Publications
198 results found
Ward HA, Murphy N, Weiderpass E, et al., 2019, Gallstones and incident colorectal cancer in a large pan-European cohort study, International Journal of Cancer, Vol: 145, Pages: 1510-1516, ISSN: 0020-7136
Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self-reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow-up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR = 1.14, 95%CI 0.99-1.31, p = 0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR = 0.81, 95%CI 0.63-1.04, p = 0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex.
Mullee A, Romaguera D, Pearson-Stuttard J, et al., 2019, Association between soft drink consumption and mortality in 10 European countries., JAMA Internal Medicine, ISSN: 2168-6106
Importance: Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date. Objective: To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality. Design, Setting, and Participants: This population-based cohort study involved participants (n = 451 743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018. Exposure: Consumption of total, sugar-sweetened, and artificially sweetened soft drinks. Main Outcomes and Measures: Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors. Results: In total, 521 330 individuals were enrolled. Of this total, 451 743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321 081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41 693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of <1 glass per month) of total soft drinks (hazard ratio [HR], 1.17; 95% CI, 1.11-1.22; P < .001), sugar-sweetened soft drinks (HR, 1.08;
Mori N, Sawada N, Iwasaki M, et al., 2019, Circulating sex hormone levels and colorectal cancer risk in Japanese postmenopausal women: The JPHC nested case-control study, INTERNATIONAL JOURNAL OF CANCER, Vol: 145, Pages: 1238-1244, ISSN: 0020-7136
- Author Web Link
- Cite
- Citations: 20
Butt J, Jenab M, Pawlita M, et al., 2019, Antibody responses to fusobacterium nucleatum proteins in prediagnostic blood samples are not associated with risk of developing colorectal cancer, Cancer Epidemiology, Biomarkers and Prevention, Vol: 28, Pages: 1552-1555, ISSN: 1055-9965
Background: There is a lack of prospective data on the potential association of Fusobacterium nucleatum (F. nucleatum) and colorectal cancer risk. In this study, we assessed whether antibody responses to F. nucleatum are associated with colorectal cancer risk in prediagnostic serum samples in the European Prospective Investigation into Nutrition and Cancer (EPIC) cohort.Methods: We applied a multiplex serology assay to simultaneously measure antibody responses to 11 F. nucleatum antigens in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI).Results: We observed neither a statistically significant colorectal cancer risk association for antibodies to individual F. nucleatum proteins nor for combined positivity to any of the 11 proteins (OR, 0.81; 95% CI, 0.62–1.06).Conclusions: Antibody responses to F. nucleatum proteins in prediagnostic serum samples from a subset of colorectal cancer cases and matched controls within the EPIC study were not associated with colorectal cancer risk.Impact: Our findings in prospectively ascertained serum samples contradict the existing literature on the association of F. nucleatum with colorectal cancer risk. Future prospective studies, specifically detecting F. nucleatum in stool or tissue biopsies, are needed to complement our findings.
Kühn T, Stepien M, López-Nogueroles M, et al., 2019, Pre-diagnostic plasma bile acid levels and colon cancer risk: A prospective study, Journal of the National Cancer Institute, Vol: 112, Pages: 516-524, ISSN: 0027-8874
BACKGROUND: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans. METHODS: Associations between pre-diagnostic plasma levels of 17 primary, secondary and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations. RESULTS: Positive associations were observed between colon cancer risk and plasma levels of 7 conjugated bile acid metabolites, i.e. primary bile acids glycocholic acid (ORQuartile 4 vs. Quartile 1=2.22,95 % confidence interval[CI]=1.52, 3.26), taurocholic acid (OR = 1.78, 95%CI=1.23, 2.58), glycochenodeoxycholic acid (OR = 1.68, 95%CI=1.13, 2.48), taurochenodeoxycholic acid (OR = 1.62, 95%CI=1.11-2.36), and glycohyocholic acid (OR = 1.65, 95%CI=1.13, 2.40) as well as the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95%CI=1.12, 2.54) and taurodeoxycholic acid (OR = 1.54, 95%CI=1.02, 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk. CONCLUSIONS: This prospective study showed that pre-diagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.
