Publications (30)192.86 Total impact
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Article: Body Mass Index and the Risk for Crohn's Disease and Ulcerative Colitis: Data From a European Prospective Cohort Study (The IBD in EPIC Study).
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ABSTRACT: OBJECTIVES:Obesity is associated with a proinflammatory state that may be involved in the etiology of inflammatory bowel disease (IBD), for which there are plausible biological mechanisms. Our aim was to perform the first prospective cohort study investigating if there is an association between obesity and the development of incident IBD.METHODS:A total of 300,724 participants were recruited into the European Prospective Investigation into Cancer and Nutrition study. At recruitment, anthropometric measurements of height and weight plus physical activity and total energy intake from validated questionnaires were recorded. The cohort was monitored identifying participants who developed either Crohn's disease (CD) or ulcerative colitis (UC). Each case was matched with four controls and conditional logistic regression used to calculate odds ratios (ORs) for body mass index (BMI) adjusted for smoking, energy intake, and physical activity.RESULTS:In the cohort, 177 participants developed incident UC and 75 participants developed incident CD. There were no associations with the four higher categories of BMI compared with a normal BMI for UC (P(trend)=0.36) or CD (P(trend)=0.83). The lack of associations was consistent when BMI was analyzed as a continuous or binary variable (BMI 18.5<25.0 vs. ≥25 kg/m(2)). Physical activity and total energy intake, factors that influence BMI, did not show any association with UC (physical activity, P(trend)=0.79; total energy intake, P(trend)=0.18) or CD (physical activity, P(trend)=0.42; total energy, P(trend)=0.11).CONCLUSIONS:Obesity as measured by BMI is not associated with the development of incident UC or CD. Alternative measures of obesity are required to further investigate the role of obesity in the development of incident IBD.Am J Gastroenterol advance online publication, 15 January 2013; doi:10.1038/ajg.2012.453.The American Journal of Gastroenterology 01/2013; · 7.28 Impact Factor -
Article: Lower educational level is a predictor of incident type 2 diabetes in European countries: the EPIC-InterAct study.
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ABSTRACT: Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide. In high-income countries, low socioeconomic status seems to be related to a high incidence of T2DM, but very little is known about the intermediate factors of this relationship. Method We performed a case-cohort study in eight Western European countries nested in the EPIC study (n = 340, 234, 3.99 million person-years of follow-up). A random sub-cohort of 16,835 individuals and a total of 12,403 incident cases of T2DM were identified. Crude and multivariate-adjusted hazard ratios (HR) were estimated for each country and pooled across countries using meta-analytical methods. Age-, gender- and country-specific relative indices of inequality (RII) were used as the measure of educational level and RII tertiles were analysed. Compared with participants with a high educational level (RII tertile 1), participants with a low educational level (RII tertile 3) had a higher risk of T2DM [HR: 1.77, 95% confidence interval (CI): 1.69-1.85; P-trend < 0.01]. The HRs adjusted for physical activity, smoking status and propensity score according to macronutrient intake were very similar to the crude HR (adjusted HR: 1.67, 95% CI: 1.52-1.83 in men; HR: 1.88, 95% CI: 1.73-2.05 in women). The HRs were attenuated only when they were further adjusted for BMI (BMI-adjusted HR: 1.36, 95% CI: 1.23-1.51 in men; HR: 1.32, 95% CI: 1.20-1.45 in women). This study demonstrates the inequalities in the risk of T2DM in Western European countries, with an inverse relationship between educational level and risk of T2DM that is only partially explained by variations in BMI.International Journal of Epidemiology 06/2012; 41(4):1162-73. · 6.41 Impact Factor -
Article: Fiber intake and total and cause-specific mortality in the European Prospective Investigation into Cancer and Nutrition cohort.
