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Background The role of diet in breast cancer aetiology is unclear; recent studies have suggested associations may differ by estrogen receptor status. Methods Baseline diet was assessed in 2000–04 using a validated questionnaire in 691 571 postmenopausal UK women without previous cancer, who had not changed their diet recently. They were followed by record linkage to national cancer and death databases. Cox regression yielded adjusted relative risks for breast cancer for 10 food items and eight macronutrients, subdivided mostly into five categories of baseline intake. Trends in risk across the baseline categories were calculated, assigning re-measured intakes to allow for measurement error and changes in intake over time; P-values allowed for multiple testing. Results Women aged 59.9 (standard deviation (SD 4.9)) years at baseline were followed for 12 (SD 3) years; 29 005 were diagnosed with invasive breast cancer. Alcohol intake had the strongest association with breast cancer incidence: relative risk (RR) 1.08 [99% confidence interval (CI) 1.05–1.11] per 10 g/day higher intake, P = 5.8 × 10−14. There were inverse associations with fruit: RR 0.94 (99% CI 0.92–0.97) per 100 g/day higher intake, P = 1.1 × 10−6, and dietary fibre: RR 0.91 (99% CI 0.87–0.96) per 5 g/day increase, P = 1.1 × 10−4. Fruit and fibre intakes were correlated (ρ = 0.62) and were greater among women who were not overweight, so residual confounding cannot be excluded. There was no heterogeneity for any association by estrogen receptor status. Conclusions By far the strongest association was between alcohol intake and an increased risk of breast cancer. Of the other 17 intakes examined, higher intakes of fruit and fibre were associated with lower risks of breast cancer, but it is unclear whether or not these associations are causal.

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow‐up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer., What's new? This prospective study is the largest investigation of metabolite profile and prostate cancer risk, to date. We found that patterns in plasma metabolite profile (characterized by higher concentrations of phosphatidylcholines and hydroxysphingomyelins; specific acylcarnitines, amino acids and a biogenic amine; and lysophosphatidylcholines, respectively) were associated with subsequent lower risk of more aggressive tumor subtypes and prostate cancer death. Moreover, the results suggest that metabolite profile may be relevant to the etiology of advanced stage disease.

Source at https://doi.org/10.1186/s13058-018-1073-0. Licensed CC BY-NC-ND 4.0. Background: Few published breast cancer (BC) risk prediction models consider the heterogeneity of predictor variables between estrogen-receptor positive (ER+) and negative (ER-) tumors. Using data from two large cohorts, we examined whether modeling this heterogeneity could improve prediction. Methods: We built two models, for ER+ (ModelER+) and ER- tumors (ModelER-) , respectively, in 281,330 women (51% postmenopausal at recruitment) from the European Prospective Investigation into Cancer and Nutrition cohort. Discrimination (C-statistic) and calibration (the agreement between predicted and observed tumor risks) were assessed both internally and externally in 82,319 postmenopausal women from the Women’s Health Initiative study. We performed decision curve analysis to compare ModelER+ and the Gail model (ModelGail) regarding their applicability in risk assessment for chemoprevention. Results: Parity, number of full-term pregnancies, age at first full-term pregnancy and body height were only associated with ER+ tumors. Menopausal status, age at menarche and at menopause, hormone replacement therapy, postmenopausal body mass index, and alcohol intake were homogeneously associated with ER+ and ER- tumors. Internal validation yielded a C-statistic of 0.64 for ModelER+ and 0.59 for ModelER-. External validation reduced the C-statistic of ModelER+ (0.59) and ModelGail (0.57). In external evaluation of calibration, ModelER+ outperformed the ModelGail: the former led to a 9% overestimation of the risk of ER+ tumors, while the latter yielded a 22% underestimation of the overall BC risk. Compared with the treat-all strategy, ModelER+ produced equal or higher net benefits irrespective of the benefit-to-harm ratio of chemoprevention, while ModelGail did not produce higher net benefits unless the benefit-to-harm ratio was below 50. The clinical applicability, i.e. the area defined by the net benefit curve and the treat-all and treat-none strategies, was 12.7 × 10− 6 for ModelER+ and 3.0 × 10− 6 for ModelGail. Conclusions: Modeling heterogeneous epidemiological risk factors might yield little improvement in BC risk prediction. Nevertheless, a model specifically predictive of ER+ tumor risk could be more applicable than an omnibus model in risk assessment for chemoprevention.

Prospective studies have observed differences in risks for several health outcomes when comparing meat-eaters and vegetarians, but the mechanisms underlying these differences remain uncertain. Identifying genetic factors related to vegetarianism may be valuable for assessing causality. We report a genome-wide association study (GWAS) of vegetarianism in 367,198 participants from UK Biobank. We identified one locus, rs10189138, near the vaccinia related kinase 2 (VRK2) gene, significantly associated with vegetarianism (β=0.153, p=3x10-8). The associations between rs10189138 and 40 traits were calculated, and the rs10189138 T allele (MAF=0.12) was found to be significantly associated with greater height, after controlling the false discovery rate (FDR). Correlations between genetically predicted vegetarianism and 855 other genetically predicted traits were also calculated, and vegetarianism had significant positive genetic correlations with fluid intelligence and age at menarche, after controlling the FDR. Future research on an independent sample is needed to see if this GWAS result can be replicated.

