Showing papers by "Cancer Epidemiology Unit published in 2017"

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Abstract: To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.

Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study

Abstract: Objective: To determine if circulating concentrations of vitamin D are causally associated with risk of cancer. There is debate on whether vitamin D status is a cause of disease or just a correlate marker of overall health. Evidence from in-vitro and animal model studies supports an anti-neoplastic role of vitamin D, but epidemiological studies and randomized controlled trials have yielded mixed results. Design: To overcome potential limitations in epidemiological studies and randomized controlled trials, a Mendelian randomization (MR) approach was used. Participants and Setting: A total of 70,563 cancer cases and 84,418 controls were used from large genetic epidemiology networks, which consisted of 22,898 cases of prostate cancer, 15,748 cases of breast cancer, 12,537 cases of lung cancer, 11,488 cases of colorectal cancer, 4,369 cases of ovarian cancer, 1,896 cases of pancreatic cancer and 1,627 cases of neuroblastoma. Exposures: Four vitamin D associated single nucleotide polymorphisms (SNPs: rs2282679, rs10741657, rs12785878 and rs6013897) were used to define a multi-SNP score for circulating 25-hydroxyvitamin D (25(OH)D) concentrations. Main outcomes and measures: The primary outcomes were the risk of incident colorectal, breast, prostate, ovarian, lung and pancreatic cancer, and neuroblastoma, which was evaluated using an inverse-variance weighted average of the SNP-specific associations and a likelihood-based approach. Secondary outcomes based on cancer subtypes by sex, anatomic location, stage and histology were also examined. Results: There was little evidence that the multi-SNP score of 25(OH)D was associated with risk of any of the seven cancers or their subtypes. Specifically, the odds ratios per 25 nmol/L increase in genetically-determined 25(OH)D concentrations were 0.92 (95% CI, 0.76-1.10) for colorectal cancer, 1.05 (95% CI, 0.89-1.24) for breast cancer, 0.89 (95% CI, 0.77-1.02) for prostate cancer, and 1.03 (95% CI, 0.87-1.23) for lung cancer. The results were consistent with the two different analytic approaches, and the study was powered to detect relative effect sizes of moderate magnitude (e.g., 1.20-1.50) per 25 nmol/L decrease in 25(OH)D for most primary cancer outcomes. The MR assumptions did not appear to be violated. Conclusions: Our results provide little evidence of a linear causal association between circulating vitamin D concentration and risk of colorectal, breast, prostate, ovarian, lung and pancreatic cancer, and neuroblastoma, but we cannot rule out existence of causal clinically relevant effects of low magnitude. These results, in combination with previous literature, provide evidence that population-wide screening for vitamin D deficiency and subsequent widespread vitamin D supplementation should not be recommended at this time as a primary cancer prevention strategy.

Fresh fruit consumption in relation to incident diabetes and diabetic vascular complications: A 7-y prospective study of 0.5 million Chinese adults.

Abstract: Background Despite the well-recognised health benefits of fresh fruit consumption, substantial uncertainties remain about its potential effects on incident diabetes and, among those with diabetes, on risks of death and major vascular complications. Methods and findings Between June 2004 and July 2008, the nationwide China Kadoorie Biobank study recruited 0.5 million adults aged 30–79 (mean 51) y from ten diverse localities across China. During ~7 y of follow-up, 9,504 new diabetes cases were recorded among 482,591 participants without prevalent (previously diagnosed or screen-detected) diabetes at baseline, with an overall incidence rate of 2.8 per 1,000 person-years. Among 30,300 (5.9%) participants who had diabetes at baseline, 3,389 deaths occurred (overall mortality rate 16.5 per 1,000), along with 9,746 cases of macrovascular disease and 1,345 cases of microvascular disease. Cox regression yielded adjusted hazard ratios (HRs) associating each disease outcome with self-reported fresh fruit consumption, adjusting for potential confounders such as age, sex, region, socio-economic status, other lifestyle factors, body mass index, and family history of diabetes. Overall, 18.8% of participants reported consuming fresh fruit daily, and 6.4% never/rarely (non-consumers), with the proportion of non-consumers about three times higher in individuals with previously diagnosed diabetes (18.9%) than in those with screen-detected diabetes (6.7%) or no diabetes (6.0%). Among those without diabetes at baseline, higher fruit consumption was associated with significantly lower risk of developing diabetes (adjusted HR = 0.88 [95% CI 0.83–0.93] for daily versus non-consumers, p < 0.001, corresponding to a 0.2% difference in 5-y absolute risk), with a clear dose–response relationship. Among those with baseline diabetes, higher fruit consumption was associated with lower risks of all-cause mortality (adjusted HR = 0.83 [95% CI 0.74–0.93] per 100 g/d) and microvascular (0.72 [0.61–0.87]) and macrovascular (0.87 [0.82–0.93]) complications (p < 0.001), with similar HRs in individuals with previously diagnosed and screen-detected diabetes; estimated differences in 5-y absolute risk between daily and non-consumers were 1.9%, 1.1%, and 5.4%, respectively. The main limitation of this study was that, owing to its observational nature, we could not fully exclude the effects of residual confounding. Conclusion In this large epidemiological study in Chinese adults, higher fresh fruit consumption was associated with significantly lower risk of diabetes and, among diabetic individuals, lower risks of death and development of major vascular complications.