Fedirko V, Mandle HB, Zhu W, et al., 2019, Vitamin D-related genes, blood vitamin D levels and colorectal cancer risk in western European populations., Nutrients, Vol: 11, Pages: 1-24, ISSN: 2072-6643
Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor β (TGFβ) signaling was associated with CRC risk (P ≤ 0.001), with most statistically significant genes being SMAD7 (PBH = 0.008) and SMAD3 (PBH = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.
Dimou N, Papadimitriou N, Gill D, et al., 2019, Sex hormone binding globulin and risk of breast cancer: a Mendelian randomization study, International Journal of Epidemiology, Vol: 48, Pages: 807-816, ISSN: 1464-3685
BackgroundThere are observational data suggesting an inverse association between circulating concentrations of sex hormone binding globulin (SHBG) and risk of postmenopausal breast cancer. However, causality is uncertain and few studies have investigated this association by tumour receptor status. We aimed to investigate these associations under the causal framework of Mendelian randomization (MR).MethodsWe used summary association estimates extracted from published genome-wide association study (GWAS) meta-analyses for SHBG and breast cancer, to perform two-sample MR analyses. Summary statistics were available for 122 977 overall breast cancer cases, of which 69 501 were estrogen receptor positive (ER+ve) and 21 468 were ER-ve, and 105 974 controls. To control for potential horizontal pleiotropy acting via body mass index (BMI), we performed multivariable inverse-variance weighted (IVW) MR as the main analysis, with the robustness of this approach further tested in sensitivity analyses.ResultsThe multivariable IVW MR analysis indicated a lower risk of overall (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.90, 0.98; P: 0.006) and ER+ve (OR: 0.92; 95% CI: 0.87, 0.97; P: 0.003) breast cancer, and a higher risk of ER-ve disease (OR: 1.09; 95% CI: 1.00, 1.18; P: 0.047) per 25 nmol/L higher SHBG levels. Sensitivity analyses were consistent with the findings of the main analysis.ConclusionsWe corroborated the previous literature evidence coming from observational studies for a potentially causal inverse association between SHBG concentrations and risk of ER+ve breast cancer, but our findings also suggested a potential novel positive association with ER-ve disease that warrants further investigation, given the low prior probability of being true.
Cirera L, Maria Huerta J, Dolores Chirlaque M, et al., 2019, Socioeconomic effect of education on pancreatic cancer risk in Western Europe: an update on the EPIC cohorts study, Cancer Epidemiology, Biomarkers and Prevention, Vol: 28, Pages: 1089-1092, ISSN: 1055-9965
Background: To analyze the potential effect of social inequality on pancreatic cancer risk in Western Europe, by reassessing the association within the European Prospective Investigation into Cancer and Nutrition (EPIC) Study, including a larger number of cases and an extended follow-up.Methods: Data on highest education attained were gathered for 459,170 participants (70% women) from 10 European countries. A relative index of inequality (RII) based on adult education was calculated for comparability across countries and generations. Cox regression models were applied to estimate relative inequality in pancreatic cancer risk, stratifying by age, gender, and center, and adjusting for known pancreatic cancer risk factors.Results: A total of 1,223 incident pancreatic cancer cases were included after a mean follow-up of 13.9 (±4.0) years. An inverse social trend was found in models adjusted for age, sex, and center for both sexes [HR of RII, 1.27; 95% confidence interval (CI), 1.02–1.59], which was also significant among women (HR, 1.42; 95% CI, 1.05–1.92). Further adjusting by smoking intensity, alcohol consumption, body mass index, prevalent diabetes, and physical activity led to an attenuation of the RII risk and loss of statistical significance.Conclusions: The present reanalysis does not sustain the existence of an independent social inequality influence on pancreatic cancer risk in Western European women and men, using an index based on adult education, the most relevant social indicator linked to individual lifestyles, in a context of very low pancreatic cancer survival from (quasi) universal public health systems.Impact: The results do not support an association between education and risk of pancreatic cancer.
