Showing papers by "Elio Riboli published in 2013"
TL;DR: This review in the Global Health series focuses on the role of smoking, alcohol, and obesity in the burden of noncommunicable disease.
Abstract: This review in the Global Health series focuses on the role of smoking, alcohol, and obesity in the burden of noncommunicable disease.
619 citations
Rosalind A. Eeles1, Ali Amin Al Olama2, Sara Benlloch2, Edward J. Saunders +153 more•Institutions (46)
TL;DR: In this paper, a custom Illumina array (iCOGS) was used to genotype 211,155 SNPs in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium.
Abstract: Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10(-8)). More than 70 prostate cancer susceptibility loci, explaining ∼30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.
523 citations
Montserrat Garcia-Closas, Fergus J. Couch1, Sara Lindström2, Kyriaki Michailidou3 +284 more•Institutions (82)
TL;DR: SNPs at four loci were associated with ER-negative but not ER-positive breast cancer (P > 0.05), providing further evidence for distinct etiological pathways associated with invasive ER- positive and ER- negative breast cancers.
Abstract: Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.
402 citations
University of Zurich1, Aarhus University2, University Medical Center Utrecht3, Institut Gustave Roussy4, South University5, Prevention Institute6, University of Cambridge7, Medical Research Council8, Cancer Epidemiology Unit9, National and Kapodistrian University of Athens10, Harvard University11, Academy of Athens12, Imperial College London13, Utrecht University14, University of Tromsø15, University of Oslo16, Andalusian School of Public Health17, Lund University18, Umeå University19, International Agency for Research on Cancer20
TL;DR: The results of this analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.
Abstract: Background: Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality. Results: As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality. Conclusions: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.
353 citations
National Institutes of Health1, International Agency for Research on Cancer2, German Cancer Research Center3, Basque Government4, University of Oxford5, University of Cambridge6, Harvard University7, National and Kapodistrian University of Athens8, Academy of Athens9, Utrecht University10, University of Naples Federico II11, Imperial College London12, Umeå University13, Lund University14
TL;DR: The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis.
Abstract: Purpose Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera. Methods We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression. Results HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative.
299 citations
Brown University1, Harvard University2, Imperial College London3, German Cancer Research Center4, Aarhus University5, International Agency for Research on Cancer6, South University7, Institut Gustave Roussy8, National and Kapodistrian University of Athens9, Academy of Athens10, University of Naples Federico II11, Utrecht University12, University of Tromsø13, Andalusian School of Public Health14, Umeå University15, Karolinska Institutet16, University of Gothenburg17, Lund University18, University of Cambridge19, Medical Research Council20, University of Oxford21
TL;DR: Monitoring of antibodies to oral bacteria in prediagnosis blood samples found that increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer.
Abstract: 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.
291 citations
TL;DR: Circulating oestrogens and androgens are positively associated with the risk for breast cancer in premenopausal women, and cross-sectional analyses in control women showed several associations of sex hormones with breast cancer risk factors.
Abstract: Background Associations between circulating concentrations of oestrogens, progesterone, and androgens with breast cancer and related risk factors in premenopausal women are not well understood We aimed to characterise these associations with a pooled analysis of data from seven studies Methods Individual participant data for prediagnostic sex hormone and sex hormone-binding globulin (SHBG) concentrations were contributed from seven prospective studies We restricted analyses to women who were premenopausal and younger than 50 years at blood collection, and to women with breast cancer diagnosed before age 50 years We estimated odds ratios (ORs) with 95% CIs for breast cancer associated with hormone concentrations by conditional logistic regression in cases and controls matched for age, date of blood collection, and day of cycle, with stratification by study and further adjustment for cycle phase We examined associations of hormones with risk factors for breast cancer in control women by comparing geometric mean hormone concentrations in categories of these risk factors, adjusted for study, age, phase of menstrual cycle, and body-mass index (BMI) All statistical tests were two-sided Findings We included data for up to 767 women with breast cancer and 1699 controls in the risk analyses Breast cancer risk was associated with a doubling in concentrations of oestradiol (OR 119, 95% CI 106-135), calculated free oestradiol (117, 103-133), oestrone (127, 105-154), androstenedione (130, 110-155), dehydroepiandrosterone sulphate (117, 104-132), testosterone (118, 103-135), and calculated free testosterone (108, 097-121) Breast cancer risk was not associated with luteal phase progesterone (doubling in concentration OR 100, 95% CI 092-109), and adjustment for other factors had little effect on any of these ORs Cross-sectional analyses in control women showed several associations of sex hormones with breast cancer risk factors Interpretation Circulating oestrogens and androgens are positively associated with the risk for breast cancer in premenopausal women
260 citations
Medical Research Council1, Lund University2, Umeå University3, Utrecht University4, University of Paris-Sud5, Wellcome Trust Sanger Institute6, University of Cambridge7, University of Helsinki8, German Cancer Research Center9, Imperial College London10, Aarhus University11, Aalborg University12, University of Naples Federico II13, International Agency for Research on Cancer14, University of Oxford15
TL;DR: The InterAct case-cohort study investigated the association between a family history of diabetes among different family members and the incidence of type 2 diabetes, as well as the extent to which genetic, anthropometric and lifestyle risk factors mediated this association.
