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1.
JAMA Intern Med ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479109

RESUMO

Importance: Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date. Objective: To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality. Design, Setting, and Participants: This population-based cohort study involved participants (n = 451 743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018. Exposure: Consumption of total, sugar-sweetened, and artificially sweetened soft drinks. Main Outcomes and Measures: Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors. Results: In total, 521 330 individuals were enrolled. Of this total, 451 743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321 081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41 693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of <1 glass per month) of total soft drinks (hazard ratio [HR], 1.17; 95% CI, 1.11-1.22; P < .001), sugar-sweetened soft drinks (HR, 1.08; 95% CI, 1.01-1.16; P = .004), and artificially sweetened soft drinks (HR, 1.26; 95% CI, 1.16-1.35; P < .001). Positive associations were also observed between artificially sweetened soft drinks and deaths from circulatory diseases (≥2 glasses per day vs <1 glass per month; HR, 1.52; 95% CI, 1.30-1.78; P < .001) and between sugar-sweetened soft drinks and deaths from digestive diseases (≥1 glass per day vs <1 glass per month; HR, 1.59; 95% CI, 1.24-2.05; P < .001). Conclusions and Relevance: This study found that consumption of total, sugar-sweetened, and artificially sweetened soft drinks was positively associated with all-cause deaths in this large European cohort; the results are supportive of public health campaigns aimed at limiting the consumption of soft drinks.

2.
Nutrients ; 11(9)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484340

RESUMO

A pro-coagulative state is related to increased risk of cardiovascular diseases but also certain cancers. Since experimental and smaller human studies suggest that diet, physical activity, and body weight may all affect coagulation, we evaluated associations between these lifestyle factors and hemostatic biomarkers in a population-based study. Cross-sectional baseline data from 2267 randomly selected participants of EPIC-Heidelberg (age range 35-65 years) was used. Fibrinogen, glycoprotein IIb/IIIa, P-selectin, thrombomodulin (TM), and thrombopoietin (TPO) were measured in baseline plasma samples. A score reflecting adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations for cancer prevention was created. Associations between the WCRF/AICR score as well as its individual components and hemostatic biomarkers were analyzed by linear regression models. Multivariable-adjusted geometric means (95% confidence intervals) of TM and TPO were higher with greater adherence to the WCRF/AICR recommendations (TM, lowest vs. highest score category: 2.90 (2.7,3.1) vs. 3.10 (2.9,3.3) ng/mL, plinear trend = 0.0001; TPO: 328 (302,356) vs. 348 (321,378) pg/mL, plinear trend = 0.0007). These associations were driven by lower alcohol and meat consumption among persons with higher WCRF/AICR scores. Our results indicate that lifestyle factors favorably affect TM and TPO, two hemostatic factors implicated in chronic disease development.

3.
Cancer Epidemiol Biomarkers Prev ; 28(9): 1552-1555, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31481495

RESUMO

BACKGROUND: There is a lack of prospective data on the potential association of Fusobacterium nucleatum (F. nucleatum) and colorectal cancer risk. In this study, we assessed whether antibody responses to F. nucleatum are associated with colorectal cancer risk in prediagnostic serum samples in the European Prospective Investigation into Nutrition and Cancer (EPIC) cohort. METHODS: We applied a multiplex serology assay to simultaneously measure antibody responses to 11 F. nucleatum antigens in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: We observed neither a statistically significant colorectal cancer risk association for antibodies to individual F. nucleatum proteins nor for combined positivity to any of the 11 proteins (OR, 0.81; 95% CI, 0.62-1.06). CONCLUSIONS: Antibody responses to F. nucleatum proteins in prediagnostic serum samples from a subset of colorectal cancer cases and matched controls within the EPIC study were not associated with colorectal cancer risk. IMPACT: Our findings in prospectively ascertained serum samples contradict the existing literature on the association of F. nucleatum with colorectal cancer risk. Future prospective studies, specifically detecting F. nucleatum in stool or tissue biopsies, are needed to complement our findings.

