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Sluijs I.,University Utrecht | Forouhi N.G.,Addenbrookes Hospital | Beulens J.W.J.,University Utrecht | Van Der Schouw Y.T.,University Utrecht | And 37 more authors.
American Journal of Clinical Nutrition | Year: 2012

Background: Dairy product intake may be inversely associated with risk of type 2 diabetes, but the evidence is inconclusive for total dairy products and sparse for types of dairy products. Objective: The objective was to investigate the prospective association of total dairy products and different dairy subtypes with incidence of diabetes in populations with marked variation of intake of these food groups. Design: A nested case-cohort within 8 European countries of the European Prospective Investigation into Cancer and Nutrition Study (n = 340,234; 3.99 million person-years of follow-up) included a random subcohort (n = 16,835) and incident diabetes cases (n = 12,403). Baseline dairy product intake was assessed by using dietary questionnaires. Country-specific Prentice-weighted Cox regression HRs were calculated and pooled by using a random-effects meta-analysis. Results: Intake of total dairy products was not associated with diabetes (HR for the comparison of the highest with the lowest quintile of total dairy products: 1.01; 95% CI: 0.83, 1.34; P-trend = 0.92) in an analysis adjusted for age, sex, BMI, diabetes risk factors, education, and dietary factors. Of the dairy subtypes, cheese intake tended to have an inverse association with diabetes (HR: 0.88; 95% CI: 0.76, 1.02; P-trend = 0.01), and a higher combined intake of fermented dairy products (cheese, yogurt, and thick fermented milk) was inversely associated with diabetes (HR: 0.88; 95% CI: 0.78, 0.99; P-trend = 0.02) in adjusted analyses that compared extreme quintiles. Conclusions: This large prospective study found no association between total dairy product intake and diabetes risk. An inverse association of cheese intake and combined fermented dairy product intake with diabetes is suggested, which merits further study. © 2012 American Society for Nutrition.


Peters T.,Addenbrookes Hospital | Brage S.,Addenbrookes Hospital | Westgate K.,Addenbrookes Hospital | Franks P.W.,Umeå University | And 42 more authors.
European Journal of Epidemiology | Year: 2012

To accurately examine associations of physical activity (PA) with disease outcomes, a valid method of assessing free-living activity is required. We examined the validity of a brief PA questionnaire (PAQ) used in the European Prospective Investigation into Cancer and Nutrition (EPIC). PA energy expenditure (PAEE) and time spent in moderate and vigorous physical activity (MVPA) was measured in 1,941 healthy individuals from 10 European countries using individually-calibrated combined heart-rate and movement sensing. Participants also completed the short EPIC-PAQ, which refers to past year's activity. Pearson (r) and Spearman (σ) correlation coefficients were calculated for each country, and random effects meta-analysis was used to calculate the combined correlation across countries to estimate the validity of two previously- and one newly-derived ordered, categorical PA indices ("Cambridge index", "total PA index", and "recreational index") that categorized individuals as inactive, moderately inactive, moderately active, or active. The strongest associations with PAEE and MVPA were observed for the Cambridge index (r = 0.33 and r = 0.25, respectively). No significant heterogeneity by country was observed for this index (I2 = 36.3%, P = 0.12; I2 = 0.0%, P = 0.85), whereas heterogeneity was suggested for other indices (I2 > 48%, P < 0.05, I2 > 47%, P < 0.05). PAEE increased linearly across self-reported PA categories (P for trend <0.001), with an average difference of approximately 460 kJ/d for men and 365 kJ/d for women, between categories of the Cambridge index. The EPIC-PAQ is suitable for categorizing European men and women into four distinct categories of overall physical activity. The difference in PAEE between categories may be useful when estimating effect sizes from observational research. © 2011 The Author(s).


McCormack V.A.,International Agency for Research on Cancer | Agudo A.,Catalan Institute of Nanoscience and Nanotechnology | Dahm C.C.,Aarhus University Hospital | Overvad K.,University of Aarhus | And 22 more authors.
International Journal of Cancer | Year: 2010

