Petra H M Peeters

Imperial College London, Londinium, England, United Kingdom

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Publications (669)3486.38 Total impact

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    ABSTRACT: Normal renal function is essential for vitamin D metabolism, but it is unclear whether circulating vitamin D is associated with risk of renal cell carcinoma (RCC). We assessed whether 25-hydroxyvitamin D3 (25(OH)D3) was associated with risk of RCC and death after RCC diagnosis in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC recruited 385,747 participants with blood samples between 1992 and 2000. The current study included 560 RCC cases, 557 individually matched controls, and 553 additional controls. Circulating 25(OH)D3 was assessed by mass spectrometry. Conditional and unconditional logistic regression models were used to calculate odds ratios and 95% confidence intervals. Death after RCC diagnosis was assessed using Cox proportional hazards models and flexible parametric survival models. A doubling of 25(OH)D3 was associated with 28% lower odds of RCC after adjustment for season of and age at blood collection, sex, and country of recruitment (odds ratio = 0.72, 95% confidence interval: 0.60, 0.86; P = 0.0004). This estimate was attenuated somewhat after additional adjustment for smoking status at baseline, circulating cotinine, body mass index (weight (kg)/height (m)2), and alcohol intake (odds ratio = 0.82, 95% confidence interval: 0.68, 0.99; P = 0.038). There was also some indication that both low and high 25(OH)D3 levels were associated with higher risk of death from any cause among RCC cases.
    American Journal of Epidemiology. 09/2014;
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    ABSTRACT: We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.
    Nature genetics. 08/2014;
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    ABSTRACT: High blood concentrations of C-reactive protein (CRP) have been associated with elevated risk of colorectal cancer in several prospective studies including the European Prospective Investigation into Cancer and Nutrition (EPIC), but it is unknown whether these observations reflect a causal relationship. We aimed to investigate whether CRP genetic variants associated with lifelong higher CRP concentrations translate into higher colorectal cancer risk. We conducted a prospective nested case–control study within EPIC including 727 cases diagnosed between 1992 and 2003 and 727 matched controls selected according to an incidence-density sampling protocol. Baseline CRP concentrations were measured in plasma samples by a high sensitivity assay. Tagging single nucleotide polymorphisms (SNPs) in the CRP gene (rs1205, rs1800947, rs1130864, rs2808630, rs3093077) were identified via HapMap. The causal effect of CRP on colorectal cancer risk was examined in a Mendelian Randomization approach utilizing multiple CRP genetic variants as instrumental variables. The SNPs rs1205, rs1800947, rs1130864 and rs3093077 were significantly associated with CRP concentrations and were incorporated in a CRP allele score which was associated with 13% higher CRP concentrations per allele count (95% confidence interval 8–19%). Using the CRP-score as instrumental variable, genetically twofold higher CRP concentrations were associated with higher risk of colorectal cancer (odds ratio 1.74, 95% confidence interval 1.06–2.85). Similar observations were made using alternative definitions of instrumental variables. Our findings give support to the hypothesis that elevated circulating CRP may play a direct role in the etiology of colorectal cancer.
    International Journal of Cancer 07/2014; · 6.20 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
    Human Molecular Genetics 07/2014; · 7.69 Impact Factor
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    ABSTRACT: Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case-control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X-ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 μg/L and 4.3 mg/L in cases and 85.6 μg/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non-significant lower CRC risk (IRR = 0.92, 95% CI: 0.82-1.03 per 25 μg/L increase). However, sub-group analyses by sex showed a statistically significant association for women (ptrend = 0.032; per 25 μg/L Se increase, IRR = 0.83, 95% CI: 0.70-0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (ptrend = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82-0.98) with the association more apparent in women (ptrend = 0.004; IRR = 0.82, 95% CI: 0.72-0.94 per 0.806 mg/L increase) than men (ptrend = 0.485; IRR = 0.98, 95% CI: 0.86-1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women.