Alcohol intake has been related to an increased risk of breast cancer (BC) while dietary fiber intake has been inversely associated to BC risk. A beneficial effect of fibers on ethanol carcinogenes ...

Background In Western populations, a higher level of fruit consumption has been associated with a lower risk of cardiovascular disease, but little is known about such associations in China, where the consumption level is low and rates of stroke are high. Methods Between 2004 and 2008, we recruited 512,891 adults, 30 to 79 years of age, from 10 diverse localities in China. During 3.2 million person-years of follow-up, 5173 deaths from cardiovascular disease, 2551 incident major coronary events (fatal or nonfatal), 14,579 ischemic strokes, and 3523 intracerebral hemorrhages were recorded among the 451,665 participants who did not have a history of cardiovascular disease or antihypertensive treatments at baseline. Cox regression yielded adjusted hazard ratios relating fresh fruit consumption to disease rates. Results Overall, 18.0% of participants reported consuming fresh fruit daily. As compared with participants who never or rarely consumed fresh fruit (the “nonconsumption” category), those who ate fresh fruit daily had lower systolic blood pressure (by 4.0 mm Hg) and blood glucose levels (by 0.5 mmol per liter [9.0 mg per deciliter]) (P Conclusions Among Chinese adults, a higher level of fruit consumption was associated with lower blood pressure and blood glucose levels and, largely independent of these and other dietary and nondietary factors, with significantly lower risks of major cardiovascular diseases.

Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow-up, 52,683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842,149 men. Cox proportional hazard models were used to calculate study-specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR [MVRR], 95% confidence interval, comparing ≥ 45 vs.

Lifestyle factors, including diet, have long been recognised as potentially important determinants of cancer risk. In addition to the significant role diet plays in affecting body fatness, a risk factor for several cancers, experimental studies have indicated that diet may influence the cancer process in several ways. Prospective studies have shown that dietary patterns characterised by higher intakes of fruits, vegetables, and whole-grain foods, and lower intakes of red and processed meats and salt, are related to reduced risks of death and cancer, and that a healthy diet can improve overall survival after diagnosis of breast and colorectal cancers. There is evidence that high intakes of fruit and vegetables may reduce the risk of cancers of the aerodigestive tract, and the evidence that dietary fibre protects against colorectal cancer is convincing. Red and processed meats increase the risk of colorectal cancer. Diets rich in high-calorie foods, such as fatty and sugary foods, may lead to increased calorie intake, thereby promoting obesity and leading to an increased risk of cancer. There is some evidence that sugary drinks are related to an increased risk of pancreatic cancer.Taking this evidence into account, the 4th edition of the European Code against Cancer recommends that people have a healthy diet to reduce their risk of cancer: they should eat plenty of whole grains, pulses, vegetables and fruits; limit high-calorie foods (foods high in sugar or fat); avoid sugary drinks and processed meat; and limit red meat and foods high in salt.

Breast cancer is the most frequent cancer in women, and incidence rates have been rising in European Union (EU) countries over recent decades due in part to a sharp decline in breastfeeding practices. Evidence for a protective association between breastfeeding and the risk of breast cancer at all ages is convincing, and modest protective relationships between breastfeeding and the risk of endometrial and ovarian cancers have been suggested. The reduction in breast cancer risk is estimated at 2% for an increase of 5 months of lifetime breastfeeding. The longer women breastfeed, the more they are protected against breast cancer. In addition, breastfeeding is associated with several health benefits for both the mother and the breastfed child. Taking all this evidence into account, the 4th edition of the European Code against Cancer recommends: “Breastfeeding reduces the mother's cancer risk. If you can, breastfeed your baby”.

There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from 375 incident pancreatic cancer cases and 375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval]=0.41-0.98; Ptrend =0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 =0.60; 95%CI=0.39-0.92; Ptrend =0.02) and docosapentaenoic acid (ORT3-T1 =0.52; 95%CI=0.32-0.85; Ptrend =0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 =3.00; 95%CI=1.13-7.99; Ptrend =0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 =0.37; 95%CI=0.17-0.81; Ptrend =0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 =3.40; 95%CI=1.39-8.34; Ptrend =0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking. This article is protected by copyright. All rights reserved.

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 = 1.54x10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87x10-6 , ptrend = 3.27x10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98x10-9 for highest vs. lowest quintile; p = 1.82x10-10 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. This article is protected by copyright. All rights reserved.

