Search results

Comparing interventions for chronic central serous chorioretinopathy: A network meta-analysis

We compare efficacy of treatments for chronic central serous chorioretinopathy (CSCR) > 3 months. Four treatment classes were considered: photodynamic therapy (PDT), subthreshold laser therapies (SLT), mineralocorticoid receptor antagonists (MRA) and antivascular endothelial growth factor (anti-VEGF) agents. Pairwise and network meta-analyses (NMA) of the primary outcomes (complete resolution of subretinal fluid (SRF), mean change in best corrected visual acuity (BCVA as logMAR) and mean change in SRF) and secondary outcomes (mean change in central retinal thickness, and central choroidal thickness (μm), recurrence of SRF, and adverse events) at 3, 6, and 12 months were compared. Confidence in Network Meta-Analysis (CINeMA) informed the certainty of NMA evidence. Eleven RCTs of 458 eyes (450 patients) were included. NMA at 3 months showed that both PDT and SLT were superior to control for resolution of SRF (OR 4.83; 95% CI 1.72–13.55 and 2.27; 1.14–4.49, respectively) and SLT was superior to control for improving BCVA (MD -0.10; -0.17 to -0.04). PDT was superior to SLT for improving CRT (MD -42.88; -75.27 to -10.50). On probability ranking, PDT and SLT were consistently the best-ranked treatments for each outcome at 3 months, but low confidence of evidence and paucity of studies preclude definitive conclusions.

The association between vitamin D levels and caries experience in children and youth participating in National Health and Nutrition Examination Survey 2011-2016: A cross-sectional study

Background: Given equivocal findings from existing nationally representative studies, the authors sought to determine associations between vitamin D levels and caries experience in US children using updated National Health and Nutrition Examination Survey data. Methods: The authors used data from 2011-2016 National Health and Nutrition Examination Survey. Vitamin D status was assessed on the basis of the sufficiency thresholds of 50 and 75 nmol/L for serum 25-hydroxyvitamin D (25[OH]D) recommended by the Institute of Medicine (now National Academy of Medicine) and Endocrine Society, respectively. Caries experience was defined as the total number of decayed or filled tooth surfaces (dfs) and decayed, missing, or filled tooth surfaces (DMFS) and a binary measure of any dfs and DMFS. Associations between 25(OH)D and any or total dfs and DMFS were examined in children aged 2 through 5, 6 through 8, 9 through 11, and 12 through 18 years, using multivariable logistic and linear regression models after adjustment for covariates. Results: Children aged 2 through 5 years with 25(OH)D above 75 nmol/L experienced fewer total dfs (β = –1.94; 95% CI, –3.60 to –0.28) than those with 25(OH)D below 75 nmol/L. Children 6 through 8 years with 25(OH)D above 75 nmol/L had lower presence of any dfs (odds ratio, 0.59; 95% CI, 0.36 to 0.95) than those with 25(OH)D below 75 nmol/L, and those with 25(OH)D above 50 nmol/L had lower presence of any DMFS (odds ratio, 0.38; 95% CI, 0.19 to 0.79) than those with 25(OH)D below 50 nmol/L. There were no associations of 25(OH)D status with either any or total DMFS in children 12 through 18 years Conclusions: There were no consistent associations of 25(OH)D status with caries experience across age groups. Practical Implications: Vitamin D status was not associated consistently with reduced caries experience.

The accuracy of ACTH as a biomarker for pituitary pars intermedia dysfunction in horses: A systematic review and meta-analysis

