Adherence to Healthy and Sustainable Dietary Patterns and Long-Term Chronic Inflammation: Data from the EPIC-Potsdam Cohort.

OBJECTIVES: We explored the prospective associations between adherence to a priori chosen dietary patterns, including EAT-Lancet (EAT-L) and Mediterranean (tMDS) diet with long-term inflammatory responses in a German population sample. DESIGN AND SETTING: Prospective cohort study. PARTICIPANTS: A subsample of 636 predominantly healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study who were on average 51-years old at baseline. MEASUREMENTS: Data was collected repeatedly between 1994/1998 - 2013. At baseline (1994/1998) and 6.8-years later (2001/2005), EAT-L and tMDS scores were derived from available food frequency questionnaires. Stable high, stable low, increasing, and decreasing adherence to EAT-L and tMDS were defined as scoring above/below baseline median at baseline and 6.8-years later. Long-term chronic inflammation was assessed based on the average values of repeated measurements of two inflammatory biomarkers - chemerin and high-sensitivity C-reactive protein (hs-CRP) - in plasma samples collected between 2010/2012 and 2013. Multivariable linear regression analysis adjusted for socio-demographic and lifestyle factors at baseline and in 2010/2012 was used to assess the association between diet adherence and long-term hs-CRP and chemerin concentrations. RESULTS: Stable high or increasing adherence to EAT-L diet compared to stable low adherence was associated with slight reduction of long-term chemerin concentrations on the long run (stable high: -4.4%; increasing: -4.0%), not reaching statistical significance. Increasing adherence to tMDS compared to stable low adherence was also associated with a minor reduction in chemerin concentrations (-3.6%). Decreasing adherence to tMDS compared stable high adherence was associated with 2.7% higher chemerin. The associations were even less pronounced when hs-CRP was used as an outcome. CONCLUSIONS: Adherence to healthy and sustainable dietary patterns defined using existing definitions for EAT-L and tMDS were associated with minor and not statistically significant reduction in the concentrations of inflammatory biomarkers on the long run. More research is needed to explore whether following these diets may represent a suitable approach for targeted prevention in the general population.

Evaluation of the Effectiveness of Various Autophagy Inhibitors in A549 Cancer Stem Cells.

Numerous studies have already established that autophagy plays a central role in the survival of all cells, including malignant ones. Autophagy is a central cog in the general mechanism that provides the intracellular proteostasis determining cellular physiological and phenotypic characteristics. The accumulated data show that autophagy largely contributes to cancer cell stemness. Thus, autophagy modulation is considered one of the promising pharmacological targets in therapy aimed at cancer stem cell elimination. However, autophagy is a multi-stage intracellular process that involves numerous protein participants. In addition, the process can be activated simultaneously by various signaling modules. Therefore, it is no small feat to select an effective pharmacological drug against autophagy. What's more, the search for potential chemotherapeutic agents that could eliminate cancer stem cells through pharmacological inhibition of autophagy is still under way. In the present work, we selected a panel of autophagy inhibitors (Autophinib, SBI-0206965, Siramesine, MRT68921, and IITZ-01), some of whom have been recently identified as effective autophagy inhibitors in cancer cells. Using A549 cancer cells, which express the core stem factors Oct4 and Sox2, we evaluated the effect of these drugs on the survival and preservation of the original properties of cancer stem cells. Among the agents selected, only Autophinib demonstrated a significant toxic effect on cancer stem cells. The obtained results demonstrate that autophagy inhibition by Autophinib downregulates the expression of the Sox2 protein in A549 cells, and that this downregulation correlates with a pronounced induction of apoptosis. Moreover, Autophinib-treated A549 cells are unable to form spheroids, which indicates a reduction in stemness. Thus, among the drugs studied, only Autophinib can be considered a potential agent against cancer stem cells.

[Changes in accommodation in children with hyperopic anisometropia and unilateral amblyopia after laser refractive surgery and pleoptic treatment]. / Izmenenie akkomodatsii u detei s gipermetropicheskoi anizometropiei i odnostoronnei ambliopiei posle refraktsionno-lazernoi operatsii i pleopticheskogo lecheniya.