The carcinogenicity of cigar and pipe smoking is established but the effect of detailed smoking characteristics is less well defined. We examined the effects on cancer incidence of exclusive cigar and pipe smoking, and in combination with cigarettes, among 102,395 men from Denmark, Germany, Spain, Sweden and the United Kingdom in the EPIC cohort. Hazard ratios (HR) and their 95% confidence intervals (CI) for cancer during a median 9-year follow-up from ages 35 to 70 years were estimated using proportional hazards models. Compared to never smokers, HR of cancers of lung, upper aerodigestive tract and bladder combined was 2.2 (95% CI: 1.3, 3.8) for exclusive cigar smokers (16 cases), 3.0 (2.1, 4.5) for exclusive pipe smokers (33 cases) and 5.3 (4.4, 6.4) for exclusive cigarette smokers (1,069 cases). For each smoking type, effects were stronger in current smokers than in ex-smokers and in inhalers than in non-inhalers. Ever smokers of both cigarettes and cigars [HR 5.7 (4.4, 7.3), 120 cases] and cigarettes and pipes [5.1 (4.1, 6.4), 247 cases] had as high a raised risk as had exclusive cigarette smokers. In these smokers, the magnitude of the raised risk was smaller if they had switched to cigars or pipes only (i.e., quit cigarettes) and had not compensated with greater smoking intensity. Cigar and pipe smoking is not a safe alternative to cigarette smoking. The lower cancer risk of cigar and pipe smokers as compared to cigarette smokers is explained by lesser degree of inhalation and lower smoking intensity. © 2010 UICC.


Golubic R.,University of Cambridge | May A.M.,University Utrecht | Benjaminsen Borch K.,University of Tromsø | Overvad K.,University of Aarhus | And 14 more authors.
PLoS ONE | Year: 2014

Objective: To examine the validity of the Recent Physical Activity Questionnaire (RPAQ) which assesses physical activity (PA) in 4 domains (leisure, work, commuting, home) during past month. Methods: 580 men and 1343 women from 10 European countries attended 2 visits at which PA energy expenditure (PAEE), time at moderate-to-vigorous PA (MVPA) and sedentary time were measured using individually-calibrated combined heart-rate and movement sensing. At the second visit, RPAQ was administered electronically. Validity was assessed using agreement analysis. Results: RPAQ significantly underestimated PAEE in women [median(IQR) 34.1 (22.1, 52.2) vs. 40.6 (32.4, 50.9) kJ/kg/day, 95%LoA: -44.4, 63.4 kJ/kg/day) and in men (43.7 (29.0, 69.0) vs. 45.5 (34.1, 57.6) kJ/kg/day, 95%LoA: -47.2, 101.3 kJ/kg/day]. Using individualised definition of 1MET, RPAQ significantly underestimated MVPA in women [median(IQR): 62.1 (29.4, 124.3) vs. 73.6 (47.8, 107.2) min/day, 95%LoA: -130.5, 305.3 min/day] and men [82.7 (38.8, 185.6) vs. 83.3 (55.1, 125.0) min/day, 95%LoA: -136.4, 400.1 min/day]. Correlations (95%CI) between subjective and objective estimates were statistically significant [PAEE: women, rho = 0.20 (0.15-0.26); men, rho = 0.37 (0.30-0.44); MVPA: women, rho = 0.18 (0.13-0.23); men, rho = 0.31 (0.24-0.39)]. When using non-individualised definition of 1MET (3.5 mlO2/kg/min), MVPA was substantially overestimated (∼30 min/day). Revisiting occupational intensity assumptions in questionnaire estimation algorithms with occupational group-level empirical distributions reduced median PAEE-bias in manual (25.1 kJ/kg/day vs. -9.0 kJ/kg/day, p<0.001) and heavy manual workers (64.1 vs. -4.6 kJ/kg/day, p<0.001) in an independent hold-out sample. Conclusion: Relative validity of RPAQ-derived PAEE and MVPA is comparable to previous studies but underestimation of PAEE is smaller. Electronic RPAQ may be used in large-scale epidemiological studies including surveys, providing information on all domains of PA. © 2014 Golubic et al.


Michaud D.S.,Brown University | Michaud D.S.,Imperial College London | Izard J.,Forsyth Institute | Izard J.,Harvard University | And 52 more authors.
Gut | Year: 2013

Objective: Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study. Design We measured antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic cancer cases and 416 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition study. Analyses were conducted using conditional logistic regression and additionally adjusted for smoking status and body mass index. Results: Individuals with high levels of antibodies against Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a twofold higher risk of pancreatic cancer than individuals with lower levels of these antibodies (OR 2.14; 95% CI 1.05 to 4.36; >200 ng/ml vs ≤200 ng/ml). To explore the association with commensal (non-pathogenic) oral bacteria, we performed a cluster analysis and identified two groups of individuals, based on their antibody profiles. A cluster with overall higher levels of antibodies had a 45% lower risk of pancreatic cancer than a cluster with overall lower levels of antibodies (OR 0.55; 95% CI 0.36 to 0.83). Conclusions: Periodontal disease might increase the risk for pancreatic cancer. Moreover, increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer. Studies are needed to determine whether oral bacteria have direct effects on pancreatic cancer pathogenesis or serve as markers of the immune response.