4.
Cancer Res ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462430

RESUMO

Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient characteristics has not been adequately explored. In this study, we pooled data from case-control studies nested within six cohorts in the Ovarian Cancer Cohort Consortium (OC3) to examine the association between CRP and epithelial ovarian cancer risk overall, by histologic subtype and by participant characteristics. CRP concentrations were measured from pre-diagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). When CRP was evaluated using tertiles, no associations with ovarian cancer risk were observed. A 67% increased ovarian cancer risk was found for women with CRP concentrations >10mg/L compared to <1mg/L (OR=1.67, 95% CI=1.12, 2.48). A CRP concentration >10mg/L was positively associated with risk of mucinous (OR=9.67, 95% CI=1.10, 84.80) and endometrioid carcinoma (OR=3.41, 95% CI=1.07, 10.92), and suggestively positive, though not statistically significant, for serous (OR=1.43, 95% CI=0.82, 2.49) and clear cell carcinoma (OR=2.05, 95% CI=0.36, 11.57; p-heterogeneity=0.20). Heterogeneity was observed with oral contraceptive use (p-interaction=0.03), where the increased risk was present only among ever users (OR=3.24, 95% CI=1.62, 6.47). The present study adds to the existing evidence that CRP plays a role in ovarian carcinogenesis, and suggests that inflammation may be particularly implicated in the etiology of endometrioid and mucinous carcinoma.

5.
J Nutr ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31396627

RESUMO

INTRODUCTION: Beverage consumption is a modifiable risk factor for type 2 diabetes (T2D), but there is insufficient evidence to inform the suitability of substituting 1 type of beverage for another. OBJECTIVE: The aim of this study was to estimate the risk of T2D when consumption of sugar-sweetened beverages (SSBs) was replaced with consumption of fruit juice, milk, coffee, or tea. METHODS: In the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study of 8 European countries (n = 27,662, with 12,333 cases of incident T2D, 1992-2007), beverage consumption was estimated at baseline by dietary questionnaires. Using Prentice-weighted Cox regression adjusting for other beverages and potential confounders, we estimated associations of substituting 1 type of beverage for another on incident T2D. RESULTS: Mean ± SD of estimated consumption of SSB was 55 ± 105 g/d. Means ± SDs for the other beverages were as follows: fruit juice, 59 ± 101 g/d; milk, 209 ± 203 g/d; coffee, 381 ± 372 g/d; and tea, 152 ± 282 g/d. Substituting coffee for SSBs by 250 g/d was associated with a 21% lower incidence of T2D (95% CI: 12%, 29%). The rate difference was -12.0 (95% CI: -20.0, -5.0) per 10,000 person-years among adults consuming SSBs ≥250 g/d (absolute rate = 48.3/10,000). Substituting tea for SSBs was estimated to lower T2D incidence by 22% (95% CI: 15%, 28%) or -11.0 (95% CI: -20.0, -2.6) per 10,000 person-years, whereas substituting fruit juice or milk was estimated not to alter T2D risk significantly. CONCLUSIONS: These findings indicate a potential benefit of substituting coffee or tea for SSBs for the primary prevention of T2D and may help formulate public health recommendations on beverage consumption in different populations.

6.
J Natl Cancer Inst ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31435679

RESUMO

BACKGROUND: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans. METHODS: Associations between pre-diagnostic plasma levels of 17 primary, secondary and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations. RESULTS: Positive associations were observed between colon cancer risk and plasma levels of 7 conjugated bile acid metabolites, i.e. primary bile acids glycocholic acid (ORQuartile 4 vs. Quartile 1=2.22,95 % confidence interval[CI]=1.52, 3.26), taurocholic acid (OR = 1.78, 95%CI=1.23, 2.58), glycochenodeoxycholic acid (OR = 1.68, 95%CI=1.13, 2.48), taurochenodeoxycholic acid (OR = 1.62, 95%CI=1.11-2.36), and glycohyocholic acid (OR = 1.65, 95%CI=1.13, 2.40) as well as the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95%CI=1.12, 2.54) and taurodeoxycholic acid (OR = 1.54, 95%CI=1.02, 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk. CONCLUSIONS: This prospective study showed that pre-diagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31292137