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ABSTRACT: Previous studies have shown that high fiber intake is associated with lower mortality. However, little is known about the association of dietary fiber with specific causes of death other than cardiovascular disease (CVD). The aim of this study was to assess the relation between fiber intake, mortality, and cause-specific mortality in a large European prospective study of 452,717 men and women. HRs and 95% CIs were estimated by using Cox proportional hazards models, stratified by age, sex, and center and adjusted for education, smoking, alcohol consumption, BMI, physical activity, total energy intake, and, in women, ever use of menopausal hormone therapy. During a mean follow-up of 12.7 y, a total of 23,582 deaths were recorded. Fiber intake was inversely associated with total mortality (HR(per 10-g/d increase): 0.90; 95% CI: 0.88, 0.92); with mortality from circulatory (HR(per 10-g/d increase): 0.90 and 0.88 for men and women, respectively), digestive (HR: 0.61 and 0.64), respiratory (HR: 0.77 and 0.62), and non-CVD noncancer inflammatory (HR: 0.85 and 0.80) diseases; and with smoking-related cancers (HR: 0.86 and 0.89) but not with non-smoking-related cancers (HR: 1.05 and 0.97). The associations were more evident for fiber from cereals and vegetables than from fruit. The associations were similar across BMI and physical activity categories but were stronger in smokers and participants who consumed >18 g alcohol/d. Higher fiber intake is associated with lower mortality, particularly from circulatory, digestive, and non-CVD noncancer inflammatory diseases. Our results support current recommendations of high dietary fiber intake for health maintenance.American Journal of Clinical Nutrition 05/2012; 96(1):164-74. · 6.67 Impact Factor -
Article: Validity of a short questionnaire to assess physical activity in 10 European countries
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ABSTRACT: To accurately examine associations of physical activity (PA) with disease outcomes, a valid method of assessing free-living activity is required. We examined the validity of a brief PA questionnaire (PAQ) used in the European Prospective Investigation into Cancer and Nutrition (EPIC). PA energy expenditure (PAEE) and time spent in moderate and vigorous physical activity (MVPA) was measured in 1,941 healthy individuals from 10 Euro-pean countries using individually-calibrated combined heart-rate and movement sensing. Participants also com-pleted the short EPIC-PAQ, which refers to past year's activity. Pearson (r) and Spearman (r) correlation coeffi-cients were calculated for each country, and random effects meta-analysis was used to calculate the combined corre-lation across countries to estimate the validity of two previously-and one newly-derived ordered, categorical PA indices (''Cambridge index'', ''total PA index'', and ''recreational index'') that categorized individuals as inactive, moderately inactive, moderately active, or active. The strongest associations with PAEE and MVPA were observed for the Cambridge index (r = 0.33 and r = 0.25, respectively). No significant heterogeneity by country was observed for this index (I 2 = 36.3%, P = 0.12; I 2 = 0.0%, P = 0.85), whereas heterogeneity was suggested for other indices (I 2 [ 48%, P \\ 0.05, I 2 [ 47%, P \\ 0.05). PAEE increased linearly across self-reported PA categories (P for trend\\0.001), with an average difference of approximately 460 kJ/d for men and 365 kJ/d for women, between cate-gories of the Cambridge index. The EPIC-PAQ is suitable for categorizing European men and women into four dis-tinct categories of overall physical activity. The difference in PAEE between categories may be useful when esti-mating effect sizes from observational research.European Journal of Epidemiology 11/2011; · 4.71 Impact Factor -
Article: Hepatocellular carcinoma risk factors and disease burden in a European cohort: a nested case-control study.
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ABSTRACT: To date, no attempt has been made to systematically determine the apportionment of the hepatocellular carcinoma burden in Europe or North America among established risk factors. Using data collected from 1992 to 2006, which included 4,409,809 person-years in the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 125 case patients with hepatocellular carcinoma, of whom 115 were matched to 229 control subjects. We calculated odds ratios (ORs) for the association of documented risk factors for hepatocellular carcinoma with incidence of this disease and estimated their importance in this European cohort. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (OR = 9.10, 95% confidence interval [CI] = 2.10 to 39.50 and OR = 13.36, 95% CI = 4.11 to 43.45, respectively), obesity (OR = 2.13, 95% CI = 1.06 to 4.29), former or current smoking (OR = 1.98, 95% CI = 0.90 to 4.39 and OR = 4.55, 95% CI = 1.90 to 10.91, respectively), and heavy alcohol intake (OR = 1.77, 95% CI = 0.73 to 4.27) were associated with hepatocellular carcinoma. Smoking contributed to almost half of all hepatocellular carcinomas (47.6%), whereas 13.2% and 20.9% were attributable to chronic HBV and HCV infection, respectively. Obesity and heavy alcohol intake contributed 16.1% and 10.2%, respectively. Almost two-thirds (65.7%, 95% CI = 50.6% to 79.3%) of hepatocellular carcinomas can be accounted for by exposure to at least one of these documented risk factors. Smoking contributed to more hepatocellular carcinomas in this Europe-wide cohort than chronic HBV and HCV infections. Heavy alcohol consumption and obesity also contributed to sizeable fractions of this disease burden. These contributions may be underestimates because EPIC volunteers are likely to be more health conscious than the general population.CancerSpectrum Knowledge Environment 11/2011; 103(22):1686-95. · 14.07 Impact Factor -
Article: Correction: A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium.
