.J.B. van - \ 2013
American Journal of Epidemiology 177 (2013)8. - ISSN 0002-9262 - p. 787 - 799.
growth-factor-i - postmenopausal women - insulin-resistance - adipose-tissue - c-peptide - nutrition - obesity - premenopausal - pathogenesis - adiponectin
A “Western” lifestyle characterized by physical inactivity and excess weight is associated with a number of metabolic and hormonal dysregulations, including increased circulating estrogen levels, hyperinsulinemia, hyperglycemia, and chronic inflammation. The same hormonal and metabolic axes might mediate the association between this lifestyle and the development of endometrial cancer. Using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study carried out in 10 European countries during 1992–2000, we conducted a factor analysis to delineate important components that summarize the variation explained by a set of biomarkers and to examine their association with endometrial cancer risk. Prediagnostic levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, estrone, estradiol, C-peptide, insulin-like growth factor-binding proteins 1 and 2, adiponectin, high- and low-density lipoprotein cholesterol, glucose, triglycerides, tumor necrosis factor (TNF) a, soluble TNF receptors 1 and 2, C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist were measured in 233 incident endometrial cancer cases and 446 matched controls. Factor analysis identified 3 components associated with postmenopausal endometrial cancer risk that could be labeled “insulin resistance/metabolic syndrome,” “steroids,” and “inflammation” factors. A fourth component, “lipids,” was not significantly associated with endometrial cancer. In conclusion, besides the well-known associations of risk with sex hormones and insulin-regulated physiological axes, our data further support the hypothesis that inflammation factors play a role in endometrial carcinogenesis.
Plasma 25(OH)vitamin D and the risk of breast cancer in the european prospective investigation into cancer and nutrition (EPIC): A nested case-control study
Kühn, T. ; Kaaks, R. ; Becker, S. ; Eomois, P.P. ; Clavel-Chapelon, F. ; Kvaskoff, M. ; Dossus, L. ; Duijnhoven, F.J.B. van - \ 2013
International Journal of Cancer 133 (2013)7. - ISSN 0020-7136 - p. 1689 - 1700.
d-binding protein - circulating vitamin-d - french e3n cohort - postmenopausal women - nurses health - serum-levels - association - prevention - calcium - time
Experimental evidence suggests that vitamin D might play a role in the development of breast cancer. Although the results of case–control studies indicate that circulating 25-hydroxyvitamin D [25(OH)D] is inversely associated with the risk of breast cancer, the results of prospective studies are inconsistent. A case–control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) was carried out comprising 1,391 incident breast cancer cases and 1,391 controls. Multivariable conditional logistic regression models did not reveal a significant overall association between season-standardized 25(OH)D levels and the risk of breast cancer (ORQ4–Q1 [95% CI]: 1.07 [0.85–1.36], ptrend = 0.67). Moreover, 25(OH)D levels were not related to the risks of estrogen receptor positive tumors (ORQ4–Q1 [95% CI]: 0.97 [0.67–1.38], ptrend = 0.90) and estrogen receptor negative tumors (ORQ4–Q1 [95% CI]: 0.97 [0.66–1.42], ptrend = 0.98). In hormone replacement therapy (HRT) users, 25(OH)D was significantly inversely associated with incident breast cancer (ORlog2 [95% CI]: 0.62 [0.42–0.90], p = 0.01), whereas no significant association was found in HRT nonusers (ORlog2 [95% CI]: 1.14 [0.80–1.62], p = 0.48). Further, a nonsignificant inverse association was found in women with body mass indices (BMI) <25 kg/m2 (ORlog2 [95% CI]: 0.83 [0.67–1.03], p = 0.09), as opposed to a borderline significant positive association in women with BMI = 25 kg/m2 (ORlog2 [95% CI]: 1.30 [1.0–1.69], p = 0.05). Overall, prediagnostic levels of circulating 25(OH)D were not related to the risk of breast cancer in the EPIC study. This result is in line with findings in the majority of prospective studies and does not support a role of vitamin D in the development of breast cancer
Alcohol consumption before and after breast cancer diagnosis: associations with survival from breast cancer, cardiovascular disease, and other causes
Newcomb, P.A. ; Kampman, E. ; Trentham-Dietz, A. ; Egan, K.M. ; Titus, L.J. ; Baron, J.A. ; Hampton, J.M. ; Passarelli, M.N. ; Willett, W.C. - \ 2013
Journal of Clinical Oncology 31 (2013)16. - ISSN 0732-183X - p. 1939 - 1946.
