Showing papers by "Cancer Epidemiology Unit published in 2019"

Association Between Soft Drink Consumption and Mortality in 10 European Countries.

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

Lung ultrasound integrated with clinical assessment for the diagnosis of acute decompensated heart failure in the emergency department: a randomized controlled trial

Abstract: AIMS Although acute decompensated heart failure (ADHF) is a common cause of dyspnoea, its diagnosis still represents a challenge. Lung ultrasound (LUS) is an emerging point-of-care diagnostic tool, but its diagnostic performance for ADHF has not been evaluated in randomized studies. We evaluated, in patients with acute dyspnoea, accuracy and clinical usefulness of combining LUS with clinical assessment compared to the use of chest radiography (CXR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in conjunction with clinical evaluation. METHODS AND RESULTS This was a randomized trial conducted in two emergency departments. After initial clinical evaluation, patients with acute dyspnoea were classified by the treating physician according to presumptive aetiology (ADHF or non-ADHF). Patients were subsequently randomized to continue with either LUS or CXR/NT-proBNP. A new diagnosis, integrating the results of both initial assessment and the newly obtained findings, was then recorded. Diagnostic accuracy and clinical usefulness of LUS and CXR/NT-proBNP approaches were calculated. A total of 518 patients were randomized. Addition of LUS had higher accuracy [area under the receiver operating characteristic curve (AUC) 0.95] than clinical evaluation alone (AUC 0.88) in identifying ADHF (P 0.05). The diagnostic accuracy of the LUS-integrated approach was higher then that of the CXR/Nt-proBNP-integrated approach (AUC 0.95 vs. 0.87, p < 0.01). Combining LUS with the clinical evaluation reduced diagnostic errors by 7.98 cases/100 patients, as compared to 2.42 cases/100 patients in the CXR/Nt-proBNP group. CONCLUSION Integration of LUS with clinical assessment for the diagnosis of ADHF in the emergency department seems to be more accurate than the current diagnostic approach based on CXR and NT-proBNP.

Primary cervical screening with high risk human papillomavirus testing: observational study

Abstract: Objective To provide the first report on the main outcomes from the prevalence and incidence rounds of a large pilot of routine primary high risk human papillomavirus (hrHPV) testing in England, compared with contemporaneous primary liquid based cytology screening. Design Observational study. Setting The English Cervical Screening Programme. Participants 578 547 women undergoing cervical screening in primary care between May 2013 and December 2014, with follow-up until May 2017; 183 970 (32%) were screened with hrHPV testing. Interventions Routine cervical screening with hrHPV testing with liquid based cytology triage and two early recalls for women who were hrHPV positive and cytology negative, following the national screening age and interval recommendations. Main outcome measures Frequency of referral for a colposcopy; adherence to early recall; and relative detection of cervical intraepithelial neoplasia grade 2 or worse from hrHPV testing compared with liquid based cytology in two consecutive screening rounds. Results Baseline hrHPV testing and early recall required approximately 80% more colposcopies, (adjusted odds ratio 1.77, 95% confidence interval 1.73 to 1.82), but detected substantially more cervical intraepithelial neoplasia than liquid based cytology (1.49 for cervical intraepithelial neoplasia grade 2 or worse, 1.43 to 1.55; 1.44 for cervical intraepithelial neoplasia grade 3 or worse, 1.36 to 1.51) and for cervical cancer (1.27, 0.99 to 1.63). Attendance at early recall and colposcopy referral were 80% and 95%, respectively. At the incidence screen, the 33 506 women screened with hrHPV testing had substantially less cervical intraepithelial neoplasia grade 3 or worse than the 77 017 women screened with liquid based cytology (0.14, 0.09 to 0.23). Conclusions In England, routine primary hrHPV screening increased the detection of cervical intraepithelial neoplasia grade 3 or worse and cervical cancer by approximately 40% and 30%, respectively, compared with liquid based cytology. The very low incidence of cervical intraepithelial neoplasia grade 3 or worse after three years supports extending the screening interval.