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ABSTRACT: [This corrects the article on p. e1001333 in vol. 7.].PLoS Genetics 04/2011; 7(4). · 8.69 Impact Factor -
Article: A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.
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ABSTRACT: Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.PLoS Genetics 03/2011; 7(3):e1001333. · 8.69 Impact Factor -
Article: Ten-year experience of selective omission of the pretransplant crossmatch test in deceased donor kidney transplantation.
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ABSTRACT: A pretransplant lymphocyte crossmatch (XM) test is usually considered mandatory but may delay deceased donor renal transplantation. We report on the safety and clinical efficacy of omitting the XM when it is predicted to be negative based on sensitization history and human leukocyte antigen-specific antibody screening. From 1998 to 2008, 606 deceased donor kidney transplants were performed at our center and the prospective donor-recipient XM omitted in 257 (42%). In all cases, a negative XM was confirmed retrospectively. Four hundred fourteen (68%) kidneys were donated after brain death (DBD) and 192 (32%) after cardiac death (DCD). The effect of this policy on cold ischemia time (CIT), delayed graft function (DGF), and transplant survival was assessed. Mean CIT was 16.7 hr with a prospective XM and 14.3 hr when it was omitted (P<0.001). The beneficial effect of omitting the XM on DGF was only apparent in recipients of DBD kidneys, where the DGF rate was 28% with a prospective XM and 18% without a prospective XM (P=0.03). The corresponding DGF rate in recipients of DCD kidneys was 52% with a prospective XM and 54% without a prospective XM. Logistic regression analysis, after adjustment for variables that influenced DGF, showed that the odds on suffering DGF were lower when the pretransplant XM test was omitted (P=0.04). Neither acute rejection rate nor long-term graft survival was influenced by omission of the XM. Rigorous recording of potential allosensitizing events and comprehensive antibody screening allows the XM to be safely omitted in selected patients and this helps limit CIT and may reduce DGF.Transplantation 01/2010; 89(2):185-93. · 4.00 Impact Factor -
Article: The INSIG2 rs7566605 polymorphism is not associated with body mass index and breast cancer risk
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ABSTRACT: Abstract Background The single nucleotide polymorphism rs7566605, located in the promoter of the INSIG2 gene, has been the subject of a strong scientific effort aimed to elucidate its possible association with body mass index (BMI). The first report showing that rs7566605 could be associated with body fatness was a genome-wide association study (GWAS) which used BMI as the primary phenotype. Many follow-up studies sought to validate the association of rs7566605 with various markers of obesity, with several publications reporting inconsistent findings. BMI is considered to be one of the measures of choice to evaluate body fatness and there is evidence that body fatness is related with an increased risk of breast cancer (BC). Methods we tested in a large-scale association study (3,973 women, including 1,269 invasive BC cases and 2,194 controls), nested within the EPIC cohort, the involvement of rs7566605 as predictor of BMI and BC risk. Results and Conclusions In this study we were not able to find any statistically significant association between this SNP and BMI, nor did we find any significant association between the SNP and an increased risk of breast cancer overall and by subgroups of age, or menopausal status.BMC Cancer. 01/2010; -
Article: Soluble CD30 levels in recipients undergoing heart transplantation do not predict post-transplant outcome.