Murphy N, Ward HA, Jenab M, et al., 2019, Heterogeneity of colorectal cancer risk factors by anatomical subsite in 10 European countries: a multinational cohort study, Clinical Gastroenterology and Hepatology, Vol: 17, Pages: 1323-1331.e6, ISSN: 1542-3565
Background and AimsColorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most have been of insufficient size to identify heterogeneous associations with precision.MethodsIn the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumors at different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests.ResultsAfter 14.9 years (median) follow-up of 521,330 men and women, 6,291 colorectal cancer cases occurred. Physical activity was inversely related to proximal colon and distal colon cancer, but not to rectal cancer (P-heterogeneity=0.03). Height was positively associated with proximal and distal colon cancer only, but not rectal cancer (P-heterogeneity=0.0001). For men, but not women, heterogeneous relationships were observed for body mass index (P-heterogeneity=0.008) and waist circumference (P-heterogeneity=0.03), with weaker positive associations found for rectal cancer, compared to proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P-heterogeneity=0.05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors.ConclusionsThe physical activity, anthropometry, and smoking relationships with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.
Pagoni P, Dimou NL, Murphy N, et al., 2019, Using Mendelian randomisation to assess causality in observational studies, EVIDENCE-BASED MENTAL HEALTH, Vol: 22, Pages: 67-71, ISSN: 1362-0347
- Author Web Link
- Cite
- Citations: 22
Fedirko V, Jenab M, Meplan C, et al., 2019, Association of sSelenoprotein and selenium pathway genotypes with risk of colorectal cancer and interaction with selenium status, Nutrients, Vol: 11, Pages: 1-19, ISSN: 2072-6643
Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10; PACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.
Smith T, Muller D, Moons K, et al., 2019, Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: A systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies, Gut, Vol: 68, Pages: 672-683, ISSN: 0017-5749
ObjectiveTo systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts.DesignModels were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed versus predicted probability).ResultsThe systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41,587 to 396,515, and the number of cases from 115 to 1,781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95%CI 0.68-0.72) in the UK Biobank and 0.71 (0.67-0.74) in EPIC. ConclusionSeveral of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained.
Costas L, Lujan-Barroso L, Benavente Y, et al., 2019, Reproductive factors, exogenous hormone use, and risk of B-cell non-Hodgkin lymphoma in a cohort of women from the European prospective investigation into cancer and nutrition, American Journal of Epidemiology, Vol: 188, Pages: 274-281, ISSN: 1476-6256
The role of hormonal factors in the etiology of lymphoid neoplasms remains unclear. Previous studies have yielded conflicting results, have lacked sufficient statistical power to assess many lymphoma subtypes, or have lacked detailed information on relevant exposures. Within the European Prospective Investigation Into Cancer and Nutrition cohort, we analyzed comprehensive data on reproductive factors and exogenous hormone use collected at baseline (1992-2000) among 343,458 women, including data on 1,427 incident cases of B-cell non-Hodgkin lymphoma (NHL) and its major subtypes identified after a mean follow-up period of 14 years (through 2015). We estimated hazard ratios and 95% confidence intervals using multivariable proportional hazards modeling. Overall, we observed no statistically significant associations between parity, age at first birth, breastfeeding, oral contraceptive use, or ever use of postmenopausal hormone therapy and risk of B-cell NHL or its subtypes. Women who had undergone surgical menopause had a 51% higher risk of B-cell NHL (based on 67 cases) than women with natural menopause (hazard ratio = 1.51, 95% confidence interval: 1.17, 1.94). Given that this result may have been due to chance, our results provide little support for the hypothesis that sex hormones play a role in lymphomagenesis.