Risks of ischaemic heart disease and stroke in meat eaters, fish eaters, and vegetarians over 18 years of follow-up: results from the prospective EPIC-Oxford study

Abstract: Objective To examine the associations of vegetarianism with risks of ischaemic heart disease and stroke. Design Prospective cohort study. Setting The EPIC-Oxford study, a cohort in the United Kingdom with a large proportion of non-meat eaters, recruited across the country between 1993 and 2001. Participants 48 188 participants with no history of ischaemic heart disease, stroke, or angina (or cardiovascular disease) were classified into three distinct diet groups: meat eaters (participants who consumed meat, regardless of whether they consumed fish, dairy, or eggs; n=24 428), fish eaters (consumed fish but no meat; n=7506), and vegetarians including vegans (n=16 254), based on dietary information collected at baseline, and subsequently around 2010 (n=28 364). Main outcome measures Incident cases of ischaemic heart disease and stroke (including ischaemic and haemorrhagic types) identified through record linkage until 2016. Results Over 18.1 years of follow-up, 2820 cases of ischaemic heart disease and 1072 cases of total stroke (519 ischaemic stroke and 300 haemorrhagic stroke) were recorded. After adjusting for sociodemographic and lifestyle confounders, fish eaters and vegetarians had 13% (hazard ratio 0.87, 95% confidence interval 0.77 to 0.99) and 22% (0.78, 0.70 to 0.87) lower rates of ischaemic heart disease than meat eaters, respectively (P Conclusions In this prospective cohort in the UK, fish eaters and vegetarians had lower rates of ischaemic heart disease than meat eaters, although vegetarians had higher rates of haemorrhagic and total stroke.

The impact of physical activity and an additional behavioural risk factor on cardiovascular disease, cancer and all-cause mortality: a systematic review.

Abstract: Regular physical activity improves overall health, and has the capacity to reduce risk of chronic diseases and death. However, better understanding of the relationship between multiple lifestyle risk behaviours and disease outcomes is pertinent for prioritising public health messaging. The aim of this systematic review is to examine the association between physical inactivity in combination with additional lifestyle risk behaviours (smoking, alcohol, diet, or sedentary behaviour) for cardiovascular disease, cancer, and all-cause mortality. We searched Ovid Medline, EMBASE, and the Cochrane Register from 1 January 2010 to 12 December 2017, for longitudinal observational studies of adults (18+ years) in the general population with a publication date of 2010 onwards and no language restriction. Main exposure variables had to include a physical activity measure plus at least one other lifestyle risk factor. In total, 25,639 studies were identified. Titles, abstracts and full-text articles of potentially relevant papers were screened for eligibility. Data was extracted and quality assessment was completed using a modified Newcastle-Ottawa Scale (NOS). Across the 25 eligible studies, those participants who reported being physically active combined with achieving other health behaviour goals compared to those who were categorised as physically inactive and did not achieve other positive lifestyle goals, were at least half as likely to experience an incident cardiovascular disease (CVD) event, die from CVD, or die from any cause. These findings were consistent across participant age, sex, and study length of follow-up, and even after excluding lower quality studies. We also observed a similar trend among the few studies which were restricted to cancer outcomes. Most studies did not consider epidemiological challenges that may bias findings, such as residual confounding, reverse causality by pre-existing disease, and measurement error from self-report data. High levels of physical activity in combination with other positive lifestyle choices is associated with better health outcomes. Applying new approaches to studying the complex relationships between multiple behavioural risk factors, including physical activity, should be a priority.

Alcohol drinking patterns and liver cirrhosis risk: analysis of the prospective UK Million Women Study.

Abstract: Summary Background Alcohol is a known cause of cirrhosis, but it is unclear if the associated risk varies by whether alcohol is drunk with meals, or by the frequency or type of alcohol consumed. Here we aim to investigate the associations between alcohol consumption with meals, daily frequency of consumption, and liver cirrhosis. Methods The Million Women Study is a prospective study that includes one in every four UK women born between 1935 and 1950, recruited between 1996 and 2001. In 2001 (IQR 2000–03), the participants reported their alcohol intake, whether consumption was usually with meals, and number of days per week it was consumed. Cox regression analysis yielded adjusted relative risks (RRs) for incident cirrhosis, identified by follow-up through electronic linkage to routinely collected national hospital admission, and death databases. Findings During a mean of 15 years (SD 3) of follow-up of 401 806 women with a mean age of 60 years (SD 5), without previous cirrhosis or hepatitis, and who reported drinking at least one alcoholic drink per week, 1560 had a hospital admission with cirrhosis (n=1518) or died from the disease (n=42). Cirrhosis incidence increased with amount of alcohol consumed (≥15 drinks [mean 220 g of alcohol] vs one to two drinks [mean 30 g of alcohol] per week; RR 3·43, 95% CI 2·87–4·10; p Interpretation In middle-aged women, cirrhosis incidence increases with total alcohol intake, even at moderate levels of consumption. For a given weekly intake of alcohol, this excess incidence of cirrhosis is higher if consumption is usually without meals, or with daily drinking. Funding UK Medical Research Council and Cancer Research UK.