Background: Accuracy of baseline ACTH for the diagnosis of PPID in horses varies between studies. Objectives: To estimate the diagnostic accuracy of ACTH as a biomarker for PPID in adult horses and appraise potential causes of heterogeneity. Study design: Systematic review and meta-analysis. Methods: A literature review identified studies reporting diagnostic accuracy data for extraction. Risk of bias was evaluated using QUADAS-2. Two random-effects models, the hierarchical summary receiver operating curve (HSROC) and the bivariate binomial normal model (BBN) were used to pool accuracy measurements. We performed meta-regression using study-level variables. The impact of diagnostic test accuracy on the frequency of false-positive and false-negative results at various pretest probabilities was calculated using the BBN model's accuracy results. Results: Patient selection and index test evaluation demonstrated significant risk of bias. Mean and 95% confidence intervals for sensitivity and specificity for all studies (n = 11) based upon the HSROC model were (0.72, 95% CI: 0.62 to 0.82) and (0.88, 95% CI: 0.79 to 0.93), respectively. When studies with a common positivity threshold of 35 pg/mL ACTH were evaluated (n = 6), sensitivity and specificity were (0.66, 95% CI:0.54 to 0.77) and (0.87, 95% CI: 0.74 to 0.94). In a hypothetical group of one thousand horses with PPID prevalence of 2%, 20%, and 90%, the frequency of resulting false-positive and false-negatives would be (127 and 7), (104 and 68) and (13 and 306), respectively. Factors leading to increased accuracy were case-control design, clinical reference standard and data-driven choice of ACTH threshold. Main limitations: A small number of primary studies (n = 11) were available, demonstrating significant biases. Conclusions: Less biased studies examining diagnostic accuracy of ACTH are needed. In horses with a high pretest probability of PPID, ACTH may be a functional “rule-in” test. Baseline ACTH is not recommended for screening purposes or use in horses without clinical signs of PPID.

Home-built environment interventions and inflammation biomarkers: a systematic review and meta-analysis protocol

Background: Inflammation control is a fundamental part of chronic care in patients with a history of cancer and comorbidity. As the risk–benefit profile of anti-inflammatory drugs is unclear in survivors of cancer, GPs and patients could benefit from alternative non-pharmacological treatment options for dysregulated inflammation. There is a potential for home-built environment (H-BE) interventions to modulate inflammation; however, discrepancies exist between studies. Aim: To evaluate the effectiveness of H-BE interventions on cancer-associated inflammation biomarkers. Design & setting: A systematic review and meta-analysis of randomised and non-randomised trials in community-dwelling adults. Method: PubMed and MEDLINE, Embase, Web of Science, and Google Scholar will be searched for clinical trials published in January 2000 onwards. The study will include H-BE interventions modifying air quality, thermal comfort, non-ionising radiation, noise, nature, and water. No restrictions to study population will be applied to allow deriving expectations for effects of the interventions in cancer survivors from available source populations. Outcome measures will be inflammatory biomarkers clinically and physiologically relevant to cancer. The first reviewer will independently screen articles together with GPs and extract data that will be verified by a second reviewer. The quality of studies will be assessed using the Cochrane risk-of-bias tools. Depending on the clinical and methodological homogeneity of populations, interventions, and outcomes, a meta-analysis will be conducted using random-effects models. Conclusion: Findings will determine the effectiveness of H-BE interventions on inflammatory parameters, guide future directions for its provision in community-dwelling survivors of cancer and support GPs with safer anti-inflammatory treatment options in high-risk patients for clinical complications.

Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium

Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity. Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis. Results: A total of 667,916 individuals were included with an overall median (P25–P75) age at recruitment of 62.3 (57–67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86–1.04; I2 = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08–1.26; I2 = 0%) and a similar HR in women (1.13; 95% CI: 0.82–1.56; I2 = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77–0.85; I2 = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89–1.03; I2 = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity. Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.

Physical activity for treatment of irritable bowel syndrome: Cochrane systematic review