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ABSTRACT: The pre-transplant serum level of soluble CD30 (sCD30), a proteolytic derivative of the lymphocyte surface receptor CD30, has been suggested as a biomarker for immunologic risk after organ transplantation. Pre-transplant serum sCD30 levels were determined in 200 consecutive adult heart transplant recipients undertaken at a single center. Transplant outcome (acute rejection in the first 12 months and patient survival up to 5 years post-transplant) was determined. Patients treated with a left ventricular assist device (LVAD) prior to transplantation (n = 28) had higher levels of sCD30 (median 64 U/ml, range 12 to 112 U/ml) than those (n = 172) with no LVAD (median 36 U/ml, range 1 to 158 U/ml, p < 0.0001). Recipients were categorized according to whether sCD30 levels were "low" (lower quartile, <24 U/ml, n = 50), "intermediate" (24 to 58 U/ml, n = 100) or "high" (upper quartile, >58 U/ml, n = 50). Neither acute rejection nor recipient survival differed according to sCD30 level, with values (mean +/- SEM) of 0.30 +/- 0.04, 0.23 +/- 0.03 and 0.30 +/- 0.05 acute rejection episodes per 100 days in the low, intermediate and high groups, respectively, with recipient survival rates at 1 year of 77.7%, 84.9% and 86% and at 5 years of 73.6%, 67.9% and 75.8%, respectively. Pre-transplant serum sCD30 level does not predict acute allograft rejection or recipient survival after heart transplantation, although sCD30 levels are increased by LVAD, possibly as a result of biomaterial-host immune interaction.The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 09/2009; 28(11):1206-10. · 3.54 Impact Factor -
Article: Level of education and the risk of lymphoma in the European prospective investigation into cancer and nutrition.
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ABSTRACT: Lymphomas belong to the few cancer sites with increasing incidence over past decades, and only a few risk factors have been established. We explored the association between education and the incidence of lymphoma in the prospective EPIC study. Within 3,567,410 person-years of follow-up, 1,319 lymphoma cases [1,253 non-Hodgkin lymphomas (NHL) and 66 Hodgkin lymphomas (HL)] were identified. Cox proportional hazard regression was used to examine the association between highest educational level (primary school or less, technical/professional school, secondary school, university) and lymphoma risk. Overall, no consistent associations between educational level and lymphoma risk were observed; however, associations were found for sub-groups of the cohort. We observed a higher risk of B-NHL (HR = 1.31, 95% CI = 1.02–1.68; n = 583) in women with the highest education level (university) but not in men. Concerning sub-classes of B-NHL, a positive association between education and risk of B cell chronic lymphatic leukaemia (BCLL) was observed only in women. In both genders, the risk of diffuse large B cell lymphoma (DLBCL) was significantly lower for subjects with university degree (HR = 0.46, 95% CI = 0.27–0.79) versus lowest educational level. No association was found for HL. We could not confirm an overall consistent association of education and risk of HL or NHL in this large prospective study; although, education was positively related to the incidence of BCLL and B-NHL (in women) but inversely to incidence of DLBCL. Due to limited number of cases in sub-classes and the large number of comparisons, the possibility of chance findings can not be excluded.Journal of Cancer Research and Clinical Oncology 08/2009; 136(1):71-7. · 2.56 Impact Factor -
Article: Lifestyle factors and serum androgens among 636 middle aged men from seven countries in the European Prospective Investigation into Cancer and Nutrition (EPIC).
Cancer Causes and Control 05/2009; · 2.88 Impact Factor -
Article: Association between endogenous plasma hormone concentrations and fracture risk in men and women: the EPIC-Oxford prospective cohort study.
