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1.
J Ovarian Res ; 12(1): 116, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771659

RESUMO

BACKGROUND: Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker. METHODS: We developed and validated linear and dichotomous (≥35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses' Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. RESULT: The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset. CONCLUSIONS: The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.

2.
Br J Nutr ; : 1-35, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31583990

RESUMO

Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent, and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterize the association between plasma concentrations of 35 polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis the odds and 95% confidence intervals (CI-s) of elevated serum hsCRP (>3 mg/L) were calculated within quartiles and per standard deviation (SD) higher level of plasma polyphenol concentrations. In multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per SD) was associated with 29% lower odds of elevated hsCRP (95% CI: 50%-1%). In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR= 0.66, 95%CI 0.46-0.96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR=0.58, 95%CI 0.39-0.86), 3,4-dihydroxyphenylpropionic acid (OR= 0.63, 95% CI 0.46-0.87), ferulic acid (OR= 0.65, 95%CI 0.44-0.96), and caffeic acid (OR= 0.69, 95%CI 0.51-0.93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR= 0.67, 95%CI 0.48-0.93). This study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies.

3.
Nutrients ; 11(8)2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434255

RESUMO

Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor ß (TGFß) signaling was associated with CRC risk (P ≤ 0.001), with most statistically significant genes being SMAD7 (PBH = 0.008) and SMAD3 (PBH = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.

4.
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.

5.
Cancer Epidemiol Biomarkers Prev ; 28(10): 1746-1754, 2019 Oct.
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 2,016 controls [n = 1,552 (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 ELISA and 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 (P trend ≤ 0.03) and higher OPG concentrations in all women (P trend ≤ 0.01). Longer duration of oral contraceptive use among premenopausal women and postmenopausal PMH users was associated with higher OPG (P trend ≤ 0.04). In postmenopausal non-PMH users, sRANKL concentrations were lower with longer duration of oral contraceptive use and current (vs. never) smoking (P ≤ 0.01). sRANKL concentrations were higher among women with higher BMI (P trend ≤ 0.01). The evaluated factors accounted for 12% of the variation in sRANKL concentrations and 21% of the variation in OPG concentrations. CONCLUSIONS: 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.

6.
J Nutr ; 149(6): 1047-1055, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31149710

RESUMO

BACKGROUND: Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence. OBJECTIVE: The aim of this study was to derive country-specific exploratory dietary patterns, investigate their association with type 2 diabetes incidence, and replicate diabetes-associated dietary patterns in other countries. METHODS: Dietary intake data were used, assessed by country-specific questionnaires at baseline of 11,183 incident diabetes cases and 14,694 subcohort members (mean age 52.9 y) from 8 countries, nested within the European Prospective Investigation into Cancer and Nutrition study (mean follow-up time 6.9 y). Exploratory dietary patterns were derived by principal component analysis. HRs for incident type 2 diabetes were calculated by Prentice-weighted Cox proportional hazard regression models. Diabetes-associated dietary patterns were simplified or replicated to be applicable in other countries. A meta-analysis across all countries evaluated the generalizability of the diabetes-association. RESULTS: Two dietary patterns per country/UK-center, of which overall 3 dietary patterns were diabetes-associated, were identified. A risk-lowering French dietary pattern was not confirmed across other countries: pooled HRFrance per 1 SD: 1.00; 95% CI: 0.90, 1.10. Risk-increasing dietary patterns, derived in Spain and UK-Norfolk, were confirmed, but only the latter statistically significantly: HRSpain: 1.09; 95% CI: 0.97, 1.22 and HRUK-Norfolk: 1.12; 95% CI: 1.04, 1.20. Respectively, this dietary pattern was characterized by relatively high intakes of potatoes, processed meat, vegetable oils, sugar, cake and cookies, and tea. CONCLUSIONS: Only few country/center-specific dietary patterns (3 of 18) were statistically significantly associated with diabetes incidence in this multicountry European study population. One pattern, whose association with diabetes was confirmed across other countries, showed overlaps in the food groups potatoes and processed meat with identified diabetes-associated dietary patterns from other studies. The study demonstrates that replication of associations of exploratory patterns with health outcomes is feasible and a necessary step to overcome population-specificity in associations from such analyses.

7.
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.

8.
Nutrients ; 11(4)2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31027226

RESUMO

Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10; PACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.