    International Journal of Cancer 07/2014; · 6.20 Impact Factor
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    ABSTRACT: Differentiated thyroid carcinoma (TC) is 3-fold more common in women than in men and, therefore, a role of female hormones in the aetiology of differentiated TC has been suggested. We assessed these hypotheses in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 345,157 women (mean age: 51) followed for an average of 11 years, 508 differentiated TC cases were identified. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models. No significant associations were observed between differentiated TC risk and number of pregnancies, breast feeding, menopausal status, and age at menarche and at menopause. Significant associations were found with history of infertility problems (HR 1.70; 95% CI 1.12-2.60), a recent pregnancy (HR for ≤5 vs >5 years before recruitment 3.87; 95% CI 1.43-10.46), menopause type (HR for surgical vs natural menopause: 2.16; 95% CI 1.41-3.31), oral contraceptive (OC) use at recruitment (HR: 0.48; 95% CI 0.25-0.92), and duration of OC use (HR for ≥9 vs ≤1 year: 0.66; 95% CI: 0.50-0.89). An increased risk was also found with hormone replacement therapy use at recruitment (HR = 1.30, 95% CI 1.02-1.67), but this was not significant after adjustment for type of menopause (HR = 1.22, 95% CI 0.95-1.57). Overall, our findings do not support a strong role of reproductive and menstrual factors, and female hormone use in the aetiology of differentiated TC. The few observed associations may be real or accounted for by increased surveillance in women who had infertility problems, recent pregnancies or underwent surgical menopause. © 2014 Wiley Periodicals, Inc.
    International journal of cancer. Journal international du cancer. 07/2014;
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    ABSTRACT: Objectives To investigate the role of factors that modulate the association between alcohol and mortality, and to provide estimates of absolute risk of death. Design The European Prospective Investigation into Cancer and nutrition (EPIC). Setting 23 centres in 10 countries. Participants 380 395 men and women, free of cancer, diabetes, heart attack or stroke at enrolment, followed up for 12.6 years on average. Main outcome measures 20 453 fatal events, of which 2053 alcohol-related cancers (ARC, including cancers of upper aerodigestive tract, liver, colorectal and female breast), 4187 cardiovascular diseases/coronary heart disease (CVD/CHD), 856 violent deaths and injuries. Lifetime alcohol use was assessed at recruitment. Results HRs comparing extreme drinkers (≥30 g/day in women and ≥60 g/day in men) to moderate drinkers (0.1–4.9 g/day) were 1.27 (95% CI 1.13 to 1.43) in women and 1.53 (1.39 to 1.68) in men. Strong associations were observed for ARC mortality, in men particularly, and for violent deaths and injuries, in men only. No associations were observed for CVD/CHD mortality among drinkers, whereby HRs were higher in never compared to moderate drinkers. Overall mortality seemed to be more strongly related to beer than wine use, particularly in men. The 10-year risks of overall death for women aged 60 years, drinking more than 30 g/day was 5% and 7%, for never and current smokers, respectively. Corresponding figures in men consuming more than 60 g/day were 11% and 18%, in never and current smokers, respectively. In competing risks analyses, mortality due to CVD/CHD was more pronounced than ARC in men, while CVD/CHD and ARC mortality were of similar magnitude in women. Conclusions In this large European cohort, alcohol use was positively associated with overall mortality, ARC and violent death and injuries, but marginally to CVD/CHD. Absolute risks of death observed in EPIC suggest that alcohol is an important determinant of total mortality.
    BMJ Open. 07/2014; 4(7):e005245.
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    ABSTRACT: Background We investigated whether prediagnostic reported intake of dairy products and dietary calcium are associated with colorectal cancer (CRC) survival. Methods Data from 3,859 subjects with CRC (42.1% male, mean age at diagnosis 64.2 ± 8.1 years) in the European Investigation into Cancer and Nutrition (EPIC) cohort were analyzed. Intake of dairy products and dietary calcium was assessed at baseline (1992-2000) using validated, country-specific dietary questionnaires. Multivariable Cox regression models were used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (95%-CI) for CRC specific death (n=1,028) and all-cause death (n=1,525) for different quartiles of intake. Results The consumption of total dairy products was not statistically significantly associated with risk of CRC-specific death (adjusted HR Q4 vs. Q1: 1.17 95%-CI 0.97-1.43) nor of all-cause death (Q4 vs. Q1: 1.16 95%-CI 0.98-1.36). Multivariable adjusted HRs for CRC-specific death (Q4 vs. Q1) were 1.21 (95%-CI 0.99-1.48) for milk, 1.09 (95%-CI 0.88-1.34) for yoghurt and 0.93 (95%-CI 0.76-1.14) for cheese. The intake of dietary calcium was not associated with the risk of CRC-specific (adjusted HR Q4 vs. Q1: 1.01 95%-CI 0.81-1.26) nor of all-cause death (Q4 vs. Q1: 1.01 95%-CI 0.84-1.21). Conclusions The prediagnostic reported intake of dairy products and dietary calcium are not associated with disease-specific or all-cause risk of death in patients diagnosed with CRC. Impact The impact of diet on cancer survival is largely unknown. This study shows that despite it's inverse association with CRC risk, the prediagnostic intake of dairy and dietary calcium do not affect CRC survival.