RESUMO

BACKGROUND: Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor κB (sRANKL) and OPG concentrations in women are limited. We evaluated reproductive and lifestyle factors as potential sources of variation in circulating sRANKL and OPG concentrations in pre- and postmenopausal women. METHODS: This study includes 2016 controls (n=1552 (76%) postmenopausal, n=757 (38%) using postmenopausal hormone therapy (PMH)) from a breast cancer case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Serum sRANKL was measured using an enzyme-linked immunosorbent assay, serum OPG using an electrochemiluminescent assay. Generalized linear models were used to evaluate associations between these analytes and reproductive and lifestyle factors. RESULTS: Older age at blood collection was associated with lower sRANKL concentrations in postmenopausal women (Ptrend<=0.03) and higher OPG concentrations in all women (Ptrend<=0.01). Longer duration of OC use among premenopausal women and postmenopausal PMH users was associated with higher OPG (Ptrend<=0.04). In postmenopausal non-PMH users, sRANKL concentrations were lower with longer duration of OC use and current (vs. never) smoking (P<=0.01). sRANKL concentrations were higher among women with higher BMI (Ptrend<=0.01). The evaluated factors accounted for 12% of the variation in sRANKL concentrations and 21% of the variation in OPG concentrations. CONCLUSION: Circulating sRANKL and OPG concentrations are minimally impacted by hormone-related factors in pre- and postmenopausal women. IMPACT: This study suggests circulating concentrations of sRANKL and OPG are unlikely to be strongly modified by hormone-related reproductive and lifestyle factors.

8.
Int J Cancer ; 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31162856

RESUMO

In 2011, the U.S. National Lung Cancer Screening Trial (NLST) reported a 20% reduction of lung cancer mortality after regular screening by low-dose computed tomography (LDCT), as compared to X-ray screening. The introduction of lung cancer screening programs in Europe awaits confirmation of these first findings from European trials that started in parallel with the NLST. The German Lung cancer Screening Intervention (LUSI) is a randomized trial among 4,052 long-term smokers, 50-69 years of age, recruited from the general population, comparing five annual rounds of LDCT screening (screening arm; n = 2,029 participants) with a control arm (n = 2,023) followed by annual postal questionnaire inquiries. Data on lung cancer incidence and mortality and vital status were collected from hospitals or office-based physicians, cancer registries, population registers and health offices. Over an average observation time of 8.8 years after randomization, the hazard ratio for lung cancer mortality was 0.74 (95% CI: 0.46-1.19; p = 0.21) among men and women combined. Modeling by sex, however showed a statistically significant reduction in lung cancer mortality among women (HR = 0.31 [95% CI: 0.10-0.96], p = 0.04), but not among men (HR = 0.94 [95% CI: 0.54-1.61], p = 0.81) screened by LDCT (pheterogeneity = 0.09). Findings from LUSI are in line with those from other trials, including NLST, that suggest a stronger reduction of lung cancer mortality after LDCT screening among women as compared to men. This heterogeneity could be the result of different relative counts of lung tumor subtypes occurring in men and women.

9.
Int J Cancer ; 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31050823

RESUMO

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5-25 kg/m2 : HR = 1.94, 95% CI: 1.25-3.03) and women (HR = 2.66, 95% CI: 1.15-6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99-6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52-4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35-14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76-18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14-0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32-0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04-3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.

10.
Sci Rep ; 9(1): 8037, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142825

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

11.
Adv Nutr ; 10(4): 673-684, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31075175

RESUMO

Short-chain fatty acids (SCFAs, mainly acetate, propionate, and butyrate), which are primarily derived from the gut microbiome, may exert anti-inflammatory and immunomodulatory effects, and regulate energy homeostasis. It has been suggested that weight loss may affect SCFA metabolism, but a systematic review of intervention studies is lacking. We aimed to systematically assess the effects of dietary, physical activity-based, and surgical weight-loss interventions among overweight [body mass index (BMI) 25-29.9 kg/m2)] or obese (BMI ≥30 kg/m2) adults (≥18 y) on concentrations of acetate, propionate, butyrate, and total SCFAs in blood, urine, or feces. We conducted a systematic literature search in PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to April 30, 2018 for randomized and nonrandomized weight-loss trials among overweight or obese adults, in which the concentrations of individual and total SCFAs were assessed. A total of 9 studies consisting of 2 randomized parallel-arm trials, 4 crossover trials, and 3 nonrandomized clinical or surgical trials were included. In the majority of studies, changes in fecal SCFA concentrations were assessed, whereas changes in serum SCFAs were reported from 1 trial. Individual and total SCFA concentrations either remained unchanged or decreased significantly following weight loss. Three of the dietary interventions that resulted in decreased SCFA concentrations were low (≤5% of energy) in total carbohydrates. Most of the studies had a high risk of bias. Decreases in SCFA concentrations may accompany weight loss induced by bariatric surgery or dietary restriction among overweight or obese adults, particularly when carbohydrate intake is reduced. However, findings were inconsistent and based on studies with high to unclear risk of bias, and small sample sizes. Because measurements of fecal SCFAs may not be ideal due to limited sample standardization, well-powered trials with repeated blood measurements of SCFAs are required. This review was registered at PROSPERO as CRD42018088716.