Association between physical activity and body fat percentage, with adjustment for BMI: a large cross-sectional analysis of UK Biobank

Abstract: Objectives The objective of this study was to examine if, in the general population, physically active adults have less body fat after taking body mass index (BMI) into account. Design A cross-sectional analysis of participants recruited into UK Biobank in 2006–2010. Setting UK Biobank assessment centres throughout the UK. Participants 119 230 men and 140 578 women aged 40–69 years, with complete physical activity information, and without a self-reported long-term illness, disability or infirmity. Exposures Physical activity measured as excess metabolic equivalent (MET)-hours per week, estimated from a combination of walking, and moderate and vigorous physical activity. BMI from measured height and weight. Main outcome measure Body fat percentage estimated from bioimpedance. Results BMI and body fat percentage were highly correlated (r=0.85 in women; r=0.79 in men), and both were inversely associated with physical activity. Compared with 2 lower BMI (27.1 vs 28.2 kg/m 2 ) and 2.8 percentage points lower body fat (23.4% vs 26.3%) in men, and 2.2 kg/m 2 lower BMI (25.6 vs 27.7 kg/m 2 ) and 4.0 percentage points lower body fat (33.9% vs 37.9%) in women. For a given BMI, greater physical activity was associated with lower average body fat percentage (for a BMI of 22.5–24.99 kg/m 2 : 2.0 (95% CI 1.8 to 2.2), percentage points lower body fat in men and 1.8 (95% CI 1.6 to 2.0) percentage points lower body fat in women, comparing ≥100 excess MET-hours per week with Conclusions In this sample of middle-aged adults, drawn from the general population, physical activity was inversely associated with BMI and body fat percentage. For people with the same BMI, those who were more active had a lower body fat percentage.

Long-Term Exposure to Ambient Air Pollution and Incidence of Postmenopausal Breast Cancer in 15 European Cohorts within the ESCAPE Project.

Abstract: BACKGROUND: Epidemiological evidence on the association between ambient air pollution and breast cancer risk is inconsistent. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in European women. METHODS: In 15 cohorts from nine European countries, individual estimates of air pollution levels at the residence were estimated by standardized land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE) and Transport related Air Pollution and Health impacts - Integrated Methodologies for Assessing Particulate Matter (TRANSPHORM) projects: particulate matter (PM) ≤2:5 μm, ≤10 μm, and 2:5–10 μm in diameter (PM2:5, PM10, and PMcoarse, respectively); PM2:5 absorbance; nitrogen oxides (NO2 and NOx); traffic intensity; and elemental composition of PM. We estimated cohort-specific associations between breast cancer and air pollutants using Cox regression models, adjusting for major lifestyle risk factors, and pooled cohort-specific estimates using random-effects meta-analyses. RESULTS: Of 74,750 postmenopausal women included in the study, 3,612 developed breast cancer during 991,353 person-years of follow-up. We found positive and statistically insignificant associations between breast cancer and PM2:5 {hazard ratio (HR) =1:08 [95% confidence interval (CI): 0.77, 1.51] per 5 μg/m3 }, PM10 [1.07 (95% CI: 0.89, 1.30) per 10 μg/m3 ], PMcoarse [1.20 (95% CI: 0.96, 1.49 per 5 μg/m3 ], and NO2 [1.02 (95% CI: 0.98, 1.07 per 10 μg/m3 ], and a statistically significant association with NOx [1.04 (95% CI: 1.00, 1.08) per 20 μg/m3, p =0:04]. CONCLUSIONS: We found suggestive evidence of an association between ambient air pollution and incidence of postmenopausal breast cancer in European women. © 2017, Public Health Services, US Dept of Health and Human Services. All rights reserved. Chemicals/CAS: copper, 15158-11-9, 7440-50-8; iron, 14093-02-8, 53858-86-9, 7439-89-6; nickel, 7440-02-0; nitrogen oxide, 11104-93-1; potassium, 7440-09-7; silicon, 7440-21-3; sulfur, 13981-57-2, 7704-34-9; vanadium, 7440-62-2; zinc, 7440-66-6, 14378-32-6

