Publications by authors named "Genevieve Buckland"

60 Publications

Prospective association between a Mediterranean-style dietary score in childhood and cardiometabolic risk in young adults from the ALSPAC birth cohort.

Eur J Nutr 2021 Sep 17. Epub 2021 Sep 17.

Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Purpose: To investigate the prospective association between a children's relative Mediterranean-style diet score (C-rMED) in childhood and a Cardiometabolic Risk (CMR) score in adolescence/young adulthood in the Avon Longitudinal Study of Parents and Children (ALSPAC).

Methods: A C-rMED was calculated at 7, 10 and 13 years from diet diary data. Anthropometric and biochemical data at 17 (N = 1940) and 24 years (N = 1961) were used to calculate CMR scores (sum of sex-specific log-transformed z-scores from triacylglycerol, HDL cholesterol, LDL cholesterol, mean arterial blood pressure, homeostatic model assessment of insulin resistance (HOMA-IR) and fat mass index (FMI)). Adjusted logistic regression models examined associations between C-rMED (categorical and 2-unit increments) and a high CMR score (≥ 80th percentile) and individual CMR components (≥ 80th percentile).

Results: A high C-rMED at 13 was associated with a 32% (OR 0.68 (95% CI: 0.49, 0.94)) decreased adjusted odds of having a high CMR score at 24 years, compared to participants with a low C-rMED. No associations were evident at other ages. Tracking of the C-rMED across the three ages showed a stronger negative association between C-rMED and CMR at 24 years when children had at least two high C-rMED scores from 7 to 13 years (adjusted OR: 0.49, 95% CI: 0.29, 0.85), compared to all low scores. FMI and HOMA-IR were the main CMR components contributing to this association.

Conclusion: Higher Mediterranean-style diet scores in early adolescence were associated with a better CMR profile in young adults (24 year olds). This underscores the importance of establishing healthy eating habits early in life for future cardiometabolic health.
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http://dx.doi.org/10.1007/s00394-021-02652-7DOI Listing
September 2021

The relationship between dietary intakes and plasma concentrations of PUFA in school-age children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.

Br J Nutr 2021 Jun 17:1-11. Epub 2021 Jun 17.

Centre for Academic Child Health, Bristol Medical School, University of Bristol, BristolBS8 1NU, UK.

An adequate intake of PUFA plays a vital role in human health. Therefore, it is important to assess PUFA intakes in different populations and validate them with biomarkers, but only a few small studies are in paediatric populations. We calculated the dietary intake of PUFA and their main food sources in children and assessed associations between PUFA intakes and plasma proportions. Dietary intakes of 7-year-old children (n 8242) enrolled in the Avon Longitudinal Study of Parents and Children were calculated from the parental-completed FFQ. Plasma PUFA were measured in 5571 children 8 months later, and 4380 children had complete dietary and plasma data. The association between dietary and plasma PUFA proportions was estimated using Spearman's correlation coefficients, quintile cross-classification and Cohen's κ coefficients. Mean total PUFA intake was 13·2 g/d (sd 4·2), contributing 6·5 % of total energy intake; n-6 PUFA contributed 5·2 % and n-3 PUFA 0·7 %. The n-6:n-3 ratio was 7·9:1. Mean intakes of EPA and DHA were 35·7 mg/d and 49·7 mg/d, respectively. Most n-3 and n-6 PUFA intakes were weakly correlated with their respective plasma lipids (0·07 ≤ r ≤ 0·16, P < 0·001). The correlation between dietary and plasma DHA was stronger though (r = 0·34, P < 0·001), supported by a modest level of agreement between quintiles (k = 0·32). The results indicate that the FFQ was able to reasonably rank the long-chain (LC) PUFA, DHA, in this paediatric population. Public health initiatives need to address the suboptimal ratio of n-6:n-3 PUFA and very low n-3 LC-PUFA intakes in school-age children in the UK.
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http://dx.doi.org/10.1017/S0007114521002191DOI Listing
June 2021

Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study.

Int J Cancer 2020 08 31;147(4):1027-1039. Epub 2020 Jan 31.

CESP, Faculté de Médecine, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.

Proinflammatory diets are associated with risk of developing colorectal cancer (CRC), however, inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute toward a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumors). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More proinflammatory diets were related to a higher CRC risk, particularly for colon cancer; hazard ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval [CI] 1.04-1.27) for CRC, 1.24 (95% CI 1.09-1.41) for colon cancer and 0.99 (95% CI 0.83-1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS was 1.62 (95% CI 1.31-2.01) for colon cancer overall and 2.11 (95% CI 1.50-2.97) for colon cancer in men. Our study shows that more proinflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men.
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http://dx.doi.org/10.1002/ijc.32870DOI Listing
August 2020

Adherence to the mediterranean diet and lymphoma risk in the european prospective investigation into cancer and nutrition.

Int J Cancer 2019 07 5;145(1):122-131. Epub 2019 Feb 5.