PURPOSE: This study comparatively analyzes the state of accommodation in children with hyperopic anisometropia and amblyopia after femtosecond laser-assisted in situ keratomileusis (Femto-LASIK) combined with pleoptic treatment, and after conventional pleoptic treatment. MATERIAL AND METHODS: The first group consisted of 30 children with medium and high hyperopia, high and medium amblyopia, and anisometropia greater than 3.0 diopters, who underwent Femto-LASIK in the amblyopic eye. The second group consisted of 28 children with similar local status, who were prescribed traditional correction and received conservative treatment. The follow-up period was 1.5 years. RESULTS: After 1.5 years, higher visual acuity (p<0.05) was achieved in the first group. A significant increase in the coefficient of accommodative response (CAR) was observed in the operated amblyopic eyes in group 1 - by 0.1±0.02 c.u. compared to the control group (p<0.05). In both groups there was an upwards trend for the coefficient of microfluctuations (CMF) in the amblyopic eye, but in the first group CMF increased more significantly (p<0.05). The objective accommodative response (OAR) and positive relative accommodation (PRA) of the amblyopic eye showed a double increase - by 1.0±0.23 and 0.9±0.38 diopters, respectively, at the end of treatment in the first group. The increase in similar indicators in the second group was insignificant (p<0.05). In children of the first group the difference in ciliary muscle thickness (CMT) of the amblyopic eye with disabled and enabled accommodation increased by 0.04±0.01 mm (p<0.05) in the anterior part of the ciliary muscle at the levels of CMTmax and CMT1. CONCLUSION: The data obtained in this study indicate the strong effect of refractive laser surgery in combination with pleoptic treatment on improving the visual acuity and the state of accommodation of the amblyopic and paired dominant eyes in children with hyperopic anisometropia, in contrast to conventional methods of treatment.

Milk intake and incident stroke and CHD in populations of European descent: a Mendelian randomisation study.

Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (ß = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

[Justification for the use of modular intraocular lens (experimental study)]. / Obosnovanie primeneniya sbornoi intraokulyarnoi linzy (eksperimental'noe issledovanie).

The rising number of cases requiring intraocular lens (IOL) exchange, including those for refractive reasons, drives the search for methods to minimize the trauma of the procedure. Lens implants with modular optics may lower complication risks. PURPOSE: To test the use of modular IOL on a laboratory animal in an experiment. MATERIAL AND METHODS: A novel modular IOL was implanted into rabbit eyes in disjointed form with subsequent intraocular assembling. Presence of long-term side effects of implantation and possibility of atraumatic optical disk exchange were evaluated 4 months after the surgery. RESULTS: A total of 3 rabbit eyes underwent IOL implantation surgery, no technical difficulties were encountered. Postoperatively two eyes were quiet with proper central IOL position and no deformations in the haptic and optical parts. Epithelial cell proliferations did not hinder intraocular disassembly/assembly of the modular IOL. Optical disk spontaneously dislocated into anterior chamber in one eye, with subsequent chronic inflammation and corneal edema. In the late postoperative period, no difficulties were observed in disconnecting the optical part from the haptic ring and their coupling. Optical disk exchange did not require extensive handling of the haptic, except that of fixation leaflets during release/capture of the optics. Mechanical impact of the procedure on the lens capsule and Zinn's zonule fibers was minimal. CONCLUSION: The experiment has validated the functionality and feasibility of the modular IOL principle designed to lower the threshold for decisions on IOL exchange in postoperative correction of clinical refraction. In most cases, rabbit eyes were demonstrated to exhibit long-term stable fixation, relative ease and safety of optical disk exchange eliminating the need for traumatic capsular bag manipulations.

[Dual-energy computed tomography in the diagnostics of urolithiasis].

