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1.
Int J Cancer ; 148(4): 825-834, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33405276

RESUMO

We investigated the association between metabolic syndrome (MetS) and its components and risk of prostate cancer (PCa) in a cohort of men enrolled in the UK Biobank. Our study cohort included 220 622 PCa-free men with baseline measurements of triglycerides (TGs), HDL-cholesterol (HDL), glycated hemoglobin (HbA1c), blood pressure (BP), and waist circumference (WC). Multivariable Cox proportional hazards regression was used to analyze associations with PCa for: individual metabolic components (TG, HDL, HbA1c, BP, WC), combinations of two and three components, and MetS overall (three or more components). We conducted mediation analyses to examine potential hormonal and inflammatory pathways (total testosterone [TT], C-reactive protein [CRP], insulin-like growth factor 1 [IGF-1]) through which MetS components may influence PCa risk. A total of 5409 men in the study developed PCa during a median follow-up of 6.9 years. We found no significant association between MetS and PCa risk (hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.92-1.06). No associations were found with PCa risk and individual measurements of TG, HDL, BP, or WC. However, an inverse association was observed with elevated HbA1c (≥42 mmol/mol) (HR = 0.89, 95% CI = 0.79-0.98). Consistent inverse associations were observed between HbA1c and risk of PCa. Mediation analysis revealed TT, CRP, and IGF-1 as potential mediating factors for this association contributing 10.2%, 7.1%, and 7.9% to the total effect, respectively. Overall MetS had no association with PCa risk. However, a consistent inverse association with PCa risk was found for HbA1c. This association may be explained in part through hormonal and inflammatory pathways.

2.
Am J Clin Nutr ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184625

RESUMO

BACKGROUND: The number of gluten-free diet followers without celiac disease (CD) is increasing. However, little is known about the characteristics of these individuals. OBJECTIVES: We address this issue by investigating a wide range of genetic and phenotypic characteristics in association with following a gluten-free diet. METHODS: The cross-sectional association between lifestyle and health-related characteristics and following a gluten-free diet was investigated in 124,447 women and men aged 40-69 y from the population-based UK Biobank study. A genome-wide association study (GWAS) of following a gluten-free diet was performed. RESULTS: A total of 1776 (1.4%) participants reported following a gluten-free diet. Gluten-free diet followers were more likely to be women, nonwhite, highly educated, living in more socioeconomically deprived areas, former smokers, have lost weight in the past year, have poorer self-reported health, and have made dietary changes as a result of illness. Conversely, these individuals were less likely to consume alcohol daily, be overweight or obese, have hypertension, or use cholesterol-lowering medication. Participants with hospital inpatient diagnosed blood and immune mechanism disorders (OR: 1.62; 95% CI: 1.18, 2.21) and non-CD digestive system diseases (OR: 1.58; 95% CI: 1.42, 1.77) were more likely to follow a gluten-free diet. The GWAS demonstrated that no genetic variants were associated with being a gluten-free diet follower. CONCLUSIONS: Gluten-free diet followers have a better cardiovascular risk profile than non-gluten-free diet followers but poorer self-reported health and a higher prevalence of blood and immune disorders and digestive conditions. Reasons for following a gluten-free diet warrant further investigation.

3.
Int J Cancer ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33252839

RESUMO

Insulin-like growth factor-I (IGF-I) and testosterone have been implicated in prostate cancer aetiology. Using data from a large prospective full-cohort with standardised assays and repeat blood measurements, and genetic data from an international consortium, we investigated the associations of circulating IGF-I, sex hormone-binding globulin (SHBG), total and calculated free testosterone concentrations with prostate cancer incidence and mortality. For prospective analyses, risk was estimated using multivariable-adjusted Cox regression in 199,698 male UK Biobank participants. Hazard ratios (HRs) were corrected for regression dilution bias using repeat hormone measurements from a subsample. 2-sample Mendelian randomization (MR) analysis of IGF-I and risk used genetic instruments identified from UK Biobank men and genetic outcome data from the PRACTICAL consortium (79,148 cases and 61,106 controls). We used cis- and all (cis and trans) SNP MR approaches. 5,402 men were diagnosed with and 295 died from prostate cancer (mean follow-up 6.9 years). Higher circulating IGF-I was associated with elevated prostate cancer diagnosis (HR per 5 nmol/L increment=1.09, 95% CI 1.05-1.12) and mortality (HR per 5 nmol/L increment=1.15,1.02-1.29). MR analyses also supported the role of IGF-I in prostate cancer diagnosis (cis-MR odds ratio per 5 nmol/L increment=1.34,1.07-1.68). In observational analyses, higher free testosterone was associated with a higher risk of prostate cancer (HR per 50 pmol/L increment=1.10,1.05-1.15). Higher SHBG was associated with a lower risk (HR per 10 nmol/L increment=0.95,0.94-0.97), neither was associated with prostate cancer mortality. Total testosterone was not associated with prostate cancer. These findings implicate IGF-I and free testosterone in prostate cancer development and/or progression. This article is protected by copyright. All rights reserved.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33008875