Abstract: Aims/hypothesis
Although family history of type 2 diabetes (T2D) is a strong risk factor for the disease, the factors mediating this excess risk are poorly understood. In the InterAct case-cohort study we investigated the association of family history of diabetes among different family members with incidence of T2D and the extent to which genetic, anthropometric and lifestyle risk factors mediated this association.
231 citations
Imperial College London1, Wageningen University and Research Centre2, Pompeu Fabra University3, South University4, French Institute of Health and Medical Research5, German Cancer Research Center6, University of Oxford7, University of Cambridge8, Aarhus University9, University of Naples Federico II10, Umeå University11
TL;DR: This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults and found that Juice and nectar consumption was not associated with type 1 diabetes incidence.
Abstract: Consumption of sugar-sweetened beverages has been shown, largely in American populations, to increase type 2 diabetes incidence. We aimed to evaluate the association of consumption of sweet beverages (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft drinks) with type 2 diabetes incidence in European adults. We established a case-cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. After exclusions, the final sample size included 11,684 incident cases and a subcohort of 15,374 participants. Cox proportional hazards regression models (modified for the case-cohort design) and random-effects meta-analyses were used to estimate the association between sweet beverage consumption (obtained from validated dietary questionnaires) and type 2 diabetes incidence. In adjusted models, one 336 g (12 oz) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 (95% CI 1.09, 1.38) and 1.52 (95% CI 1.26, 1.83), respectively. After further adjustment for energy intake and BMI, the association of sugar-sweetened soft drinks with type 2 diabetes persisted (HR 1.18, 95% CI 1.06, 1.32), but the association of artificially sweetened soft drinks became statistically not significant (HR 1.11, 95% CI 0.95, 1.31). Juice and nectar consumption was not associated with type 2 diabetes incidence. This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults.
224 citations
National Institutes of Health1, University of Alabama2, University of California, Berkeley3, Memorial Sloan Kettering Cancer Center4, University of Utah5, University of Freiburg6, University of Southern California7, French Institute of Health and Medical Research8, City of Hope National Medical Center9, Imperial College London10, American Cancer Society11, Simon Fraser University12, University of British Columbia13, Harvard University14, University of Sydney15, University of Cagliari16, Yale University17, Cancer Council Victoria18, New York University19, Mayo Clinic20, Karolinska Institutet21, Statens Serum Institut22, Uppsala University23, Stanford University24, Exponent25, Veterans Health Administration26, University of Iowa27, University of California, San Francisco28, Ohio State University29, Fred Hutchinson Cancer Research Center30, German Cancer Research Center31, Icahn School of Medicine at Mount Sinai32, International Agency for Research on Cancer33, University of Burgundy34, Dublin City University35, University of Texas MD Anderson Cancer Center36, Duke University37, University of Minnesota38, Wayne State University39, Academy of Athens40, Utrecht University41, University of Oxford42, National Institute for Health and Welfare43, Macquarie University44, University of New South Wales45, University of Bari46, University of York47, Dongguk University48, University of North Carolina at Chapel Hill49, University of Sheffield50, University of Santiago de Compostela51, University of Oviedo52, University of Barcelona53
TL;DR: The largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls, identified ten independent associated SNPs in nine new loci and found evidence for two additional promising loci below genome-wide significance.