THE AIM: To assess the diagnostic performance of dual-energy computed tomography (DECT) in the evaluation of the composition of urinary stones "in vivo". MATERIALS AND METHODS: A total of 91 patients aged from 20 to 70 years old (mean 42.7) with urinary stone disease were examined at Sechenov University, including 68 men (75%) and 23 women (25%). Prior to surgery, all patients underwent DECT (Canon, Japan) in order to predict the chemical composition of urinary stones in vivo. Extracorporeal shockwave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL) and ureteroscopy (URS) was performed in 53 (58.2%), 18 (19.7%) and 20 (22.1%) patients, respectively. Postoperatively, all stones or stone fragments (n=91; 100%) were examined using a comprehensive physical and chemical analysis (X-ray phase analysis, electron microscopy, infrared spectroscopy). RESULTS: In 6 patients (6.6%) staghorn stones were diagnosed, while in 15 (16.5%), 17 (18.7%), 22 (24.2%) and 31 (34.1%) stones were located in ureteropelvic junction, pelvis and ureter, respectively, including 24 patients with lower ureteric stones (26.4%). Prediction of the stone composition in vivo was carried out on the basis of the one indicator, the dual energy ratio (DER). The threshold values of DER for different types of stones were taken from the literature. All stones were divided into 4 groups according to the DECT results: vevellite stones (n=40, 43.9%), Ca-containing stones without vevellite (n=34, 37.3%), uric acid stones (n=10, 10.9%) and struvite stones (n=7, 7.9%). Thus, when comparing the results of DECT and physical and chemical analysis, in the first group four stones were incorrectly assigned by DECT to the group of Ca-containing stones without vevellite and three stones were incorrectly assigned to the group of struvite stones; in the second group four stones were incorrectly assigned to the group of vevellite stones; in the third group one stone was incorrectly assigned to the group of struvite stones; in the fourth group one stone was incorrectly assigned to the group of vevellite stones and one stone in the group of uric acid stones. In order to increase the diagnostic efficiency of DECT, we performed a comprehensive analysis of five specific DECT indicators (stone density at 135 kV, Z eff of the stone, DER, DEI, DED) using discriminant analysis. Thus, the sensitivity, specificity and overall accuracy of DECT with the use of just one indicator (DER) were 83.3%, 89.8%, 86.8% for vevellite, 88.2%, 92.9%, 91.2% for Ca-containing stones without vevellite, 90%, 98.8%, 97.8% for uric acid stones and 60%, 95.3%, 93.4% for struvite stones, respectively. When using discriminant analysis with five specific DECT indicators, higher values of sensitivity, specificity and overall accuracy were seen: 95.2%, 89.8%, 92.3% for a vevellite, 85,3%, 96,4%, 92,3% for Ca-containing stones without a vevellite and 100%, 100% and 100% for both uric acid and struvite stones, respectively. CONCLUSIONS: Dual-energy computed tomography is a highly informative method which allows to perform preoperatively the reliable assessment of the chemical composition. DECT in patients with urinary stone disease allows to optimize the treatment strategy and carry out preventive measures on individual basis, taking into account the stone type.

Adult weight gain and colorectal adenomas-a systematic review and meta-analysis.

BACKGROUND: Colorectal adenomas are known as precursors for the majority of colorectal carcinomas. While weight gain during adulthood has been identified as a risk factor for colorectal cancer, the association is less clear for colorectal adenomas. We conducted a systematic review and meta-analysis to quantify the evidence on this association. METHODS: We searched Medline up to September 2016 to identify observational (prospective, cross-sectional and retrospective) studies on weight gain during adulthood and colorectal adenoma occurrence and recurrence. We conducted meta-analysis on high weight gain versus stable weight, linear and non-linear dose-response meta-analyses to analyze the association. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a random effects model. RESULTS: For colorectal adenoma occurrence, the summary OR was 1.39 (95% CI: 1.17-1.65; I2: 43%, N = 9 studies, cases = 5507) comparing high (midpoint: 17.4 kg) versus stable weight gain during adulthood and with each 5 kg weight gain the odds increased by 7% (2%-11%; I2: 65%, N = 7 studies). Although there was indication of non-linearity (Pnon-linearity < 0.001) there was an increased odds of colorectal adenoma throughout the whole range of weight gain. Three studies were identified investigating the association between weight gain and colorectal adenoma recurrence and data were limited to draw firm conclusions. CONCLUSIONS: Even a small amount of adult weight gain was related to a higher odds of colorectal adenoma occurrence. Our findings add to the benefits of weight control in adulthood regarding colorectal adenoma occurrence, which might be relevant for early prevention of colorectal cancer.

Association between omentin-1, adiponectin and bone health under consideration of osteoprotegerin as possible mediator.