Bakken K.,University of Tromsø | Fournier A.,French Institute of Health and Medical Research | Lund E.,University of Tromsø | Waaseth M.,University of Tromsø | And 33 more authors.
International Journal of Cancer | Year: 2011

Menopausal hormone therapy (MHT) is characterized by use of different constituents, regimens and routes of administration. We investigated the association between the use of different types of MHT and breast cancer risk in the EPIC cohort study. The analysis is based on data from 133,744 postmenopausal women. Approximately 133,744 postmenopausal women contributed to this analysis. Information on MHT was derived from country-specific self-administered questionnaires with a single baseline assessment. Incident breast cancers were identified through population cancer registries or by active follow-up (mean: 8.6 yr). Overall relative risks (RR) and 95% confidence interval (CI) were derived from country-specific Cox proportional hazard models estimates. A total of 4312 primary breast cancers were diagnosed during 1,153,747 person-years of follow-up. Compared with MHT never users, breast cancer risk was higher among current users of estrogen only (RR: 1.42, 95% CI 1.23 1.64) and higher still among current users of combined MHT (RR: 1.77, 95% CI 1.40 2.24; p = 0.02 for combined vs. estrogen-only). Continuous combined regimens conferred a 43% (95% CI: 19 72%) greater risk compared with sequential regimens. There was no significant difference between progesterone and testosterone derivatives in sequential regimens. There was no significant variation in risk linked to the estrogenic component of MHT, neither for oral vs. cutaneous administration nor for estradiol compounds vs. conjugated equine estrogens. Estrogen-only and combined MHT uses were associated with increased breast cancer risk. Continuous combined preparations were associated with the highest risk. Further studies are needed to disentangle the effects of the regimen and the progestin component. © 2010 UICC.


Shui I.M.,Harvard University | Lindstrom S.,Harvard University | Kibel A.S.,Harvard University | Berndt S.I.,U.S. National Cancer Institute | And 43 more authors.
European Urology | Year: 2014

Background Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM). Objective To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM. Design, setting, and participants We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred. Outcome measurements and statistical analysis The main outcome was PCSM. The risk allele was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls. Results and limitations Among the cases, we found that 8 of the 47 SNPs were significantly associated (p < 0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [C2orf43], rs17021918 [PDLIM5], rs10486567 [JAZF1], rs6465657 [LMTK2], rs7127900 (intergenic), rs2735839 [KLK3], rs10993994 [MSMB], rs13385191 [C2orf43]). In the case-control analysis, 22 SNPs were associated (p < 0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only. Conclusions Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa. Patient summary In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction. © 2013 European Association of Urology.


PubMed | Civile Mp Arezzo Hospital, Danish Cancer Society, International Agency for Research on Cancer IARC WHO, Public Health Directorate and 24 more.
Type: Journal Article | Journal: European journal of nutrition | Year: 2016

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.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).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).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.


PubMed | Danish Cancer Society, Public Health Directorate, National and Kapodistrian University of Athens, Murcia Regional Health Authority and 20 more.
Type: Journal Article | Journal: International journal of cancer | Year: 2015

Alcohol intake has been associated to breast cancer in pre and postmenopausal women; however results are inconclusive regarding tumor hormonal receptor status, and potential modifying factors like age at start drinking. Therefore, we investigated the relation between alcohol intake and the risk of breast cancer using prospective observational data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Up to 334,850 women, aged 35-70 years at baseline, were recruited in ten European countries and followed up an average of 11 years. Alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. The study outcomes were the Hazard ratios (HR) of developing breast cancer according to hormonal receptor status. During 3,670,439 person-years, 11,576 incident breast cancer cases were diagnosed. Alcohol intake was significantly related to breast cancer risk, for each 10 g/day increase in alcohol intake the HR increased by 4.2% (95% CI: 2.7-5.8%). Taking 0 to 5 g/day as reference, alcohol intake of >5 to 15 g/day was related to a 5.9% increase in breast cancer risk (95% CI: 1-11%). Significant increasing trends were observed between alcohol intake and ER+/PR+, ER-/PR-, HER2- and ER-/PR-HER2- tumors. Breast cancer risk was stronger among women who started drinking prior to first full-time pregnancy. Overall, our results confirm the association between alcohol intake and both hormone receptor positive and hormone receptor negative breast tumors, suggesting that timing of exposure to alcohol drinking may affect the risk. Therefore, women should be advised to control their alcohol consumption.


PubMed | Danish Cancer Society, BioDonostia Reserach Institute, International Agency for Research on Cancer IARC, Public Health Directorate and 23 more.
Type: | Journal: Breast cancer research : BCR | Year: 2015

The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects.We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2=1.35 (95% CI 1.04-1.76), Ptrend=0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (Phet=0.98) or baseline HT use (Phet=0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (Ptrend=0.06 vs Ptrend=0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors<4 years compared to 4 years after blood donation (Ptrend=0.01 vs Ptrend=0.63; Phet=0.04) and among nulliparous women compared to parous women (Ptrend=0.03 vs Ptrend=0.15; Phet=0.07).Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.

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