Expert consensus document: Reporting checklist for quantification of pulmonary congestion by lung ultrasound in heart failure.

Abstract: Lung ultrasound is a useful tool for the assessment of patients with both acute and chronic heart failure, but the use of different image acquisition methods, inconsistent reporting of the technique employed and variable quantification of ‘B‐lines,’ have all made it difficult to compare published reports. We therefore need to ensure that future studies utilizing lung ultrasound in the assessment of heart failure adopt a standardized approach to reporting the quantification of pulmonary congestion. Strategies to improve patient care by use of lung ultrasound in the assessment of heart failure have been difficult to develop. In the present document, key aspects of standardization are discussed, including equipment used, number of chest zones assessed, the method of quantifying B‐lines, the presence and timing of additional investigations (e.g. natriuretic peptides and echocardiography) and the impact of therapy. This consensus report includes a checklist to provide standardization in the preparation, review and analysis of manuscripts. This will serve as a guide for investigators and clinicians and enhance the quality and transparency of lung ultrasound research.

Validation of the Oxford WebQ Online 24-Hour Dietary Questionnaire Using Biomarkers.

Abstract: Oxford WebQ is an online dietary questionnaire covering 24 hours, appropriate for repeated administration in large-scale prospective studies including UK Biobank and the Million Women Study. We compared performance of the Oxford WebQ and a traditional interviewer-administered multi-pass 24-hour recall against biomarkers for protein, potassium and total sugar intake, and total energy expenditure estimated by accelerometry. 160 participants were recruited between 2014 and 2016 in London, UK, and measured at 3 non-consecutive time-points. The measurement error model simultaneously compared all 3 methods. Attenuation factors for protein, potassium, sugars and total energy intake estimated by the mean of 2 Oxford WebQs were 0.37, 0.42, 0.45, and 0.31 respectively, with performance improving incrementally for the mean of more measures. Correlation between the mean of 2 Oxford WebQs and estimated true intakes, reflecting attenuation when intake is categorised or ranked, was 0.47, 0.39, 0.40, and 0.38 respectively, also improving with repeated administration. These were similar to the more administratively burdensome interviewer-based recall. Using objective biomarkers as the standard, Oxford WebQ performs well across key nutrients in comparison with more administratively burdensome interviewer-based 24-hour recalls. Attenuation improves when the average is taken over repeated administration, reducing measurement error bias in assessment of diet-disease associations.

Epidemiology report: trends in sex-specific cerebrovascular disease mortality in Europe based on WHO mortality data.

Abstract: Aims There have been substantial declines in cerebrovascular disease mortality across much of Europe, mirroring trends in deaths from cardiovascular disease as a whole. No study has investigated trends in cerebrovascular disease, and its subtypes within all European countries. This study aimed to examine sex-specific trends in cerebrovascular disease, and three of its sub-types: ischaemic stroke, haemorrhagic stroke, and subarachnoid haemorrhage (SAH), in Europe between 1980 and 2016. Methods and results Sex-specific mortality data for each country of the World Health Organization (WHO) Europe region were extracted from the WHO global mortality database and analysed using Joinpoint software to examine trends. The number and location of significant joinpoints for each country by sex and subtype was determined using a log-linear model. The annual percentage change within each segment was calculated along with the average annual percentage change over the duration of all available data. The last 35 years have seen large overall declines in cerebrovascular disease mortality rates in the majority of European countries. While these declines have continued steadily in more than half of countries, this analysis has revealed evidence of recent plateauing and even increases in stroke mortality in a number of countries, in both sexes, and in all four geographical sub-regions of Europe. Analysis by stroke sub-type revealed that recent plateauing was most common for haemorraghic stroke and increases were most common for ischaemic stroke. Conclusion These findings highlight the need for continued research into the inequalities in both current stroke mortality outcomes and trends across Europe, as well as the causes behind any recent plateauing of total cerebrovascular disease or its subtypes.

USP1 links platinum resistance to cancer cell dissemination by regulating Snail stability.