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

There is a growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, no prospective study has yet investigated its influence on lymphoma. We evaluated the association between adherence to the MD and risk of lymphoma and its subtypes in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The analysis included 476,160 participants, recruited from 10 European countries between 1991 and 2001. Adherence to the MD was estimated through the adapted relative MD (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for potential confounders. During an average follow-up of 13.9 years, 3,136 lymphomas (135 Hodgkin lymphoma [HL], 2,606 non-HL and 395 lymphoma not otherwise specified) were identified. Overall, a 1-unit increase in the arMED score was associated with a 2% lower risk of lymphoma (95% CI: 0.97; 1.00, p-trend = 0.03) while a statistically nonsignificant inverse association between a high versus low arMED score and risk of lymphoma was observed (hazard ratio [HR]: 0.91 [95% CI 0.80; 1.03], p-trend = 0.12). Analyses by lymphoma subtype did not reveal any statistically significant associations. Albeit with small numbers of cases (N = 135), a suggestive inverse association was found for HL (HR 1-unit increase = 0.93 [95% CI: 0.86; 1.01], p-trend = 0.07). However, the study may have lacked statistical power to detect small effect sizes for lymphoma subtype. Our findings suggest that an increasing arMED score was inversely related to the risk of overall lymphoma in EPIC but not by subtypes. Further large prospective studies are warranted to confirm these findings.
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http://dx.doi.org/10.1002/ijc.32091DOI Listing
July 2019

Timing of eating across ten European countries - results from the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study.

Public Health Nutr 2019 02 17;22(2):324-335. Epub 2018 Oct 17.

22Public Health Directorate,Asturias,Spain.

Objective: To examine timing of eating across ten European countries.

Design: Cross-sectional analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study using standardized 24 h diet recalls collected during 1995-2000. Eleven predefined food consumption occasions were assessed during the recall interview. We present time of consumption of meals and snacks as well as the later:earlier energy intake ratio, with earlier and later intakes defined as 06.00-14.00 and 15.00-24.00 hours, respectively. Type III tests were used to examine associations of sociodemographic, lifestyle and health variables with timing of energy intake.

Setting: Ten Western European countries.

Subjects: In total, 22 985 women and 13 035 men aged 35-74 years (n 36 020).

Results: A south-north gradient was observed for timing of eating, with later consumption of meals and snacks in Mediterranean countries compared with Central and Northern European countries. However, the energy load was reversed, with the later:earlier energy intake ratio ranging from 0·68 (France) to 1·39 (Norway) among women, and from 0·71 (Greece) to 1·35 (the Netherlands) among men. Among women, country, age, education, marital status, smoking, day of recall and season were all independently associated with timing of energy intake (all P<0·05). Among men, the corresponding variables were country, age, education, smoking, physical activity, BMI and day of recall (all P<0·05).

Conclusions: We found pronounced differences in timing of eating across Europe, with later meal timetables but greater energy load earlier during the day in Mediterranean countries compared with Central and Northern European countries.
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http://dx.doi.org/10.1017/S1368980018002288DOI Listing
February 2019

Changes in metabolic risk, insulin resistance, leptin and adiponectin following a lifestyle intervention in overweight and obese breast cancer survivors.

Eur J Cancer Care (Engl) 2018 Jul 5;27(4):e12861. Epub 2018 Jun 5.

Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.

Adiposity and physical activity are modifiable factors that could be important determinants of breast cancer (BC) prognosis through their effects on endogenous reproductive hormones, chronic inflammation and metabolic changes. Therefore, it is necessary to evaluate whether offering lifestyle interventions to BC survivors could affect the levels of certain biomarkers involved in these mechanisms. We designed a pre-post intervention study offering diet and exercise sessions over 12 weeks to 42 overweight/obese BC survivors. Before and after the intervention, we obtained dietary information, anthropometry and cardiorespiratory fitness (CRF) measurements and blood samples to measure metabolic risk, insulin resistance and adipokines biomarkers. Wilcoxon signed-rank tests and Spearman partial correlation coefficients were used to compare pre- and post-measurements and assess the correlations between changes in biomarkers and changes in anthropometry and CRF. Breast cancer survivors showed significant improvements in metabolic risk biomarkers and insulin resistance indicators along with a non-significant leptin decrease and a significant adiponectin decrease. The improvements in metabolic risk biomarkers, insulin resistance indicators and leptin were moderately correlated (0.32 ≤ |r| ≤ 0.55) with the decrease in body mass index and the increase in CRF. Diet and exercise interventions implemented in overweight/obese BC survivors may improve metabolic risk, insulin resistance and leptin biomarkers.
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http://dx.doi.org/10.1111/ecc.12861DOI Listing
July 2018

Determination of oleanolic acid in human plasma and its association with olive oil intake in healthy Spanish adults within the EPIC Spain cohort study.

Mol Nutr Food Res 2017 08 20;61(8). Epub 2017 Mar 20.

Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.

Scope: Oleanolic acid (OA) is an important triterpenic compound found in olive oil, however little is known about its concentrations in human plasma. We aimed to determine plasma OA levels in a healthy Spanish population and compare them with estimates of dietary olive oil intake.

Methods And Results: The final study sample included 141 individuals randomly selected from the European Prospective Investigation into Cancer and Nutrition Spanish cohort. Dietary olive oil intake was estimated using validated dietary history questionnaires. OA concentrations were determined in plasma (from the participants' stored blood samples) using a HPLC-MS method. Correlation coefficients between OA and olive oil intake were calculated, adjusting for center; sex; age; consumption of olives, apples, grapes, and red wine; and fasting state. The mean OA concentration in olive oil nonconsumers was 0.72 ng/mL (SD 0.82), while in the high olive oil intake group it was 1.32 ng/mL (SD 1.14). The fully adjusted partial Spearman correlations coefficients reached 0.36 (p-value < 0.001) overall, varying minimally by sex and fasting state.

Conclusion: This is the first study providing steady-state concentrations of triterpenes in humans. The results show that there was low-to-moderate correlation between OA concentrations and olive oil intake in this population.
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http://dx.doi.org/10.1002/mnfr.201600927DOI Listing
August 2017

Mediterranean diet and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition cohort.