Body mass index and healthcare costs: a systematic literature review of individual participant data studies.

Abstract: Summary Excess weight is associated with increased total healthcare costs, but it is less well known how the associations between excess weight and costs vary across different types of healthcare service. We reviewed studies using individual participant data to estimate associations between body mass index and healthcare costs, and summarized how annual healthcare costs for overweight (body mass index 25 to <30 kg/m2) and obese (≥30 kg/m2) individuals compared with those for healthy weight individuals (18.5 to <25 kg/m2). EMBASE and MEDLINE were searched from January 1990 to September 2016, and 75 studies were included in the review. Of these, 34 studies presented adequate information to contribute to a quantitative summary of results. Compared with individuals at healthy weight, the median increases in mean total annual healthcare costs were 12% for overweight and 36% for obese individuals. The percentage increases in costs were highest for medications (18% for overweight and 68% for obese), followed by inpatient care (12% and 34%) and ambulatory care (4% and 26%). Percentage increases in costs associated with obesity were higher for women than men. The substantial costs associated with excess weight in different healthcare settings emphasize the need for investment to tackle this major public health problem.

Lifelong Residential Exposure to Green Space and Attention: A Population-based Prospective Study.

Abstract: BACKGROUND: Natural environments, including green spaces, may have beneficial impacts on brain development However, longitudinal evidence of an association between long-term exposure to green spaces and cognitive development (including attention) in children is limited OBJECTIVES: We evaluated the association between lifelong residential exposure to green space and attention during preschool and early primary school years METHODS: This longitudinal study was based on data from two well-established population-based birth cohorts in Spain We assessed lifelong exposure to residential surrounding greenness and tree cover as the average of satellite-based normalized difference vegetation index and vegetation continuous fields, respectively, surrounding the child's residential addresses at birth, 4-5 y, and 7 y Attention was characterized using two computer-based tests: Conners' Kiddie Continuous Performance Test (K-CPT) at 4-5 y (n=888) and Attentional Network Task (ANT) at 7 y (n=987) We used adjusted mixed effects models with cohort random effects to estimate associations between exposure to greenness and attention at ages 4-5 and 7 y RESULTS: Higher lifelong residential surrounding greenness was associated with fewer K-CPT omission errors and lower K-CPT hit reaction time-standard error (HRT-SE) at 4-5 y and lower ANT HRT-SE at 7 y, consistent with better attention This exposure was not associated with K-CPT commission errors or with ANT omission or commission errors Associations with residential surrounding tree cover also were close to the null, or were negative (for ANT HRT-SE) but not statistically significant CONCLUSION: Exposure to residential surrounding greenness was associated with better scores on tests of attention at 4-5 y and 7 y of age in our longitudinal cohort https://doiorg/101289/EHP694

Risk factors for cryptorchidism.

Abstract: Undescended testis - known as cryptorchidism - is one of the most common congenital abnormalities observed in boys, and is one of the few known risk factors for testicular cancer. The key factors that contribute to the occurrence of cryptorchidism remain elusive. Testicular descent is thought to occur during two hormonally-controlled phases in fetal development - between 8-15 weeks (the first phase of decent) and 25-35 weeks gestation (the second phase of descent); the failure of a testis to descend permanently is probably caused by disruptions to one or both of these phases, but the causes and mechanisms of such disruptions are still unclear. A broad range of putative risk factors have been evaluated in relation to the development of cryptorchidism but their plausibility is still in question. Consistent evidence of an association with cryptorchidism exists for only a few factors, and in those cases in which evidence seems unequivocal the factor is likely to be a surrogate for the true causal exposure. The relative importance of each risk factor could vary considerably between mother-son pairs depending on an array of genetic, maternal, placental and fetal factors - all of which could vary between regions. Thus, the role of causative factors in aetiology of cryptorchidism requires further research.