9.
Diabetes Care ; 42(4): 568-575, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30728219

RESUMO

OBJECTIVE: To estimate the causal association between intake of dairy products and incident type 2 diabetes. RESEARCH DESIGN AND METHODS: The analysis included 21,820 European individuals (9,686 diabetes cases) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study. Participants were genotyped, and rs4988235 (LCT-12910C>T), a single nucleotide polymorphism (SNP) for lactase persistence (LP) that enables digestion of dairy sugar, i.e., lactose, was imputed. Baseline dietary intakes were assessed with diet questionnaires. We investigated the associations between imputed SNP dosage for rs4988235 and intake of dairy products and other foods through linear regression. Mendelian randomization (MR) estimates for the milk-diabetes relationship were obtained through a two-stage least squares regression. RESULTS: Each additional LP allele was associated with a higher intake of milk (ß 17.1 g/day, 95% CI 10.6-23.6) and milk beverages (ß 2.8 g/day, 95% CI 1.0-4.5) but not with intake of other dairy products. Other dietary intakes associated with rs4988235 included fruits (ß -7.0 g/day, 95% CI -12.4 to -1.7 per additional LP allele), nonalcoholic beverages (ß -18.0 g/day, 95% CI -34.4 to -1.6), and wine (ß -4.8 g/day, 95% CI -9.1 to -0.6). In instrumental variable analysis, LP-associated milk intake was not associated with diabetes (hazard ratioper 15 g/day 0.99, 95% CI 0.93-1.05). CONCLUSIONS: rs4988235 was associated with milk intake but not with intake of other dairy products. This MR study does not suggest that milk intake is associated with diabetes, which is consistent with previous observational and genetic associations. LP may be associated with intake of other foods as well, but owing to the modest associations, we consider it unlikely that this caused the observed null result.

10.
Int J Cancer ; 145(1): 122-131, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30588620

RESUMO

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


Assuntos
Dieta Mediterrânea/estatística & dados numéricos , Linfoma/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco
11.
Int J Cancer ; 144(2): 240-250, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29943826

RESUMO

The epidemiological evidence regarding the association of coffee and tea consumption with prostate cancer risk is inconclusive, and few cohort studies have assessed these associations by disease stage and grade. We examined the associations of coffee (total, caffeinated and decaffeinated) and tea intake with prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 142,196 men, 7,036 incident prostate cancer cases were diagnosed over 14 years of follow-up. Data on coffee and tea consumption were collected through validated country-specific food questionnaires at baseline. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI). Models were stratified by center and age, and adjusted for anthropometric, lifestyle and dietary factors. Median coffee and tea intake were 375 and 106 mL/day, respectively, but large variations existed by country. Comparing the highest (median of 855 mL/day) versus lowest (median of 103 mL/day) consumers of coffee and tea (450 vs. 12 mL/day) the HRs were 1.02 (95% CI, 0.94-1.09) and 0.98 (95% CI, 0.90-1.07) for risk of total prostate cancer and 0.97 (95% CI, 0.79-1.21) and 0.89 (95% CI, 0.70-1.13) for risk of fatal disease, respectively. No evidence of association was seen for consumption of total, caffeinated or decaffeinated coffee or tea and risk of total prostate cancer or cancer by stage, grade or fatality in this large cohort. Further investigations are needed to clarify whether an association exists by different preparations or by concentrations and constituents of these beverages.


Assuntos
Café , Neoplasias da Próstata/epidemiologia , Chá , Adulto , Idoso , Estudos de Coortes , Inquéritos sobre Dietas , Europa (Continente) , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco
12.
Eur J Nutr ; 58(8): 3303-3312, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30535794

RESUMO

PURPOSE: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study. METHODS: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires. RESULTS: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97-1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95-1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95-1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81-0.99), but this association was based on a sub-analysis with a small number of cancer cases. CONCLUSIONS: In this large prospective study, coffee and tea consumptions were not associated with TC risk.

13.
Int J Cancer ; 145(6): 1510-1516, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30585640

RESUMO

Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self-reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow-up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR = 1.14, 95%CI 0.99-1.31, p = 0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR = 0.81, 95%CI 0.63-1.04, p = 0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex.

14.
Eur J Cancer Prev ; 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30489354

RESUMO

Helicobacter pylori (H. pylori) chronic infection causes severe digestive diseases, including gastric cancer, and certain strains entail a higher risk. Risk factors for this infection are still not fully understood. The aim of this study was to describe the association of adult and childhood sociodemographic factors with the seroprevalence of H. pylori, and with CagA and VacA antigen-specific seropositivity among H. pylori-seropositive individuals in the Spanish adult population. Serum antibody reactivity to H. pylori proteins was evaluated using multiplex serology in 2555 population-based controls enrolled in the MCC-Spain study, a multicase-control study recruiting participants from 2008 to 2013 in different areas of Spain. H. pylori seroprevalence was defined as seropositivity against at least four bacterial proteins. Information on sociodemographics, lifestyles, and environmental exposures was collected through personal interviews. Prevalence ratios and 95% confidence intervals were estimated using Poisson regression models to assess the association of lifetime sociodemographic factors with H. pylori seroprevalence and with seropositivity for CagA and VacA. H. pylori seroprevalence was 87.2%. Seropositivity was statistically significantly higher in men, increased with age, BMI, and number of siblings, and decreased with education and socioeconomic family level at birth. Among H. pylori-seropositive individuals, seropositivity was 53.3% for CagA, 61.4% for VacA, and 38.8% for both CagA and VacA. Ever smokers had lower seroprevalence for CagA and VacA than never smokers. H. pylori seroprevalence among this Spanish adult population was high and one third of the population was seropositive for two well-known markers of gastric cancer risk: CagA and VacA. Sex, age, education, and BMI were associated with H. pylori seroprevalence.

15.
Int J Cancer ; 2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30259989

RESUMO

Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. Our study provides a first prospective evaluation of an ApoA2 isoform ("ApoA2-ATQ/AT"), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤ 18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤ 18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging.