Br J Cancer 2017 Mar 7;116(6):811-820. Epub 2017 Feb 7.

Cancer Registry and Histopathology Unit, 'Civic-M.P.Arezzo' Hospital, ASP Ragusa, Ragusa, Italy.

Background: The Mediterranean diet (MD) has been proposed as a means for cancer prevention, but little evidence has been accrued regarding its potential to prevent pancreatic cancer. We investigated the association between the adherence to the MD and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods: Over half a million participants from 10 European countries were followed up for over 11 years, after which 865 newly diagnosed exocrine pancreatic cancer cases were identified. Adherence to the MD was estimated through an adapted score without the alcohol component (arMED) to discount alcohol-related harmful effects. Cox proportional hazards regression models, stratified by age, sex and centre, and adjusted for energy intake, body mass index, smoking status, alcohol intake and diabetes status at recruitment, were used to estimate hazard ratios (HRs) associated with pancreatic cancer and their corresponding 95% confidence intervals (CIs).

Results: Adherence to the arMED score was not associated with risk of pancreatic cancer (HR high vs low adherence=0.99; 95% CI: 0.77-1.26, and HR per increments of two units in adherence to arMED=1.00; 95% CI: 0.94-1.06). There was no convincing evidence for heterogeneity by smoking status, body mass index, diabetes or European region. There was also no evidence of significant associations in analyses involving microscopically confirmed cases, plausible reporters of energy intake or other definitions of the MD pattern.

Conclusions: A high adherence to the MD is not associated with pancreatic cancer risk in the EPIC study.
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http://dx.doi.org/10.1038/bjc.2017.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355922PMC
March 2017

Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study.

Br J Cancer 2016 Nov 20;115(11):1430-1440. Epub 2016 Oct 20.

Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø N-9037, Norway.

Background: Much of the current literature on diet-colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Methods: Among 477 312 participants, intakes of 23 nutrients were estimated from validated dietary questionnaires. Using results from a previous principal component (PC) analysis, four major nutrient patterns were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed for the association of each of the four patterns and CRC incidence using multivariate Cox proportional hazards models with adjustment for established CRC risk factors.

Results: During an average of 11 years of follow-up, 4517 incident cases of CRC were documented. A nutrient pattern characterised by high intakes of vitamins and minerals was inversely associated with CRC (HR per 1 s.d.=0.94, 95% CI: 0.92-0.98) as was a pattern characterised by total protein, riboflavin, phosphorus and calcium (HR (1 s.d.)=0.96, 95% CI: 0.93-0.99). The remaining two patterns were not significantly associated with CRC risk.

Conclusions: Analysing nutrient patterns may improve our understanding of how groups of nutrients relate to CRC.
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http://dx.doi.org/10.1038/bjc.2016.334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129834PMC
November 2016

Work, household, and leisure-time physical activity and risk of mortality in the EPIC-Spain cohort.

Prev Med 2016 Apr 6;85:106-112. Epub 2016 Feb 6.

Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Ronda de Levante, 11, 30008, Murcia, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Melchor Fernández Almagro, 3-5, 28029, Madrid, Spain; Department of Health and Social Sciences, University of Murcia, Campus Universitario de Espinardo, 30100, Murcia, Spain. Electronic address:

Objective: Large-scale longitudinal data on the association of domain-specific physical activity (PA) and mortality is limited. Our objective was to evaluate the association of work, household (HPA), and leisure time PA (LTPA) with overall and cause-specific mortality in the EPIC-Spain study.

Methods: 38,379 participants (62.4% women), 30-65years old, and free of chronic disease at baseline were followed-up from recruitment (1992 - 1996) to December 31st, 2008 to ascertain vital status and cause of death. PA was evaluated at baseline and at a 3-year follow-up with a validated questionnaire (EPIC-PAQ) and combined variables were used to classify the participants by sub-domains of PA. Associations with overall, cancer, and cardiovascular mortality risks were assessed using competing risk Cox regression models adjusted by potential confounders.

Results: After 13.6years of mean follow-up, 1371 deaths were available for analyses. HPA was strongly associated to reduced overall (hazard ratio (HR) for Q4 vs. Q1=0.47 (0.34, 0.64)) and cause-specific mortalities in women and to lower cancer mortality in men (P for trend=0.004), irrespective of age, education, and lifestyle and morbidity variables. LTPA was associated with lower mortality in women (HR for Q4 vs. Q1=0.71 (0.52, 0.98)), but not men. No relationships were found between sedentariness at work and overall mortality.

Conclusions: HPA was associated to lower mortality risk in men and women from the EPIC-Spain cohort, whereas LTPA also contributed to reduce risk of death in women. Considering the large proportion of total daily PA that HPA represents in some population groups, these results are of public health importance.
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http://dx.doi.org/10.1016/j.ypmed.2016.02.009DOI Listing
April 2016

Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort.

Am J Clin Nutr 2016 Feb 20;103(2):454-64. Epub 2016 Jan 20.

Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway;

Background: Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity.

Objective: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer.

Design: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for α-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided.

Results: In quintile 5 compared with quintile 1, α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution).

Conclusion: Our results indicate that higher concentrations of plasma β-carotene and α-carotene are associated with lower breast cancer risk of ER- tumors.
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http://dx.doi.org/10.3945/ajcn.114.101659DOI Listing
February 2016

WHO guidelines for a healthy diet and mortality from cardiovascular disease in European and American elderly: the CHANCES project.