    06/2014;
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    ABSTRACT: It has been suggested that mitochondrial dysfunction and DNA damage are involved in lymphomagenesis. Increased copy number of mitochondrial DNA (mtDNA) as a compensatory mechanism of mitochondrial dysfunction previously has been associated with B-cell lymphomas, in particular chronic lymphocytic leukemia (CLL). However, current evidence is limited and based on a relatively small number of cases. Using a nested case-control study, we extended these findings with a focus on subtype specific analyses. Relative mtDNA copy number was measured in the buffy coat of prospectively collected blood of 469 lymphoma cases and 469 matched controls. The association between mtDNA copy number and the risk of developing lymphoma and histologic subtypes was examined using logistic regression models. We found no overall association between mtDNA and risk of lymphoma. Subtype analyses revealed, significant increased risks of CLL (n=102) with increasing mtDNA copy number (OR=1.34, 1.44 and 1.80 for quartiles 2-4, respectively P-trend=0.001). mtDNA copy number was not associated with follow-up time suggesting that this observation is not strongly influenced by indolent disease status. This study substantially strengthens the evidence that mtDNA copy number is related to risk of CLL and supports the importance of mitochondrial dysfunction as a possible mechanistic pathway in CLL ontogenesis.
    Blood 06/2014; · 9.78 Impact Factor
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    ABSTRACT: The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n=183,257). A total of 565 eligible women developed EOC; two controls (n=1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2 =0.79, 95% confidence interval [CI]=[0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2 =1.99 [0.98- 4.06]; high grade: ORlog2 =0.75 [0.61-0.93], phet ≤0.01), similar associations were observed for type I/ II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed. © 2014 Wiley Periodicals, Inc.
    International journal of cancer. Journal international du cancer. 05/2014;
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    ABSTRACT: Principal component analysis (PCA) and cluster analysis are used frequently to derive dietary patterns. Decisions on how many patterns to extract are primarily based on subjective criteria, whereas different solutions vary in their food-group composition and perhaps association with disease outcome. Literature on reliability of dietary patterns is scarce, and previous studies validated only 1 preselected solution. Therefore, we assessed reliability of different pattern solutions ranging from 2 to 6 patterns, derived from the aforementioned methods. A validated food frequency questionnaire was administered at baseline (1993-1997) to 39,678 participants in the European Prospective Investigation into Cancer and Nutrition-The Netherlands (EPIC-NL) cohort. Food items were grouped into 31 food groups for dietary pattern analysis. The cohort was randomly half-split, and dietary pattern solutions derived in 1 sample through PCA were replicated through confirmatory factor analysis in sample 2. For cluster analysis, cluster stability and split-half reproducibility were assessed for various solutions. With PCA, we found the 3-component solution to be best replicated, although all solutions contained ≥1 poorly confirmed component. No quantitative criterion was in agreement with these results. Associations with disease outcome (coronary heart disease) differed between the component solutions. For all cluster solutions, stability was excellent and deviations between split samples was negligible, indicating good reproducibility. All quantitative criteria identified the 2-cluster solution as optimal. Associations with disease outcome were comparable for different cluster solutions. In conclusion, reliability of obtained dietary patterns differed considerably for different solutions using PCA, whereas cluster analysis derived generally stable, reproducible clusters across different solutions. Quantitative criteria for determining the number of patterns to retain were valuable for cluster analysis but not for PCA. Associations with disease risk were influenced by the number of patterns that are retained, especially when using PCA. Therefore, studies on associations between dietary patterns and disease risk should report reasons to choose the number of retained patterns.