ObjectiveTo examine timing of eating across ten European countries.DesignCross-sectional analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study using standardized 24 h diet recalls collected during 1995–2000. Eleven predefined food consumption occasions were assessed during the recall interview. We present time of consumption of meals and snacks as well as the later:earlier energy intake ratio, with earlier and later intakes defined as 06.00–14.00 and 15.00–24.00 hours, respectively. Type III tests were used to examine associations of sociodemographic, lifestyle and health variables with timing of energy intake.SettingTen Western European countries.SubjectsIn total, 22 985 women and 13 035 men aged 35–74 years (n 36 020).ResultsA south–north gradient was observed for timing of eating, with later consumption of meals and snacks in Mediterranean countries compared with Central and Northern European countries. However, the energy load was reversed, with the later:earlier energy intake ratio ranging from 0·68 (France) to 1·39 (Norway) among women, and from 0·71 (Greece) to 1·35 (the Netherlands) among men. Among women, country, age, education, marital status, smoking, day of recall and season were all independently associated with timing of energy intake (all PPConclusionsWe found pronounced differences in timing of eating across Europe, with later meal timetables but greater energy load earlier during the day in Mediterranean countries compared with Central and Northern European countries.

Source at https://doi.org/10.1002/ijc.31854. Insulin‐like growth factor‐I (IGF‐I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF‐I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF‐I concentrations and melanoma risk. A nested case–control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF‐I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF‐I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF‐I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF‐I measured in adulthood and the risk of melanoma.

Previous in vitro and case–control studies have found an association between the insulin‐like growth factor (IGF)‐axis and bladder cancer risk. Circulating concentrations of IGF‐I have also been found to be associated with an increased risk of several cancer types; however, the relationship between pre‐diagnostic circulating IGF‐I concentrations and bladder cancer has never been studied prospectively. We investigated the association of pre‐diagnostic plasma concentrations of IGF‐I with risk of overall bladder cancer and urothelial cell carcinoma (UCC) in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 843 men and women diagnosed with bladder cancer between 1992 and 2005 were matched with 843 controls by recruitment centre, sex, age at recruitment, date of blood collection, duration of follow‐up, time of day and fasting status at blood collection using an incidence density sampling protocol. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression with adjustment for smoking status. No association was found between pre‐diagnostic circulating IGF‐I concentration and overall bladder cancer risk (adjusted OR for highest versus lowest fourth: 0.91, 95% CI: 0.66–1.24, p trend = 0.40) or UCC (n of cases = 776; 0.91, 0.65–1.26, p trend = 0.40). There was no significant evidence of heterogeneity in the association of IGF‐I with bladder cancer risk by tumour aggressiveness, sex, smoking status, or by time between blood collection and diagnosis (p heterogeneity > 0.05 for all). This first prospective study indicates no evidence of an association between plasma IGF‐I concentrations and bladder cancer risk., What's new? Past prospective studies have shown a positive association between circulating insulin‐like growth factor I (IGF‐I) concentration and colorectal, prostate, and breast cancer risk. However, the association between circulating IGF‐I concentrations and bladder cancer risk remains uncertain. Using a nested‐case control study with 843 bladder cancer cases across 9 European countries, for the first time here the authors examined prospectively the association between pre‐diagnostic circulating IGF‐I concentrations and bladder cancer risk. IGF‐I was not associated with overall risk of bladder cancer or urothelial cell carcinoma. Further prospective data, including on tumour aggressiveness, are required to examine the association in greater detail.

The future of meat Meat consumption is rising annually as human populations grow and affluence increases. Godfray et al. review this trend, which has major negative consequences for land and water use and environmental change. Although meat is a concentrated source of nutrients for low-income families, it also enhances the risks of chronic ill health, such as from colorectal cancer and cardiovascular disease. Changing meat consumption habits is a challenge that requires identifying the complex social factors associated with meat eating and developing policies for effective interventions. Science , this issue p. eaam5324

Pancreatic neuroendocrine neoplasms (pNEN) account for less than 5% of all pancreatic neoplasms and genetic association studies on susceptibility to the disease are limited. We sought to identify possible overlap of genetic susceptibility loci between pancreatic ductal adenocarcinoma (PDAC) and pNEN; therefore, PDAC susceptibility variants (n = 23) from Caucasian genome-wide association studies (GWAS) were genotyped in 369 pNEN cases and 3277 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium to evaluate the odds associated with pNEN risk, disease onset and tumor characteristics. Main effect analyses showed four PDAC susceptibility variants-rs9854771, rs1561927, rs9543325 and rs10919791 to be associated with pNEN risk. Subsequently, only associations with rs9543325, rs10919791 and rs1561927 were noteworthy with false positive report probability (FPRP) tests. Stratified analyses considering age at onset (50-year threshold), showed rs2736098, rs16986825 and rs9854771 to be associated with risk of developing pNEN at a younger age. Stratified analyses also showed some single nucleotide polymorphisms to be associated with different degrees of tumor grade, metastatic potential and functionality. Our results identify known GWAS PDAC susceptibility loci, which may also be involved in sporadic pNEN etiology and suggest that some genetic mechanisms governing pathogenesis of these two entities may be similar, with few of these loci being more influential in younger cases or tumor subtypes.