Abstract: Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
202 citations
University of Barcelona1, Institut Gustave Roussy2, South University3, National and Kapodistrian University of Athens4, Harvard University5, Academy of Athens6, Utrecht University7, Imperial College London8, University Medical Center Utrecht9, Wageningen University and Research Centre10, Cancer Epidemiology Unit11, University of Cambridge12, Prevention Institute13, Andalusian School of Public Health14, Aarhus University Hospital15, Lund University16, Umeå University17, University of Tromsø18, University of Oslo19
TL;DR: The 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, which support the potential scope for BC prevention through dietary modification.
Abstract: 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.
Utrecht University1, University of Cambridge2, Basque Government3, Institut Gustave Roussy4, University of Oxford5, Umeå University6, Lund University7, University of Helsinki8, German Cancer Research Center9, Aalborg University10, Aarhus University11, University of Naples Federico II12, International Agency for Research on Cancer13, Wageningen University and Research Centre14, Imperial College London15
TL;DR: Early menopause is associated with a greater risk of type 2 diabetes, and a shorter reproductive life span wasassociated with a higher diabetes risk.
Abstract: OBJECTIVE-Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk. RESEARCH DESIGN AND METHODS-Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied. RESULTS-Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04-1.69), 1.09 (0.90-1.31), 0.97 (0.86-1.10), and 0.85 (0.70-1.03) for women with menopause at ages = 55 years, respectively, relative to those with menopause at age 50-54 years. The HR per SD younger age at menopause was 1.08 (1.02-1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [ 1.01-1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05). CONCLUSIONS-Early menopause is associated with a greater risk of type 2 diabetes. Diabetes Care 36:1012-1019, 2013
University of Kiel1, Max Delbrück Center for Molecular Medicine2, International Agency for Research on Cancer3, Icahn School of Medicine at Mount Sinai4, Aarhus University Hospital5, Aarhus University6, South University7, French Institute of Health and Medical Research8, German Cancer Research Center9, National and Kapodistrian University of Athens10, Harvard University11, Academy of Athens12, Prevention Institute13, Imperial College London14, University Medical Center Utrecht15, Utrecht University16, Karolinska Institutet17, Andalusian School of Public Health18, University of Gothenburg19, Lund University20, Umeå University21, University of Cambridge22, Cancer Epidemiology Unit23
TL;DR: Evidence of an association between obesity, particularly abdominal obesity, and risk of HCC and GBC is provided and public health recommendations to reduce the prevalence of obesity and weight gain in adulthood for HCCand GBC prevention in Western populations are supported.
Abstract: General obesity has been positively associated with risk of liver and probably with biliary tract cancer, but little is known about abdominal obesity or weight gain during adulthood. We used multivariable Cox proportional hazard models to investigate associations between weight, body mass index, waist and hip circumference, waist-to-hip and waist-to-height ratio (WHtR), weight change during adulthood and risk of hepatocellular carcinoma (HCC), intrahepatic (IBDC) and extrahepatic bile duct system cancer [EBDSC including gallbladder cancer (GBC)] among 359,525 men and women in the European Prospective Investigation into Cancer and Nutrition study. Hepatitis B and C virus status was measured in a nested casecontrol subset. During a mean follow-up of 8.6 years, 177 cases of HCC, 58 cases of IBDC and 210 cases of EBDSC, including 76 cases of GBC, occurred. All anthropometric measures were positively associated with risk of HCC and GBC. WHtR showed the strongest association with HCC [relative risk (RR) comparing extreme tertiles 3.51, 95% confidence interval (95% CI): 2.095.87; ptrend < 0.0001] and with GBC (RR: 1.56, 95% CI: 1.122.16 for an increment of one unit in WHtR). Weight gain during adulthood was also positively associated with HCC when comparing extreme tertiles (RR: 2.48, 95% CI: 1.494.13; <0.001). No statistically significant association was observed between obesity and risk of IBDC and EBDSC. Our results provide evidence of an association between obesity, particularly abdominal obesity, and risk of HCC and GBC. Our findings support public health recommendations to reduce the prevalence of obesity and weight gain in adulthood for HCC and GBC prevention in Western populations.
Utrecht University1, University Medical Center Groningen2, Radboud University Nijmegen3, South University4, German Cancer Research Center5, Wageningen University and Research Centre6, International Agency for Research on Cancer7, Aalborg University8, French Institute of Health and Medical Research9, Aarhus University10, University of London11, University of Oxford12, National and Kapodistrian University of Athens13, Medical Research Council14, University of Cambridge15, Umeå University16, Academy of Athens17, Lund University18, University of Naples Federico II19, Imperial College London20, University of Murcia21, University of Tromsø22
TL;DR: In this article, the relation between fruit and vegetable consumption and mortality was investigated within the European Prospective Investigation Into Cancer and Nutrition (EPCIN) within 10 European countries, recruited between 1992 and 2000 and followed until 2010.