Prospective investigation of risk factors for prostate cancer in the UK Biobank cohort study.

Abstract: Prostate cancer is the most common cancer in British men but its aetiology is not well understood. We aimed to identify risk factors for prostate cancer in British males. We studied 219 335 men from the UK Biobank study who were free from cancer at baseline. Exposure data were collected at recruitment. Prostate cancer risk by the different exposures was estimated using multivariable-adjusted Cox proportional hazards models. In all, 4575 incident cases of prostate cancer occurred during 5.6 years of follow-up. Prostate cancer risk was positively associated with the following: black ethnicity (hazard ratio black vs white=2.61, 95% confidence interval=2.10–3.24); having ever had a prostate-specific antigen test (1.31, 1.23–1.40); being diagnosed with an enlarged prostate (1.54, 1.38–1.71); and having a family history of prostate cancer (1.94, 1.77–2.13). Conversely, Asian ethnicity (Asian vs white hazard ratio=0.62, 0.47–0.83), excess adiposity (body mass index (⩾35 vs <25 kg m−2=0.75, 0.64–0.88) and body fat (⩾30.1 vs <20.5%=0.81, 0.73–0.89)), cigarette smoking (current vs never smokers=0.85, 0.77–0.95), having diabetes (0.70, 0.62–0.80), and never having had children (0.89, 0.81–0.97) or sexual intercourse (0.53, 0.33–0.84) were related to a lower risk. In this new large British prospective study, we identified associations with already-established, putative and possible novel risk factors for being diagnosed with prostate cancer. Future research will examine associations by tumour characteristics.

Dietary Intake of High-Protein Foods and Other Major Foods in Meat-Eaters, Poultry-Eaters, Fish-Eaters, Vegetarians, and Vegans in UK Biobank

Abstract: Vegetarian diets are defined by the absence of meat and fish, but differences in the intake of other foods between meat-eaters and low or non-meat eaters are also important to document. We examined intakes of high-protein foods (meat, poultry, fish, legumes, nuts, vegetarian protein alternatives, dairy products, and eggs) and other major food groups (fruit, vegetables, bread, pasta, rice, snack foods, and beverages) in regular meat-eaters, low meat-eaters, poultry-eaters, fish-eaters, vegetarians, and vegans of white ethnicity participating in UK Biobank who had completed at least one web-based 24-h dietary assessment (n = 199,944). In regular meat-eaters, around 25% of total energy came from meat, fish, dairy and plant milk, cheese, yogurt, and eggs. In vegetarians, around 20% of energy came from dairy and plant milk, cheese, yoghurt, eggs, legumes, nuts, and vegetarian protein alternatives, and in vegans around 15% came from plant milk, legumes, vegetarian alternatives, and nuts. Low and non-meat eaters had higher intakes of fruit and vegetables and lower intakes of roast or fried potatoes compared to regular meat-eaters. The differences in the intakes of meat, plant-based high-protein foods, and other foods between meat-eaters and low and non-meat eaters in UK Biobank may contribute to differences in health outcomes.

Tall height and obesity are associated with an increased risk of aggressive prostate cancer : results from the EPIC cohort study

Abstract: The relationship between body size and prostate cancer risk, and in particular risk by tumour characteristics, is not clear because most studies have not differentiated between high-grade or advanced stage tumours, but rather have assessed risk with a combined category of aggressive disease. We investigated the association of height and adiposity with incidence of and death from prostate cancer in 141,896 men in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average of 13.9 years of follow-up, there were 7024 incident prostate cancers and 934 prostate cancer deaths. Height was not associated with total prostate cancer risk. Subgroup analyses showed heterogeneity in the association with height by tumour grade (P heterogeneity = 0.002), with a positive association with risk for high-grade but not low-intermediate-grade disease (HR for high-grade disease tallest versus shortest fifth of height, 1.54; 95% CI, 1.18–2.03). Greater height was also associated with a higher risk for prostate cancer death (HR = 1.43, 1.14–1.80). Body mass index (BMI) was significantly inversely associated with total prostate cancer, but there was evidence of heterogeneity by tumour grade (P heterogeneity = 0.01; HR = 0.89, 0.79–0.99 for low-intermediate grade and HR = 1.32, 1.01–1.72 for high-grade prostate cancer) and stage (P heterogeneity = 0.01; HR = 0.86, 0.75–0.99 for localised stage and HR = 1.11, 0.92–1.33 for advanced stage). BMI was positively associated with prostate cancer death (HR = 1.35, 1.09–1.68). The results for waist circumference were generally similar to those for BMI, but the associations were slightly stronger for high-grade (HR = 1.43, 1.07–1.92) and fatal prostate cancer (HR = 1.55, 1.23–1.96). The findings from this large prospective study show that men who are taller and who have greater adiposity have an elevated risk of high-grade prostate cancer and prostate cancer death.