Background: Coffee and tea are among the most commonly consumed nonalcoholic beverages worldwide, but methodological differences in assessing intake often hamper comparisons across populations. We aimed to (i) describe coffee and tea intakes and (ii) assess their contribution to intakes of selected nutrients in adults across 10 European countries. Method: Between 1995 and 2000, a standardized 24-h dietary recall was conducted among 36,018 men and women from 27 European Prospective Investigation into Cancer and Nutrition (EPIC) study centres. Adjusted arithmetic means of intakes were estimated in grams (=volume) per day by sex and centre. Means of intake across centres were compared by sociodemographic characteristics and lifestyle factors. Results: In women, the mean daily intake of coffee ranged from 94 g/day (~0.6 cups) in Greece to 781 g/day (~4.4 cups) in Aarhus (Denmark), and tea from 14 g/day (~0.1 cups) in Navarra (Spain) to 788 g/day (~4.3 cups) in the UK general population. Similar geographical patterns for mean daily intakes of both coffee and tea were observed in men. Current smokers as compared with those who reported never smoking tended to drink on average up to 500 g/day more coffee and tea combined, but with substantial variation across centres. Other individuals&rsquo, characteristics such as educational attainment or age were less predictive. In all centres, coffee and tea contributed to less than 10% of the energy intake. The greatest contribution to total sugar intakes was observed in Southern European centres (up to ~20%). Conclusion: Coffee and tea intake and their contribution to energy and sugar intake differed greatly among European adults. Variation in consumption was mostly driven by geographical region.

Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. We aimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A–encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 µg/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.

Background This study aimed to investigate the effects of long-term exposure to road traffic noise and air pollution on incident cardiovascular disease (CVD) in three large cohorts: HUNT, EPIC-Oxford and UK Biobank. Methods In pooled complete-case sample of the three cohorts from Norway and the United Kingdom (N = 355,732), 21,081 incident all CVD cases including 5259 ischemic heart disease (IHD) and 2871 cerebrovascular cases were ascertained between baseline (1993–2010) and end of follow-up (2008–2013) through medical record linkage. Annual mean 24-hour weighted road traffic noise (Lden) and air pollution (particulate matter with aerodynamic diameter ≤ 10 μm [PM10], ≤2.5 μm [PM2.5] and nitrogen dioxide [NO2]) exposure at baseline address was modelled using a simplified version of the Common Noise Assessment Methods in Europe (CNOSSOS-EU) and European-wide Land Use Regression models. Individual-level covariate data were harmonised and physically pooled across the three cohorts. Analysis was via Cox proportional hazard model with mutual adjustments for both noise and air pollution and potential confounders. Results No significant associations were found between annual mean Lden and incident CVD, IHD or cerebrovascular disease in the overall population except that the association with incident IHD was significant among current-smokers. In the fully adjusted models including adjustment for Lden, an interquartile range (IQR) higher PM10 (4.1 μg/m3) or PM2.5 (1.4 μg/m3) was associated with a 5.8% (95%CI: 2.5%–9.3%) and 3.7% (95%CI: 0.2%–7.4%) higher risk for all incident CVD respectively. No significant associations were found between NO2 and any of the CVD outcomes. Conclusions We found suggestive evidence of a possible association between road traffic noise and incident IHD, consistent with current literature. Long-term particulate air pollution exposure, even at concentrations below current European air quality standards, was significantly associated with incident CVD.

Body size is an important modifiable risk factor for postmenopausal breast cancer. However, it remains unclear whether direct measures of fat mass are better indicators of risk than anthropometric measures, or whether central adiposity may contribute to risk beyond overall adiposity. We analyzed data from 162,691 postmenopausal women in UK Biobank followed from 2006 to 2014. Body size was measured by trained technicians. Multivariable‐adjusted Cox regression was used to estimate relative risks. Analyses were stratified by age at recruitment, region and socioeconomic status, and adjusted for family history of breast cancer, age at menarche, age at first birth, parity, age at menopause, previous hormone replacement therapy use, smoking, alcohol intake, height, physical activity and ethnicity. We observed 2,913 incident invasive breast cancers during a mean 5.7 years of follow‐up. There was a continuous increase in risk of postmenopausal breast cancer with increasing adiposity, across all measures. The point estimate, comparing women in the top (median 37.6 kg) to bottom (median 17.6 kg) quartile of body fat mass was 1.70 (95% confidence interval 1.52–1.90). The magnitudes of the associations between per SD increase in BMI and body fat mass with breast cancer risk were similar, suggesting impedance measures of fat were not substantially better indicators of risk than anthropometric measures. After adjusting for body fat mass, the associations between anthropometric measures of central adiposity and breast cancer risk were attenuated. The magnitude of risk, across all measures of adiposity, was greater in women who had been postmenopausal for 12 or more years., What's new? Obesity is associated with an increased risk of postmenopausal breast cancer. However, whether direct anaylses of fat mass using bioelectrical impedance measures are better indicators of breast cancer risk than anthropometric measures, such as body mass index (BMI) and waist circumference, remains unclear. In this study, based on data for postmenopausal women obtained from UK Biobank, the authors found that BMI, waist circumference, and direct bioimpedance measures of fat showed similarly strong associations with postmenopausal breast cancer risk. Central adiposity was no longer associated with breast cancer risk after adjusting for overall body fat mass.

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa 1 .

Background: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases.Objectives: First, to summarize the main design features of a prospective case-control study –nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort– on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles.Methods: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models.Results: There were differences among countries in subjects’ characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p’-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB.Conclusions: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects’ characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.