Abstract: In this study, the relation between fruit and vegetable consumption and mortality was investigated within the European Prospective Investigation Into Cancer and Nutrition. Survival analyses were performed, including 451,151 participants from 10 European countries, recruited between 1992 and 2000 and followed until 2010. Hazard ratios, rate advancement periods, and preventable proportions to respectively compare risk of death between quartiles of consumption, to estimate the period by which the risk of death was postponed among high consumers, and to estimate proportions of deaths that could be prevented if all participants would shift their consumption 1 quartile upward. Consumption of fruits and vegetables was inversely associated with all-cause mortality (for the highest quartile, hazard ratio = 0.90, 95% confidence interval (CI): 0.86, 0.94), with a rate advancement period of 1.12 years (95% CI: 0.70, 1.54), and with a preventable proportion of 2.95%. This association was driven mainly by cardiovascular disease mortality (for the highest quartile, hazard ratio = 0.85, 95% CI: 0.77, 0.93). Stronger inverse associations were observed for participants with high alcohol consumption or high body mass index and suggested in smokers. Inverse associations were stronger for raw than for cooked vegetable consumption. These results support the evidence that fruit and vegetable consumption is associated with a lower risk of death.
TL;DR: Obesity as measured by BMI is not associated with the development of incident UC or CD, and alternative measures of obesity are required to further investigate the role of obesity in theDevelopment of incident IBD.
Medical Research Council1, Utrecht University2, Imperial College London3, Basque Government4, University of Paris-Sud5, French Institute of Health and Medical Research6, Lund University7, Umeå University8, German Cancer Research Center9, Cancer Epidemiology Unit10, University of Cambridge11, University of Naples Federico II12, Aarhus University13, Aarhus University Hospital14, International Agency for Research on Cancer15, Andalusian School of Public Health16, University of Murcia17
TL;DR: Less than half of this association appears to be mediated by higher adult BMI, suggesting that early pubertal development also may directly increase type 2 diabetes risk.
Abstract: OBJECTIVE Younger age at menarche, a marker of pubertal timing in girls, is associated with higher risk of later type 2 diabetes. We aimed to confirm this association and to examine whether it is e ...
Medical Research Council1, University of Paris-Sud2, University of Oxford3, Aalborg University4, Utrecht University5, French Institute of Health and Medical Research6, Lund University7, University of Cambridge8, German Cancer Research Center9, University of Naples Federico II10, Umeå University11, International Agency for Research on Cancer12, Wageningen University and Research Centre13, Imperial College London14
TL;DR: A positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults is confirmed and is not evident among obese participants.
Abstract: Aims/hypothesis A diet rich in meat has been reported to contribute to the risk of type 2 diabetes. The present study aims to investigate the association between meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods During 11.7 years of follow-up, 12,403 incident cases of type 2 diabetes were identified among 340,234 adults from eight European countries. A centre-stratified random subsample of 16,835 individuals was selected in order to perform a case-cohort design. Prentice-weighted Cox regression analyses were used to estimate HR and 95% CI for incident diabetes according to meat consumption. Results Overall, multivariate analyses showed significant positive associations with incident type 2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08; 95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR 1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron intake. Effect modifications by sex and class of BMI were observed. In men, the results of the overall analyses were confirmed. In women, the association with total and red meat persisted, although attenuated, while an association with poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations were not evident among obese participants. Conclusions/interpretation This prospective study confirms a positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults.
Imperial College London1, Utrecht University2, International Agency for Research on Cancer3, South University4, German Cancer Research Center5, Aarhus University6, Andalusian School of Public Health7, University of Cambridge8, University of Oxford9, Harvard University10, Academy of Athens11, Lund University12, Umeå University13, University of Naples Federico II14, University of Oslo15
TL;DR: Following WCRF/AICR recommendations could significantly increase longevity and was significantly associated with a lower hazard of dying from cancer, circulatory disease, and respiratory disease.