RESUMO

BACKGROUND: Adiposity increases endometrial cancer risk, possibly through inflammation, hyperinsulinemia, and increasing estrogens. We aimed to quantify the mediating effects of adiponectin (anti-inflammatory adipocytokine); IL6, IL1-receptor antagonist, TNF receptor 1 and 2, and C-reactive protein (inflammatory status biomarkers); C-peptide (hyperinsulinemia biomarker); and free estradiol and estrone (estrogen biomarkers) in the adiposity-endometrial cancer link in postmenopausal women. METHODS: We used data from a case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Eligible women did not have cancer, hysterectomy, and diabetes; did not use oral contraceptives or hormone therapy; and were postmenopausal at recruitment. Mediating pathways from adiposity to endometrial cancer were investigated by estimating natural indirect (NIE) and direct (NDE) effects using sequential mediation analysis. RESULTS: The study included 163 cases and 306 controls. The adjusted OR for endometrial cancer for body mass index (BMI) ≥30 versus ≥18.5-<25 kg/m2 was 2.51 (95% confidence interval, 1.26-5.02). The ORsNIE were 1.95 (1.01-3.74) through all biomarkers [72% proportion mediated (PM)] decomposed as: 1.35 (1.06-1.73) through pathways originating with adiponectin (33% PM); 1.13 (0.71-1.80) through inflammation beyond (the potential influence of) adiponectin (13% PM); 1.05 (0.88-1.24) through C-peptide beyond adiponectin and inflammation (5% PM); and 1.22 (0.89-1.67) through estrogens beyond preceding biomarkers (21% PM). The ORNDE not through biomarkers was 1.29 (0.54-3.09). Waist circumference gave similar results. CONCLUSIONS: Reduced adiponectin and increased inflammatory biomarkers, C-peptide, and estrogens mediated approximately 70% of increased odds of endometrial cancer in women with obesity versus normal weight. IMPACT: If replicated, these results could have implications for identifying targets for intervention to reduce endometrial cancer risk in women with obesity.

5.
Br J Cancer ; 123(12): 1808-1817, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32963348

RESUMO

BACKGROUND: Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank. METHODS: A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure. RESULTS: After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death. CONCLUSION: We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.

6.
Cancer Epidemiol Biomarkers Prev ; 29(10): 2010-2018, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32732252

RESUMO

BACKGROUND: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites. METHODS: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests. RESULTS: Most associations did not vary by tumor site (P het ≥ 0.05). Associations between first pregnancy (P het = 0.04), tubal ligation (P het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases. CONCLUSIONS: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site. IMPACT: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.

7.
Cancer Epidemiol Biomarkers Prev ; 29(9): 1739-1749, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32616494

RESUMO

BACKGROUND: Fatty acids impact obesity, estrogens, and inflammation, which are risk factors for ovarian cancer. Few epidemiologic studies have investigated the association of fatty acids with ovarian cancer. METHODS: Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 1,486 incident ovarian cancer cases were identified. Cox proportional hazard models with adjustment for ovarian cancer risk factors were used to estimate HRs of ovarian cancer across quintiles of intake of fatty acids. False discovery rate was computed to control for multiple testing. Multivariable conditional logistic regression models were used to estimate ORs of ovarian cancer across tertiles of plasma fatty acids among 633 cases and two matched controls in a nested case-control analysis. RESULTS: A positive association was found between ovarian cancer and intake of industrial trans elaidic acid [HR comparing fifth with first quintileQ5-Q1 = 1.29; 95% confidence interval (CI) = 1.03-1.62; P trend = 0.02, q-value = 0.06]. Dietary intakes of n-6 linoleic acid (HRQ5-Q1 = 1.10; 95% CI = 1.01-1.21; P trend = 0.03) and n-3 α-linolenic acid (HRQ5-Q1 = 1.18; 95% CI = 1.05-1.34; P trend = 0.007) from deep-frying fats were also positively associated with ovarian cancer. Suggestive associations were reported for circulating elaidic (OR comparing third with first tertileT3-T1 = 1.39; 95% CI = 0.99-1.94; P trend = 0.06) and α-linolenic acids (ORT3-T1 = 1.30; 95% CI = 0.98-1.72; P trend = 0.06). CONCLUSIONS: Our results suggest that higher intakes and circulating levels of industrial trans elaidic acid, and higher intakes of linoleic acid and α-linolenic acid from deep-frying fat, may be associated with greater risk of ovarian cancer. IMPACT: If causal, eliminating industrial trans-fatty acids could offer a straightforward public health action for reducing ovarian cancer risk.