OBJECTIVE:To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. DESIGN:Multicentre case-cohort study. SETTING:A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. PARTICIPANTS:32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. MAIN OUTCOME MEASURES:Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). RESULTS:There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. CONCLUSIONS:Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.

Key Points Question What is the association between body mass index and risk for breast cancer diagnosed before menopause? Finding In this large pooled analysis of data on 758 592 premenopausal women, an inverse association of breast cancer risk with body mass index at 18 through 54 years of age was found, most strongly for body mass index at ages 18 through 24 years. The inverse association was strongest for hormone receptor–positive breast cancer, was evident across the entire distribution of body mass index, and did not materially vary by attained age or other characteristics of women. Meaning Increased adiposity, in particular during early adulthood, may be associated with reductions in the risk of premenopausal breast cancer., This pooled analysis of individual patient data investigates the association of body mass index with subsequent breast cancer risk, in particular by age, attained age, risk factors for breast cancer, and tumor characteristics, in premenopausal women., Importance The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. Objective To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. Design, Setting, and Participants This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017. Exposures Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years. Main Outcomes and Measures Invasive or in situ premenopausal breast cancer. Results Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs

Aims/hypothesis Gene–macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes. Methods We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution. Results No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0–51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined. Conclusions/interpretation Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions.

Accurate diet measurement is challenging and strategies to support researchers in selecting the most appropriate dietary assessment tools (DATs) are required. DIET@NET (DIETary Assessment tools NETwork) partnership aimed to create an online resource that provides guidelines for selecting tools with access to validated DATs. The Nutritools website(1) (www.nutritools.org), was developed using 3 approaches. 1) Creation of Best Practice Guidelines(2), enabling researchers to choose the most appropriate DAT for their work. These were generated using the Delphi method which enabled integration of expert views. 2) Creating an interactive DAT e-library, with the DATs being identified through a systematic review of systematic reviews(3). Bubble charts and summary plots are used to compare DATs. 3) Development of a Food Questionnaire Creator (FQC), an online interface between food tables and the DATs which allows users to create their own food questionnaires. This work was overseen by the DIET@NET partnership. Other useful information includes links to food composition databases and a detailed glossary of terms. Results from the systematic review of reviews generated information for Nutritools. The website includes 127 international validated tools, of which 63 tools were validated in the UK (with 45 validated from year 2000 onwards). The majority (n = 34) of the validated tools were food frequency questionnaires, developed from 1981 to 2016. Numbers of foods included ranged from 8–692 items. Five of the 12 dietary recalls included were web-based. Tools were usually validated against another self-reported dietary assessment method, mainly weighed food diaries. More than 1500 papers with non-UK tools were identified, of these, data on 64 international tools and their validation studies were added to Nutritools. The FQC allows for food questionnaires to be created using data from the UK National Diet and Nutrition Survey (NDNS) Year 6 and the Composition of Foods Integrated Dataset. Results from the NDNS can be used to formulate food questions that capture a large proportion of the nutrients of interest and to inform portion sizes. In conclusion, Nutritools (www.nutritools.org), is an online platform that hosts international validated and interactive DATs. Researchers can use the interactive Best Practice Guidelines and features in the selection of the most appropriate DAT for their study, and the Food Questionnaire Creator to develop their own online food questionnaires. This project was funded by the Medical Research Council (MRC) (ref: MR/L02019X/1). 1. Warthon-Medina M, Hooson J, Hancock N, et al. (2017) The Lancet 390, pS94. 2. Cade JE, Warthon-Medina M, Albar S, et al. (2017) BMC Medicine 15(1), p202. 3. Hooson J, Hancock N, Greenwood DC, et al. (2016) Proc Nutr Soc 75(OCE3).

Objectives To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age. Design Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa. Setting Multiple institutions that were members of international PRACTICAL consortium. Participants All consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men. Main Outcome Measure Prediction with hazard score of age of onset of aggressive cancer in validation set. Results In the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score. Conclusions Polygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa.

Objectives To examine differences in health-related behaviours such as screening or testing for cancer, use of hormone replacement therapy (HRT) and use of other medications in different diet groups. Design We studied 31 260 participants across four diet groups (18 155 meat eaters, 5012 fish eaters, 7179 vegetarians, 914 vegans) in the UK EPIC-Oxford cohort. Information was collected in 5-year (around 2000–2003) or 10-year (around 2007) follow-up questionnaires regarding participation in breast screening, cervical screening, prostate-specific antigen (PSA) testing, use of HRT and use of medications for the past 4 weeks. Using Poisson regression, we estimated the prevalence ratios (PR) for each behaviour across people of different diet groups, using meat eaters as the reference group. Results Compared with meat eaters, vegetarian (PR: 0.94, 95% CI 0.89 to 0.98) and vegan (PR: 0.82, 95% CI 0.71 to 0.95) women reported lower participation in breast screening, and vegetarian men were less likely to report PSA testing (PR: 0.82, 95% CI 0.71 to 0.96). No differences were observed among women for cervical screening. In women, all non-meat-eating groups reported lower use of HRT compared with meat eaters (P heterogeneity

Background: There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer.Methods: We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline.Results: High physical activity was associated with a lower risk of colon cancer: relative risk ≥91 MET-h/week vs Conclusions: Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.