Imperial College London1, International Agency for Research on Cancer2, University of London3, University of Cambridge4, Umeå University5, National and Kapodistrian University of Athens6, Istituto Superiore di Sanità7, Academic Center for Education, Culture and Research8, German Cancer Research Center9, University of Naples Federico II10, Utrecht University11, Oklahoma State University Center for Health Sciences12, University of Oxford13, Aarhus University14, South University15, Institut Gustave Roussy16
TL;DR: Investigating the association between body fat and risk of amyotrophic lateral sclerosis with an appropriate prospective study design found increased prediagnostic body fat is associated with a decreased risk of ALS mortality.
Abstract: Objectives: The aim of this study was to investigate for the first time the association between body fat and risk of amyotrophic lateral sclerosis (ALS) with an appropriate prospective study design ...
Ali Amin Al Olama, Zsofia Kote-Jarai, Fredrick R. Schumacher1, Fredrik Wiklund2 +154 more•Institutions (53)
TL;DR: In this article, the authors conducted a meta-analysis of four GWAS including 5953 cases of aggressive prostate cancer and 11 463 controls (men without PrCa) and computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples through the international PRACTICAL and BPC3 consortia.
Abstract: Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03-1.21), P = 1.4 × 10(-8)]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.
TL;DR: Factor analysis identified 3 components associated with postmenopausal endometrial cancer risk that could be labeled "insulin resistance/metabolic syndrome," "steroids," and "inflammation" factors, which further support the hypothesis that inflammation factors play a role inendometrial carcinogenesis.
Abstract: 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) α, 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.
University of Toronto1, Dresden University of Technology2, University of the Witwatersrand3, Utrecht University4, Aarhus University5, University of Paris-Sud6, German Cancer Research Center7, National and Kapodistrian University of Athens8, Academy of Athens9, Harvard University10, Imperial College London11, University of Oxford12, University of Cambridge13, Medical Research Council14, International Agency for Research on Cancer15, Universidade Federal do Rio Grande do Sul16
TL;DR: Limiting alcohol use throughout life is associated with a lower risk of death, largely due to cardiovascular disease but also other causes, however, the potential health benefits of alcohol use are difficult to establish.
Abstract: Background There is limited evidence for an association between the pattern of lifetime alcohol use and cause-specific risk of death.
Methods Multivariable hazard ratios were estimated for different causes of death according to patterns of lifetime alcohol consumption using a competing risks approach: 111 953 men and 268 442 women from eight countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study were included. Self-reported alcohol consumption at ages 20, 30, 40 or 50 years and at enrolment were used for the analysis; 26 411 deaths were observed during an average of 12.6 years of follow-up.
Results The association between lifetime alcohol use and death from cardiovascular diseases was different from the association seen for alcohol-related cancers, digestive, respiratory, external and other causes. Heavy users (>5 drinks/day for men and >2.5 drinks/day for women), regardless of time of cessation, had a 2- to 5-times higher risk of dying due to alcohol-related cancers, compared with subjects with lifetime light use (≤1 and ≤0.5 drink/week for men and women, respectively). Compared with lifetime light users, men who used <5 drinks/day throughout their lifetime had a 24% lower cardiovascular disease mortality (95% confidence interval 2-41). The risk of death from coronary heart disease was also found to be 34–46% lower among women who were moderate to occasionally heavy alcohol users compared with light users. However, this relationship was only evident among men and women who had no chronic disease at enrolment.
Conclusions Limiting alcohol use throughout life is associated with a lower risk of death, largely due to cardiovascular disease but also other causes. However, the potential health benefits of alcohol use are difficult to establish due to the possibility of selection bias and competing risks related to diseases occurring later in life.
International Agency for Research on Cancer1, University of Oslo2, University of Tromsø3, Aarhus University4, Technical University of Denmark5, University of Oxford6, University of Cambridge7, University of Gothenburg8, Umeå University9, Imperial College London10, University of Naples Federico II11, National and Kapodistrian University of Athens12, German Cancer Research Center13, Prevention Institute14, French Institute of Health and Medical Research15
TL;DR: There are significant differences in flavonoid class intakes, food sources and some characteristics between MED and non-MED countries, which should be considered in studies about the relationships between flavonoids intake and chronic diseases.