    The Journal of nutrition. 05/2014;
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    ABSTRACT: Disturbances in one carbon-metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can serve as alternative methyl group donors when folate status is low. We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1,367 incident CRC cases (965 colon; 402 rectum) and 2,323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) for CRC risk were estimated by conditional logistic regression comparing the fifth to the first quintile of plasma concentrations. Overall, methionine (OR: 0.79, 95%CI: 0.63-0.99, P-trend=0.05), choline (OR: 0.77, 95%CI: 0.60-0.99, P-trend=0.07), and betaine (OR: 0.85, 95%CI: 0.66-1.09, P-trend=0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3 nmol/L, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95%CI: 0.50-1.00, P-trend=0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95%CI: 0.43-0.88, P-trend=0.01). Plasma DMG was not associated with CRC risk. Individuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of colorectal cancer.
    Annals of Oncology 05/2014; · 7.38 Impact Factor
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    ABSTRACT: Increased levels of thyroglobulin (Tg) and thyroid-stimulating hormone (TSH) are associated with differentiated thyroid carcinoma (TC) risk, but strong epidemiological evidence is lacking. Three hundred fifty-seven incident TC case patients (n = 300 women and 57 men; mean age at blood collection = 51.5 years) were identified in the EPIC cohort study and matched with 2 (women) or 3 (men) control subjects using incidence density sampling. Matching included study center, sex, age, date, time, and fasting status at blood collection. Levels of total and free (f) thyroxine (T4) and triiodo-thyronine (T3), TSH, Tg, and anti-Tg antibodies (TgAb) were measured by commercially available immunoassays. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression. All statistical tests were two-sided. TC risk was positively associated with Tg (OR for the highest vs lowest quartile = 9.15; 95% CI = 5.28 to 15.90; P < .001) and negatively associated with TSH level (OR = 0.56; 95% CI = 0.38 to 0.81; P = .001). Odds ratios were not modified by adjustment for weight and height and were consistent across sexes, age groups, and countries. The association with Tg was stronger in follicular than papillary TC. The odds ratio for TgAb-positivity was 1.50 (95% CI = 1.05 to 2.15; P = .03). Among case patients, TSH level was stable over time, whereas Tg level was higher in proximity to TC diagnosis. Areas under the receiver operating characteristic curve were 57% and 74% for TSH and Tg level, respectively. High Tg levels precede by up to 8 years the detection of TC, pointing to a long sojourn time of the disease. Low TSH levels may predispose to TC onset. Neither marker has sufficient accuracy to be a screening test.
    CancerSpectrum Knowledge Environment 05/2014; · 14.07 Impact Factor
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    ABSTRACT: We studied the interplay between 39 breast cancer (BC) risk SNPs and established BC risk (body mass index, height, age at menarche, parity, age at menopause, smoking, alcohol and family history of BC) and prognostic factors (TNM stage, tumor grade, tumor size, age at diagnosis, estrogen receptor status and progesterone receptor status) as joint determinants of BC risk. We used a nested case-control design within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), with 16 285 BC cases and 19 376 controls. We performed stratified analyses for both the risk and prognostic factors, testing for heterogeneity for the risk factors, and case-case comparisons for differential associations of polymorphisms by subgroups of the prognostic factors. We analyzed multiplicative interactions between the SNPs and the risk factors. Finally, we also performed a meta-analysis of the interaction ORs from BPC3 and the Breast Cancer Association Consortium. After correction for multiple testing, no significant interaction between the SNPs and the established risk factors in the BPC3 study was found. The meta-analysis showed a suggestive interaction between smoking status and SLC4A7-rs4973768 (Pinteraction = 8.84 × 10(-4)) which, although not significant after considering multiple comparison, has a plausible biological explanation. In conclusion, in this study of up to almost 79 000 women we can conclusively exclude any novel major interactions between genome-wide association studies hits and the epidemiologic risk factors taken into consideration, but we propose a suggestive interaction between smoking status and SLC4A7-rs4973768 that if further replicated could help our understanding in the etiology of BC.
    Human Molecular Genetics 05/2014; · 7.69 Impact Factor
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    ABSTRACT: A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development.