Added sugars and sugar-sweetened beverage consumption, dietary carbohydrate index and depression risk in the Seguimiento Universidad de Navarra (SUN) Project.

Abstract: The association between added sugars or sugar-sweetened beverage consumption and the risk of depression, as well as the role of carbohydrate quality in depression risk, remains unclear. Among 15 546 Spanish university graduates from the Seguimiento Universidad de Navarra (SUN) prospective cohort study, diet was assessed with a validated 136-item semi-quantitative FFQ at baseline and at 10-year follow-up. Cumulative average consumption of added sugars, sweetened drinks and an overall carbohydrate quality index (CQI) were calculated. A better CQI was associated with higher whole-grain consumption and fibre intake and lower glycaemic index and consumption of solid (instead of liquid) carbohydrates. Clinical diagnoses of depression during follow-up were classified as incident cases. Multivariable time-dependent Cox regression models were used to estimate hazard ratios (HR) of depression according to consumption of added sugars, sweetened drinks and CQI. We observed 769 incident cases of depression. Participants in the highest quartile of added sugars consumption showed a significant increment in the risk of depression (HR=1·35; 95 % CI 1·09, 1·67, P=0·034), whereas those in the highest quartile of CQI (upper quartile of the CQI) showed a relative risk reduction of 30 % compared with those in the lowest quartile of the CQI (HR=0·70; 95 % CI 0·56, 0·88). No significant association between sugar-sweetened beverage consumption and depression risk was found. Higher added sugars and lower quality of carbohydrate consumption were associated with depression risk in the SUN Cohort. Further studies are necessary to confirm the reported results.

A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes: The EPIC-InterAct case-cohort study.

Abstract: Background Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) ...

Evidence for a comprehensive approach to Aboriginal tobacco control to maintain the decline in smoking: an overview of reviews among Indigenous peoples

Abstract: Tobacco smoking is a leading cause of disease and premature mortality among Aboriginal and Torres Strait Islander (Indigenous) Australians. While the daily smoking prevalence among Indigenous Australians has declined significantly from 49% in 2001, it remains about three times higher than that of non-Indigenous Australians (39 and 14%, respectively, for age ≥15 years in 2014–15). This overview of systematic reviews aimed to synthesise evidence about reducing tobacco consumption among Indigenous peoples using a comprehensive framework for Indigenous tobacco control in Australia comprised of the National Tobacco Strategy (NTS) and National Aboriginal and Torres Strait Islander Health Plan (NATSIHP) principles and priorities. MEDLINE, EMBASE, systematic review and Indigenous health databases were searched (2000 to Jan 2016) for reviews examining the effects of tobacco control interventions among Indigenous peoples. Two reviewers independently screened reviews, extracted data, and assessed review quality using Assessing the Methodological Quality of Systematic Reviews. Data were synthesised narratively by framework domain. Reporting followed the PRISMA statement. Twenty-one reviews of varying quality were included. There was generally limited Indigenous-specific evidence of effective interventions for reducing smoking; however, many reviewers recommended multifaceted interventions which incorporate Indigenous leadership, partnership and engagement and cultural tailoring. Under the NTS priority areas, reviewers reported evidence for brief smoking cessation interventions and pharmacological support, mass media campaigns (on knowledge and attitudes) and reducing affordability and regulation of tobacco sales. Aspects of intervention implementation related to the NATSIHP domains were less well described and evidence was limited; however, reviewers suggested that cultural tailoring, holistic approaches and building workforce capacity were important strategies to address barriers. There was limited evidence regarding social media and mobile applications, for Indigenous youth, pregnant women and prisoners, and no evidence regarding interventions to protect communities from industry interference, the use of electronic cigarettes, interventions for people experiencing mental illness, juvenile justice, linguistic diversity or ‘pubs, clubs and restaurants’. There is limited Indigenous-specific evidence for most tobacco interventions. A ‘comprehensive approach’ incorporating NTS and NATSIHP Principles and Priorities of partnership and engagement, evidence from other settings, programme logic and responsive evaluation plans may improve intervention acceptability, effectiveness and implementation and mitigate risks of adapting tobacco evidence for Indigenous Australians.