Abstract: A greater adherence to the traditional Mediterranean (MED) diet is associated with a reduced risk of developing chronic diseases. This dietary pattern is based on higher consumption of plant products that are rich in flavonoids. We compared the total flavonoid dietary intakes, their food sources and various lifestyle factors between MED and non-MED countries participating in the EPIC study. Flavonoid intakes and their food sources for 35 628 subjects, aged 35-74 years and recruited between 1992 and 2000, in twenty-six study centres were estimated using standardised 24 h dietary recall software (EPIC-Soft (R)). An ad hoc food composition database on flavonoids was compiled using analytical data from the United States Department of Agriculture and Phenol-Explorer databases. Moreover, it was expanded to include using recipes, estimations of missing values and flavonoid retention factors. No significant differences in total flavonoid mean intake between non-MED countries (373.7 mg/d) and MED countries (370.2 mg/d) were observed. In the non-MED region, the main contributors were proanthocyanidins (48.2 %) and flavan-3-ol monomers (24.9 %) and the principal food sources were tea (25.7 %) and fruits (32.8 %). In the MED region, proanthocyanidins (59.0 %) were by far the most abundant contributor and fruits (55.1 %), wines (16.7 %) and tea (6.8 %) were the main food sources. The present study shows similar results for total dietary flavonoid intakes, but significant differences in flavonoid class intakes, food sources and some characteristics between MED and non-MED countries. These differences should be considered in studies about the relationships between flavonoid intake and chronic diseases.
University of Kiel1, Max Delbrück Center for Molecular Medicine2, International Agency for Research on Cancer3, Emory University4, Aarhus University5, French Institute of Health and Medical Research6, German Cancer Research Center7, National and Kapodistrian University of Athens8, University of Naples Federico II9, Prevention Institute10, Imperial College London11, Utrecht University12, University Medical Center Utrecht13, Andalusian School of Public Health14, Basque Government15, Lund University16, University of Gothenburg17, Umeå University18, University of Cambridge19, Medical Research Council20, Cancer Epidemiology Unit21, University of Bonn22
TL;DR: This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC, and further research is required to establish whether diabetes treatment or duration is associated with these cancers.
TL;DR: Increased adherence to Mediterranean diet appears to protect against hip fracture occurrence, particularly among men, in a cohort of adults from eight European countries.
Abstract: Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89–0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79–0.94) and high fruit (HR = 0.89; 95 % CI = 0.82–0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06–1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32–2.31) was also a risk factor. In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.
Medical Research Council1, Utrecht University2, Technical University of Denmark3, South University4, French Institute of Health and Medical Research5, Lund University6, German Cancer Research Center7, Cancer Epidemiology Unit8, University of Cambridge9, Prevention Institute10, University of Naples Federico II11, Andalusian School of Public Health12, Aarhus University13, International Agency for Research on Cancer14, University of Murcia15, Imperial College London16
TL;DR: Prospective findings in this large European cohort demonstrate inverse associations between flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes, which suggests a potential protective role of eating a diet rich in flavonoid, a dietary pattern based on plant-based foods, in the prevention of type 1 diabetes.
Abstract: OBJECTIVE To study the association between dietary flavonoid and lignan intakes, and the risk of development of type 2 diabetes among European populations.
RESEARCH DESIGN AND METHODS The European Prospective Investigation into Cancer and Nutrition-InterAct case-cohort study included 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants from among 340,234 participants with 3.99 million person-years of follow-up in eight European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the Phenol-Explorer, the U.K. Food Standards Agency, and the U.S. Department of Agriculture databases. Hazard ratios (HRs) from country-specific Prentice-weighted Cox regression models were pooled using random-effects meta-analysis.
RESULTS In multivariable models, a trend for an inverse association between total flavonoid intake and type 2 diabetes was observed (HR for the highest vs. the lowest quintile, 0.90 [95% CI 0.77–1.04]; P value trend = 0.040), but not with lignans (HR 0.88 [95% CI 0.72–1.07]; P value trend = 0.119). Among flavonoid subclasses, flavonols (HR 0.81 [95% CI 0.69–0.95]; P value trend = 0.020) and flavanols (HR 0.82 [95% CI 0.68–0.99]; P value trend = 0.012), including flavan-3-ol monomers (HR 0.73 [95% CI 0.57–0.93]; P value trend = 0.029), were associated with a significantly reduced hazard of diabetes.
CONCLUSIONS Prospective findings in this large European cohort demonstrate inverse associations between flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes. This suggests a potential protective role of eating a diet rich in flavonoids, a dietary pattern based on plant-based foods, in the prevention of type 2 diabetes.