Am J Clin Nutr 2015 Oct 9;102(4):745-56. Epub 2015 Sep 9.

Division of Human Nutrition, Wageningen University, Wageningen, Netherlands;

Background: Cardiovascular disease (CVD) represents a leading cause of mortality worldwide, especially in the elderly. Lowering the number of CVD deaths requires preventive strategies targeted on the elderly.

Objective: The objective was to generate evidence on the association between WHO dietary recommendations and mortality from CVD, coronary artery disease (CAD), and stroke in the elderly aged ≥60 y.

Design: We analyzed data from 10 prospective cohort studies from Europe and the United States comprising a total sample of 281,874 men and women free from chronic diseases at baseline. Components of the Healthy Diet Indicator (HDI) included saturated fatty acids, polyunsaturated fatty acids, mono- and disaccharides, protein, cholesterol, dietary fiber, and fruit and vegetables. Cohort-specific HRs adjusted for sex, education, smoking, physical activity, and energy and alcohol intakes were pooled by using a random-effects model.

Results: During 3,322,768 person-years of follow-up, 12,492 people died of CVD. An increase of 10 HDI points (complete adherence to an additional WHO guideline) was, on average, not associated with CVD mortality (HR: 0.94; 95% CI: 0.86, 1.03), CAD mortality (HR: 0.99; 95% CI: 0.85, 1.14), or stroke mortality (HR: 0.95; 95% CI: 0.88, 1.03). However, after stratification of the data by geographic region, adherence to the HDI was associated with reduced CVD mortality in the southern European cohorts (HR: 0.87; 95% CI: 0.79, 0.96; I(2) = 0%) and in the US cohort (HR: 0.85; 95% CI: 0.83, 0.87; I(2) = not applicable).

Conclusion: Overall, greater adherence to the WHO dietary guidelines was not significantly associated with CVD mortality, but the results varied across regions. Clear inverse associations were observed in elderly populations in southern Europe and the United States.
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http://dx.doi.org/10.3945/ajcn.114.095117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588736PMC
October 2015

The role of olive oil in disease prevention: a focus on the recent epidemiological evidence from cohort studies and dietary intervention trials.

Br J Nutr 2015 Apr;113 Suppl 2:S94-101

Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL),Avda Gran Via 199-203,Barcelona08907,Spain.

Consumption of olive oil within the Mediterranean diet has been long known to have many health benefits. However, only over the last decade has epidemiological research confirmed its protective role against developing several chronic diseases. The objective of this review was to give an overview of the state of art epidemiological evidence concerning the relationship between olive oil and key public health outcomes including mortality, CVD, diabetes, metabolic syndrome (MetS), obesity and cancer, with a particular focus on recent results from cohort studies and dietary intervention trials. Recent epidemiological research has shown that regular consumption of olive oil is associated with increased longevity. This benefit is partly due to the olive oil's unequivocal cardio-protective role. There is converging evidence on the benefits of olive oil for preventing several CVD risk factors, including diabetes, MetS and obesity. Olive oil is also implicated in preventing certain cancers, with the most promising findings for breast and digestive tract cancers, although the data are still not entirely consistent and mainly from case-control studies. These health benefits are supported by strong mechanistic evidence from experimental studies, demonstrating that specific components of olive oil have antihypertensive, antithrombotic, antioxidant, antiinflammatory and anticarcinogenic action. Despite the accumulating epidemiological research, there is still a lack of consistent results from high-quality studies for many health outcomes (i.e. certain cancers and metabolism-related disorders). Further research is mandatory, above all from prospective studies and randomised dietary intervention trials when feasible, to confirm some of the still potential health benefits.
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http://dx.doi.org/10.1017/S0007114514003936DOI Listing
April 2015

Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients: a cohort study.

BMC Med 2015 May 7;13:107. Epub 2015 May 7.

Department of Gastroenterology and Hepatology, University Medical Centre, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.

Background: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients.

Methods: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality.

Results: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend <0.0001), compared to participants with the lowest concordance with the recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall mortality were observed (P for trend 0.004). Meeting the recommendations on body fatness and plant food consumption were associated with improved survival among CRC cases in mutually adjusted models.

Conclusions: Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.
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http://dx.doi.org/10.1186/s12916-015-0332-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423114PMC
May 2015

Is Quality of Life Related to Cardiorespiratory Fitness in Overweight and Obese Breast Cancer Survivors?

Women Health 2015 2;55(5):505-24. Epub 2015 Apr 2.

a Unit of Nutrition, Environment and Cancer , Catalan Institute of Oncology (ICO-IDIBELL) , Barcelona , Spain.

This study assessed changes in quality of life (QoL) and cardiorespiratory fitness (CRF) during a diet and physical activity (PA) intervention in breast cancer (BC) survivors and investigated the relation between these changes. The intervention of this single-arm pre-post study involved supervised, 1-hour weekly, diet sessions and 75-minute bi-weekly PA sessions of moderate-to-high intensity. This 12-week intervention targeted overweight/obese women who had recently completed BC treatment. Pre- and post-CRF and QoL measurements were compared using paired t-tests. Linear regression models, including baseline participants' characteristics and weight change, were used to assess the association between changes in CRF and QoL. The 37 BC survivors who completed the intervention between May 7, 2012 and July 27, 2012 showed significant increases in CRF and QoL. Peak oxygen uptake (mL/kg/min) increased from 19.0 ± 2.8 to 24.0 ± 4.1 while peak workload (watts/kg) increased from 1.3 ± 0.3 to 1.7 ± 0.3. Although statistical significance was not reached, the increase in workload seemed associated with increases in physical, mental, and general health and with a decrease in fatigue. This lifestyle intervention improved BC survivors' QoL and CRF and suggested possible relationships between CRF and QoL. More research needs to confirm these associations and promote lifestyle interventions aiming at improving BC survivors' QoL.
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http://dx.doi.org/10.1080/03630242.2015.1022817DOI Listing
January 2016

Coffee and tea consumption and risk of pre- and postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study.