8.
Cancer Epidemiol Biomarkers Prev ; 29(8): 1615-1626, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32457180

RESUMO

BACKGROUND: Risk factors for prostate cancer are not well understood. Red blood cell, platelet, and white blood cell indices may be markers of a range of exposures that might be related to prostate cancer risk. Therefore, we examined the associations of hematologic parameters with prostate cancer risk. METHODS: Complete blood count data from 209,686 male UK Biobank participants who were free from cancer at study baseline were analyzed. Participants were followed up via data linkage. After a mean follow-up of 6.8 years, 5,723 men were diagnosed with prostate cancer and 323 men died from prostate cancer. Multivariable-adjusted Cox regression was used to estimate adjusted HRs and 95% confidence intervals (CI) for prostate cancer incidence and mortality by hematologic parameters, and corrected for regression dilution bias. RESULTS: Higher red blood cell (HR per 1 SD increase = 1.09, 95% CI, 1.05-1.13) and platelet counts (HR = 1.07, 1.04-1.11) were associated with an increased risk of prostate cancer. Higher mean corpuscular volume (HR = 0.90, 0.87-0.93), mean corpuscular hemoglobin (HR = 0.90, 0.87-0.93), mean corpuscular hemoglobin concentration (HR = 0.87, 0.77-0.97), and mean sphered cell volume (HR = 0.91, 0.87-0.94) were associated with a lower prostate cancer risk. Higher white blood cell (HR = 1.14, 1.05-1.24) and neutrophil count (HR = 1.27, 1.09-1.48) were associated with prostate cancer mortality. CONCLUSIONS: These associations of blood indices of prostate cancer risk and mortality may implicate shared common causes, including testosterone, nutrition, and inflammation/infection among several others in prostate cancer development and/or progression. IMPACT: These associations provide insights into prostate cancer development and progression.

9.
Nat Commun ; 11(1): 2624, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32457287

RESUMO

UK Biobank is a population-based cohort of half a million participants aged 40-69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world's largest multi-modal imaging study, with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future directions.


Assuntos
Bancos de Espécimes Biológicos , Aumento da Imagem , Gestão da Informação , Adulto , Idoso , Bancos de Espécimes Biológicos/organização & administração , Feminino , Humanos , Aumento da Imagem/métodos , Aumento da Imagem/normas , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Reino Unido
10.
Int J Cancer ; 147(9): 2405-2415, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32338769

RESUMO

Previous studies on the association of adiposity with endometrial cancer risk have mostly used body mass index (BMI) as the main exposure of interest. Whether more precise measures of body fat, such as body fat percentage and fat mass estimated by bioimpedance analyses, are better indicators of risk than BMI is unknown. The role of central adiposity and fat-free mass in endometrial cancer development remains unclear. We used Cox regression models to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI) for the associations of various measures of body size/composition with the risk of endometrial cancer among 135 110 postmenopausal women enrolled in UK Biobank. During a mean follow up of 6.8 years, 706 endometrial cancers were diagnosed, with a mean age at diagnosis of 65.5 years. The HRs (95% CIs) for endometrial cancer per 1 SD increase in BMI, body fat percentage and fat mass were broadly comparable, being 1.71 (1.61-1.82), 1.92 (1.75-2.11) and 1.73 (1.63-1.85), respectively. There was an indication of positive association between central adiposity, as reflected by waist circumference (HRper 1-SD increase = 1.08, 95% CI: 1.00-1.17) and waist to hip ratio (HRper 1-SD increase = 1.13, 95% CI: 1.01-1.26), and endometrial cancer risk after accounting for BMI. Fat-free mass was not an independent predictor of risk in this cohort. These findings suggest that body fat percentage and fat mass are not better indicators of endometrial cancer risk than BMI. Further studies are needed to establish whether central adiposity contributes to risk beyond overall adiposity.