Outdoor air pollution and risk for kidney parenchyma cancer in 14 European cohorts

Abstract: Several studies have indicated weakly increased risk for kidney cancer among occupational groups exposed to gasoline vapors, engine exhaust, polycyclic aromatic hydrocarbons and other air pollutant ...

Blood Metabolic Signatures of Body Mass Index : A Targeted Metabolomics Study in the EPIC Cohort

Abstract: Metabolomics is now widely used to characterize metabolic phenotypes associated with lifestyle risk factors such as obesity. The objective of the present study was to explore the associations of body mass index (BMI) with 145 metabolites measured in blood samples in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolites were measured in blood from 392 men from the Oxford (UK) cohort (EPIC-Oxford) and in 327 control subjects who were part of a nested case-control study on hepatobiliary carcinomas (EPIC-Hepatobiliary). Measured metabolites included amino acids, acylcarnitines, hexoses, biogenic amines, phosphatidylcholines, and sphingomyelins. Linear regression models controlled for potential confounders and multiple testing were run to evaluate the associations of metabolite concentrations with BMI. 40 and 45 individual metabolites showed significant differences according to BMI variations, in the EPIC-Oxford and EPIC-Hepatobiliary subcohorts, respectively. Twenty two individual metabolites (kynurenine, one sphingomyelin, glutamate and 19 phosphatidylcholines) were associated with BMI in both subcohorts. The present findings provide additional knowledge on blood metabolic signatures of BMI in European adults, which may help identify mechanisms mediating the relationship of BMI with obesity-related diseases.

Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans

Abstract: Background: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating le ...

Pre-diagnostic metabolite concentrations and prostate cancer risk in 1077 cases and 1077 matched controls in the European Prospective Investigation into Cancer and Nutrition.

Abstract: Little is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition, pre-diagnostic plasma concentrations of 122 metabolites (including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit) and compared between 1077 prostate cancer cases and 1077 matched controls. Risk of prostate cancer associated with metabolite concentrations was estimated by multi-variable conditional logistic regression, and multiple testing was accounted for by using a false discovery rate controlling procedure. Seven metabolite concentrations, i.e. acylcarnitine C18:1, amino acids citrulline and trans-4-hydroxyproline, glycerophospholipids PC aa C28:1, PC ae C30:0 and PC ae C30:2, and sphingolipid SM (OH) C14:1, were associated with prostate cancer (p < 0.05), but none of the associations were statistically significant after controlling for multiple testing. Citrulline was associated with a decreased risk of prostate cancer (odds ratio (OR1SD) = 0.73; 95% confidence interval (CI) 0.62–0.86; p trend = 0.0002) in the first 5 years of follow-up after taking multiple testing into account, but not after longer follow-up; results for other metabolites did not vary by time to diagnosis. After controlling for multiple testing, 12 glycerophospholipids were inversely associated with advanced stage disease, with risk reduction up to 46% per standard deviation increase in concentration (OR1SD = 0.54; 95% CI 0.40–0.72; p trend = 0.00004 for PC aa C40:3). Death from prostate cancer was associated with higher concentrations of acylcarnitine C3, amino acids methionine and trans-4-hydroxyproline, biogenic amine ADMA, hexose and sphingolipid SM (OH) C14:1 and lower concentration of glycerophospholipid PC aa C42:4. Several metabolites, i.e. C18:1, citrulline, trans-4-hydroxyproline, three glycerophospholipids and SM (OH) C14:1, might be related to prostate cancer. Analyses by time to diagnosis indicated that citrulline may be a marker of subclinical prostate cancer, while other metabolites might be related to aetiology. Several glycerophospholipids were inversely related to advanced stage disease. More prospective data are needed to confirm these associations.

Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries : A cross-sectional analysis in the EPIC-InterAct study

Abstract: Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways. We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested. Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption. Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.

Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium.