Breast Cancer Res 2015 Jan 31;17:15. Epub 2015 Jan 31.

Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.

Introduction: Specific coffee subtypes and tea may impact risk of pre- and post-menopausal breast cancer differently. We investigated the association between coffee (total, caffeinated, decaffeinated) and tea intake and risk of breast cancer.

Methods: A total of 335,060 women participating in the European Prospective Investigation into Nutrition and Cancer (EPIC) Study, completed a dietary questionnaire from 1992 to 2000, and were followed-up until 2010 for incidence of breast cancer. Hazard ratios (HR) of breast cancer by country-specific, as well as cohort-wide categories of beverage intake were estimated.

Results: During an average follow-up of 11 years, 1064 premenopausal, and 9134 postmenopausal breast cancers were diagnosed. Caffeinated coffee intake was associated with lower risk of postmenopausal breast cancer: adjusted HR=0.90, 95% confidence interval (CI): 0.82 to 0.98, for high versus low consumption; Ptrend=0.029. While there was no significant effect modification by hormone receptor status (P=0.711), linear trend for lower risk of breast cancer with increasing caffeinated coffee intake was clearest for estrogen and progesterone receptor negative (ER-PR-), postmenopausal breast cancer (P=0.008). For every 100 ml increase in caffeinated coffee intake, the risk of ER-PR- breast cancer was lower by 4% (adjusted HR: 0.96, 95% CI: 0.93 to 1.00). Non-consumers of decaffeinated coffee had lower risk of postmenopausal breast cancer (adjusted HR=0.89; 95% CI: 0.80 to 0.99) compared to low consumers, without evidence of dose-response relationship (Ptrend=0.128). Exclusive decaffeinated coffee consumption was not related to postmenopausal breast cancer risk, compared to any decaffeinated-low caffeinated intake (adjusted HR=0.97; 95% CI: 0.82 to 1.14), or to no intake of any coffee (HR: 0.96; 95%: 0.82 to 1.14). Caffeinated and decaffeinated coffee were not associated with premenopausal breast cancer. Tea intake was neither associated with pre- nor post-menopausal breast cancer.

Conclusions: Higher caffeinated coffee intake may be associated with lower risk of postmenopausal breast cancer. Decaffeinated coffee intake does not seem to be associated with breast cancer.
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http://dx.doi.org/10.1186/s13058-015-0521-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349221PMC
January 2015

Consumption of soft drinks and juices and risk of liver and biliary tract cancers in a European cohort.

Eur J Nutr 2016 Feb 21;55(1):7-20. Epub 2014 Dec 21.

Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain.

Purpose: The aim of the study was to assess associations between intake of combined soft drinks (sugar sweetened and artificially sweetened) and fruit and vegetable juices and the risk of hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBC) and biliary tract cancers (GBTC) using data from the European Prospective Investigation into Cancer and Nutrition cohort of 477,206 participants from 10 European countries.

Methods: After 11.4 years of follow-up, 191 HCC, 66 IHBC and 236 GBTC cases were identified. Hazard ratios and 95% confidence intervals (HR; 95% CI) were estimated with Cox regression models with multivariable adjustment (baseline total energy intake, alcohol consumption and intake pattern, body mass index, physical activity, level of educational attainment and self-reported diabetes status).

Results: No risk associations were observed for IHBC or GBTC. Combined soft drinks consumption of >6 servings/week was positively associated with HCC risk: HR 1.83; 95% CI 1.11-3.02, p trend = 0.01 versus non-consumers. In sub-group analyses available for 91% of the cohort artificially sweetened soft drinks increased HCC risk by 6% per 1 serving increment (HR 1.06, 95% CI 1.03-1.09, n cases = 101); for sugar-sweetened soft drinks, this association was null (HR 1.00, 95% CI 0.95-1.06; n cases = 127, p heterogeneity = 0.07). Juice consumption was not associated with HCC risk, except at very low intakes (<1 serving/week: HR 0.60; 95% CI 0.38-0.95; p trend = 0.02 vs. non-consumers).

Conclusions: Daily intake of combined soft drinks is positively associated with HCC, but a differential association between sugar and artificially sweetened cannot be discounted. This study provides some insight into possible associations of HCC with sugary drinks intake. Further exploration in other settings is required.
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http://dx.doi.org/10.1007/s00394-014-0818-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284800PMC
February 2016

Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition cohort study.

Int J Cancer 2015 Jun 16;136(11):2640-8. Epub 2014 Nov 16.

International Agency for Research on Cancer (IARC), Lyon, France; Centre for Public Health Research, Massey University, Wellington, New Zealand.

Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed at baseline. The HLIS was constructed from five factors (diet, physical activity, smoking, alcohol consumption and anthropometry) by assigning scores of 0-4 to categories of each component, for which higher values indicate healthier behaviours. Hazard ratios (HR) were estimated by Cox proportional regression models. During 10.9 years of median follow-up, 7,756 incident breast cancer cases were identified. There was a 3% lower risk of breast cancer per point increase of the HLIS. Breast cancer risk was inversely associated with a high HLIS when fourth versus second (reference) categories were compared [adjusted HR = 0.74; 95% confidence interval (CI): 0.66-0.83]. The fourth versus the second category of the HLIS was associated with a lower risk for hormone receptor double positive (adjusted HR = 0.81, 95% CI: 0.67-0.98) and hormone receptor double negative breast cancer (adjusted HR = 0.60, 95% CI: 0.40-0.90). Findings suggest having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women. Programmes which engage women in long term health behaviours should be supported.
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http://dx.doi.org/10.1002/ijc.29315DOI Listing
June 2015

Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study.

BMC Med 2014 Oct 10;12:168. Epub 2014 Oct 10.

Cancer Registry and Histopathology Unit, "M.P.Arezzo" Hospital, Ragusa, Italy.

Background: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors--healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated.

Results: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend<0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend<0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend<0.0001) for rectal cancer, respectively (P-difference by cancer sub-site=0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index.

Conclusions: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.
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http://dx.doi.org/10.1186/s12916-014-0168-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192278PMC
October 2014

Prolactin determinants in healthy women: A large cross-sectional study within the EPIC cohort.

Cancer Epidemiol Biomarkers Prev 2014 Nov 20;23(11):2532-42. Epub 2014 Aug 20.

Department of Clinical Sciences, Obstetrics and Gynaecology, Faculty of Medicine, Umeå University, Umeå, Sweden.

Background: Experimental and epidemiologic data suggest that higher circulating prolactin is associated with breast cancer risk; however, how various risk factors for breast cancer influence prolactin levels in healthy women is not clear.

Methods: We analyzed cross-sectional associations between several suggested reproductive and lifestyle risk factors for breast cancer and circulating prolactin among pre- and postmenopausal women, taking into account the use of current postmenopausal hormone therapy, among 2,560 controls from a breast cancer nested case-control study within the EPIC cohort.

Results: Adjusted geometric mean prolactin levels were significantly higher among premenopausal women, and among postmenopausal women using hormone therapy compared with nonusers (8.2, 7.0, and 6.3 ng/mL, respectively; Pcat = <0.0001). Furthermore, prolactin levels were significantly higher among users of combined estrogen-progestin hormone therapy compared with users of estrogen-alone hormone therapy (6.66 vs. 5.90 ng/mL; Pcat = 0.001). Prolactin levels were lower among parous women compared with nulliparous women (8.61 vs. 10.95 ng/mL; Pcat = 0.0002, premenopausal women); the magnitude of this difference depended on the number of full-term pregnancies (22.1% lower, ≥3 vs. 1 pregnancy, Ptrend = 0.01). Results for parity were similar but lower in magnitude among postmenopausal women. Prolactin did not vary by other studied factors, with the exception of lower levels among postmenopausal smokers compared with never smokers.

Conclusions: Our study shows that current hormone therapy use, especially the use of combined hormone therapy, is associated with higher circulating prolactin levels in postmenopausal women, and confirms prior findings of lower circulating prolactin in parous women.

Impact: Our study extends the knowledge linking various breast cancer risk factors with circulating prolactin.
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http://dx.doi.org/10.1158/1055-9965.EPI-14-0613DOI Listing
November 2014

Nutrient patterns and their food sources in an International Study Setting: report from the EPIC study.

PLoS One 2014 5;9(6):e98647. Epub 2014 Jun 5.

WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece; Hellenic Health Foundation, Athens, Greece.

Background: Compared to food patterns, nutrient patterns have been rarely used particularly at international level. We studied, in the context of a multi-center study with heterogeneous data, the methodological challenges regarding pattern analyses.

Methodology/principal Findings: We identified nutrient patterns from food frequency questionnaires (FFQ) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study and used 24-hour dietary recall (24-HDR) data to validate and describe the nutrient patterns and their related food sources. Associations between lifestyle factors and the nutrient patterns were also examined. Principal component analysis (PCA) was applied on 23 nutrients derived from country-specific FFQ combining data from all EPIC centers (N = 477,312). Harmonized 24-HDRs available for a representative sample of the EPIC populations (N = 34,436) provided accurate mean group estimates of nutrients and foods by quintiles of pattern scores, presented graphically. An overall PCA combining all data captured a good proportion of the variance explained in each EPIC center. Four nutrient patterns were identified explaining 67% of the total variance: Principle component (PC) 1 was characterized by a high contribution of nutrients from plant food sources and a low contribution of nutrients from animal food sources; PC2 by a high contribution of micro-nutrients and proteins; PC3 was characterized by polyunsaturated fatty acids and vitamin D; PC4 was characterized by calcium, proteins, riboflavin, and phosphorus. The nutrients with high loadings on a particular pattern as derived from country-specific FFQ also showed high deviations in their mean EPIC intakes by quintiles of pattern scores when estimated from 24-HDR. Center and energy intake explained most of the variability in pattern scores.

Conclusion/significance: The use of 24-HDR enabled internal validation and facilitated the interpretation of the nutrient patterns derived from FFQs in term of food sources. These outcomes open research opportunities and perspectives of using nutrient patterns in future studies particularly at international level.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098647PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047062PMC
August 2015

Adherence to the Spanish dietary guidelines and its association with obesity in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Granada study.

Public Health Nutr 2014 Nov 24;17(11):2425-35. Epub 2014 Apr 24.