Cancer Research UK1, University of Cambridge2, University of Oxford3, University of Bristol4, University of Warwick5, Cancer Council Victoria6, University of Melbourne7, Karolinska Institutet8, University of Southern California9, Harvard University10, American Cancer Society11, National Institutes of Health12, Washington University in St. Louis13, University of Turku14, University of Copenhagen15, German Cancer Research Center16, Imperial College London17, Cancer Prevention Institute of California18, Stanford University19, New York University20, Fred Hutchinson Cancer Research Center21, University of Washington22, Vanderbilt University23, Mayo Clinic24, University of Ulm25, Pomeranian Medical University26, Veterans Health Administration27, University of Utah28, University of South Florida29, Sofia Medical University30, Queensland University of Technology31, QIMR Berghofer Medical Research Institute32, University of Porto33, Instituto Português de Oncologia Francisco Gentil34, McGill University35
TL;DR: Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.
Abstract: Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.
TL;DR: The results may have profound clinical implications in patients with severe T2D, given the increased risk of cancer in CME carriers, and the presence of CMEs in 7,659 individuals using DNA arrays.
Abstract: Large chromosomal clonal mosaic events (CMEs) have been suggested to be linked to aging and to predict cancer. Type 2 diabetes (T2D) has been conceptualized as an accelerated-aging disease and is associated with higher prevalence of cancers. Here we aimed to assess the association between T2D and CME occurrence in blood. We evaluated the presence of CMEs in 7,659 individuals (including 2,208 with T2D) using DNA arrays. A significant association between CME occurrence and T2D was found (odds ratio (OR) = 5.3; P = 5.1 × 10(-5)) and was stronger when we only considered non-obese individuals with T2D (OR = 5.6; P = 4.9 × 10(-5)). Notably, CME carriers with T2D had higher prevalence of vascular complications than non-carriers with T2D (71.4% versus 37.1%, respectively; P = 7.7 × 10(-4)). In CME carriers, we found an increase in the percentage of abnormal cells over 6 years (P = 8.60 × 10(-3)). In conclusion, given the increased risk of cancer in CME carriers, our results may have profound clinical implications in patients with severe T2D.
International Agency for Research on Cancer1, German Cancer Research Center2, National and Kapodistrian University of Athens3, University of Kiel4, Icahn School of Medicine at Mount Sinai5, Aarhus University6, South University7, French Institute of Health and Medical Research8, Imperial College London9, University of Naples Federico II10, University Medical Center Utrecht11, Utrecht University12, University of Tromsø13, Andalusian School of Public Health14, University of Gothenburg15, Umeå University16, University of Oxford17, University of Cambridge18
TL;DR: Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk, and in addition, high dietary fiber intake could be associated with higher IBD cancer risk.
Utrecht University1, French Institute of Health and Medical Research2, German Cancer Research Center3, University of Oxford4, Lund University5, Prevention Institute6, Umeå University7, Andalusian School of Public Health8, International Agency for Research on Cancer9, Medical Research Council10, Imperial College London11
TL;DR: It is shown that digestible carbohydrate intake is not associated with diabetes risk and suggests that diabetes risk with high-GI and -GL diets may be more modest than initial studies suggested.
Abstract: The association of glycemic index (GI) and glycemic load (GL) with the risk of type 2 diabetes remains unclear. We investigated associations of dietary GI, GL, and digestible carbohydrate with incident type 2 diabetes. We performed a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition Study, including a random subcohort (n = 16,835) and incident type 2 diabetes cases (n = 12,403). The median follow-up time was 12 y. Baseline dietary intakes were assessed using country-specific dietary questionnaires. Country-specific HR were calculated and pooled using random effects meta-analysis. Dietary GI, GL, and digestible carbohydrate in the subcohort were (mean ± SD) 56 ± 4, 127 ± 23, and 226 ± 36 g/d, respectively. After adjustment for confounders, GI and GL were not associated with incident diabetes [HR highest vs. lowest quartile (HR(Q4)) for GI: 1.05 (95% CI = 0.96, 1.16); HR(Q4) for GL: 1.07 (95% CI = 0.95, 1.20)]. Digestible carbohydrate intake was not associated with incident diabetes [HR(Q4): 0.98 (95% CI = 0.86, 1.10)]. In additional analyses, we found that discrepancies in the GI value assignment to foods possibly explain differences in GI associations with diabetes within the same study population. In conclusion, an expansion of the GI tables and systematic GI value assignment to foods may be needed to improve the validity of GI values derived in such studies, after which GI associations may need reevaluation. Our study shows that digestible carbohydrate intake is not associated with diabetes risk and suggests that diabetes risk with high-GI and -GL diets may be more modest than initial studies suggested.