Abstract: Invasive epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The etiology of EOC remains elusive; however, experimental and epidemiologic data suggest a role for hormone-related exposures in ovarian carcinogenesis and risk factor differences by histologic phenotypes and developmental pathways. Research on prediagnosis androgen concentrations and EOC risk has yielded inconclusive results, and analyses incorporating EOC subtypes are sparse. We conducted a pooled analysis of 7 nested case-control studies in the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis circulating androgens [testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS)], sex hormone binding globulin (SHBG), and EOC risk by tumor characteristics (i.e., histology, grade, and stage). The final study population included 1,331 EOC cases and 3,017 matched controls. Multivariable conditional logistic regression was used to assess risk associations in pooled individual data. Testosterone was positively associated with EOC risk (all subtypes combined, ORlog2 = 1.12; 95% confidence interval 1.02-1.24); other endogenous androgens and SHBG were not associated with overall risk. Higher concentrations of testosterone and androstenedione associated with an increased risk in endometrioid and mucinous tumors [e.g., testosterone, endometrioid tumors, ORlog2 = 1.40 (1.03-1.91)], but not serous or clear cell. An inverse association was observed between androstenedione and high grade serous tumors [ORlog2 = 0.76 (0.60-0.96)]. Our analyses provide further evidence for a role of hormone-related pathways in EOC risk, with differences in associations between androgens and histologic subtypes of EOC. Cancer Res; 77(14); 3951-60. ©2017 AACR.

Heterogeneity of colorectal cancer risk by tumour characteristics: Large prospective study of UK women

Abstract: Associations between behavioural and other personal factors and colorectal cancer risk have been reported to vary by tumour characteristics, but evidence is inconsistent. In a large UK-based prospective study we examined associations of 14 postulated risk factors with colorectal cancer risk overall, and across three anatomical sites and four morphological subtypes. Among 1.3 million women, 18,518 incident colorectal cancers were identified during 13.8 (SD 3.4) years follow-up via record linkage to national cancer registry data. Cox regression yielded adjusted relative risks. Statistical significance was assessed using correction for multiple testing. Overall, colorectal cancer risk was significantly associated with height, body mass index (BMI), smoking, alcohol intake, physical activity, parity and menopausal hormone therapy use. For smoking there was substantial heterogeneity across morphological types; relative risks around two or greater were seen in current smokers both for signet ring cell and for neuroendocrine tumours. Obese women were also at higher risk for signet ring cell tumours. For adenocarcinomas, the large majority of colorectal cancers in the cohort, all risk factor associations were weak. There was little or no heterogeneity in risk between tumours of the right colon, left colon and rectum for any of the 14 factors examined. These epidemiological findings complement an emerging picture from molecular studies of possible different developmental pathways for different tumour types.

Fish and seafood consumption during pregnancy and the risk of asthma and allergic rhinitis in childhood: a pooled analysis of 18 European and US birth cohorts

Abstract: Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis. Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence was collected using validated questionnaires. The time periods of interest were: infancy (0-2 years), preschool age (3-4 years), and school age (5-8 years). We used multivariable generalized models to assess associations of fish and seafood (other than fish) consumption during pregnancy with child respiratory outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses. Results: The median fish consumption during pregnancy ranged from 0.44 times/week in The Netherlands to 4.46 times/week in Spain. Maternal fish intake during pregnancy was not associated with offspring wheeze symptoms in any age group nor with the risk of child asthma [adjusted meta-analysis relative risk (RR) per 1-time/week = 1.01, 95% confidence interval 0.97-1.05)] and allergic rhinitis at school age (RR = 1.01, 0.99-1.03). These results were consistently found in further analyses by type of fish and seafood consumption and in sensitivity analyses. Conclusion: We found no evidence supporting a protective association of fish and seafood consumption during pregnancy with offspring symptoms of wheeze, asthma and allergic rhinitis from infancy to mid childhood.

Cancer incidence rates and trends among children and adolescents in Piedmont, 1967-2011