1Andalusian School of Public Health,Granada Cancer Registry,Instituto de Investigación Biosanitaria de Granada (Granada.bs),Campus Universitario de Cartuja,Cuesta del Observatorio 4,E-18080 Granada,Spain.

Objective: Dietary guidelines are intended to prevent chronic diseases and obesity. The aim of the present study was to develop a diet quality index based on the Spanish Food Pyramid (SFP) and to further explore its association with obesity in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Granada study.

Design: Cross-sectional study. The SFP score considered recommendations given for twelve food groups, and for physical activity and alcohol consumption. Obesity was defined as BMI over 30 kg/m2 and abdominal obesity as waist circumference larger than 102 cm (men) and 88 cm (women). Logistic regression was conducted to estimate odds ratios of obesity by quintiles and by 10-point increment in adherence to the score, controlling for potential confounders.

Setting: EPIC-Granada study.

Subjects: Participants (n 6717) aged 35-69 years (77 % women).

Results: A 10-point increase in adherence to the SFP score was associated with a 14 % (OR=0·86; 95 % CI 0·79, 0·94) lower odds of obesity in men (P interaction by sex=0·02). The odds of abdominal obesity decreased globally by 12 % (OR=0·88; 95 % CI 0·84, 0·93) per 10-point increase in adherence to this score. The effect of higher adherence to the score on abdominal obesity was stronger in physically inactive men and women (ORper 10-point increase=0·79; 95 % CI 0·68, 0·92 and ORper 10-point increase=0·89; 95 % CI 0·84, 0·95, respectively).

Conclusions: These findings support that the Spanish dietary guidelines might be an effective tool for obesity prevention. However, prospective studies investigating this association are warranted.
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http://dx.doi.org/10.1017/S1368980014000688DOI Listing
November 2014

Dietary fat intake and development of specific breast cancer subtypes.

J Natl Cancer Inst 2014 Apr 9;106(5). Epub 2014 Apr 9.

Affiliations of authors: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy (SS, CA, VP, FB, SG, VK); Medical Statistics Unit, Second University of Naples, Naples, Italy (PC); Hellenic Health Foundation, Athens, Greece (ATr); Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece (VB, EV); Escuela Andaluza de Salud Pública, Granada, Spain (M-JS); CIBER de Epidemiología y Salud Pública, Madrid, Spain (M-JS, M-DC, PA, EA); Instituto de Investigación Biosanitaria de Granada, Granada, Spain (M-JS); Department of Epidemiology, Murcia Health Authority, Murcia, Spain (M-DC); Public Health Division of Gipuzkoa, BioDonostia Research Institute, Health Department of Basque Region, San Sebastian, Spain (PA); Health Information Unit, Public Health and Health Planning Directorate, Asturias, Spain (JRQ); Navarre Public Health Institute, Pamplona, Spain (EA); Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Barcelona, Spain (GB); Molecular and Nutritional Epidemiology Unit, ISPO-Cancer Research and Prevention Institute, Florence, Italy (GM); Department of Clinical and Experimental Medicine, University of Naples Federico II, Naples, Italy (SP); Center for Cancer Prevention, Turin, Italy (CS); Human Genetics Foundation, Turin, Italy (CS); Department of Oncology, Histopathology Unit (RT), and Cancer Registry (RT), Ospedale Civile "M.P. Arezzo," Ragusa, Italy; INSERM, Centre for Research in Epidemiology and Population Health, U1018, Nutrition, Hormones and Women's Health team, F-94805, Villejuif, France (MC-BR); Univ Paris Sud, UMRS 1018, F-94805, Villejuif, France (FC-C); IGR, F-94805, Villejuif, France (GF); Department of Epidemiology, Julius Center for Health Sciences and Primary Care (PHMP, CHvG), and Department of Gastroenterology and Hepatology (HBB-d-M), University Medical Center Utrecht, Utrecht, the Netherlands;

We prospectively evaluated fat intake as predictor of developing breast cancer (BC) subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2), in a large (n = 337327) heterogeneous cohort of women, with 10062 BC case patients after 11.5 years, estimating BC hazard ratios (HRs) by Cox proportional hazard modeling. High total and saturated fat were associated with greater risk of ER(+)PR(+) disease (HR = 1.20, 95% confidence interval [CI] = 1.00 to 1.45; HR = 1.28, 95% CI = 1.09 to 1.52; highest vs lowest quintiles) but not ER(-)PR(-) disease. High saturated fat was statistically significantly associated with greater risk of HER2(-) disease. High saturated fat intake particularly increases risk of receptor-positive disease, suggesting saturated fat involvement in the etiology of this BC subtype.
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http://dx.doi.org/10.1093/jnci/dju068DOI Listing
April 2014

Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study.

BMC Cancer 2013 Dec 9;13:584. Epub 2013 Dec 9.

Background: The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain.

Methods: Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) breast tumors.

Results: A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors (≥35 vs. ≤19 years HR: 1.47 [95% CI 1.15-1.88] p(trend) < 0.001 for ER+PR+ tumors; ≥35 vs. ≤19 years HR: 0.93 [95% CI 0.53-1.65] p(trend) = 0.96 for ER-PR- tumors; P(het) = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (p(het) = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age- and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk.

Conclusion: Our study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant.
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http://dx.doi.org/10.1186/1471-2407-13-584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866571PMC
December 2013

Insulin-like growth factor I and risk of breast cancer by age and hormone receptor status-A prospective study within the EPIC cohort.

Int J Cancer 2014 Jun 19;134(11):2683-90. Epub 2013 Nov 19.