    European Journal of Epidemiology 05/2014; · 5.12 Impact Factor
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    ABSTRACT: Long-term weight gain (i.e. weight gain since age 20) has been related to higher risk of postmenopausal breast cancer, but a lower risk of premenopausal breast cancer. The effect of weight change in middle adulthood is unclear. We investigated the association between weight change in middle adulthood (i.e. women aged 40-50 years) and the risk of breast cancer before and after the age of 50. We included female participants of the EPIC cohort, with information on anthropometric measures at recruitment and after a median follow-up of 4.3 years. Annual weight change was categorized using quintiles taking quintile 2 and 3 as the reference category (-0.44 to 0.36 kg/y). Multivariable Cox proportional hazards regression analysis was used to examine the association. 205,723 women were included and 4,663 incident breast cancer cases were diagnosed during a median follow-up of 7.5 years (from second weight assessment onwards). High weight gain (Q5: 0.83 to 4.98 kg/y) was related to a slightly, but significantly higher breast cancer risk (HRQ5_versus_ Q2/3 : 1.09, 95% CI: 1.01-1.18). The association was more pronounced for breast cancer diagnosed before or at age 50 (HRQ5_versus_ Q2/3 : 1.37, 95% CI: 1.02-1.85). Weight loss was not associated with breast cancer risk. There was no evidence for heterogeneity by hormone receptor status. In conclusion, high weight gain in middle adulthood increases the risk of breast cancer. The association seems to be more pronounced for breast cancer diagnosed before or at age 50. Our results illustrate the importance of avoiding weight gain in middle adulthood. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 04/2014; · 6.20 Impact Factor
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    ABSTRACT: Recent epidemiological investigations have reported on the association between telomere length (TL) and a number of malignancies, including B-cell lymphoma. The reported results for B-cell lymphomas are however inconsistent. We carried out a nested case-control study to determine whether TL is associated with future risk of B-cell lymphoma. Using Quantitative Polymerase Chain Reaction, the relative TL (i.e. the ratio of telomere repeat copy number to single gene copy number) was measured in mononuclear cell DNA of pre-diagnostic peripheral blood samples of 464 lymphoma cases and 464 matched controls (median time between blood collection and diagnosis, 4.6 years). Conditional logistic regression was used to analyze the association between TL and the risk of developing lymphoma and histologic subtypes. TL was significantly longer in cases compared to controls (p=0.01). Multivariable models showed a significantly increased risk of B-cell lymphoma (OR=1.66, 1.80 and 3.20 for quartiles 2-4, respectively p-trend= 0.001), diffuse large B-cell lymphoma (DLBCL) (OR=1.20, 2.48 and 2.36 for quartiles 2-4, respectively p-trend= 0.03) and follicular lymphoma (FL) (OR=1.39, 1.90 and 2.69 for quartiles 2-4, respectively p-trend= 0.02) with increasing TL. This study suggests an association between longer leucocyte TL and increased risk of B-cell lymphoma which was most pronounced for DLBCL and FL. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 04/2014; · 6.20 Impact Factor
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    ABSTRACT: Anthropometric measures have been related to risk of several cancers. For bladder cancer, however, evidence is sparse. Comparability of existing studies is hampered by use of different obesity-measures, inadequate control for smoking, and few female cases. This study examined associations between height, weight, waist and hip circumference, waist-hip-ratio, waist-height-ratio, BMI, recalled weight at age 20 and bladder cancer, and investigated effect modification by age, tumor aggressiveness and smoking. The study was conducted in the European Prospective Investigation into Cancer and Nutrition cohort, in 390,878 participants. Associations were calculated using Cox Proportional Hazards Models. During follow-up, 1,391 bladder cancers (1,018 male; 373 female) occurred. Height was unrelated to bladder cancer in both genders. We found a small but significant positive association with weight (1.04 (1.01-1.07) per 5 kilo), BMI (1.05 (1.02-1.08) per 2 units), waist circumference (1.04 (1.01-1.08) per 5 cm), waist-hip-ratio (1.07 (1.02-1.13) per 0.05 unit) and waist-height ratio (1.07 (1.01-1.13) per 0.05 unit) in men. Stratification by smoking status confined associations in men to former smokers. In never smokers, we found no significant associations, suggesting residual confounding by smoking. Results did not differ with tumor aggressiveness and age. Residual analyses on BMI/waist circumference showed a significantly higher disease risk with BMI in men (p = 0.01), but no association with waist circumference. In conclusion, in this large study, height was unrelated to bladder cancer, whereas overweight was associated with a slightly higher bladder cancer risk in men. This association may, however, be distorted by residual confounding by smoking. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 04/2014; · 6.20 Impact Factor
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    ABSTRACT: Prospective cohort studies recruit relatively healthy population samples, resulting in lower morbidity and mortality rates than in the source population. This is known as the healthy volunteer effect. The aim of this study was to define the magnitude and the development over time of the healthy volunteer effect in the EPIC-NL cohort. We studied mortality rates in the EPIC-NL cohort, which comprises 37 551 men and women aged 20-70 years at recruitment in 1993-97. The date and cause of death of deceased participants until 2010 were obtained through linkage with the municipal registry and Statistics Netherlands. Standardized mortality ratios (SMRs) were computed by dividing the observed number of deaths by the number of deaths expected from the general Dutch population. Additionally, standardized incidence ratios were calculated to compare cancer incidence. After an average follow-up of 14.9 years, 3029 deaths were documented. Overall mortality in men [SMR 73.5%, 95% confidence interval (CI): 68.1-79.3] and women (SMR 65.9%, 95% CI: 63.2-68.6) was lower compared with the general population for the whole follow-up period. The SMRs clearly increased over the follow-up period. Among women, the SMR was lower for death due to cardiovascular diseases than death due to cancer. Cancer incidence was also lower in EPIC-NL than in the general population (SMR 78.3 and 82.7% for men and women, respectively). The results show a healthy volunteer effect in the EPIC-NL cohort, which tapers off with longer follow-up. Therefore, in the first years of follow-up, power might not be sufficient to detect small associations.
    The European Journal of Public Health 04/2014; · 2.52 Impact Factor
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    ABSTRACT: We prospectively evaluated fat intake as predictor of developing breast cancer (BC) subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2), in a large (n = 337327) heterogeneous cohort of women, with 10062 BC case patients after 11.5 years, estimating BC hazard ratios (HRs) by Cox proportional hazard modeling. High total and saturated fat were associated with greater risk of ER(+)PR(+) disease (HR = 1.20, 95% confidence interval [CI] = 1.00 to 1.45; HR = 1.28, 95% CI = 1.09 to 1.52; highest vs lowest quintiles) but not ER(-)PR(-) disease. High saturated fat was statistically significantly associated with greater risk of HER2(-) disease. High saturated fat intake particularly increases risk of receptor-positive disease, suggesting saturated fat involvement in the etiology of this BC subtype.
    CancerSpectrum Knowledge Environment 04/2014; · 14.07 Impact Factor

Publication Stats

16k Citations
3,486.38 Total Impact Points

Institutions

  • 2005–2014
    • Imperial College London
      • • Department of Epidemiology and Biostatistics
      • • School of Public Health
      • • Department of Primary Care and Public Health
      Londinium, England, United Kingdom
    • Mario Negri Institute for Pharmacological Research
      • Department of Environmental Health Sciences
      Milano, Lombardy, Italy
  • 1998–2014
    • University Medical Center Utrecht
      • • Julius Center for Health Sciences and Primary Care
      • • Department of Epidemiology
      Utrecht, Utrecht, Netherlands
  • 2013
    • Brown University
      • Department of Epidemiology
      Providence, RI, United States
    • University of Malaya
      Kuala Lumpor, Kuala Lumpur, Malaysia
    • Umeå University
      Umeå, Västerbotten, Sweden
  • 2011–2013
    • IDIBELL Bellvitge Biomedical Research Institute
      Barcino, Catalonia, Spain
    • Helmholtz Zentrum München
      • Institute of Epidemiology II
      München, Bavaria, Germany