Telephone counselling for smoking cessation

Background Telephone services can provide information and support for smokers. Counselling may be provided proactively or offered reactively to callers to smoking cessation helplines. Objectives To evaluate the effect of telephone support to help smokers quit, including proactive or reactive counselling, or the provision of other information to smokers calling a helpline. Search methods We searched the Cochrane Tobacco Addiction Group Specialised Register, clinicaltrials.gov, and the ICTRP for studies of telephone counselling, using search terms including ’hotlines’ or ’quitline’ or ’helpline’. Date of the most recent search: May 2018. Selection criteria Randomised or quasi-randomised controlled trials which offered proactive or reactive telephone counselling to smokers to assist smoking cessation. Data collection and analysis We used standard methodological procedures expected by Cochrane. We pooled studies using a random-effects model and assessed statistical heterogeneity amongst subgroups of clinically comparable studies using the I 2 statistic. In trials including smokers who did not call a quitline, we used meta-regression to investigate moderation of the effect of telephone counselling by the planned number of calls in the intervention, trial selection of participants that were motivated to quit, and the baseline support provided together with telephone counselling (either self-help only, brief face-to-face intervention, pharmacotherapy, or financial incentives). Main results We identified 104 trials including 111,653 participants that met the inclusion criteria. Participants were mostly adult smokers from the general population, but some studies included teenagers, pregnant women, and people with long-term or mental health conditions. Most trials (58.7%) were at high risk of bias, while 30.8% were at unclear risk, and only 11.5% were at low risk of bias for all domains assessed. Most studies (100/104) assessed proactive telephone counselling, as opposed to reactive forms. Among trials including smokers who contacted helplines (32,484 participants), quit rates were higher for smokers receiving multiple sessions of proactive counselling (risk ratio (RR) 1.38, 95% confidence interval (CI) 1.19 to 1.61; 14 trials, 32,484 participants; I 2 = 72%) compared with a control condition providing self-help materials or brief counselling in a single call. Due to the substantial unexplained heterogeneity between studies, we downgraded the certainty of the evidence to moderate. In studies that recruited smokers who did not call a helpline, the provision of telephone counselling increased quit rates (RR 1.25, 95% CI 1.15 to 1.35; 65 trials, 41,233 participants; I 2 = 52%). Due to the substantial unexplained heterogeneity between studies, we downgraded the certainty of the evidence to moderate. In subgroup analysis, we found no evidence that the effect of telephone counselling depended upon whether or not other interventions were provided (P = 0.21), no evidence that more intensive support was more effective than less intensive (P = 0.43), or that the effect of telephone support depended upon whether or not people were actively trying to quit smoking (P = 0.32). However, in meta-regression, telephone counselling was associated with greater effectiveness when provided as an adjunct to self-help written support (P < 0.01), or to a brief intervention from a health professional (P = 0.02); telephone counselling was less effective when provided as an adjunct to more intensive counselling. Further, telephone support was more effective for people who were motivated to try to quit smoking (P = 0.02). The findings from three additional trials of smokers who had not proactively called a helpline but were offered telephone counselling, found quit rates were higher in those offered three to five telephone calls compared to those offered just one call (RR 1.27, 95% CI 1.12 to 1.44; 2602 participants; I 2 = 0%). Authors’ conclusions There is moderate-certainty evidence that proactive telephone counselling aids smokers who seek help from quitlines, and moderate-certainty evidence that proactive telephone counselling increases quit rates in smokers in other settings. There is currently insufficient evidence to assess potential variations in effect from differences in the number of contacts, type or timing of telephone counselling, or when telephone counselling is provided as an adjunct to other smoking cessation therapies. Evidence was inconclusive on the effect of reactive telephone counselling, due to a limited number studies, which reflects the difficulty of studying this intervention.

Impact of prediagnostic smoking and smoking cessation on colorectal cancer prognosis: A meta-analysis of individual patient data from cohorts within the CHANCES consortium

Background: Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies and might also be associated with prognosis after CRC diagnosis. However, current evidence on smoking in association with CRC prognosis is limited. Patients and methods: For this individual patient data meta-analysis, sociodemographic and smoking behavior information of 12 414 incident CRC patients (median age at diagnosis: 64.3 years), recruited within 14 prospective cohort studies among previously cancer-free adults, was collected at baseline and harmonized across studies. Vital status and causes of death were collected for a mean follow-up time of 5.1 years following cancer diagnosis. Associations of smoking behavior with overall and CRC-specific survival were evaluated using Cox regression and standard meta-analysis methodology. Results: A total of 5229 participants died, 3194 from CRC. Cox regression revealed significant associations between former [hazard ratio (HR)=1.12; 95 % confidence interval (CI)=1.04-1.20] and current smoking (HR=1.29; 95% CI=1.04-1.60) and poorer overall survival compared with never smoking. Compared with current smoking, smoking cessation was associated with improved overall (HR<10 years=0.78; 95% CI=0.69-0.88; HR≥10 years=0.78; 95% CI=0.63-0.97) and CRC-specific survival (HR≥10 years=0.76; 95% CI=0.67-0.85). Conclusion: In this large meta-analysis including primary data of incident CRC patients from 14 prospective cohort studies on the association between smoking and CRC prognosis, former and current smoking were associated with poorer CRC prognosis compared with never smoking. Smoking cessation was associated with improved survival when compared with current smokers. Future studies should further quantify the benefits of nonsmoking, both for cancer prevention and for improving survival among CRC patients, in particular also in terms of treatment response.