Abstract: Resistance to platinum-based chemotherapy is a common event in patients with cancer, generally associated with tumor dissemination and metastasis. Whether platinum treatment per se activates molecular pathways linked to tumor spreading is not known. Here, we report that the ubiquitin-specific protease 1 (USP1) mediates ovarian cancer cell resistance to platinum, by regulating the stability of Snail, which, in turn, promotes tumor dissemination. At the molecular level, we observed that upon platinum treatment, USP1 is phosphorylated by ATM and ATR and binds to Snail. Then, USP1 de-ubiquitinates and stabilizes Snail expression, conferring resistance to platinum, increased stem cell–like features, and metastatic ability. Consistently, knockout or pharmacological inhibition of USP1 increased platinum sensitivity and decreased metastatic dissemination in a Snail-dependent manner. Our findings identify Snail as a USP1 target and open the way to a novel strategy to overcome platinum resistance and more successfully treat patients with ovarian cancer.

The Consortium of Metabolomics Studies (COMETS): Metabolomics in 47 Prospective Cohort Studies

Abstract: The Consortium of Metabolomics Studies (COMETS) was established in 2014 to facilitate large-scale collaborative research on the human metabolome and its relationship with disease etiology, diagnosis, and prognosis. COMETS comprises 47 cohorts from Asia, Europe, North America, and South America that together include more than 136,000 participants with blood metabolomics data on samples collected from 1985 to 2017. Metabolomics data were provided by 17 different platforms, with the most frequently used labs being Metabolon, Inc. (14 cohorts), the Broad Institute (15 cohorts), and Nightingale Health (11 cohorts). Participants have been followed for a median of 23 years for health outcomes including death, cancer, cardiovascular disease, diabetes, and others; many of the studies are ongoing. Available exposure-related data include common clinical measurements and behavioral factors, as well as genome-wide genotype data. Two feasibility studies were conducted to evaluate the comparability of metabolomics platforms used by COMETS cohorts. The first study showed that the overlap between any 2 different laboratories ranged from 6 to 121 metabolites at 5 leading laboratories. The second study showed that the median Spearman correlation comparing 111 overlapping metabolites captured by Metabolon and the Broad Institute was 0.79 (interquartile range, 0.56-0.89).

Prospective analysis of circulating metabolites and breast cancer in EPIC

Abstract: Metabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk. A nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression. Among women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70–0.90), asparagine (OR = 0.83 (0.74–0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76–0.90)), aa C36:3 (OR = 0.84 (0.77–0.93)), ae C34:2 (OR = 0.85 (0.78–0.94)), ae C36:2 (OR = 0.85 (0.78–0.88)), and ae C38:2 (OR = 0.84 (0.76–0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11–1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06–1.24)) and PC ae C36:3 (OR = 0.88 (0.82–0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity. These findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.

Thyroid cancer “epidemic” also occurs in low‐ and middle‐income countries

Abstract: Thyroid cancer incidence varies greatly between and within high-income countries (HICs), and overdiagnosis likely plays a major role in these differences. Yet, little is known about the situation in low- and middle-income countries (LMICs). We compare up-to-date thyroid cancer incidence and mortality at national and subnational levels. 599,851 thyroid cancer cases in subjects aged 20-74 reported in Cancer Incidence in Five Continents volume XI from 55 countries with at least 0.5 million population, aged 20-74 years, covered by population-based cancer registration, and 22,179 deaths from the WHO Mortality Database for 36 of the selected countries, over 2008-2012, were included. Age-standardized rates were computed. National incidence rates varied 50-fold. Rates were 4 times higher among women than men, with similar patterns between countries. The highest rates (>25 cases per 100,000 women) were observed in the Republic of Korea, Israel, Canada, the United States, Italy, France, and LMICs such as Turkey, Costa Rica, Brazil, and Ecuador. Incidence rates were low (<8) in a few HICs (the Netherlands, the United Kingdom, and Denmark) and lowest (3-4) in some LMICs (such as Uganda and India). Within-country incidence rates varied up to 45-fold, with the largest differences recorded between rural and urban areas in Canada (HIC) and Brazil, India, and China (LMICs). National mortality rates were very low (<2) in all countries and in both sexes, and highest in LMICs. The very high thyroid cancer incidence and low mortality rates in some LMICs also strongly suggest a major role of overdiagnosis in these countries.