BACKGROUND. ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney, and skin, but has not been evaluated in relation to risk of aggressive prostate cancer. ...

Although it appears biologically plausible for iron to be associated with gastric carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body iron status and gastric cancer risk, we conducted a nested case-control study in the multicentric European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured prediagnostic serum iron, ferritin, transferrin and C-reactive protein, and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by iron metrics were estimated from multivariable conditional logistic regression models. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2 = 0.80, 95% CI = 0.72-0.88; OR10%increment = 0.87, 95% CI = 0.78-0.97, respectively). These associations appear to be restricted to noncardia gastric cancer (ferritin showed a p for heterogeneity = 0.04 and TS had a p for heterogeneity = 0.02), and no differences were found by histological type. TIBC increased risk of overall gastric cancer (OR50 µg/dl = 1.13, 95% CI = 1.02-1.2) and also with noncardia gastric cancer (p for heterogeneity = 0.04). Additional analysis suggests that time between blood draw and gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of gastric cancer related to higher body iron stores as measured by serum iron and ferritin. Further investigation is needed to clarify the role of iron in gastric carcinogenesis.

Previously, a lower risk of colorectal cancer was observed with fruit and vegetable consumption in the European Prospective Investigation into Cancer and Nutrition within a follow-up period of 9 years which was not fully supported by a recent meta-analysis. Therefore, we were interested in the relation with extended follow-up, also focusing on single subtypes and a variety of intake of fruit and vegetables. Fruit and vegetable consumption was assessed at baseline. After an average of 13 years of follow-up, 3,370 participants were diagnosed with colon or rectal cancer. Diet diversity scores were constructed to quantify variety in fruit and vegetable consumption. A lower risk of colon cancer was observed with higher self-reported consumption of fruit and vegetable combined (HR Q4 vs. Q1 0.87, 95% CI 0.75-1.01, p for trend 0.02), but no consistent association was observed for separate consumption of fruits and vegetables. No associations with risk of rectal cancer were observed. The few observed associations for some fruit and vegetable subtypes with colon cancer risk may have been due to chance. Variety in consumption of fruits and vegetables was not associated with a lower risk of colon or rectal cancer. Although a lower risk of colon cancer is suggested with high consumption of fruit and vegetables, this study does not support a clear inverse association between fruit and vegetable consumption and colon or rectal cancer beyond a follow-up of more than 10 years. Attenuation of the risk estimates from dietary changes over time cannot be excluded, but appears unlikely.

BACKGROUND: Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. METHODS: We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS: The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. CONCLUSIONS: Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction.

Alcohol intake has been associated to breast cancer in pre and postmenopausal women; however results are inconclusive regarding tumor hormonal receptor status, and potential modifying factors like age at start drinking. Therefore, we investigated the relation between alcohol intake and the risk of breast cancer using prospective observational data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Up to 334,850 women, aged 35-70 years at baseline, were recruited in ten European countries and followed up an average of 11 years. Alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. The study outcomes were the Hazard ratios (HR) of developing breast cancer according to hormonal receptor status. During 3,670,439 person-years, 11,576 incident breast cancer cases were diagnosed. Alcohol intake was significantly related to breast cancer risk, for each 10 g/day increase in alcohol intake the HR increased by 4.2% (95% CI: 2.7-5.8%). Taking 0 to 5 g/day as reference, alcohol intake of >5 to 15 g/day was related to a 5.9% increase in breast cancer risk (95% CI: 1-11%). Significant increasing trends were observed between alcohol intake and ER+/PR+, ER-/PR-, HER2- and ER-/PR-HER2- tumors. Breast cancer risk was stronger among women who started drinking prior to first full-time pregnancy. Overall, our results confirm the association between alcohol intake and both hormone receptor positive and hormone receptor negative breast tumors, suggesting that timing of exposure to alcohol drinking may affect the risk. Therefore, women should be advised to control their alcohol consumption.

Purpose Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones. Patients and Methods Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes. Results Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men. Conclusion Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers.

A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio=0.85; 95% confidence interval=0.80-0.90, p=8.3 × 10-8). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r2=0.07, D′=0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p=3.0 × 10-5), rs4583925 (p=4.0 × 10-5) and rs2735948 (p=5.0 × 10-5). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants. What's new? Most pancreatic cancer patients do not survive long after diagnosis, and, so far, there are not many genetic markers to help screen for the disease. In search of genetic predictors of pancreatic cancer, the authors zoomed in on a region linked to susceptibility to the disease. They measured the frequency of different variants of two genes, telomerase reverse transcriptase and telomerase RNA component, among thousands of pancreatic cancer patients and controls. They identified several variants of the TERT gene that indicate a boosted pancreatic cancer risk, and which may develop into useful prognostic tools.