Solarium use and risk for malignant melanoma: Meta-analysis and evidence-based medicine systematic review

Background: There is an ongoing debate whether solarium use (indoor tanning/artificial UV) may increase the risk for primary cutaneous malignant melanoma. Aim: A systematic literature search was conducted using MEDLINE and ISI Web of Science. Included studies were critically assessed regarding their risk of bias, and methodological shortcomings. Levels of evidence and grades of recommendation were determined according to guidelines of the Oxford Centre for Evidence-Based Medicine. Summary risk estimates and 95% confidence intervals for four different outcomes (ever exposure, exposure at younger age, high/low exposure vs. non-exposure) were derived from random-effects meta-analyses to account for possible heterogeneity across studies. Results: Two cohort and twenty-nine case-controlstudies were eligible. Overall, quality of included studies was poor as a result of severe limitations, including possible recall and selection bias, and due to lack of interventional trials. Summary risk estimates suggested a weak association (odds ratio (OR)=1.19, 95% confidence interval (CI)=1.04- 1.35, p=0.009) for ever-exposure to UV radiation from a solarium with melanoma risk. However, sensitivity analyses did not show an association for studies from Europe (OR=1.10; 95%CI=0.95-1.27, p=0.218), studies with low risk of bias (OR=1.15; 95%CI=0.94-1.41, p=0.179), and studies conducted after 1990 (OR 1.09; 95%CI=0.93-1.29, p=0.295). Moreover, moderate associations were found for first exposure to UV radiation from a solarium at younger age (<25 years) and high exposure (>10 sessions in lifetime) with melanoma risk. However, for all outcomes analyzed, overall study quality and resulting levels of evidence (3a-) and grades of recommendation (D) were low due to lack of interventional studies and severe limitations including unobserved or unrecorded confounding. Conclusion: Current scientific knowledge is mainly based on observational studies with poor quality data, which report associations but do not prove causality. At present, there is no convincing evidence that moderate/responsible solarium use increases melanoma risk.

No Association of Vitamin D pathway genetic variants with cancer risks in a population-based cohort of German older adults

Background: Several investigations assessed the association of Vitamin D receptor (VDR) SNPs with cancer risk. Less is known about the implications of other Vitamin D pathway SNPs on cancer risk. Methods: In a population-based cohort study of 9,949 German older adults, we used Cox regression to assess the association of 6 SNPs in the VDR, Vitamin D-binding protein (GC), 7-dehydrocholesterol reductase (DHCR7), Vitamin D 25- hydroxylase (CYP2R1), and Vitamin D 24-hydroxylase (CYP24A1) genes with total and site-specific cancer incidence endpoints. Results: Overall, no association of SNPs with cancer incidence endpoints was observed, except for a genotype score based on SNPs associated with lower 25(OH)D, which was associated with higher lung cancer risk [HR, 1.20; 95% confidence intervals (CI), 1.03-1.39], although this was no longer significant after correcting for multiple testing. Conclusions: Our data provide little to no evidence of a major influence of Vitamin D genetic predisposition on cancer risks. Impact: Large-scale genetic epidemiology consortia and metaanalysis of smaller published studies are needed to verify a potential modest influence of genetic variation in the association of Vitamin D with the risk of cancer.

Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: Meta-analysis of individual participant data of seven prospective cohorts in Europe

Background:We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence.Methods:This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models.Results:After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02-1.21) for BMI, 1.13 (95% CI 1.04-1.23) for WC, 1.09 (95% CI 0.98-1.21) for HC, and 1.15 (95% CI 1.00-1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone therapy (HT) use was observed for postmenopausal breast cancer (P interaction <0.001), where never HT users showed an ∼20% increased risk per s.d. of BMI, WC, and HC compared to ever users.Conclusions:BMI, WC, HC, and WHR show comparable positive associations with obesity-related cancers combined and with colorectal cancer in older adults. For postmenopausal breast cancer we report evidence for effect modification by HT use.

Alcoholic beverage preference and diabetes incidence across Europe: The Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) project

Background/Objectives:It is unknown if wine, beer and spirit intake lead to a similar association with diabetes. We studied the association between alcoholic beverage preference and type 2 diabetes incidence in persons who reported to consume alcohol.Subjects/Methods:Ten European cohort studies from the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States were included, comprising participant data of 62 458 adults who reported alcohol consumption at baseline. Diabetes incidence was based on documented and/or self-reported diagnosis during follow-up. Preference was defined when ≥70% of total alcohol consumed was either beer, wine or spirits. Adjusted hazard ratios (HRs) were computed using Cox proportional hazard regression. Single-cohort HRs were pooled by random-effects meta-analysis.Results:Beer, wine or spirit preference was not related to diabetes risk compared with having no preference. The pooled HRs were HR 1.06 (95% confidence interval (CI) 0.93, 1.20) for beer, HR 0.99 (95% CI 0.88, 1.11) for wine, and HR 1.19 (95% CI 0.97, 1.46) for spirit preference. Absolute wine intake, adjusted for total alcohol, was associated with a lower diabetes risk: Pooled HR per 6 g/day was 0.96 (95% CI 0.93, 0.99). A spirit preference was related to a higher diabetes risk in those with a higher body mass index, in men and women separately, but not after excluding persons with prevalent diseases.Conclusions:This large individual-level meta-analysis among persons who reported alcohol consumption revealed that the preference for beer, wine, and spirits was similarly associated with diabetes incidence compared with having no preference.

Genetic variants in the Vitamin D pathway, 25(OH)D Levels, and mortality in a large population-based cohort study

Context: Low 25-hydroxyvitamin D[25(OH)D] concentrations have been consistently associated with excess mortality in epidemiological studies, but this association could be due to confounding by health impairments associated with low 25(OH)D levels. An association of vitamin D-related genetic variants with all-cause mortality could strengthen the claims of causality, because this association is assumed to be unaffected by confounding. Objective: To assess the associations of low 25(OH)D with mortality in the presence or absence of genetic variants in the vitamin D pathway. Design, Setting, and Participants: The study consisted of a population-based cohort of 8417 German older adults in whom genetic variants were genotyped. Main Outcome Measures: The primary outcome measure was all-cause mortality. Results: Two single nucleotide polymorphisms (SNPs), rs3755967 (GC) and rs11603330 (DHCR7), were associated with higher risk of low vitamin D status [odds ratio (95% confidence interval) per minor allele, 1.27 (1.18 to 1.36) and 1.16 (1.08 to 1.25), respectively]. Low 25(OH)D (less than the seasonspecific 33rd percentile) was associated with increased mortality. However, none of the SNPs was associated with increased mortality. Furthermore, the increase in mortality for those with low 25(OH)D was generally smaller in the presence of the risk alleles for low 25(OH)D ["genetically low 25(OH)D"] than in the absence of those risk alleles ["otherwise low 25(OH)D"]. Conclusions: Although we may have been limited by a low statistical power to detect small associations, our study showed that the strong relationship between low 25(OH)D and increased mortality may be at least partly due to other factors related to low 25(OH)D levels.