12.
Cancer Epidemiol Biomarkers Prev ; 28(7): 1221-1227, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31015200

RESUMO

BACKGROUND: While enhanced platelet activation and a procoagulant state may drive lung cancer progression and metastases, less is known about their role in earlier phases of cancer development. Thus, we evaluated whether prediagnostic biomarkers of platelet activation and coagulation are related to the risk of lung cancer in the prospective EPIC-Heidelberg Study using a case-cohort design. METHODS: Levels of fibrinogen, soluble glycoprotein (sGP) IIb/IIIa, soluble P-selectin (sP-selectin), soluble thrombomodulin (sTM), and thrombopoietin (TPO) were measured in baseline plasma samples of a random subcohort (n = 2,480) and incident cases of lung cancer (n = 190). Multivariable-adjusted Cox proportional hazards regression analyses were used to obtain HRs of lung cancer across quartiles of biomarker levels. RESULTS: Fibrinogen [HR highest vs. lowest quartile: 1.91 (95% confidence interval: 1.09-3.34)] and sP-Selectin [HR: 2.51 (1.39-4.52)] were significantly associated with lung cancer risk in multivariable adjusted Cox regression models. Adding both biomarkers to the established PLCOm2012 algorithm, which alone showed a C-statistic of 0.788, led to a slight increment in lung cancer risk prediction, with a C-statistic of 0.814. CONCLUSION: Our findings indicate that enhanced platelet activation and a procoagulative state contribute to lung carcinogenesis. IMPACT: The current prospective study supports the hypothesis of increased coagulation being a possible driver of lung carcinogenesis, as strong positive associations were found between two procoagulative markers, sP-Selectin and fibrinogen, with lung cancer risk. Both biomarkers could improve lung cancer risk prediction, but external validation of the results is needed.

13.
Int J Cancer ; 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30951192

RESUMO

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD ) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD = 0.77, 95% confidence interval 0.66-0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD = 0.72, 0.57-0.90), or lysophosphatidylcholines (OR1SD = 0.81, 0.69-0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD = 0.77, 0.61-0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.

14.
Int J Cancer ; 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30968961

RESUMO

Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.

15.
Cancer Epidemiol Biomarkers Prev ; 28(6): 1076-1085, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30948451

RESUMO

BACKGROUND: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. METHODS: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (≥35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). RESULTS: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC (r = 0.22) and in EPIC (r = 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78). CONCLUSIONS: We identified a combination of factors associated with CA125 levels in premenopausal women. IMPACT: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.

16.
Nutrients ; 11(4)2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31018616

RESUMO

BACKGROUND: Obesity can lead to ectopic pancreatic fat accumulation and increase the risk for type 2 diabetes. Smaller intervention trials have shown a decrease in pancreatic fat content (PFC) with weight loss, and we intended to investigate the effects of weight loss on PFC in a larger trial. METHODS: Data from the HELENA-Trial, a randomized controlled trial (RCT) among 137 non-diabetic obese adults were used. The study cohort was classified into 4 quartiles based on weight change between baseline and 12 weeks post-intervention. Changes in PFC (baseline, 12 weeks and 50 weeks post-intervention) upon weight loss were analyzed by linear mixed models. Spearman's coefficients were used to obtain correlations between anthropometric parameters, blood biochemical markers, and PFC. RESULTS: At baseline, PFC only showed a significant correlation with visceral adipose tissue (VAT) (r = 0.41). Relative changes in PFC were significantly (p = 0.01) greater in Q4 (-30.8 ± 5.7%) than in Q1 (1.3 ± 6.7%). These differences remained similar after one year. However, when adjusting the statistical analyses for changes in VAT, the differences in PFC between Q1 and Q4 were no longer statistically significant. CONCLUSION: Weight loss is associated with a decrease in PFC. However, the reduction of PFC is not independent from reductions in VAT. Unlike VAT, PFC was not associated with metabolic biomarkers.