food frequency questionnaire - progesterone-receptor status - hormone replacement therapy - national death index - womens health - risk-factors - postmenopausal women - mammographic density - prognostic-factors - physical-activity
Purpose Alcohol intake is associated with increased risk of breast cancer. In contrast, the relation between alcohol consumption and breast cancer survival is less clear. Patients and Methods We assessed pre- and postdiagnostic alcohol intake in a cohort of 22,890 women with incident invasive breast cancer who were residents of Wisconsin, Massachusetts, or New Hampshire and diagnosed from 198 to 200 at ages 20 to 79 years. All women reported on prediagnostic intake; a subsample of 4,881 reported on postdiagnostic intake. Results During a median follow-up of 11.3 years from diagnosis, 7,780 deaths occurred, including 3,484 resulting from breast cancer. Hazard ratios (HR) and 95% CIs were estimated. Based on a quadratic analysis, moderate alcohol consumption before diagnosis was modestly associated with disease-specific survival (compared with nondrinkers, HR = 0.93 [95% CI, 0.85 to 1.02], 0.85 [95% CI, 0.75 to 0.95], 0.88 [95% CI, 0.75 to 1.02], and 0.89 [95% CI, 0.77 to 1.04] for two or more, three to six, seven to nine, and = 10 drinks/wk, respectively). Alcohol consumption after diagnosis was not associated with disease-specific survival (compared with nondrinkers, HR = 0.88 [95% CI, 0.61 to 1.27], 0.80 [95% CI, 0.49 to 1.32], 1.01 [95% CI, 0.55 to 1.87], and 0.83 [95% CI, 0.45 to 1.54] for two or more, three to six, seven to nine, and = 10 drinks/wk, respectively). Results did not vary by beverage type. Women consuming moderate levels of alcohol, either before or after diagnosis, experienced better cardiovascular and overall survival than nondrinkers. Conclusion Overall alcohol consumption before diagnosis was not associated with disease-specific survival, but we found a suggestion favoring moderate consumption. There was no evidence for an association with postdiagnosis alcohol intake and breast cancer survival. This study, however, does provide support for a benefit of limited alcohol intake for cardiovascular and overall survival in women with breast cancer.
Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis
Ras, R.T. ; Streppel, M.T. ; Draijer, R. ; Zock, P.L. - \ 2013
International Journal of Cardiology 168 (2013)1. - ISSN 0167-5273 - p. 344 - 351.
coronary-artery-disease - chronic heart-failure - endothelial dysfunction - brachial-artery - prognostic role - chest-pain - postmenopausal women - mortality risk - events - vasodilation
Background Flow-mediated dilation (FMD) is an accepted technique to quantify endothelial function and has shown to have prognostic value for future cardiovascular disease (CVD). The predictive strength of FMD in CVD patients compared to populations not diagnosed for CVD warrants further investigation. We systematically reviewed prospective studies that investigated the association between brachial FMD and future cardiovascular events, with particular focus on the role of underlying health status. Methods To obtain eligible studies, several literature databases were systematically searched through March 2011. Pooled overall risk estimates were calculated separately for continuous risk estimates for CVD (per 1% higher FMD) and for categorical risk estimates for CVD (having high vs. low FMD), based on random-effects models. Results A total of 23 studies including 14,753 subjects were eligible for inclusion in the meta-analysis. For studies reporting continuous risk estimates, the pooled overall CVD risk was 0.92 (95%CI: 0.88; 0.95) per 1% higher FMD. The observed association seemed stronger (P-value <0.01) in diseased populations than in asymptomatic populations (0.87 (95%CI: 0.83; 0.92) and 0.96 (95%CI: 0.92; 1.00) per 1% higher FMD, respectively). For studies reporting categorical risk estimates, the pooled overall CVD risk for high vs. low FMD was similar in both types of populations, on average 0.49 (95%CI: 0.39; 0.62). Conclusions Our findings show that brachial FMD is inversely associated with future CVD events, with some indications for a stronger relation in diseased populations. Endothelial dysfunction may be considered relevant for classifying subjects in terms of CVD risk.
Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study
Buckland, G. ; Travier, N. ; Cottet, V. ; Gonzalez, C.A. ; Lujan-Barroso, L. ; Agudo, A. ; Trichopoulou, A. ; Lagiou, P. ; Trichopoulos, D. ; Duijnhoven, F.J.B. van - \ 2013
International Journal of Cancer 132 (2013)12. - ISSN 0020-7136 - p. 2918 - 2927.
postmenopausal women - fatty-acid - patterns - estrogen - population - metaanalysis - calibration - rationale - validity - disease
Epidemiological evidence suggests that the Mediterranean diet (MD) could reduce the risk of breast cancer (BC). As evidence from the prospective studies remains scarce and conflicting, we investigated the association between adherence to the MD and risk of BC among 335,062 women recruited from 1992 to 2000, in ten European countries, and followed for 11 years on average. Adherence to the MD was estimated through an adapted relative Mediterranean diet (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for BC risk factors. A total of 9,009 postmenopausal and 1,216 premenopausal first primary incident invasive BC were identified (5,862 estrogen or progesterone receptor positive [ER+/PR+] and 1,018 estrogen and progesterone receptor negative [ER-/PR-]). The arMED was inversely associated with the risk of BC overall and in postmenopausal women (high vs. low arMED score; hazard ratio [HR] = 0.94 [95% confidence interval [CI]: 0.88, 1.00] ptrend = 0.048, and HR = 0.93 [95% CI: 0.87, 0.99] ptrend = 0.037, respectively). The association was more pronounced in ER-/PR- tumors (HR = 0.80 [95% CI: 0.65, 0.99] ptrend = 0.043). The arMED score was not associated with BC in premenopausal women. Our findings show that adherence to a MD excluding alcohol was related to a modest reduced risk of BC in postmenopausal women, and this association was stronger in receptor-negative tumors. The results support the potential scope for BC prevention through dietary modification.
Physical activity and risk of breast cancer overall and by hormone receptor status: The European prospective investigation into cancer and nutrition
Steindorf, K. ; Ritte, R. ; Eomois, P.P. ; Lukanova, A. ; Tjonneland, A. ; Johnsen, N.F. ; Overvad, K. ; Ostergaard, J.N. ; Clavel-Chapelon, F. ; Duijnhoven, F.J.B. van - \ 2013
International Journal of Cancer 132 (2013)7. - ISSN 0020-7136 - p. 1667 - 1678.
postmenopausal women - estrogen-receptor - activity questionnaire - body-size - repeatability - validity - health - prevention - exercise - age
Physical activity is associated with reduced risks of invasive breast cancer. However, whether this holds true for breast cancer subtypes defined by the estrogen receptor (ER) and the progesterone receptor (PR) status is controversial. The study included 257,805 women from the multinational EPIC-cohort study with detailed information on occupational, recreational and household physical activity and important cofactors assessed at baseline. During 11.6 years of median follow-up, 8,034 incident invasive breast cancer cases were identified. Data on ER, PR and combined ER/PR expression were available for 6,007 (67.6%), 4,814 (54.2%) and 4,798 (53.9%) cases, respectively. Adjusted hazard ratios (HR) were estimated by proportional hazards models. Breast cancer risk was inversely associated with moderate and high levels of total physical activity (HR = 0.92, 95% confidence interval (CI): 0.86–0.99, HR = 0.87, 95%-CI: 0.79–0.97, respectively; p-trend = 0.002), compared to the lowest quartile. Among women diagnosed with breast cancer after age 50, the largest risk reduction was found with highest activity (HR = 0.86, 95%-CI: 0.77–0.97), whereas for cancers diagnosed before age 50 strongest associations were found for moderate total physical activity (HR = 0.78, 95%-CI: 0.64–0.94). Analyses by hormone receptor status suggested differential associations for total physical activity (p-heterogeneity = 0.04), with a somewhat stronger inverse relationship for ER+/PR+ breast tumors, primarily driven by PR+ tumors (p-heterogeneity <0.01). Household physical activity was inversely associated with ER–/PR– tumors. The results of this largest prospective study on the protective effects of physical activity indicate that moderate and high physical activity are associated with modest decreased breast cancer risk. Heterogeneities by receptor status indicate hormone-related mechanisms.