Adherence to the WCRF/AICR dietary recommendations for cancer prevention and risk of cancer in elderly from Europe and the United States: A meta-Analysis within the CHANCES Project

Background: It is unknown whether dietary recommendations for cancer prevention are applicable to the elderly. We analyzed WCRF/AICR recommendations in cohorts of European and U.S. adults ages 60 years and above. Methods: Individual participant data meta-Analysis included 362,114 participants (43% women), from seven prospective cohort studies, free from cancer at enrollment. The WCRF/AICR diet score was based on: (i) energy-dense foods and sugary drinks, (ii) plant foods, (iii) red and processed meat, and (iv) alcoholic drinks. Cox proportional hazards regression was used to examine the association between the diet score and cancer risks. Adjusted, cohort-specific HRs were pooled using random-effects metaanalysis. Risk advancement periods (RAP) were calculated to quantify the time period by which the risk of cancer was postponed among those adhering to the recommendations. Results: After a median follow-up of 11 to 15 years across cohorts, 70,877 cancer cases were identified. Each one-point increase in the WCRF/AICR diet score [range, 0 (no) to 4 (complete adherence)] was significantly associated with a lower risk of total cancer [HR, 0.94; 95% confidence interval (CI), 0.92-0.97], cancers of the colorectum (HR, 0.84; 95% CI, 0.80-0.89) and prostate (HR, 0.94; 95% CI, 0.92-0.97), but not breast or lung. Adherence to an additional component of the WCRF/AICR diet score significantly postponed the incidence of cancer at any site by 1.6 years (RAP, 1.6; 95% CI, 4.09 to 2.16). Conclusions: Adherence to WCRF/AICR dietary recommendations is associated with lower risk of cancer among older adults. Impact: Dietary recommendations for cancer prevention are applicable to the elderly.

Does indoor tanning increase the risk for cutaneous melanoma? A meta-analysis and systematic review of the literature

Burden of Cancer in a Large Consortium of Prospective Cohorts in Europe

Background: Disability-adjusted life-years (DALYs) are an indicator of mortality, morbidity, and disability. We calculated DALYs for cancer in middle-aged and older adults participating in the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) consortium. Methods: A total of 90 199 participants from five European cohorts with 10 455 incident cancers and 4399 deaths were included in this study. DALYs were calculated as the sum of the years of life lost because of premature mortality (YLLs) and the years lost because of disability (YLDs). Population-attributable fractions (PAFs) were also estimated for five cancer risk factors, ie, smoking, adiposity, physical inactivity, alcohol intake, and type II diabetes. Results: After a median follow-up of 12 years, the total number of DALYs lost from cancer was 34 474 (382 per 1000 individuals) with a similar distribution by sex. Lung cancer was responsible for the largest number of lost DALYs (22.9%), followed by colorectal (15.3%), prostate (10.2%), and breast cancer (8.7%). Mortality (81.6% of DALYs) predominated over disability. Ever cigarette smoking was the risk factor responsible for the greatest total cancer burden (24.0%, 95% confidence interval [CI] = 22.2% to 26.0%), followed by physical inactivity (4.9%, 95% CI = 0.8% to 8.1%) and adiposity (1.8%, 95% CI = 0.2% to 2.8%). Conclusions: DALYs lost from cancer were substantial in this large European sample of middle-aged and older adults. Even if the burden of disease because of cancer is predominantly caused by mortality, some cancers have sizeable consequences for disability. Smoking remained the predominant risk factor for total cancer burden.

Overweight duration in older adults and cancer risk: a study of cohorts in Europe and the United States

Recent studies have shown that cancer risk related to overweight and obesity is mediated by time and might be better approximated by using life years lived with excess weight. In this study we aimed to assess the impact of overweight duration and intensity in older adults on the risk of developing different forms of cancer. Study participants from seven European and one US cohort study with two or more weight assessments during follow-up were included (n = 329,576). Trajectories of body mass index (BMI) across ages were estimated using a quadratic growth model; overweight duration (BMI ≥ 25) and cumulative weighted overweight years were calculated. In multivariate Cox models and random effects analyses, a longer duration of overweight was significantly associated with the incidence of obesity-related cancer [overall hazard ratio (HR) per 10-year increment: 1.36; 95 % CI 1.12–1.60], but also increased the risk of postmenopausal breast and colorectal cancer. Additionally accounting for the degree of overweight further increased the risk of obesity-related cancer. Risks associated with a longer overweight duration were higher in men than in women and were attenuated by smoking. For postmenopausal breast cancer, increased risks were confined to women who never used hormone therapy. Overall, 8.4 % of all obesity-related cancers could be attributed to overweight at any age. These findings provide further insights into the role of overweight duration in the etiology of cancer and indicate that weight control is relevant at all ages. This knowledge is vital for the development of effective and targeted cancer prevention strategies.