Comparison of Major Protein-Source Foods and Other Food Groups in Meat-Eaters and Non-Meat-Eaters in the EPIC-Oxford Cohort

Abstract: Differences in health outcomes between meat-eaters and non-meat-eaters might relate to differences in dietary intakes between these diet groups. We assessed intakes of major protein-source foods and other food groups in six groups of meat-eaters and non-meat-eaters participating in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study. The data were from 30,239 participants who answered questions regarding their consumption of meat, fish, dairy or eggs and completed a food frequency questionnaire (FFQ) in 2010. Participants were categorized as regular meat-eaters, low meat-eaters, poultry-eaters, fish-eaters, vegetarians and vegans. FFQ foods were categorized into 45 food groups and analysis of variance was used to test for differences between age-adjusted mean intakes of each food group by diet group. Regular meat-eaters, vegetarians and vegans, respectively, consumed about a third, quarter and a fifth of their total energy intake from high protein-source foods. Compared with regular meat-eaters, low and non-meat-eaters consumed higher amounts of high-protein meat alternatives (soy, legumes, pulses, nuts, seeds) and other plant-based foods (whole grains, vegetables, fruits) and lower amounts of refined grains, fried foods, alcohol and sugar-sweetened beverages. These findings provide insight into potential nutritional explanations for differences in health outcomes between diet groups.

Maternal anxiety, depression and sleep disorders before and during pregnancy, and preschool ADHD symptoms in the NINFEA birth cohort study.

Abstract: Aims. Maternal mental disorders have been associated with the risk of attention-deficit/hyperactivity disorder (ADHD) in children. Within the context of a mother-child cohort, we examined whether maternal anxiety, depression and sleep disorders are associated with pre-school ADHD symptoms. Methods. The study included 3634 singletons from the Italian NINFEA (Nascita e INFanzia: gli Effetti dell'Ambiente') cohort. Maternal doctor-diagnosed anxiety, depression and sleep disorders before and during pregnancy were assessed from the questionnaires completed during pregnancy and 6 months after delivery. Mothers rated child ADHD symptoms at 4 years of age, according to the Diagnostic and Statistical Manual of Mental Disorders. Hyperactive-impulsive (ADHD-H), inattentive (ADHD-I) and total ADHD scores were analysed in the models adjusted for child's gender, first-born status, maternal age, education, alcohol consumption and smoking during pregnancy. Results. The total ADHD score at age 4 was associated with maternal lifetime anxiety (17.1% percentage difference in score compared with never; 95% CI 7.3-27.9%), sleep disorders (35.7%; 95% CI 10.7-66.5%) and depression (17.5%; 95% CI 3.2-33.8%). Similar positive associations were observed also for ADHD-H and ADHD-I traits, with slightly attenuated associations between maternal sleep disorders and child ADHD-I score, and maternal depression and both ADHD scores. All the estimates were enhanced when the disorders were active during pregnancy and attenuated for disorders active only during the pre-pregnancy period. Conclusions. Maternal anxiety, depression and sleep disorders are associated with a relative increase in the number of ADHD-H, ADHD-I and total ADHD symptoms in preschoolers.

Minor Hepatectomies: Focusing a Blurred Picture: Analysis of the Outcome of 4471 Open Resections in Patients Without Cirrhosis.

Abstract: Objective:To elucidate minor hepatectomy (MiH) outcomes.Summary Background Data:Liver surgery has moved toward a parenchyma-sparing approach, favoring MiHs over major resections. MiHs encompass a wide range of procedures.Methods:We retrospectively evaluated consecutive patients who underwent open li

Cohort Profile: the Million Women Study.