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

Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case-control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR)Q4-Q1 = 1.41 [95% confidence interval (CI) 1.01-1.98] for the highest vs. lowest quartile; OR = 1.17 [95% CI 1.04-1.33] per 1-standard deviation (SD) increase in IGF-I, ptrend = 0.01) and among women who were diagnosed with breast cancer at 50 years or older (ORQ3-Q1 = 1.38 [95% CI 1.01-1.89]; OR = 1.19 [95% CI 1.04-1.36] per 1-SD increase in IGF-I, ptrend = 0.01) but not with receptor-positive disease diagnosed at an earlier age. No statistically significant associations were observed for ER- breast tumors overall and by age at diagnosis. Tests for heterogeneity by receptor status of the tumor were not statistically significant, except for women diagnosed with breast cancer at 50 years or older (phet = 0.03 for ER+/PR+ vs. ER-/PR- disease). Our data add to a global body of evidence indicating that higher circulating IGF-I levels may increase risk specifically of receptor-positive, but not receptor-negative, breast cancer diagnosed at 50 years or older.
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http://dx.doi.org/10.1002/ijc.28589DOI Listing
June 2014

Premenopausal serum sex hormone levels in relation to breast cancer risk, overall and by hormone receptor status - results from the EPIC cohort.

Int J Cancer 2014 Apr 24;134(8):1947-57. Epub 2013 Oct 24.

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

Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1  = 1.56 (95% CI 1.15-2.13), ptrend  = 0.02 for testosterone and ORQ4-Q1  = 1.33 (95% CI 0.99-1.79), ptrend  = 0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1  = 1.32 (95% CI 0.87-2.01), ptrend  = 0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1  = 0.94 (95% CI 0.60-1.47), ptrend  = 0.34, phet  = 0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen.
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http://dx.doi.org/10.1002/ijc.28528DOI Listing
April 2014

Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study.

Int J Cancer 2014 Feb 5;134(3):612-21. Epub 2013 Aug 5.

Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.

Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; ptrend  = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; ptrend  = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.
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http://dx.doi.org/10.1002/ijc.28368DOI Listing
February 2014

Mediterranean diet and colorectal cancer risk: results from a European cohort.

Eur J Epidemiol 2013 Apr 12;28(4):317-28. Epub 2013 Apr 12.

Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, 75 Mikras Asias St, Goudi, 115 27 Athens, Greece.

The authors investigated the association of adherence to Mediterranean diet with colorectal cancer (CRC) risk in the European Prospective Investigation into Cancer and nutrition study. Adherence to Mediterranean diet was expressed through two 10-unit scales, the Modified Mediterranean diet score (MMDS) and the Centre-Specific MMDS (CSMMDS). Both scales share the same dietary components but differ in the cut-off values that were used for these components in the construction of the scales. Adjusted hazard ratios (HR) for the associations of these scales with CRC incidence were estimated. After 5,296,617 person-years of follow-up, 4,355 incident CRC cases were identified. A decreased risk of CRC, of 8 and 11 % was estimated when comparing the highest (scores 6-9) with the lowest (scores 0-3) adherence to CSMMDS and MMDS respectively. For MMDS the HR was 0.89 (95 % confidence interval (CI): 0.80, 0.99). A 2-unit increment in either Mediterranean scale was associated with a borderline statistically significant 3 to 4 % reduction in CRC risk (HR for MMDS: 0.96; 95 % CI: 0.92, 1.00). These associations were somewhat more evident, among women, were mainly manifested for colon cancer risk and their magnitude was not altered when alcohol was excluded from MMDS. These findings suggest that following a Mediterranean diet may have a modest beneficial effect on CRC risk.
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http://dx.doi.org/10.1007/s10654-013-9795-xDOI Listing
April 2013

Plasma 25-hydroxyvitamin D and the risk of breast cancer in the European prospective investigation into cancer and nutrition: a nested case-control study.

Int J Cancer 2013 Oct 22;133(7):1689-700. Epub 2013 Apr 22.

Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 581, Heidelberg, Germany.

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/m(2) (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/m(2) (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.
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http://dx.doi.org/10.1002/ijc.28172DOI Listing
October 2013

Dietary intake of vitamin D and calcium and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition.

Nutr Cancer 2013 ;65(2):178-87

German Cancer Research Center, Division of Cancer Epidemiology, Heidelberg, Germany.

Studies assessing the effects of vitamin D or calcium intake on breast cancer risk have been inconclusive. Furthermore, few studies have evaluated them jointly. This study is the largest so far examining the association of dietary vitamin D and calcium intake with breast cancer risk in the European Prospective Investigation into Cancer and Nutrition. During a mean follow-up of 8.8 yr, 7760 incident invasive breast cancer cases were identified among 319,985 women. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for pre- and postmenopausal breast cancer risk. Comparing the highest with the lowest quintile of vitamin D intake, HR and 95% CI were 1.07 (0.87-1.32) and 1.02 (0.90-1.16) for pre- and postmenopausal women, respectively. The corresponding HR and 95% CIs for calcium intake were 0.98 (0.80-1.19) and 0.90 (0.79-1.02), respectively. For calcium intake in postmenopausal women, the test for trend was borderline statistically significant (P(trend) = 0.05). There was no significant interaction between vitamin D and calcium intake and cancer risk (P(interaction) = 0.57 and 0.22 in pre- and postmenopausal women, respectively). In this large prospective cohort, we found no evidence for an association between dietary vitamin D or calcium intake and breast cancer risk.
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http://dx.doi.org/10.1080/01635581.2013.752018DOI Listing
December 2013
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