Quantification of the smoking-associated cancer risk with rate advancement periods: Meta-analysis of individual participant data from cohorts of the CHANCES consortium

Background: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality. Methods: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs. Results: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking. Conclusions: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.

Pre-diagnostic vitamin D concentrations and cancer risks in older individuals: an analysis of cohorts participating in the CHANCES consortium

The associations of circulating 25-hydroxyvitamin D [25(OH)D] concentrations with total and site-specific cancer incidence have been examined in several epidemiological studies with overall inconclusive findings. Very little is known about the association of vitamin D with cancer incidence in older populations. We assessed the association of pre-diagnostic serum 25(OH)D levels with incidence of all cancers combined and incidence of lung, colorectal, breast, prostate and lymphoid malignancies among older adults. Pre-diagnostic 25(OH)D concentrations and cancer incidence were available in total for 15,486 older adults (mean age 63, range 50–84 years) participating in two cohort studies: ESTHER (Germany) and TROMSØ (Norway); and a subset of previously published nested-case control data from a another cohort study: EPIC-Elderly (Greece, Denmark, Netherlands, Spain and Sweden) from the CHANCES consortium on health and aging. Cox proportional hazards or logistic regression were used to derive multivariable adjusted hazard and odds ratios, respectively, and their 95 % confidence intervals across 25(OH)D categories. Meta-analyses with random effects models were used to pool study-specific risk estimates. Overall, lower 25(OH)D concentrations were not significantly associated with increased incidence of most of the cancers assessed. However, there was some evidence of increased breast cancer and decreased lymphoma risk with higher 25(OH)D concentrations. Our meta-analyses with individual participant data from three large European population-based cohort studies provide at best limited support for the hypothesis that vitamin D may have a major role in cancer development and prevention among European older adults.

F2RL3 methylation, lung cancer incidence and mortality

© 2015 UICC.Smoking accounts for a large share of lung cancer. F2RL3 methylation was recently identified as a biomarker closely reflecting both current and past smoking exposure. We aimed to assess the associations of F2RL3 methylation with lung cancer incidence and mortality. In a large population-based cohort study, F2RL3 methylation was measured in baseline blood samples of 4,987 participants by MassARRAY. Associations of F2RL3 methylation and smoking with lung cancer incidence/mortality during a median follow-up of 10.9 years were assessed by Cox regression, controlling for potential confounders. The ability of F2RL3 methylation to predict lung cancer was examined by Harrell's C statistics. Hypomethylation at F2RL3 was strongly associated with both lung cancer incidence and mortality, with age- and sex-adjusted hazard ratios (HR; 95% CI) of 9.99 (5.61-17.79) and 16.86 (8.53-33.34), respectively, for participants whose methylation intensity were ≤0.54 compared with whose methylation intensity were ≥0.75. Strongly elevated HRs of 2.88 (1.42-5.84) and 5.17 (2.28-11.70) persisted even after controlling for multiple covariates including smoking status and pack-years. With fully adjusted HRs of 9.92 (2.88-34.12) and 16.48 (4.10-66.15), the associations between methylation and the two outcomes were particularly strong among participants≥65 years. Combination of F2RL3 methylation and pack-years predicted lung cancer incidence with high accuracy (optimism-corrected Harrell's C statistics=0.86 for participants≥65 years). These findings suggested that F2RL3 methylation is a very strong predictor of lung cancer risk and mortality, particularly at older age. The potential implications of F2RL3 methylation for early detection, risk stratification and prevention of lung cancer warrant further exploration.