Schmit SL, Edlund CK, Schumacher FR, et al., 2019, Novel Common Genetic Susceptibility Loci for Colorectal Cancer, JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, Vol: 111, Pages: 146-157, ISSN: 0027-8874
- Author Web Link
- Cite
- Citations: 97
Sen A, Papadimitriou N, Lagiou P, et al., 2019, Coffee and tea consumption and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition, International Journal of Cancer, Vol: 144, Pages: 240-250, ISSN: 0020-7136
The epidemiological evidence regarding the association of coffee and tea consumption with prostate cancer risk is inconclusive, and few cohort studies have assessed these associations by disease stage and grade. We examined the associations of coffee (total, caffeinated and decaffeinated) and tea intake with prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 142,196 men, 7,036 incident prostate cancer cases were diagnosed over 14 years of follow-up. Data on coffee and tea consumption were collected through validated country-specific food questionnaires at baseline. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI). Models were stratified by center and age, and adjusted for anthropometric, lifestyle and dietary factors. Median coffee and tea intake were 375 mL/day and 106 mL/day, respectively, but large variations existed by country. Comparing the highest (median of 855 mL/day) versus lowest (median of 103 mL/day) consumers of coffee and tea (450 mL/day versus 12 mL/day) the HRs were 1.02 (95% CI, 0.94-1.09) and 0.98 (95% CI, 0.90-1.07) for risk of total prostate cancer, and 0.97 (95% CI, 0.79-1.21) and 0.89 (95% CI, 0.70-1.13) for risk of fatal disease, respectively. No evidence of association was seen for consumption of total, caffeinated or decaffeinated coffee or tea and risk of total prostate cancer or cancer by stage, grade or fatality in this large cohort. Further investigations are needed to clarify whether an association exists by different preparations or by concentrations and constituents of these beverages. This article is protected by copyright. All rights reserved.
Huyghe JR, Bien SA, Harrison TA, et al., 2019, Discovery of common and rare genetic risk variants for colorectal cancer, Nature Genetics, Vol: 51, Pages: 76-87, ISSN: 1061-4036
To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10−8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
Murphy N, Jenab M, Gunter MJ, 2018, Adiposity and gastrointestinal cancers: epidemiology, mechanisms and future directions, NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, Vol: 15, Pages: 659-670, ISSN: 1759-5045
- Author Web Link
- Cite
- Citations: 104
Cairat M, Fournier A, Murphy N, et al., 2018, Nonsteroidal anti-inflammatory drug use and breast cancer risk in a European prospective cohort study, International Journal of Cancer, Vol: 143, Pages: 1688-1695, ISSN: 0020-7136
Experimental studies have shown a protective effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer development. However, results from epidemiological cohort studies are less consistent. Our objective was to assess the association between NSAID use and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Self-reported information on NSAID use at baseline has been collected in five EPIC countries. Multivariable Cox regression models were used to estimate hazard ratios for the association of NSAID use with breast cancer incidence with adjustment for potential confounders. We also assessed effect modification by breast cancer risk factors and examined the associations within specific breast cancer subtypes. Among the 140,981 women included in the analysis, 7% were regularly using NSAIDs at baseline. During a median follow-up time period of 13 years, 7,379 incident breast cancer cases were diagnosed (816 in situ and 6,563 invasive). There were no statistically significant associations between NSAID use and breast cancer risk, overall and by subtypes. However, a statistically significant interaction was observed for invasive cases between NSAID use and ever use of menopausal hormonal therapy (MHT) among postmenopausal women [MHT users: HRNSAID use =0.84 (0.73 - 0.96); non MHT users: HRNSAID use = 1.08 (0.93 - 1.25); Pinteraction = 0.05]. Our results indicate potential effect modification of MHT use on the association between use of NSAIDs and breast cancer risk which deserves in-depth investigation in studies with accurate data on both NSAID and MHT use.
Murphy N, Achaintre D, Zamora-Ros R, et al., 2018, A prospective evaluation of plasma polyphenol levels and colon cancer risk, International Journal of Cancer, Vol: 143, Pages: 1620-1631, ISSN: 0020-7136
Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre-diagnostic plasma polyphenols and colon cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (qvalues ) was computed to control for multiple comparisons. All statistical tests were two-sided. After false discovery rate correction and in continuous log2 -transformed multivariable models, equol (odds ratio [OR] per log2 -value, 0.86, 95% confidence interval [95%CI]=0.79-0.93; qvalue =0.01) and homovanillic acid (OR per log2 -value, 1.46, 95%CI=1.16-1.84; qvalue =0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR=0.61, 95%CI=0.41-0.91, ptrend =0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR=1.72, 95%CI=1.17-2.53, ptrend <0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk, of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis. This article is protected by copyright. All rights reserved.