11.
Int J Cancer ; 147(5): 1325-1333, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32011733

RESUMO

Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m2 ), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m2 ) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.

12.
Eur Urol Focus ; 6(4): 752-761, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31085062

RESUMO

BACKGROUND: Fluid intake and diet are thought to influence kidney stone risk. However, prospective studies have been limited to small samples sizes and/or restricted measures. OBJECTIVE: To investigate whether fluid intake and dietary factors are associated with the risk of developing a first kidney stone. DESIGN, SETTING, AND PARTICIPANTS: Participants were selected from UK Biobank, a population-based prospective cohort study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazards models were used to investigate the association between fluid intake and dietary factors and the risk of a first incident kidney stone, ascertained from hospital inpatient records. RESULTS AND LIMITATIONS: After exclusion, 439 072 participants were available for the analysis, of whom 2057 had hospital admission with an incident kidney stone over a mean of 6.1 yr of follow-up. For every additional drink (200 ml) consumed per day of total fluid, the risk of kidney stones declined by 13% (hazard ratio [HR] = 0.87, 95% confidence interval [CI] 0.85-0.89). Similar patterns of associations were observed for tea, coffee, and alcohol, although no association was observed for water intake. Fruit and fibre intake was also associated with a lower risk (HR per 100 g increase of fruits per day = 0.88, 95% CI 0.83-0.93, and HR per 10 g fibre per day = 0.82, 95% CI 0.77-0.87), whereas meat and salt intake was associated with a higher risk (HR per 50 g increase in meat per week = 1.17, 95% CI 1.05-1.29, and HR for always vs never/rarely added salt to food = 1.33, 95% CI 1.12-1.58). Vegetable, fish, and cheese intake was not associated with kidney stone risk. CONCLUSIONS: The finding that high intake of total fluid, fruit, and fibre was associated with a lower risk of hospitalisation for a first kidney stone suggests that modifiable dietary factors could be targeted to prevent kidney stone development. PATIENT SUMMARY: We found that higher intake of total fluid, specifically tea, coffee, and alcohol (but not water), and consumption of fruit and foods high in fibre are linked with a reduced likelihood of developing kidney stones.

13.
Int J Cancer ; 147(3): 803-810, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31755099

RESUMO

Insulin-like growth factor-I (IGF-I) and testosterone may be related to prostate cancer risk. Acromegaly is associated with clinically high IGF-I concentrations. Klinefelter's syndrome, testicular hypofunction and hypopituitarism are associated with clinically low testosterone concentrations. We aimed to investigate whether diagnosis with these conditions was associated with subsequent prostate cancer diagnosis and mortality. We used linked English national Hospital Episode Statistics and mortality data from 1999 to 2017 to construct and follow-up cohorts of men aged ≥35 years diagnosed with (i) acromegaly (n = 2,495) and (ii) hypogonadal-associated diseases (n = 18,763): Klinefelter's syndrome (n = 1,992), testicular hypofunction (n = 8,086) and hypopituitarism (n = 10,331). We estimated adjusted hazard ratios (HRs) and confidence intervals (CIs) for prostate cancer diagnosis and death using Cox regression in comparison with an unexposed reference cohort of 4.3 million men, who were admitted to hospital for a range of minor surgeries and conditions (n observed cases = 130,000, n prostate cancer deaths = 30,000). For men diagnosed with acromegaly, HR for prostate cancer diagnosis was 1.33 (95% CI 1.09-1.63; p = 0.005; n observed cases = 96), HR for prostate cancer death was 1.44 (95% CI 0.92-2.26; p = 0.11; n deaths = 19). Diagnosis with Klinefelter's syndrome was associated with a lower prostate cancer risk (HR = 0.58, 95% CI 0.37-0.91; p = 0.02; n observed cases = 19) and hypopituitarism was associated with a reduction in prostate cancer death (HR = 0.53, 95% CI 0.35-0.79; p = 0.002; n deaths = 23). These results support the hypothesised roles of IGF-I and testosterone in prostate cancer development and/or progression. These findings are important because they provide insight into prostate cancer aetiology.