16.
BMC Public Health ; 18(1): 1134, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30241493

RESUMO

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used despite their risk of gastrointestinal bleeding or cardiovascular events. We report the profile of people taking NSAIDs in Spain, and we include demographic factors, health-related behaviours and cardiovascular disease history. METHODS: Four thousand sixtyparticipants were selected using a pseudorandom number list from Family Practice lists in 12 Spanish provinces. They completed a face-to-face computerized interview on their NSAID consumption, demographic characteristics, body mass index, alcohol and tobacco consumption and medical history. In addition, participants completed a self-administered food-frequency and alcohol consumption questionnaire. Factors associated with ever and current NSAID consumption were identified by logistic regression. RESULTS: Women consumed more non-aspirin NSAIDs (38.8% [36.7-41.0]) than men (22.3 [20.5-24.2]), but men consumed more aspirin (11.7% [10.3-13.2]) than women (5.2% [4.3-6.3]). Consumption of non-aspirin NSAIDs decrease with age from 44.2% (39.4-49.1) in younger than 45 to 21.1% (18.3-24.2) in older than 75, but the age-pattern for aspirin usage was the opposite. Aspirin was reported by about 11% patients, as being twice as used in men (11.7%) than in women (5.2%); its consumption increased with age from 1.7% (< 45 years old) to 12.4% (≥75 years old). Aspirin was strongly associated with the presence of cardiovascular risk factors or established cardiovascular disease, reaching odds ratios of 15.2 (7.4-31.2) in women with acute coronary syndrome, 13.3 (6.2-28.3) in women with strokes and 11.1 (7.8-15.9) in men with acute coronary syndrome. Participants with cardiovascular risk factors or diseases consumed as much non-aspirin NSAID as participants without such conditions. CONCLUSIONS: Non-aspirin NSAIDs were more consumed by women and aspirin by men. The age patterns of aspirin and non-aspirin NSAIDs were opposite: the higher the age, the lower the non-aspirin NSAIDs usage and the higher the aspirin consumption. People with cardiovascular risk factors or diseases consumed more aspirin, but they did not decrease their non-aspirin NSAIDs usage.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Adulto , Distribuição por Idade , Idoso , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Feminino , Hemorragia Gastrointestinal , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Espanha/epidemiologia , Inquéritos e Questionários
17.
Am J Hum Biol ; 30(6): e23181, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30251288

RESUMO

OBJECTIVE: To determinate the role of lifestyle factors, recent diet, menstrual factors, and reproductive history in age at natural menopause in adult Spanish women. METHODS: In total, 12 562 pre-menopausal women were available for analysis from the EPIC-Spain sub-cohort. Women were recruited between 1992 and 1996 in five regions of Spain (Asturias, Granada, Murcia, Navarra, and San Sebastian) and, for these analyses, were followed for 3 years. Questionnaires on diet, lifestyle, anthropometric measurements, and reproductive and exogenous hormones history were collected at baseline. Menopause status was updated at a median of 3 years of follow-up. RESULTS: After a median of 3 years of follow-up 1166 women became postmenopausal. An earlier age at menopause was observed in current smokers (HR: 1.29; 95%CI 1.08-1.55) and in non-users of oral contraceptives (HR: 1.32; 95%CI 1.01-1.57). A later age at menopause was observed in women with irregular menses (HR: 0.71; 95%CI 0.56-0.91) and in women with a higher number of pregnancies (HR: 0.74; 95%CI 0.56-0.94). CONCLUSIONS: Our results confirm that women who smoked had an earlier age at natural menopause, while use of oral contraceptives, higher number of pregnancies, and irregularity of menses were associated with a prolonged reproductive lifespan. No associations were observed for dietary habits assessed after the age of 40 years.

18.
Int J Cancer ; 2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30191956

RESUMO

Insulin-like growth factor (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1221 melanoma cases and 1221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity, and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth=0.93 (95% confidence interval (CI): 0.71 to 1.22)). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by sex, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma. This article is protected by copyright. All rights reserved.

19.
Nature ; 559(7714): 400-404, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29988082

RESUMO

The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure1. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion2,3. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)4-8. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.

20.
Artigo em Inglês | MEDLINE | ID: mdl-30056182

RESUMO

BACKGROUND & AIMS: Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most studies have been of insufficient size to identify heterogeneous associations with precision. METHODS: In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumors at different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests. RESULTS: After a median of 14.9 years of follow-up evaluation of 521,330 men and women, 6291 colorectal cancer cases occurred. Physical activity was related inversely to proximal colon and distal colon cancer, but not to rectal cancer (P heterogeneity = .03). Height was associated positively with proximal and distal colon cancer only, but not rectal cancer (P heterogeneity = .0001). For men, but not women, heterogeneous relationships were observed for body mass index (P heterogeneity = .008) and waist circumference (P heterogeneity = .03), with weaker positive associations found for rectal cancer, compared with proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P heterogeneity = .05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors. CONCLUSIONS: The physical activity, anthropometry, and smoking relationships with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.

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