Consumption of dairy products and associations with incident diabetes, CHD and mortality in the Whitehall II study
Soedamah-Muthu, S.S. ; Masset, G. ; Verberne, L.D.M. ; Geleijnse, J.M. ; Brunner, E.J. - \ 2013
British Journal of Nutrition 109 (2013)4. - ISSN 0007-1145 - p. 718 - 726.
ischemic-heart-disease - postmenopausal women - metabolic syndrome - vascular-disease - life-style - fat intake - vitamin-d - risk - mellitus - milk
Few prospective studies have examined the effects of different types of dairy food on the risks of type 2 diabetes, CHD and mortality. We examined whether intakes of total dairy, high-fat dairy, low-fat dairy, milk and fermented dairy products were related to these outcomes in the Whitehall II prospective cohort study. At baseline, dairy consumption was assessed by FFQ among 4526 subjects (72 % men) with a mean age 56 (sd 6) years. Death certificates and medical records were used to ascertain CHD mortality and non-fatal myocardial infarction. Incident diabetes was detected by the oral glucose tolerance test or self-report. Incidence data were analysed using Cox proportional hazards models, adjusted for lifestyle and dietary factors. During approximately 10 years of follow-up, 273 diabetes, 323 CHD and 237 all-cause mortality cases occurred. In multivariable models, intakes of total dairy and types of dairy products were not significantly associated with incident diabetes or CHD (all P values for trend >0·1). Fermented dairy products was inversely associated with overall mortality (hazard ratios approximately 0·7 in the middle and highest tertiles; P for trend <0·01) but not with incident CHD or diabetes (P>0·3). In conclusion, intakes of total dairy and types of dairy products showed no consistent relationship with incident diabetes, CHD or all-cause mortality.
Recreational physical activity, body mass index, and survival in women with colorectal cancer
Kuiper, J. ; Phipps, A.I. ; Neuhouser, M.L. ; Chlebowski, R.T. ; Thomson, C.A. ; Irwin, M.L. ; Lane, D.S. ; Wactawski-Wende, J. ; Hou, L. ; Jackson, R.D. ; Kampman, E. ; Newcomb, P.A. - \ 2012
Cancer Causes and Control 23 (2012)12. - ISSN 0957-5243 - p. 1939 - 1948.
treatment-related toxicity - iii colon-cancer - breast-cancer - rectal-cancer - united-states - activity questionnaire - adjuvant chemotherapy - postmenopausal women - patient survival - risk
Previous studies have shown that physical inactivity and obesity are risk factors for the development of colorectal cancer. However, controversy exists regarding the influence of these factors on survival in colorectal cancer patients. We evaluated the impact of recreational physical activity and body mass index (BMI) before and after colorectal cancer diagnosis on disease-specific mortality and all-cause mortality. Patients and methods This prospective cohort study included 1,339 women enrolled in the Women’s Health Initiative study who were diagnosed with colorectal cancer subsequent to study enrollment. BMI and recreational physical activity were measured before cancer diagnosis at study entry (pre-diagnostic) and after diagnosis at study follow-up interviews (post-diagnostic). We used Cox regression to estimate the association between pre- and post-diagnostic exposures and survival after colorectal cancer diagnosis. Results Among women diagnosed with colorectal cancer, 265 (13 %) deaths occurred during a median study follow-up of 11.9 years, of which 171 (65 %) were attributed to colorectal cancer. Compared with women reporting no pre-diagnostic recreational physical activity, those reporting activity levels of =18 MET-h/week had significantly lower colorectal cancer-specific mortality (hazard ratio (HR) = 0.68; 95 % confidence interval (CI): 0.41–1.13) and all-cause mortality (HR = 0.63; 95 % CI: 0.42–0.96). Similar inverse associations were seen for post-diagnostic recreational physical activity. Neither pre- nor post-diagnostic BMI were associated with mortality after colorectal cancer diagnosis. Conclusion Recreational physical activity before and after colorectal cancer diagnosis, but not BMI, is associated with more favorable survival.