14.
Cancer Res ; 79(20): 5442-5451, 2019 10 15.
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 prediagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI). 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 >10 mg/L compared with <1 mg/L (OR = 1.67; 95% CI = 1.12-2.48). A CRP concentration >10 mg/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, although 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). This 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. SIGNIFICANCE: C-reactive protein is involved in ovarian carcinogenesis, and chronic inflammation may be particularly implicated in the etiology of mucinous and endometrioid carcinomas.


Assuntos
Biomarcadores Tumorais/sangue , Proteína C-Reativa/análise , Carcinoma/sangue , Proteínas de Neoplasias/sangue , Neoplasias Ovarianas/sangue , Idoso , Carcinogênese , Carcinoma/classificação , Carcinoma/epidemiologia , Estudos de Casos e Controles , Intervalos de Confiança , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Inflamação , Pessoa de Meia-Idade , Razão de Chances , Neoplasias Ovarianas/epidemiologia , Estudos Prospectivos , Risco , Fatores de Risco , Sensibilidade e Especificidade , Estados Unidos/epidemiologia
15.
PLoS One ; 14(6): e0218267, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31206530

RESUMO

BACKGROUND: Feedback of potentially serious incidental findings (PSIFs) to imaging research participants generates clinical assessment in most cases. Understanding the factors associated with increased risks of PSIFs and of serious final diagnoses may influence individuals' decisions to participate in imaging research and will inform the design of PSIFs protocols for future research studies. We aimed to determine whether, and to what extent, socio-demographic, lifestyle, other health-related factors and PSIFs protocol are associated with detection of both a PSIF and a final diagnosis of serious disease. METHODS AND FINDINGS: Our cohort consisted of all UK Biobank participants who underwent imaging up to December 2015 (n = 7334, median age 63, 51.9% women). Brain, cardiac and body magnetic resonance, and dual-energy x-ray absorptiometry images from the first 1000 participants were reviewed systematically by radiologists for PSIFs. Thereafter, radiographers flagged concerning images for radiologists' review. We classified final diagnoses as serious or not using data from participant surveys and clinical correspondence from GPs up to six months following imaging (either participant or GP correspondence, or both, were available for 93% of participants with PSIFs). We used binomial logistic regression models to investigate associations between age, sex, ethnicity, socio-economic deprivation, private healthcare use, alcohol intake, diet, physical activity, smoking, body mass index and morbidity, with both PSIFs and serious final diagnoses. Systematic radiologist review generated 13 times more PSIFs than radiographer flagging (179/1000 [17.9%] versus 104/6334 [1.6%]; age- and sex-adjusted OR 13.3 [95% confidence interval (CI) 10.3-17.1] p<0.001) and proportionally fewer serious final diagnoses (21/179 [11.7%]; 33/104 [31.7%]). Risks of both PSIFs and of serious final diagnoses increased with age (sex-adjusted ORs [95% CI] for oldest [67-79 years] versus youngest [44-58 years] participants for PSIFs and serious final diagnoses respectively: 1.59 [1.07-2.38] and 2.79 [0.86 to 9.0] for systematic radiologist review; 1.88 [1.14-3.09] and 2.99 [1.09-8.19] for radiographer flagging). No other factor was significantly associated with either PSIFs or serious final diagnoses. Our study is the largest so far to investigate the factors associated with PSIFs and serious final diagnoses, but despite this, we still may have missed some associations due to sparsity of these outcomes within our cohort and small numbers within some exposure categories. CONCLUSION: Risks of PSIFs and serious final diagnosis are substantially influenced by PSIFs protocol and to a lesser extent by age. As only 1/5 PSIFs represent serious disease, evidence-based PSIFs protocols are paramount to minimise over-investigation of healthy research participants and diversion of limited health services away from patients in need.