Abstract: The Million Women Study started recruiting participants over 20 years ago, in 1996. The initial stimulus was to obtain robust prospective information on the risk of breast cancer associated with use of different types of menopausal hormone therapy (HT). When planning the necessary largescale prospective study, an equally important aim was to obtain reliable information on the effects of other potentially modifiable factors that affect women’s health as they age. In the early 1990s use of HT increased rapidly in the UK and elsewhere, stimulated in part by claims that use of HT could improve general well-being and increase life expectancy. By the mid-1990s, however, worldwide evidence was beginning to show that HT preparations increased breast cancer risk, though there was little information about the effect of the type of HT most commonly used in Europe, containing both oestrogens and progestagens. It was also clear that women born in the 1940s, who reached adulthood in the 1960s, had considerably different lifestyles compared with previous generations. For example, large proportions had begun smoking and using oral contraceptives as teenagers and young adults, and the long-term effects of these behaviours could not be studied reliably until the 1990s. At the same time there was growing concern about the effects of the increasing prevalence of obesity, and claims that other factors such as diet had important effects on health, all of which required largescale prospective evidence. The UK National Health Service (NHS) provides extraordinarily efficient ways of establishing and maintaining long-term follow-up for large prospective epidemiological studies. Over 99% of the UK population, and all Million Women Study participants, are registered with the NHS, and every individual has a unique NHS number. Electronic linkage, using each individual’s NHS number, to routinely collected NHS databases provides virtually complete follow-up information about deaths, emigrations, cancer registrations and hospital admissions. The NHS Breast Screening Programme invites all UK women registered with the NHS, of a specified age, for free routine breast screening every 3 years. In 1996–2001 the programme routinely invited women aged 50–64 years for mammographic screening, by sending each individual a letter offering them a specific date and time at a specific screening centre. In 66 NHS screening centres, the Million Women Study recruitment questionnaire was included with the invitation letter for screening. Pilot studies in 1994–96 had shown that inclusion of a questionnaire with the invitation did not affect uptake of breast screening. The coordinating centre for the Million Women Study is based in the Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford.

Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium.

Abstract: Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.

The REAL (REctal Anastomotic Leak) score for prediction of anastomotic leak after rectal cancer surgery

Abstract: Anastomotic leak after rectal cancer surgery is a severe complication associated with poorer oncologic outcome and quality of life. Preoperative assessment of the risk for anastomotic leak is a key component of surgical planning, including the opportunity to create a defunctioning stoma. The purpose of this study was to identify and quantify the risk factors for anastomotic leak to minimize risk by either not restoring bowel continuity or protecting the anastomosis with a temporary diverting stoma. Potentially relevant studies were identified from the following databases: PubMed, Embase and Cochrane Library. This meta-analysis included studies on transabdominal resection for rectal cancer that reported data about anastomotic leak. The risk for anastomotic leak after rectal cancer surgery was investigated. Preoperative, intraoperative, and postoperative factors were extracted and used to compare anastomotic leak rates. All variables demonstrating a p value 0.0791 to identify anastomotic leak were 79.1% and 32.9%, respectively. Accuracy of the threshold value was confirmed in the validation set with 77.8% sensitivity and 35.2% specificity. We trust that, with further refinement using prospective data, this nomogram based on preoperative risk factors may assist surgeons in decision making. The score is now available online ( http://www.real-score.org ).

Genetic determinants of telomere length and risk of pancreatic cancer: a PANDoRA study.

Abstract: Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10-6 , ptrend = 3.27 × 10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10-9 for highest vs. lowest quintile; p = 1.82 × 10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer.

Sex hormone binding globulin and risk of breast cancer: a Mendelian randomization study.

Abstract: BACKGROUND There are observational data suggesting an inverse association between circulating concentrations of sex hormone binding globulin (SHBG) and risk of postmenopausal breast cancer. However, causality is uncertain and few studies have investigated this association by tumour receptor status. We aimed to investigate these associations under the causal framework of Mendelian randomization (MR). METHODS We used summary association estimates extracted from published genome-wide association study (GWAS) meta-analyses for SHBG and breast cancer, to perform two-sample MR analyses. Summary statistics were available for 122 977 overall breast cancer cases, of which 69 501 were estrogen receptor positive (ER+ve) and 21 468 were ER-ve, and 105 974 controls. To control for potential horizontal pleiotropy acting via body mass index (BMI), we performed multivariable inverse-variance weighted (IVW) MR as the main analysis, with the robustness of this approach further tested in sensitivity analyses. RESULTS The multivariable IVW MR analysis indicated a lower risk of overall (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.90, 0.98; P: 0.006) and ER+ve (OR: 0.92; 95% CI: 0.87, 0.97; P: 0.003) breast cancer, and a higher risk of ER-ve disease (OR: 1.09; 95% CI: 1.00, 1.18; P: 0.047) per 25 nmol/L higher SHBG levels. Sensitivity analyses were consistent with the findings of the main analysis. CONCLUSIONS We corroborated the previous literature evidence coming from observational studies for a potentially causal inverse association between SHBG concentrations and risk of ER+ve breast cancer, but our findings also suggested a potential novel positive association with ER-ve disease that warrants further investigation, given the low prior probability of being true.