    • INRAN - Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione
      Roma, Latium, Italy
    • National Institutes of Health
      • Division of Cancer Epidemiology and Genetics
      Bethesda, MD, United States
    • Harvard University
      • Department of Epidemiology
      Cambridge, MA, United States
    • University of São Paulo
      • Faculdade de Saúde Pública (FSP) (São Paulo)
      Ribeirão Preto, Estado de Sao Paulo, Brazil
  • 2005–2013
    • National and Kapodistrian University of Athens
      • Division of Hygiene - Epidemiology
      Athens, Attiki, Greece
  • 2003–2013
    • German Cancer Research Center
      • Division of Cancer Epidemiology
      Heidelberg, Baden-Wuerttemberg, Germany
    • Technische Universität München
      München, Bavaria, Germany
    • University of Oslo
      • Department of Biostatistics
      Oslo, Oslo, Norway
    • Lund University
      Lund, Skåne, Sweden
    • CRO Centro di Riferimento Oncologico di Aviano
      Aviano, Friuli Venezia Giulia, Italy
  • 2002–2013
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Potsdam, Brandenburg, Germany
    • Catalan Institute of Oncology
      • • Cancer Epidemiology Research Programme (PREC)
      • • Translational Research Laboratory
      Badalona, Catalonia, Spain
    • National Institute for Public Health and the Environment (RIVM)
      • Centre for Nutrition and Health
      Utrecht, Utrecht, Netherlands
  • 1994–2013
    • Universiteit Utrecht
      • • Division of Environmental Epidemiology
      • • Julius Centre for Health Sciences and Primary Care
      • • Department of Epidemiology
      • • University Medical Center Utrecht
      Utrecht, Provincie Utrecht, Netherlands
  • 2012
    • University of Zurich
      • Epidemiology and Prevention of Cancer
      Zürich, ZH, Switzerland
    • University of Texas MD Anderson Cancer Center
      • Division of Cancer Prevention & Population Sciences
      Houston, TX, United States
    • Emory University
      Atlanta, Georgia, United States
  • 2004–2012
    • University of Oxford
      • Nuffield Department of Clinical Medicine
      Oxford, ENG, United Kingdom
    • Netherlands Cancer Institute
      • Division of Experimental Therapy
      Amsterdamo, North Holland, Netherlands
  • 1998–2012
    • International Agency for Research on Cancer
      • Nutritional Epidemiology Group
      Lyons, Rhône-Alpes, France
  • 2009–2011
    • University of Cambridge
      • • MRC Epidemiology Unit
      • • Department of Public Health and Primary Care
      Cambridge, ENG, United Kingdom
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
    • Universität Bremen
      • Bremen Institute for Prevention Research and Social Medicine (BIPS)
      Bremen, Bremen, Germany
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
  • 2008–2011
    • Hellenic Health Foundation
      Athínai, Attica, Greece
    • VU University Medical Center
      • Department of Pathology
      Amsterdam, North Holland, Netherlands
    • Imperial Valley College
      Imperial, California, United States
    • University of Groningen
      • Laboratory for Medical Microbiology
      Groningen, Province of Groningen, Netherlands
  • 2010
    • Icahn School of Medicine at Mount Sinai
      Manhattan, New York, United States
    • Mayo Clinic - Rochester
      • Department of Health Science Research
      Rochester, MN, United States
    • Athens State University
      Athens, Alabama, United States
  • 2007–2010
    • University of Bergen
      • Institute of Medicine
      Bergen, Hordaland Fylke, Norway
    • ISI Foundation
      Torino, Piedmont, Italy
    • University of Southern California
      • Department of Preventive Medicine
      Los Angeles, CA, United States
  • 2008–2009
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      Milano, Lombardy, Italy
  • 2007–2009
    • Danish Cancer Society
      København, Capital Region, Denmark
  • 2006–2009
    • Universitetet i Tromsø
      • Department of Community Medicine
      Tromsø, Troms Fylke, Norway
    • Università degli Studi di Torino
      • Dipartimento di Scienze Cliniche e Biologiche
      Torino, Piedmont, Italy
    • University of California, San Diego
      San Diego, California, United States
  • 2002–2004
    • Martini Ziekenhuis
      Groningen, Groningen, Netherlands
  • 1988–1990
    • Sociaal en Cultureel Planbureau
      's-Gravenhage, South Holland, Netherlands
  • 1984–1989
    • Radboud University Nijmegen
      Nymegen, Gelderland, Netherlands