Assuntos
Bancos de Espécimes Biológicos/estatística & dados numéricos , Imagem Multimodal/estatística & dados numéricos , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Índice de Massa Corporal , Exercício Físico/fisiologia , Feminino , Humanos , Achados Incidentais , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fumar/efeitos adversos , Reino Unido
16.
Eur J Epidemiol ; 34(6): 557-565, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30806901

RESUMO

Prospective, population-based studies that recruit participants in mid-life are valuable resources for dementia research. Follow-up in these studies is often through linkage to routinely-collected healthcare datasets. We investigated the accuracy of these datasets for dementia case ascertainment in a validation study using data from UK Biobank-an open access, population-based study of > 500,000 adults aged 40-69 years at recruitment in 2006-2010. From 17,198 UK Biobank participants recruited in Edinburgh, we identified those with ≥ 1 dementia code in their linked primary care, hospital admissions or mortality data and compared their coded diagnoses to clinical expert adjudication of their full-text medical record. We calculated the positive predictive value (PPV, the proportion of cases identified that were true positives) for all-cause dementia, Alzheimer's disease and vascular dementia for each dataset alone and in combination, and explored algorithmic code combinations to improve PPV. Among 120 participants, PPVs for all-cause dementia were 86.8%, 87.3% and 80.0% for primary care, hospital admissions and mortality data respectively and 82.5% across all datasets. We identified three algorithms that balanced a high PPV with reasonable case ascertainment. For Alzheimer's disease, PPVs were 74.1% for primary care, 68.2% for hospital admissions, 50.0% for mortality data and 71.4% in combination. PPV for vascular dementia was 43.8% across all sources. UK routinely-collected healthcare data can be used to identify all-cause dementia in prospective studies. PPVs for Alzheimer's disease and vascular dementia are lower. Further research is required to explore the geographic generalisability of these findings.


Assuntos
Demência/terapia , Adulto , Idoso , Bancos de Espécimes Biológicos , Demência/mortalidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde , Resultado do Tratamento , Reino Unido/epidemiologia
17.
Int J Cancer ; 144(5): 957-966, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30191956

RESUMO

Insulin-like growth factor-I (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 1,221 melanoma cases and 1,221 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 gender, 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.


Assuntos
Fator de Crescimento Insulin-Like I/metabolismo , Melanoma/etiologia , Melanoma/metabolismo , Estado Nutricional/fisiologia , Adulto , Idoso , Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Neoplasias da Próstata/etiologia , Fatores de Risco
18.
Am J Epidemiol ; 188(2): 274-281, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30481275

RESUMO

The role of hormonal factors in the etiology of lymphoid neoplasms remains unclear. Previous studies have yielded conflicting results, have lacked sufficient statistical power to assess many lymphoma subtypes, or have lacked detailed information on relevant exposures. Within the European Prospective Investigation Into Cancer and Nutrition cohort, we analyzed comprehensive data on reproductive factors and exogenous hormone use collected at baseline (1992-2000) among 343,458 women, including data on 1,427 incident cases of B-cell non-Hodgkin lymphoma (NHL) and its major subtypes identified after a mean follow-up period of 14 years (through 2015). We estimated hazard ratios and 95% confidence intervals using multivariable proportional hazards modeling. Overall, we observed no statistically significant associations between parity, age at first birth, breastfeeding, oral contraceptive use, or ever use of postmenopausal hormone therapy and risk of B-cell NHL or its subtypes. Women who had undergone surgical menopause had a 51% higher risk of B-cell NHL (based on 67 cases) than women with natural menopause (hazard ratio = 1.51, 95% confidence interval: 1.17, 1.94). Given that this result may have been due to chance, our results provide little support for the hypothesis that sex hormones play a role in lymphomagenesis.


Assuntos
Terapia de Reposição de Estrogênios/estatística & dados numéricos , Linfoma de Células B/epidemiologia , História Reprodutiva , Aleitamento Materno , Europa (Continente)/epidemiologia , Feminino , Humanos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Saúde da Mulher
20.
Eur Urol ; 74(5): 585-594, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30077399

RESUMO

BACKGROUND: Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting. OBJECTIVE: To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration. RESULTS AND LIMITATIONS: Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p<0.001) compared with men with higher concentrations (2nd-10th tenths of the distribution). Heterogeneity was present by tumour grade (phet=0.01), with a lower risk of low-grade disease (OR=0.76, 95% CI 0.67-0.88) and a nonsignificantly higher risk of high-grade disease (OR=1.56, 95% CI 0.95-2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation. CONCLUSIONS: Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade. PATIENT SUMMARY: In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer.


Assuntos
Neoplasias da Próstata/sangue , Testosterona/deficiência , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Regulação para Baixo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/prevenção & controle , Fatores de Proteção , Medição de Risco , Fatores de Risco , Testosterona/sangue , Fatores de Tempo
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