PURPOSE: Several studies implicated a crosstalk between bone and fat in the pathogenesis of osteoporosis. Few studies indicated an association between adiponectin and omentin-1 on the bone remodeling process and bone mineral density, and suggested osteoprotegerin (OPG) as a mediator of this relationship. However, only limited evidence on this relationship is available in humans. Therefore, this study aimed to investigate the association between omentin-1, adiponectin and broadband ultrasound attenuation (BUA) in peri-/premenopausal and postmenopausal women, and to assess the role of OPG as a possible mediator. METHODS: Data from the German population-based EPIC-Potsdam cohort comprising 637 women were analyzed. Multivariable-adjusted ANCOVA including age, BMI, waist circumference, smoking status, education, physical activity, adiponectin or omentin-1 and hormone use was used to investigate potential relationships between the adipokines and BUA levels. A mediation analysis assessed the mediating effect of OPG on the association of BUA and omentin-1 levels. RESULTS: Peri-/premenopausal women had higher BUA levels (112.5 ± 10.1 dB/MHz), compared to postmenopausal women (106.3 ± 10.0 dB/MHz). In peri-/premenopausal women neither adiponectin nor omentin-1 was significantly associated with BUA. In postmenopausal women, adiponectin was not associated with BUA, but 10 % increase in the omentin-1 concentration was significantly associated with 0.44 dB/MHz lower BUA levels (p = 0.01). Omentin-1 was positively associated with OPG (p = 0.02); however, OPG was not significantly related to BUA (p = 0.62). CONCLUSION: Our study provides evidence for an inverse association between circulating omentin-1 and BUA levels in postmenopausal women. However, the present findings do not support a mediating effect of OPG in the adipose tissue-bone pathway.

Effect of plant-based diets on obesity-related inflammatory profiles: a systematic review and meta-analysis of intervention trials.

Plant-based dietary interventions have been proposed to reduce obesity induced chronic low-grade inflammation and hence prevent chronic disease risk; however, human evidence remains unclear. This systematic review and meta-analysis of intervention trials aimed to assess the effect of plant-based diets on obesity-related inflammatory biomarker profiles. Medline, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published until January 2016 and mean differences in biomarkers of inflammatory status were assessed for: C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-ɑ), soluble intercellular adhesion molecule 1 (sICAM), leptin, adiponectin and resistin. Of initially identified 2,583 publications, 29 met the meta-analysis inclusion criteria [a total of 2,689 participants]. Consumption of plant-based diets was associated with a reduction in the mean concentrations of the following biomarkers: CRP [effect size, -0.55 mg/l, 95% confidence intervals (CI): -0.78; -0.32, I2 = 94.4%], IL-6 [effect size, -0.25 ng/l, 95% CI: -0.56; 0.06, I2 = 74%], and, to some degree, sICAM (-25.07 ng/ml [95% CI: -52.32; 2.17, I2 = 93.2%]). No substantial effects were revealed for TNF-ɑ, resistin, adiponectin and leptin. Plant-based diets are associated with an improvement in obesity-related inflammatory profiles and could provide means for therapy and prevention of chronic disease risk.

Body weight gain and risk of colorectal cancer: a systematic review and meta-analysis of observational studies.

While the relationship between body mass index as an indicator of excess body weight and the risk of colorectal cancer (CRC) is well established, the association between body weight gain in adulthood and risk of CRC remains unresolved. We quantified this association in a meta-analysis of 12 observational studies published until November 2014 with a total of 16,151 incident CRC cases. Random effect models were used to obtain summary relative risks (RR) and 95% confidence intervals (95% CIs). Between-study heterogeneity was assessed using I(2) statistics. Overall, the summary RR (95% CI) was 1.22 (1.14-1.30) for high body weight gain (midpoint: 15.2 kg) compared with stable weight (P for heterogeneity = 0.182; I(2) = 21.2%). In a dose-response analysis, each 5 kg weight gain was associated with a 4% (95% CI: 2%-5%) higher risk of CRC. The association persisted after adjustment for body weight at younger age and was present for both men and women, as well as for colon and rectal cancer. Differences by sex were detected for colon cancer (P for interaction = 0.003, with higher risk for men than women), but not for rectal cancer (P for interaction = 0.613). In conclusion, these data underscore the importance of body weight management from early adulthood onwards for the prevention of CRC development.

Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study.

BACKGROUND: Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations. METHODS: In 486,799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes. RESULTS: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11. CONCLUSIONS: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.

Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort.

BACKGROUND: Evidence on associations between self-reported diabetes mellitus, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce. PATIENTS AND METHODS: We conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case-control subset, analyses were carried out in HCV/HBV-negative individuals. RESULTS: During 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00-3.13) and 2.17 (1.36-3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17-6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals. CONCLUSION(S): This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC. Further research is required to establish whether diabetes treatment or duration is associated with these cancers.

Consumption of fish and meats and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: While higher intake of fish and lower consumption of red/processed meats have been suggested to play a protective role in the etiology of several cancers, prospective evidence for hepatocellular carcinoma (HCC) is limited, particularly in Western European populations. METHODS: The associations of fish and meats with HCC risk were analyzed in the EPIC cohort. Between 1992 and 2010, 191 incident HCC were identified among 477 206 participants. Baseline diet was assessed using validated dietary questionnaires. A single 24-h diet recall from a cohort subsample was used for calibration. Multivariable proportional hazard regression was utilized to estimate hazard ratios (HR) and 95% confidence intervals (CI). In a nested case-control subset (HCC = 122), HBV/HCV status and liver function biomarkers were measured. RESULTS: HCC risk was inversely associated with intake of total fish (per 20 g/day increase, HR = 0.83, 95% CI 0.74-0.95 and HR = 0.80, 95% CI 0.69-0.97 before and after calibration, respectively). This inverse association was also suggested after adjusting for HBV/HCV status and liver function score (per 20-g/day increase, RR = 0.86, 95% CI 0.66-1.11 and RR = 0.74, 95% CI 0.50-1.09, respectively) in a nested case-control subset. Intakes of total meats or subgroups of red/processed meats, and poultry were not associated with HCC risk. CONCLUSIONS: In this large European cohort, total fish intake is associated with lower HCC risk.

Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans.

BACKGROUND: The type and quantity of dietary carbohydrate as quantified by glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the risk of liver and biliary tract cancers, but convincing evidence is lacking. PATIENTS AND METHODS: The association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD; N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206 participants of the European Prospective Investigation into Cancer and Nutrition cohort. Dietary intake was assessed by country-specific, validated dietary questionnaires. Hazard ratios and 95% confidence intervals were estimated from proportional hazard models. HBV/HCV status was measured in a nested case-control subset. RESULTS: Higher dietary GI, GL, or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk. For HCC, divergent risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day, total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70 (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract cancer. CONCLUSIONS: Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk. In addition, high dietary fiber intake could be associated with lower IBD cancer risk.

Primary brain tumours and specific serum immunoglobulin E: a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Case-control studies suggest that patients with allergic diseases have a lower risk of developing glioma but not meningioma or schwannoma. However, those data can be differentially biased. Prospective studies with objective measurements of immunologic biomarkers, like immunoglobulin E (IgE), in blood obtained before cancer diagnosis could help to clarify whether an aetiological association exists. METHODS: The present case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) measured specific serum IgE as a biomarker for the most common inhalant allergens in 275 glioma, 175 meningioma and 49 schwannoma cases and 963 matched controls using the ImmunoCAP specific IgE test. Subjects with an IgE level ≥0.35 kUA/l (kilo antibody units per litre) were classified as sensitized by allergens. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by adjusted conditional logistic regression models for each tumour subtype. The effect of dose-response relationship was assessed in five increasing IgE level categories to estimate P-values for trend. RESULTS: The risk of glioma was inversely related to allergic sensitization (OR = 0.73; 95% CI 0.51-1.06), especially pronounced in women (OR = 0.53; 95% CI 0.30-0.95). In dose-response analyses, for high-grade glioma, the lowest OR was observed in sera with the highest IgE levels (P for trend = 0.04). No association was seen for meningioma and schwannoma. CONCLUSION: The results, based on serum samples prospectively collected in a cohort study, provide some support for the hypothesis that individuals with allergic sensitization are at reduced risk of glioma and confirm results from previous case-control studies.