Association between body mass index (BMI) and hypertension in south Asian population: evidence from nationally-representative surveys.

Abstract: Although there has been a well-established association between overweight-obesity and hypertension, whether such associations are heterogeneous for South Asian populations, or for different socioeconomic groups is not well-known. We explored the associations of overweight and obesity using South Asian cut-offs with hypertension, and also examined the relationships between body mass index (BMI) and hypertension in various socioeconomic subgroups. We analysed the recent Demographic and Health Survey (DHS) data from Bangladesh, India, and Nepal, with a total of 821,040 men and women. Hypertension was defined by 2017 ACC/AHA cut-offs and by Joint National Committee 7 (JNC7) cut-offs for measured blood pressure and overweight and obesity were defined by measured height and weight. We used multiple logistic regressions to estimate the odds ratios (ORs) with 95% confidence intervals (CIs) of hypertension for overweight and obesity as well as for each 5-unit increase in BMI. The prevalence of hypertension using JNC7 cut-offs among participants increased by age in all three countries. The prevalence ranged from 17.4% in 35–44 years to 34.9% in ≥55 years in Bangladesh, from 4.6% in 18–24 years to 28.6% in 45–54 years in India, and from 3.8% in 18–24 years to 39.2% in ≥55 years in Nepal. Men were more likely to be hypertensive than women in India and Nepal, but not in Bangladesh. Overweight and obesity using both WHO and South Asian cut-offs were associated with higher odds of hypertension in all countries. For each 5 kg/m2 increase in BMI, the ORs for hypertension were 1.79 (95% CI: 1.65–1.93), 1.59 (95% CI: 1.58–1.61), and 2.03 (95% CI: 1.90–2.16) in Bangladesh, India, and Nepal, respectively. The associations between BMI and hypertension were consistent across various subgroups defined by sex, age, urbanicity, educational attainment and household’s wealth index. Our study shows that the association of BMI with hypertension is stronger for South Asian populations at even lower cut-offs points for overweight and obesity. Therefore, public health measures to reduce population-level reduction in BMI in all population groups would also help in lowering the burden of hypertension.

Body Fat Distribution and Systolic Blood Pressure in 10,000 Adults with Whole-Body Imaging: UK Biobank and Oxford BioBank

Abstract: Objective This study aimed to quantify the associations of regional fat mass and fat-free mass with systolic blood pressure. Methods This analysis combined individual participant data from two large-scale imaging studies: UK Biobank and Oxford BioBank. In both studies, participants were interviewed and measured, and they underwent dual-energy x-ray absorptiometry imaging. Linear regression was used to relate systolic blood pressure to anthropometric measures of adiposity (BMI, waist circumference, and waist to hip ratio) and dual-energy x-ray absorptiometry-derived measures of body composition (visceral android fat, subcutaneous android fat, subcutaneous gynoid fat, and fat-free mass). Results Among 10,260 participants (mean age 49; 96% white), systolic blood pressure was positively associated with visceral android fat (3.2 mmHg/SD in men; 2.8 mmHg/SD in women) and fat-free mass (1.92 mmHg/SD in men; 1.64 mmHg/SD in women), but there was no evidence of an association with subcutaneous android or gynoid fat. Associations of systolic blood pressure with BMI were slightly steeper than those with waist circumference or waist to hip ratio; these associations remained unchanged following adjustment for fat-free mass, but adjustment for visceral android fat eliminated associations with waist circumference and waist to hip ratio and more than halved associations with BMI. Conclusions This analysis indicates that visceral fat is the primary etiological component of excess adiposity underlying the development of adiposity-related hypertension.

Diet and risk of glioma: combined analysis of 3 large prospective studies in the UK and USA.

Abstract: BACKGROUND Available evidence on diet and glioma risk comes mainly from studies with retrospective collection of dietary data. To minimize possible differential dietary recall between those with and without glioma, we present findings from 3 large prospective studies. METHODS Participants included 692 176 from the UK Million Women Study, 470 780 from the US National Institutes of Health-AARP study, and 99 148 from the US Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cox regression yielded study-specific adjusted relative risks for glioma in relation to 15 food groups, 14 nutrients, and 3 dietary patterns, which were combined, weighted by inverse variances of the relative risks. Separate analyses by <5 and ≥5 years follow-up assessed potential biases related to changes of diet before glioma diagnosis. RESULTS The 1 262 104 participants (mean age, 60.6 y [SD 5.5] at baseline) were followed for 15.4 million person-years (mean 12.2 y/participant), during which 2313 incident gliomas occurred, at mean age 68.2 (SD 6.4). Overall, there was weak evidence for increased glioma risks associated with increasing intakes of total fruit, citrus fruit, and fiber and healthy dietary patterns, but these associations were generally null after excluding the first 5 years of follow-up. There was little evidence for heterogeneity of results by study or by sex. CONCLUSIONS The largest prospective evidence to date suggests little, if any, association between major food groups, nutrients, or common healthy dietary patterns and glioma incidence. With the statistical power of this study and the comprehensive nature of the investigation here, it seems unlikely we have overlooked major effects of diet on risk of glioma that would be of public health concern.