Prospective study on physical activity and risk of in situ breast cancer
Steindorf, K. ; Ritte, R. ; Tjonneland, A. ; Johnsen, N.F. ; Overvad, K. ; Ostergaard, J.N. ; Boeing, H. ; Trichopoulou, A. ; Bueno de Mesquita, H.B. ; Duijnhoven, F.J.B. van; Monninkhof, E.M. ; Khaw, K.T. ; Wareham, N.J. ; Wark, P.A. ; Riboli, E. ; Kaaks, R. - \ 2012
Cancer Epidemiology Biomarkers and Prevention 21 (2012)12. - ISSN 1055-9965 - p. 2209 - 2219.
postmenopausal women - activity questionnaire - biologic mechanisms - ductal carcinoma - nutrition - validity - repeatability - exercise - cohort
Background: Physical activity has been identified as protective factor for invasive breast cancer risk, whereas comparable studies on in situ carcinoma are rare. Methods: The study included data from 283,827 women of the multinational European Prospective Investigation into C7ancer and Nutrition (EPIC)-cohort study. Detailed information on different types of physical activity conducted during the prior year, such as occupational, recreational, and household activity, as well as on important cofactors, was assessed at baseline. Adjusted HRs for in situ breast cancer were estimated by Cox proportional hazards models. Results: During a median follow-up period of 11.7 years, 1,059 incidents of breast carcinoma in situ were identified, in crude and adjusted multivariable models, no associations were found for occupational, household, and recreational physical activity. Furthermore, total physical activity was not associated with risk of in situ breast cancer. Comparing moderately inactive, moderately active, and active participants with inactive study participants resulted in adjusted HRs of 0.99 [95% confidence interval (CI), 0.83-1.19], 0.99 (95% CI, 0.82-1.20), and 1.07(95% CI, 0.81-1.40), respectively (P value of trend test: 0.788). No inverse associations were found in any substrata defined by age at diagnosis or body mass index (BMI) status. Conclusions: In this large prospective study, we did not find any evidence of an association between physical activity and in situ breast cancer risk. It not by chance, the contrast between our results for carcinoma in situ and the recognized inverse association for invasive breast cancer suggests that physical activity may have stronger effects on proliferation and late stage carcinogenesis. Cancer Epidemiol Biomarkers Prev; 21(12); 2209-19. (C)2012 AACR.
Leptin and soluble leptin receptor in risk of Nutrition cohort
Aleksandrova, K. ; Boeing, H. ; Jenab, M. ; Bueno de Mesquita, H.B. ; Jansen, E. ; Duijnhoven, F.J.B. van; Rinaldi, S. ; Fedirko, V. ; Romieu, I. ; Riboli, E. - \ 2012
Cancer Research 72 (2012)20. - ISSN 0008-5472 - p. 5328 - 5337.
rectal-cancer - postmenopausal women - insulin-resistance - plasma leptin - colon-cancer - healthy-men - obesity - humans - participants - adiponectin
Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40–0.76; Ptrend = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28–0.63, Ptrend = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48–1.44, Ptrend = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56–1.29, Ptrend = 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations, and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis.