Several modifiable lifestyle factors, including smoking, alcohol, certain dietary factors and weight are independently associated with gastric cancer (GC); however, their combined impact on GC risk is unknown. We constructed a healthy lifestyle index to investigate the joint influence of these behaviors on GC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The analysis included 461,550 participants (662 first incident GC cases) with a mean follow-up of 11.4 years. A healthy lifestyle index was constructed, assigning 1 point for each healthy behavior related to smoking status, alcohol consumption and diet quality (represented by the Mediterranean diet) for assessing overall GC and also body mass index for cardia GC and 0 points otherwise. Risk of GC was calculated using Cox proportional hazards regression models while adjusting for relevant confounders. The highest versus lowest score in the healthy lifestyle index was associated with a significant lower risk of GC, by 51% overall (HR 0.49 95% CI 0.35, 0.70), by 77% for cardia GC (HR 0.23 95% CI 0.08, 0.68) and by 47% for noncardia GC (HR 0.53 (95% CI 0.32, 0.87), p-trends

General obesity, as reflected by BMI, is an established risk factor for esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia adenocarcinoma (GCC) and appears unrelated to gastric non-cardia adenocarcinoma (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC), relates to these cancers remains largely unexplored. Using measured anthropometric data from 391,456 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow-up, we comprehensively assessed the association of anthropometric measures with risk of EAC, GCC and GNCC using multivariable proportional hazards regression. One hundred twenty-four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual adjustment, BMI was unrelated to EAC, while WC showed a strong positive association (highest vs. lowest quintile HR = 1.19; 95% CI, 0.63-2.22 and HR = 3.76; 1.72-8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HR = 0.35; 0.18-0.68, and HR=4.10; 1.94-8.63, respectively). BMI was not associated with GCC or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more strongly after adjustment for HC (highest vs. lowest quintile HR = 1.91; 1.09-3.37, and HR = 2.23; 1.28-3.90, respectively). Our study demonstrates that abdominal, rather than general, obesity is an indisputable risk factor for EAC and also provides evidence for a protective effect of gluteofemoral (subcutaneous) adipose tissue in EAC. Our study further shows that general obesity is not a risk factor for GCC and GNCC, while the role of abdominal obesity in GCC needs further investigation.

Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 × 10(-14)), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 × 10(-8)) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 × 10(-8)). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 × 10(-9)), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.

Prostate cancer is the second most common malignancy and the sixth most common cause of cancer death for men worldwide. The highest incidence and mortality rates are in populations that originated in Africa, such as African Americans. Rates are also high in Western countries and generally low in East and South Asia. Incidence rates are increasing in some countries which until recently had low rates, but are not changing much in countries which already have high rates. The only well-established risk factors are increasing age, African ancestry, family history of the disease, and certain genetic factors, none of which is modifiable. Many potential risk factors have been investigated in epidemiological studies and randomized trials. Observational studies have shown that prostate cancer risk is positively associated with the plasma concentration of insulin-like growth factor-I, but is not strongly associated with testosterone or other sex hormones. Studies of nutritional factors suggest that risk may be higher in men with a high intake of animal foods and dairy products, but this relationship is not clear enough to be considered as established. Some studies of other nutritional factors such as fat, lycopene and other carotenoids, vitamin D, vitamin E and selenium have suggested possible associations, but overall do not show any clear relationships. Research on other possible risk factors has shown a small positive association of risk with height, but little association with obesity, smoking or alcohol intake, and evidence on sexual behaviour and sexually transmitted infections is inconclusive. Further research is needed, particularly to determine whether potential risk factors may be related more to aggressive than to indolent prostate cancer.

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

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

Background and Aims: Population-based prospective cohort studies investigating fibre intake and development of inflammatory bowel disease are lacking. Our aim was to investigate the association between fibre intake and the development of Crohn's disease [CD] and ulcerative colitis [UC] in a large European population.Methods: In total, 401326 participants, aged 20-80 years, were recruited in eight countries in Europe between 1991 and 1998. At baseline, fibre intake [total fibres, fibres from fruit, vegetables and cereals] was recorded using food frequency questionnaires. The cohort was monitored for the development of inflammatory bowel disease. Each case was matched with four controls and odds ratios [ORs] for the exposures were calculated using conditional logistic regression. Sensitivity analyses according to smoking status were computed.Results: In total, 104 and 221 participants developed incident CD and UC, respectively. For both CD and UC, there were no statistically significant associations with either quartiles, or trends across quartiles, for total fibre or any of the individual sources. The associations were not affected by adjusting for smoking and energy intake. Stratification according to smoking status showed null findings apart from an inverse association with cereal fibre and CD in non-smokers [Quartile 4 vs 1 OR = 0.12, 95% confidence interval = 0.02-0.75, p = 0.023, OR trend across quartiles = 0.50, 95% confidence interval = 0.29-0.86, p = 0.017].Conclusion: The results do not support the hypothesis that dietary fibre is involved in the aetiology of UC, although future work should investigate whether there may be a protective effect of specific types of fibre according to smoking status in CD.