Deschasaux M, Huybrechts I, Murphy N, et al., 2018, Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: results from the EPIC prospective cohort study, PLoS Medicine, Vol: 15, ISSN: 1549-1277
BackgroundHelping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations.Methods and findingsThis prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992–2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus Q1 = 1.07; 95% CI 1.03–1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all
Butt J, Jenab M, Willhauck-Fleckenstein M, et al., 2018, Prospective evaluation of antibody response to Streptococcus gallolyticus and risk of colorectal cancer, International Journal of Cancer, Vol: 143, Pages: 245-252, ISSN: 0020-7136
The gut microbiome is increasingly implicated in colorectal cancer (CRC) development. A subgroup of patients diagnosed with CRC show high antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG). However, it is unclear whether the association is also present pre‐diagnostically. We assessed the association of antibody responses to SGG proteins in pre‐diagnostic serum samples with CRC risk in a case–control study nested within a prospective cohort. Pre‐diagnostic serum samples from 485 first incident CRC cases (mean time between blood draw and diagnosis 3.4 years) and 485 matched controls in the European Prospective Investigation into Nutrition and Cancer (EPIC) study were analyzed for antibody responses to 11 SGG proteins using multiplex serology. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable conditional logistic regression models. Antibody positivity for any of the 11 SGG proteins was significantly associated with CRC risk with 56% positive controls compared to 63% positive cases (OR: 1.36, 95% CI: 1.04–1.77). Positivity for two or more proteins of a previously identified SGG 6‐marker panel with greater CRC‐specificity was also observed among 9% of controls compared to 17% of CRC cases, corresponding to a significantly increased CRC risk (OR: 2.17, 95% CI: 1.44–3.27). In this prospective nested case–control study, we observed a positive association between antibody responses to SGG and CRC development in serum samples taken before evident disease onset. Further work is required to establish the possibly etiological significance of these observations and whether SGG serology may be applicable for CRC risk stratification.
Perez-Cornago A, Appleby PN, Boeing H, et al., 2018, Circulating isoflavone and lignan concentrations and prostate cancer risk: A meta-analysis of individual participant data from seven prospective studies including 2828 cases and 5593 controls, International Journal of Cancer, Vol: 143, Pages: 2677-2686, ISSN: 0020-7136
Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between pre-diagnostic circulating concentrations of isoflavones (genistein, daidzein, equol) and lignans (enterolactone and enterodiol) and the risk of prostate cancer. Individual participant data were available from seven prospective studies (two studies from Japan with 241 cases and 503 controls and five studies from Europe with 2,828 cases and 5,593 controls). Because of the large difference in circulating isoflavone concentrations between Japan and Europe, analyses of the associations of isoflavone concentrations and prostate cancer risk were evaluated separately. Prostate cancer risk by study-specific fourths of circulating concentrations of each phytoestrogen was estimated using multivariable-adjusted conditional logistic regression. In men from Japan, those with high compared to low circulating equol concentrations had a lower risk of prostate cancer (multivariable-adjusted OR for upper quartile [Q4] vs Q1=0.61, 95% confidence interval [CI]=0.39-0.97), although there was no significant trend (OR per 75 percentile increase=0.69, 95 CI=0.46-1.05, Ptrend =0.085); Genistein and daidzein concentrations were not significantly associated with risk (ORs for Q4 vs Q1=0.70, 0.45-1.10, and 0.71, 0.45-1.12, respectively). In men from Europe, circulating concentrations of genistein, daidzein and equol were not associated with risk. Circulating lignan concentrations were not associated with the risk of prostate cancer, overall or by disease aggressiveness or time to diagnosis. There was no strong evidence that pre-diagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high.
Morris JS, Bradbury KE, Cross AJ, et al., 2018, Physical activity, sedentary behaviour and colorectal cancer risk in the UK Biobank, British Journal of Cancer, Vol: 118, Pages: 920-929, ISSN: 0007-0920
BACKGROUND: Observational studies have shown that physical activity levels are inversely, and sedentary behaviours are positively, associated with colorectal cancer risk; however, whether these relationships are consistent across anatomical subsites is uncertain. METHODS: We investigated the associations between colorectal cancer and physical activity (metabolic equivalents (METs)-hours per week), and indicators of sedentary behaviour (television watching time and time spent using computers) among 430 584 men and women enroled in the UK Biobank. Multivariable hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. RESULTS: After a median follow-up time of 5.6 years, 2391 incident colorectal cancer cases were recorded. High (⩾60-MET-hours per week) vs low (<10-MET-hours per week) total physical activity was associated with a lower colon cancer risk (HR=0.84, 95% CI: 0.72-0.98; p-trend=0.04), with comparable relationships observed for proximal and distal colon tumours, but no association for rectal cancer. Higher levels of television watching time were associated with greater colon cancer risk (HR for ⩾5 h per day vs ⩽1 h per day=1.32, 95% CI: 1.04-1.68; p-trend=0.007). Time spent using computers was not associated with colorectal cancer risk. CONCLUSIONS: Higher levels of physical activity were associated with lower colon cancer risk, with no heterogeneity by colonic subsite. Sedentary behaviour (television watching) was associated with elevated colon cancer risk.British Journal of Cancer advance online publication, 8 March 2018; doi:10.1038/bjc.2017.496 www.bjcancer.com.