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ABSTRACT: Sex steroids have an important role in bone health, however previous studies on fracture risk have been carried out in older populations. The EPIC-Oxford study is a prospective cohort of men and women living in the UK. Five years after recruitment, participants self-reported previous fractures. Sex steroid concentrations (plasma estradiol, testosterone and sex hormone binding globulin) were measured in 436 cases (155 men, 46 premenopausal women and 235 postmenopausal women) with an incident fracture and 868 matched controls. Fracture risk was inversely related to concentrations of estradiol among men (RR for a doubling of estradiol 0.35, 95% CI 0.44-0.96) but there was no association between fracture risk and testosterone levels. There were no clear associations between fracture risk and hormone levels among postmenopausal women, however there was suggestion of an inverse association for both estradiol and testosterone as the RR in the highest compared with the lowest tertile for estradiol was 0.74 (95% CI 0.46, 1.18) and testosterone was 0.75 (95% CI 0.49, 1.16). Among premenopausal women fracture risk was inversely associated with levels of testosterone (RR for doubling of testosterone 0.46, 95% CI 0.26-0.81), with no association between estradiol and fracture risk. SHBG was not associated with risk of fracture among either men or women. In summary, this study finds evidence of an inverse association between endogenous estradiol and risk of fracture in men, and between endogenous testosterone and risk of fracture in premenopausal women but no clear associations among postmenopausal women.Journal of Bone and Mineral Metabolism 04/2009; 27(4):485-93. · 2.27 Impact Factor -
Article: Prospective study of the association between grapefruit intake and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).
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ABSTRACT: Grapefruit inhibits cytochrome P450 3A4 and may affect estrogen metabolism. In the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the relationships of grapefruit intake with risk of breast cancer and with serum sex hormone levels. 114,504 women with information on dietary intake of grapefruit and on reproductive and lifestyle risk factors were followed for a median 9.5 years and 3,747 incident breast cancers were identified. Fifty-nine percent of women reported eating grapefruit, 4% ate > or = 60 g/day. Cox proportional hazard models were used to estimate the hazard ratio (HR) for breast cancer according to grapefruit intake, adjusting for study centre, reproductive factors, body mass index, energy intake, and alcohol intake. Grapefruit intake was not related to the risk of breast cancer: compared with women who ate no grapefruit, women with the highest intake of > or =60 g/day had a HR of 0.93 (95% CI 0.77-1.13), p for linear trend = 0.5. There was no relationship between grapefruit intake and breast cancer risk among premenopausal women, all postmenopausal women, or postmenopausal women categorized by hormone replacement therapy use (all p>0.05). There was no association between grapefruit intake and estradiol or estrone among postmenopausal women. In this study, we found no evidence of an association between grapefruit intake and risk of breast cancer.Cancer Causes and Control 02/2009; 20(6):803-9. · 2.88 Impact Factor -
Article: Lung cancer susceptibility locus at 5p15.33.
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ABSTRACT: We carried out a genome-wide association study of lung cancer (3,259 cases and 4,159 controls), followed by replication in 2,899 cases and 5,573 controls. Two uncorrelated disease markers at 5p15.33, rs402710 and rs2736100 were detected by the genome-wide data (P = 2 x 10(-7) and P = 4 x 10(-6)) and replicated by the independent study series (P = 7 x 10(-5) and P = 0.016). The susceptibility region contains two genes, TERT and CLPTM1L, suggesting that one or both may have a role in lung cancer etiology.Nature Genetics 01/2009; 40(12):1404-6. · 35.53 Impact Factor -
Article: Anthropometric characteristics and non-Hodgkin's lymphoma and multiple myeloma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).