Abstract: In the past, increases in childhood cancer incidence were reported in Europe and North America. The aim of this study is to show updated patterns of temporal behavior using data of the Childhood Cancer Registry of Piedmont (CCRP), a region with approximately 4.5 million inhabitants in North-West Italy. CCRP has been recording incident cases in children (0-14 years) since 1967 and in adolescents (15-19) since 2000. Time trends were estimated as annual percent change (APC) over the 1976-2011 period for children, and over 2000-2011 for both children and adolescents. CCRP registered 5020 incident cases from 1967 to 2011. Incidence rates were 157 per million person-years for children (1967-2011) and 282 for adolescents (2000-2011). From 1976-2011, increasing trends were observed in children for all neoplasms (APC 1.1, 95%CI: 0.8; 1.5) and for both embryonal and non-embryonal tumors: 1.1%, (0.5; 1.6) and 1.2%, (0.7; 1.6), respectively. Increases were observed in several tumor types, including leukemia, lymphoma, central nervous system tumors and neuroblastoma. In 2000-2011, incidence rates showed mostly non statistically significant variations and large variability. The observation of trends over a long period shows that the incidence of most tumors has increased, and this is only partially explained by diagnostic changes. Large rate variability hampers interpretation of trend patterns in short periods. Given that no satisfying explanation for the increases observed in the past was ever found, efforts must be made to understand and interpret this peculiar and still ununderstood pattern of childhood cancer incidence.

Antidepressants, Depression, and Venous Thromboembolism Risk: Large Prospective Study of UK Women

Abstract: Background Some investigators have reported an excess risk of venous thromboembolism (VTE) associated with depression and with use of antidepressant drugs We explored these associations in a large prospective study of UK women Methods and Results The Million Women Study recruited 13 million women through the National Health Service Breast Screening Programme in England and Scotland Three years after recruitment, women were sent a second questionnaire that enquired about depression and regular use of medications in the previous 4 weeks The present analysis included those who responded and did not have prior VTE, cancer, or recent surgery Follow‐up for VTE was through linkage to routinely collected National Health Service statistics Cox regression analyses yielded adjusted hazard ratios and 95% CIs A total of 734 092 women (mean age 599 years) were included in the analysis; 69% reported use of antidepressants, 27% reported use of other psychotropic drugs, and 18% reported being treated for depression or anxiety but not use of psychotropic drugs During follow‐up for an average of 73 years , 3922 women were hospitalized for and/or died from VTE Women who reported antidepressant use had a significantly higher risk of VTE than women who reported neither depression nor use of psychotropic drugs (hazard ratio, 139; 95% CI, 123–156) VTE risk was not significantly increased in women who reported being treated for depression or anxiety but no use of antidepressants or other psychotropic drugs (hazard ratio, 119; 95% CI, 095–149) Conclusions Use of antidepressants is common in UK women and is associated with an increased risk of VTE

Hospital costs in relation to body-mass index in 1·1 million women in England: a prospective cohort study

Abstract: Summary Background Excess weight is associated with poor health and increased health-care costs. However, a detailed understanding of the effects of excess weight on total hospital costs and costs for different health conditions is needed. Methods Women in England aged 50–64 years were recruited into the prospective Million Women Study cohort in 1996–2001 through 60 NHS breast cancer screening centres. Participants were followed up and annual hospital costs and admission rates were estimated for April 1, 2006, to March 31, 2011, in relation to body-mass index (BMI) at recruitment, overall and for categories of health conditions defined by the International Classification of Diseases 10th revision chapter of the primary diagnosis at admission. Associations of BMI with hospital costs were projected to the 2013 population of women aged 55–79 years in England. Findings 1 093 866 women who provided information on height and weight, had a BMI of at least 18·5 kg/m 2 , and had no previous cancer at recruitment, were followed up for an average of 4·9 years from April 1, 2006 (12·3 years from recruitment), during which time 1·84 million hospital admissions were recorded. Annual hospital costs were lowest for women with a BMI of 20·0 kg/m 2 to less than 22·5 kg/m 2 (£567 per woman per year, 99% CI 556–577). Every 2 kg/m 2 increase in BMI above 20 kg/m 2 was associated with a 7·4% (7·1–7·6) increase in annual hospital costs. Excess weight was associated with increased costs for all diagnostic categories, except respiratory conditions and fractures. £662 million (14·6%) of the estimated £4·5 billion of total annual hospital costs among all women aged 55–79 years in England was attributed to excess weight (BMI ≥25 kg/m 2 ), of which £517 million (78%) arose from hospital admissions with procedures. £258 million (39%) of the costs attributed to excess weight were due to musculoskeletal admissions, mainly for knee replacement surgeries. Interpretation Excess body weight is associated with increased hospital costs for middle-aged and older women in England across a broad range of conditions, especially knee replacement surgery and diabetes. These results provide reliable up-to-date estimates of the health-care costs of excess weight and emphasise the need for investment to tackle this public health issue. Funding Cancer Research UK; Medical Research Council; National Institute for Health Research.