Background: Prostate cancer is the most common cancer in British men but its aetiology is not well understood. We aimed to identify risk factors for prostate cancer in British males. Methods: We studied 219 335 men from the UK Biobank study who were free from cancer at baseline. Exposure data were collected at recruitment. Prostate cancer risk by the different exposures was estimated using multivariable-adjusted Cox proportional hazards models. Results: In all, 4575 incident cases of prostate cancer occurred during 5.6 years of follow-up. Prostate cancer risk was positively associated with the following: black ethnicity (hazard ratio black vs white=2.61, 95% confidence interval=2.10–3.24); having ever had a prostate-specific antigen test (1.31, 1.23–1.40); being diagnosed with an enlarged prostate (1.54, 1.38–1.71); and having a family history of prostate cancer (1.94, 1.77–2.13). Conversely, Asian ethnicity (Asian vs white hazard ratio=0.62, 0.47–0.83), excess adiposity (body mass index (⩾35 vs

BACKGROUND: Oxidative stress may be involved in the aetiology of inflammatory bowel disease and whether dietary polyphenols, which possess antioxidants properties, prevent its development is unknown.METHODS: A total of 401,326 men and women aged 20 to 80 years from 8 countries were recruited between 1991 and 1998 and at baseline completed validated food frequency questionnaires. Dietary polyphenol intake was measured using Phenol-Explorer, a database with information on the content of 502 polyphenols. Incident cases of Crohn's diseases (CD) and ulcerative colitis (UC) were identified during the follow-up period of up to December 2010. A nested case-control study using conditional logistic regression estimated the odds ratios (ORs), and 95% confidence intervals, for polyphenol intake (categories based on quartiles) and developing CD or UC.RESULTS: In total, 110 CD (73% women) and 244 UC (57% women) cases were identified and matched to 440 and 976 controls, respectively. Total polyphenol intake was not associated with CD (P trend = 0.17) or UC (P trend = 0.16). For flavones and CD, there were reduced odds for all quartiles, which were statistically significant for the third (OR3rd versus 1st quartile = 0.33; 95% confidence interval, 0.15-0.69) and there was an inverse trend across quartiles (P = 0.03). Similarly, for resveratrol, there was an inverse association with CD (OR4th versus 1st quartile = 0.40; 95% confidence interval, 0.20-0.82) with an inverse trend across quartiles (P = 0.02). No significant associations between subtypes of polyphenols and UC were found. Effect modification by smoking in CD was documented with borderline statistical significance.CONCLUSIONS: The data supports a potential role of flavones and resveratrol in the risk of developing CD; future aetiological studies should investigate these dietary components and further examine the potential for residual confounding.

The underlying goal of most cancer epidemiology is to reduce the cancer burden, and the current volume of Epidemiologic Reviews comprises eleven reviews across a range of topics including cancer surveillance, risk factor identification, and the evaluation of approaches to care of patients and predictors of prognosis and death.

BACKGROUND: The consumption of sweet beverages has been associated with greater risk of type 2 diabetes and obesity, which may be involved in the development of pancreatic cancer. Therefore, it has been hypothesized that sweet beverages may increase pancreatic cancer risk as well.OBJECTIVE: We examined the association between sweet-beverage consumption (including total, sugar-sweetened, and artificially sweetened soft drink and juice and nectar consumption) and pancreatic cancer risk.DESIGN: The study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 477,199 participants (70.2% women) with a mean age of 51 y at baseline were included, and 865 exocrine pancreatic cancers were diagnosed after a median follow-up of 11.60 y (IQR: 10.10-12.60 y). Sweet-beverage consumption was assessed with the use of validated dietary questionnaires at baseline. HRs and 95% CIs were obtained with the use of multivariable Cox regression models that were stratified by age, sex, and center and adjusted for educational level, physical activity, smoking status, and alcohol consumption. Associations with total soft-drink consumption were adjusted for juice and nectar consumption and vice versa.RESULTS: Total soft-drink consumption (HR per 100 g/d: 1.03; 95% CI: 0.99, 1.07), sugar-sweetened soft-drink consumption (HR per 100 g/d: 1.02; 95% CI: 0.97, 1.08), and artificially sweetened soft-drink consumption (HR per 100 g/d: 1.04; 95% CI: 0.98, 1.10) were not associated with pancreatic cancer risk. Juice and nectar consumption was inversely associated with pancreatic cancer risk (HR per 100 g/d: 0.91; 95% CI: 0.84, 0.99); this association remained statistically significant after adjustment for body size, type 2 diabetes, and energy intake.CONCLUSIONS: Soft-drink consumption does not seem to be associated with pancreatic cancer risk. Juice and nectar consumption might be associated with a modest decreased pancreatic cancer risk. Additional studies with specific information on juice and nectar subtypes are warranted to clarify these results.

Objectives The objective of this study was to examine if, in the general population, physically active adults have less body fat after taking body mass index (BMI) into account. Design A cross-sectional analysis of participants recruited into UK Biobank in 2006–2010. Setting UK Biobank assessment centres throughout the UK. Participants 119 230 men and 140 578 women aged 40–69 years, with complete physical activity information, and without a self-reported long-term illness, disability or infirmity. Exposures Physical activity measured as excess metabolic equivalent (MET)-hours per week, estimated from a combination of walking, and moderate and vigorous physical activity. BMI from measured height and weight. Main outcome measure Body fat percentage estimated from bioimpedance. Results BMI and body fat percentage were highly correlated (r=0.85 in women; r=0.79 in men), and both were inversely associated with physical activity. Compared with