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ABSTRACT: The incidences of non-Hodgkin's lymphoma and multiple myeloma are increasing steadily. It has been hypothesized that this may be due, in part, to the parallel rising prevalence of obesity. It is biologically plausible that anthropometric characteristics can infuence the risk of non-Hodgkin's lymphoma and multiple myeloma. In the context of the European Prospective Investigation into Cancer and Nutrition (EPIC), anthropometric characteristics were assessed in 371,983 cancer-free individuals at baseline. During the 8.5 years of follow-up, 1,219 histologically confirmed incident cases of non-Hodgkin's lymphoma and multiple myeloma occurred in 609 men and 610 women. Gender-specific proportional hazards models were used to estimate relative risks and 95% confidence intervals (95% CI) of development of non-Hodgkin's lymphoma and multiple myeloma in relation to the anthropometric characteristics. Height was associated with overall non-Hodgkin's lymphoma and multiple myeloma in women (RR 1.50, 95% CI 1.14-1.98) for highest versus lowest quartile; p-trend < 0.01) but not in men. Neither obesity (weight and body mass index) nor abdominal fat (waist-to-hip ratio, waist or hip circumference) measures were positively associated with overall non-Hodgkin's lymphoma and multiple myeloma. Relative risks for highest versus lowest body mass index quartile were 1.09 (95% CI 0.85-1.38) and 0.92 (95% CI 0.71-1.19) for men and women, respectively. Women in the upper body mass index quartile were at greater risk of diffuse large B-cell lymphoma (RR 2.18, 95% CI 1.05-4.53) and taller women had an elevated risk of follicular lymphoma (RR 1.25, 95% CI 0.59-2.62). Among men, height and body mass index were non-significantly, positively related to follicular lymphoma. Multiple myeloma risk alone was elevated for taller women (RR 2.34, 95% CI 1.29-4.21) and heavier men (RR 1.77, 95% CI 1.02-3.05). The EPIC analyses support an association between height and overall non-Hodgkin's lymphoma and multiple myeloma among women and suggest heterogeneous subtype associations. This is one of the first prospective studies focusing on central adiposity and non-Hodgkin's lymphoma subtypes.Haematologica 10/2008; 93(11):1666-77. · 6.42 Impact Factor -
Article: Predicting the immunogenicity of human leukocyte antigen class I alloantigens using structural epitope analysis determined by HLAMatchmaker.
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ABSTRACT: Human leukocyte antigen (HLA) matching strategies for kidney transplantation assign equal weighting to mismatches at a particular locus and take no account of variation in immunogenicity according to recipient HLA type. We examined the ability of intra- and interlocus analysis of amino-acid polymorphisms at continuous (triplet) and discontinuous positions (eplet) defined by the HLAMatchmaker program to predict alloantigen immunogenicity. Sera from highly sensitized patients were screened for HLA class-I alloantibodies and mismatched combinations were analyzed using HLAMatchmaker to determine the number of triplet or extended-triplet and eplet mismatches. Logistic regression analysis revealed a strong correlation between the number of triplet or extended-triplet and eplet mismatches and both the presence and magnitude of alloantibody to mismatched HLA-A and -B specificities. The additional structural information provided by eplet analysis gave increased discrimination of mismatched-HLA specificities for alloantigens with greatest sequence disparity but this did not further improve the ability of triplet analysis to predict alloantigen immunogenicity. High antibody levels were observed for several mismatched-HLA combinations with zero triplet or eplet mismatches indicating that self triplets or eplets expressed in different conformations do not always predict nonimmunogenic epitopes. Analysis of recipient HLA type and mismatched-HLA alloantigens using the HLAMatchmaker algorithm allows prediction of immunogenic donor HLA types.Transplantation 07/2008; 85(12):1817-25. · 4.00 Impact Factor -
Article: Phytanic acid: measurement of plasma concentrations by gas-liquid chromatography-mass spectrometry analysis and associations with diet and other plasma fatty acids.
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ABSTRACT: Epidemiological data suggest that a diet rich in animal foods may be associated with an increased risk of several cancers, including cancers of the prostate, colorectum and breast, but the possible mechanism is unclear. It is hypothesised that phytanic acid, a C20 branched-chain fatty acid found predominantly in foods from ruminant animals, may be involved in early cancer development because it has been shown to up regulate activity of alpha-methylacyl-coenzyme A racemase, an enzyme commonly found to be over-expressed in tumour cells compared with normal tissue. However, little is known about the distribution of plasma phytanic acid concentrations or its dietary determinants in the general population. The primary aim of the present cross-sectional study was to determine circulating phytanic acid concentrations among ninety-six meat-eating, lacto-ovo-vegetarian and vegan women, aged 20-69 years, recruited into the Oxford component of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford). Meat-eaters had, on average, a 6.7-fold higher geometric mean plasma phytanic acid concentration than the vegans (5.77 v. 0.86 micromol/l; P < 0.0001) and a 47 % higher mean concentration than the vegetarians (5.77 v. 3.93 micromol/l; P = 0.016). The strongest determinant of plasma phytanic acid concentration appeared to be dairy fat intake (r 0.68; P < 0.0001); phytanic acid levels were not associated with age or other lifestyle factors. These data show that a diet high in fat from dairy products is associated with increased plasma phytanic acid concentration, which may play a role in cancer development.British Journal Of Nutrition 04/2008; 99(3):653-9. · 3.01 Impact Factor -
Article: Diet in the aetiology of ulcerative colitis: a European prospective cohort study.