No effects of n)3 fatty acid supplementation on serum total testosterone levels in older men: the Alpha Omega Trial
Giltay, E.J. ; Geleijnse, J.M. ; Heijboer, A.C. ; Goede, J. de; Oude Griep, L.M. ; Blankenstein, M.A. ; Kromhout, D. - \ 2012
International Journal of Andrology 35 (2012)5. - ISSN 0105-6263 - p. 680 - 687.
prostate-cancer risk - hormone-binding globulin - endogenous sex-hormones - late-onset hypogonadism - coronary-heart-disease - postmenopausal women - metabolic syndrome - linolenic acid - elderly-men - fish-oil
The intake of the n-3 fatty acids alpha-linolenic acid (ALA), acid (EPA) and docosahexaenoic acid (DHA) has been related to testosterone levels in epidemiological analyses. The aim of this study was to assess whether the n-3 fatty acids affects testosterone levels in post-myocardial infarction (MI) patients, who are at risk of testosterone deficiency. In a double-blind, placebo-controlled trial of low-dose supplementation of n-3 fatty acids, we included 1850 male post-MI patients aged 60–80 years who participated in the Alpha Omega Trial. Patients were randomly allocated to margarines that provided 400 mg/day of EPA–DHA (n = 453), 2 mg/day of ALA (n = 467), EPA–DHA plus ALA (n = 458), or placebo (n = 472). Serum testosterone levels were assessed at baseline and after 41 months using whole day blood samples obtained at the subjects’ home or at the hospital. Subjects were on average age of 68.4 (SD 5.3) years old and had baseline mean serum total testosterone of 14.8 (SD 5.6) nmol/L. The four randomized groups did not differ for baseline characteristics. ALA, EPA–DHA, and EPA–DHA plus ALA supplementation did not affect serum total testosterone compared to placebo. Moreover, n-3 fatty acid supplementation did not affect the risk of incident testosterone deficiency (n = 76 with total testosterone
Prenylated isoflavonoids from plants as selective estrogen receptor modulators (phytoSERMs)
Simons, R. ; Gruppen, H. ; Bovee, T.F.H. ; Verbruggen, M.A. ; Vincken, J.P. - \ 2012
Food & Function 3 (2012)8. - ISSN 2042-6496 - p. 810 - 827.
hops humulus-lupulus - breast-cancer cells - ionization mass-spectrometry - human liver-microsomes - glycyrrhiza-glabra l - in-vitro - dietary phytoestrogens - antiestrogenic activities - human urine - postmenopausal women
Isoflavonoids are a class of secondary metabolites, which comprise amongst others the subclasses of isoflavones, isoflavans, pterocarpans and coumestans. Isoflavonoids are abundant in Leguminosae, and many of them can bind to the human estrogen receptor (hER) with affinities similar to or lower than that of estradiol. Dietary intake of these so-called phytoestrogens has been associated with positive effects on menopausal complaints, hormone-related cancers, and osteoporosis. Therefore, phytoestrogens are used as nutraceuticals in functional foods or food supplements. Most of the isoflavonoids show agonistic activity towards both hERa and hERß, the extent of which is modulated by the substitution pattern of their skeleton (i.e.-OH, -OCH(3)). Interestingly, substitutions consisting of a five-carbon prenyl group often seem to result in an antiestrogenic activity. There is growing evidence that the action of some of these prenylated isoflavonoids is tissue-specific, suggesting that they act like selective estrogen receptor modulators (SERMs), such as the well-known chemically synthesized raloxifene and tamoxifen. These so-called phytoSERMS might have high potential for realizing new food and pharma applications. In this review, the structural features of isoflavonoids (i.e. the kind of skeleton and prenylation (e.g. chain or pyran), position of the prenyl group on the skeleton, and the extent of prenylation (single, double)) are discussed in relation to their estrogenic activity. Anti-estrogenic and SERM activity of isoflavonoids was always associated with prenylation, but these activities did not seem to be confined to one particular kind/position of prenylation or isoflavonoid subclass. Few estrogens with agonistic activity were prenylated, but these were not tested for antagonistic activity; possibly, these molecules will turn out to be phytoSERMs as well. Furthermore, the data on the dietary occurrence, bioavailability and metabolism of prenylated isoflavonoids are discussed.
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