Zhou B, Bentham J, Di Cesare M, et al., 2018, Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: a pooled analysis of 1,018 population-based measurement studies with 88.6 million participants, International Journal of Epidemiology, Vol: 47, Pages: 872-883i, ISSN: 1464-3685
BackgroundChange in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure.MethodsWe pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20–29 years to 70–79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure.ResultsIn 2005–16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association.ConclusionsChange in mean bloo
Li SX, Imamura F, Schulze MB, et al., 2018, Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries, Diabetologia, Vol: 61, Pages: 1325-1332, ISSN: 0012-186X
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 (I2range 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.
van Roekel EH, Trijsburg L, Assi N, et al., 2018, Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort, Nutrients, Vol: 10, ISSN: 2072-6643
Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions.
Hosgood HD, Gunter MJ, Murphy N, et al., 2018, The Relation of Obesity-Related Hormonal and Cytokine Levels with Multiple Myeloma and Non-Hodgkin Lymphoma, FRONTIERS IN ONCOLOGY, Vol: 8, ISSN: 2234-943X
- Author Web Link
- Cite
- Citations: 25
Gunter MJ, Murphy N, Muller DC, et al., 2018, Coffee Drinking and Mortality in 10 European Countries Response, ANNALS OF INTERNAL MEDICINE, Vol: 168, Pages: 380-381, ISSN: 0003-4819
Ortega LS, Bradbury KE, Cross AJ, et al., 2017, A prospective investigation of body size, body fat composition and colorectal cancer risk in the UK biobank, Scientific Reports, Vol: 7, ISSN: 2045-2322
Obesity has been consistently associated with a greater colorectal cancer risk, but this relationship is weaker among women. In the UK Biobank, we investigated the associations between body size (body mass index [BMI], height, waist circumference, and waist-to-hip ratio) and body fat composition (total body fat percentage and trunk fat percentage) measurements with colorectal cancer risk among 472,526 men and women followed for 5.6 years on average. Multivariable hazard ratios (HRs) and 95% confidence intervals (95%CI) for developing colorectal cancer (2,636 incident cases) were estimated using Cox proportional hazards models. Among men, when the highest and lowest fifths were compared, BMI (HR = 1.35, 95%CI: 1.13–1.61; Ptrend < 0.0001), waist circumference (HR = 1.66, 95%CI: 1.39–1.99; Ptrend < 0.0001), waist-to-hip ratio (HR = 1.58, 95%CI: 1.31–1.91; Ptrend < 0.0001), total body fat percentage (HR = 1.27, 95%CI: 1.06–1.53; Ptrend = 0.002), and trunk fat percentage (HR = 1.31, 95%CI: 1.09–1.58; Ptrend = 0.002) were associated with greater colorectal cancer risk. For women, only waist-to-hip ratio (HR for highest versus lowest fifth = 1.33, 95%CI: 1.08–1.65; Ptrend = 0.005) was positively associated with colorectal cancer risk. Greater body size (overall and abdominal adiposity) was positively associated with colorectal cancer development in men. For women, abdominal adiposity, rather than overall body size, was associated with a greater colorectal cancer risk.
van Duijnhoven FJB, Jenab M, Hveem K, et al., 2017, Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations, International Journal of Cancer, Vol: 142, Pages: 1189-1201, ISSN: 0020-7136
Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow-up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42–1.20); 0.94 (0.72–1.22); 1.12 (0.82–1.53) and 1.26 (0.79–2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.