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ABSTRACT: The causes of ulcerative colitis are unknown, although it is plausible that dietary factors are involved. Case-control studies of diet and ulcerative colitis are subject to recall biases. The aim of this study was to examine the prospective relationship between the intake of nutrients and the development of ulcerative colitis in a cohort study. The study population was 260,686 men and women aged 20-80 years, participating in a large European prospective cohort study (EPIC). Participants were residents in the UK, Sweden, Denmark, Germany or Italy. Information on diet was supplied and the subjects were followed up for the development of ulcerative colitis. Each incident case was matched with four controls and dietary variables were divided into quartiles. A total of 139 subjects with incident ulcerative colitis were identified. No dietary associations were detected, apart from a marginally significant positive association with an increasing percentage intake of energy from total polyunsaturated fatty acids (trend across quartiles OR = 1.19 (95% CI = 0.99-1.43) p = 0.07). No associations between ulcerative colitis and diet were detected, apart from a possible increased risk with a higher total polyunsaturated fatty acid intake. A biological mechanism exists in that polyunsaturated fatty acids are metabolised to pro-inflammatory mediators.Digestion 02/2008; 77(1):57-64. · 2.05 Impact Factor -
Article: Serum C-peptide, IGFBP-1 and IGFBP-2 and risk of colon and rectal cancers in the European Prospective Investigation into Cancer and Nutrition.
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ABSTRACT: Western style diets and lifestyles are associated with increasing rates of obesity, diabetes and insulin resistance. Higher circulating insulin levels may modulate cell proliferation and apoptosis either directly or indirectly by increasing the bioactivity of IGF-I and decreasing the bioactivity of some of its binding proteins. The objective of this study was to determine the association of increasing levels of serum C-peptide, a biomarker of pancreatic insulin secretion, and IGF binding proteins (IGFBP) -1 and -2 with colorectal cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 Western European countries. A total of 1,078 colorectal cancer cases were matched (age, date of blood donation, fasting status, gender, study center) to an equal number of control subjects. Relative cancer risks were estimated using conditional logistic regression models. Serum C-peptide concentration was positively associated with an increased colorectal cancer risk for the highest versus the lowest quintile (OR=1.56, 95% CI=1.16-2.09, p(trend)<0.01), which was slightly attenuated after adjustment for BMI and physical activity (OR=1.37, 95% CI=1.00-1.88, p(trend)=0.10). When stratified by anatomical site, the cancer risk was stronger in the colon (OR=1.67, 95% CI=1.14-2.46, p(trend)<0.01) than in the rectum (OR=1.42, 95% CI=0.90-2.25, p(trend)=0.35). The cancer risk estimates were not heterogeneous by gender or fasting status. No clear colorectal cancer risk associations were observed for IGFBP-1 or -2. This large prospective study confirms that hyperinsulinemia, as determined by C-peptide levels, is associated with an increased colorectal cancer risk.International Journal of Cancer 08/2007; 121(2):368-76. · 5.44 Impact Factor
Top co-authors
Top Journals
Institutions
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2011
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Harvard University
- Department of Epidemiology
Cambridge, MA, USA
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2005–2011
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International Agency for Research on Cancer
Lyon, Rhone-Alpes, France
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2009
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Deutsches Krebsforschungszentrum
- Division of Cancer Epidemiology
Heidelberg, Baden-Wuerttemberg, Germany
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2007–2009
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University of Oxford
- • Cancer Epidemiology Unit
- • Nuffield Department of Clinical Medicine
Oxford, ENG, United Kingdom -
University of Cambridge
- Department of Public Health and Primary Care
Cambridge, ENG, United Kingdom -
University of North Carolina at Chapel Hill
- Department of Epidemiology
Chapel Hill, NC, USA
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2008
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Imperial College London
- Department of Epidemiology and Biostatistics
London, ENG, United Kingdom
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