Outcomes of idiopathic chronic large pericardial effusion

Abstract: Objective Aim of this paper is to evaluate the outcomes of ‘idiopathic’ chronic large pericardial effusions without initial evidence of pericarditis. Methods All consecutive cases of idiopathic chronic large pericardial effusions evaluated from 2000 to 2015 in three Italian tertiary referral centres for pericardial diseases were enrolled in a prospective cohort study. The term ‘idiopathic’ was applied to cases that performed a complete diagnostic evaluation to exclude a specific aetiology. A clinical and echocardiographic follow-up was performed every 3–6 months. Results 100 patients were included (mean age 61.3±14.6 years, 54 females, 44 patients were asymptomatic according to clinical evaluation) with a mean follow-up of 50 months. The baseline median size of the effusion (evaluated as the largest end-diastolic echo-free space) was 25 mm (IQR 8) and decreased to a mean value of 7 mm (IQR 19; p Conclusions The evolution of ‘idiopathic’ chronic large pericardial effusions is usually benign with reduction of the size of the effusion in the majority of cases, and regression in about 40% of cases. The risk of cardiac tamponade is 2.2%/year and recurrence/complications survival was better in patients treated conservatively without interventions.

Worldwide Age at Onset of Female Breast Cancer: A 25-Year Population-Based Cancer Registry Study.

Abstract: A higher frequency of early onset female breast cancers (BC) has been observed in low/middle income countries than in high income countries. We quantified the role of population ageing to this pattern using data from all population-based cancer registries (CRs) worldwide. Patients’ median age at BC onset and that of the general population were extracted for CRs listed in volumes VI (1983–1987 years) through XI (2008–2012 years) of Cancer Incidence in Five Continents. Their association was assessed at cross-sectional level by linear regression model and longitudinally considering 25-year ageing of the population in long-standing CRs listed at the beginning and at the end of the study. During 2008–2012, each one-year increase of population ageing was associated with a nearly ½ year increase of age at BC diagnosis. Population demographics explained forty-two percent of the age variance for BC. In 1983–1987, long-standing CRs with a median age at BC below age 61.8 years showed an increase of age at BC after 25-years. Worldwide, age at BC diagnosis essentially reflected the median age of the population. Changes in BC detection methodology likely lessened this association. Nevertheless, the elevated absolute number of BCs in young populations deserves strategies of BC prevention.

The Genotype for DPYD Risk Variants in Patients With Colorectal Cancer and the Related Toxicity Management Costs in Clinical Practice.

Abstract: Lack of information on the clinical utility of preemptive DPYD screening before fluoropyrimidine treatment is a major barrier preventing its use in clinical practice. This study aimed to define the association between DPYD variants and fluoropyrimidine-related toxicity management costs. A cost analysis was conducted on the toxicities experienced by 550 patients with colorectal cancer treated with fluoropyrimidine-based chemotherapy. Genotyping for DPYD*2A, DPYD*13, DPYDc. 2846A>T, DPYD-HapB3, and UGT1A1*28 was done retrospectively and did not affect patients' treatments. Carriers of at least one DPYD variant experienced higher toxicity management costs (€2,972; 95% confidence interval (CI), €2,456-€3,505) than noncarriers (€825; 95% CI, €785-€864) (P < 0.0001) and had a higher risk for toxicity requiring hospitalization (odds ratio, 4.14; 95% CI, 1.87-9.14). In patients receiving fluoropyrimidine/irinotecan, the incremental cost between DPYD variant and UGT1A1*28/*28 carriers and noncarriers was €2,975. This study suggests that the toxicity management costs during fluoropyrimidine-based therapy are associated with DPYD and UGT1A1*28 variants and supports the utility of genotyping.