17.
Sci Rep ; 9(1): 3004, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30816120

RESUMO

Little is known about circulating biomarkers of vascular injury in relation to cardiovascular disease risk. Thus, we evaluated associations between six novel markers (E-Selectin, P-Selectin, thrombomodulin, thrombopoietin, intercellular adhesion molecule 3 and GPIIb/IIIa) and established cardiovascular risk factors as well as the risk of myocardial infarction (MI) in a population-based study. Biomarkers were measured in pre-diagnostic plasma samples of a case-cohort subset of EPIC-Heidelberg (incident MI cases: n = 369, random sub-cohort: n = 2,418). Generalized Linear models were used to analyse cross-sectional associations between biomarkers and cardiovascular risk factors. Multivariable Cox Regression analyses were carried out to obtain Hazard Ratios (HRs) of MI across quartiles of biomarkers levels. Cross-sectional analyses showed that sex, smoking, alcohol consumption, diabetes and exogenous hormone use were associated with biomarker levels. However, while fibrinogen was associated with MI risk (HR per standard deviation: 2.97 [95% confidence interval: 1.61, 5.46]), none of the six novel biomarkers was associated with MI risk after multivariable adjustment. In a population-based cohort, biomarkers of vascular injury were associated with established cardiovascular risk factors, but not MI risk. The tested biomarkers may reflect pathophysiological alterations in cardiovascular disease development rather than constituting independent MI risk factors.

18.
Nutrients ; 11(3)2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30836637

RESUMO

BACKGROUND: Preliminary evidence suggests that weight loss among obese has differential metabolic effects depending on the presence of non-alcoholic fatty liver disease (NAFLD). We assessed whether NAFLD predisposes to differential changes in liver fat content, liver function, and metabolic parameters upon diet-induced weight loss in a 50-week intervention trial. METHODS: 143 overweight and obese non-smokers underwent a 12-week dietary intervention and a 38-week follow-up. Diet-induced changes in anthropometric measures, circulating biomarkers, and magnetic resonance (MR)-derived liver fat content and adipose tissue volumes were evaluated by mixed linear models stratifying by NAFLD at baseline. RESULTS: The prevalence of NAFLD at baseline was 52%. Diet-induced weight loss after 12 (NAFLD: 4.8 ± 0.5%, No NAFLD: 5.1 ± 0.5%) and 50 weeks (NAFLD: 3.5 ± 0.7%, No NAFLD: 3.5 ± 0.9%) was similar in both groups, while the decrease in liver fat was significantly greater in the NAFLD group (week 12: 32.9 ± 9.5% vs. 6.3 ± 4.0%; week 50: 23.3 ± 4.4% vs. 5.0 ± 4.2%). Decreases in biomarkers of liver dysfunction (GGT, ALT, AST) and HOMA IR were also significantly greater in the NAFLD group. Other metabolic parameters showed no significant differences. CONCLUSION: Our data suggest that individuals with NAFLD show greater improvements of liver function and insulin sensitivity after moderate diet-induced weight loss than individuals without NAFLD.


Assuntos
Resistência à Insulina/fisiologia , Fígado/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Obesidade/dietoterapia , Perda de Peso/fisiologia , Adulto , Biomarcadores/sangue , Dieta Redutora , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia , Resultado do Tratamento
19.
Eur J Nutr ; 2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30903361

RESUMO

INTRODUCTION: Chronic inflammation plays a critical role in lymphomagenesis and several dietary factors seem to be involved its regulation. The aim of the current study was to assess the association between the inflammatory potential of the diet and the risk of lymphoma and its subtypes in the European Investigation into Cancer and Nutrition (EPIC) study. METHODS: The analysis included 476,160 subjects with an average follow-up of 13.9 years, during which 3,136 lymphomas (135 Hodgkin lymphoma (HL), 2606 non-Hodgkin lymphoma (NHL) and 395 NOS) were identified. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated using 28 dietary components and their corresponding inflammatory weights. The association between the ISD and lymphoma risk was estimated by hazard ratios (HR) and 95% confidence intervals (CI) calculated by multivariable Cox regression models adjusted for potential confounders. RESULTS: The ISD was not associated with overall lymphoma risk. Among lymphoma subtypes, a positive association between the ISD and mature B-cell NHL (HR for a 1-SD increase: 1.07 (95% CI 1.01; 1.14), p trend = 0.03) was observed. No statistically significant association was found among other subtypes. However, albeit with smaller number of cases, a suggestive association was observed for HL (HR for a 1-SD increase = 1.22 (95% CI 0.94; 1.57), p trend 0.13). CONCLUSIONS: Our findings suggested that a high ISD score, reflecting a pro-inflammatory diet, was modestly positively associated with the risk of B-cell lymphoma subtypes. Further large prospective studies on low-grade inflammation induced by diet are warranted to confirm these findings.

20.
Int J Cancer ; 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30873591

RESUMO

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

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