Petra H M Peeters

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (514)2525.54 Total impact

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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: 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: 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.
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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: 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: 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
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    ABSTRACT: The (14;18) translocation constitutes both a genetic hallmark and critical early event in the natural history of follicular lymphoma (FL). However, t(14;18) is also detectable in the blood of otherwise healthy persons, and its relationship with progression to disease remains unclear. Here we sought to determine whether t(14;18)-positive cells in healthy individuals represent tumor precursors and whether their detection could be used as an early predictor for FL. Among 520,000 healthy participants enrolled onto the EPIC (European Prospective Investigation Into Cancer and Nutrition) cohort, we identified 100 who developed FL 2 to 161 months after enrollment. Prediagnostic blood from these and 218 controls were screened for t(14;18) using sensitive polymerase chain reaction-based assays. Results were subsequently validated in an independent cohort (65 case participants; 128 controls). Clonal relationships between t(14;18) cells and FL were also assessed by molecular backtracking of paired prediagnostic blood and tumor samples. Clonal analysis of t(14;18) junctions in paired prediagnostic blood versus tumor samples demonstrated that progression to FL occurred from t(14;18)-positive committed precursors. Furthermore, healthy participants at enrollment who developed FL up to 15 years later showed a markedly higher t(14;18) prevalence and frequency than controls (P < .001). Altogether, we estimated a 23-fold higher risk of subsequent FL in blood samples associated with a frequency > 10(-4) (odds ratio, 23.17; 95% CI, 9.98 to 67.31; P < .001). Remarkably, risk estimates remained high and significant up to 15 years before diagnosis. High t(14;18) frequency in blood from healthy individuals defines the first predictive biomarker for FL, effective years before diagnosis.
    Journal of Clinical Oncology 03/2014; · 18.04 Impact Factor
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    ABSTRACT: Background: Little is known about the causes of thyroid cancer, but insulin-like growth factor-I (IGF-I) might play an important role in its development due to its mitogenic and anti-apoptotic properties. Methods: This study prospectively investigated the association between serum IGF-I concentrations and risk of differentiated thyroid carcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. 345 incident cases of differentiated thyroid carcinoma were individually matched to 735 controls by study centre, sex, and age, date, time, and fasting status at blood collection, follow-up duration, and for women menopausal status, use of exogenous hormones, and phase of menstrual cycle at blood collection. Serum IGF-I concentrations were measured by immunoassay, and risk of differentiated thyroid cancer in relation to IGF-I concentration was estimated using conditional logistic regression. Results: There was a positive association between IGF-I concentrations and risk of differentiated thyroid carcinoma: the odds ratio for a doubling in IGF-I concentration was 1.48 (95% confidence interval: 1.06 - 2.08; ptrend = 0.02). The positive association with IGF-I was stable over time between blood collection and cancer diagnosis. Conclusion: These findings suggest that IGF-I concentrations may be positively associated with risk of differentiated thyroid carcinoma. Impact: This study provides the first prospective evidence of a potential association between circulating IGF-I concentrations and risk of differentiated thyroid carcinoma and may prompt the further investigations needed to confirm the association.
    Cancer Epidemiology Biomarkers &amp Prevention 03/2014; · 4.56 Impact Factor
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    ABSTRACT: Background Evidence for the association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarised the published evidence and evaluated the association using individual patient data from multiple case cohorts. Materials and Methods A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates for survival time in "moderate drinkers" versus non-drinkers. An analysis of individual participant data using Cox regression was carried out using data from eleven case cohorts. Results We identified eleven published studies suitable for inclusion in the meta-analysis. Moderate post-diagnosis alcohol consumption was not associated with overall survival (HR = 0.95, 95% CI 0.85-1.05), but there was some evidence of better survival associated with pre-diagnosis consumption (HR = 0.80, 95% CI 0.73-0.88). Individual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the eleven case cohorts, all of which had data on ER status. For women with ER-positive disease there was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer-specific mortality, with some evidence of a reduction in all-cause mortality. Based on a single study, moderate post-diagnosis alcohol intake was associated with a small reduction in breast cancer-specific mortality in women with ER-negative disease. There was no association for pre-diagnosis intake in women with ER-negative disease. Impact Considering the totality of the evidence, moderate post-diagnosis alcohol consumption is unlikely to have a major adverse effect on survival of women with breast cancer.
    Cancer Epidemiology Biomarkers &amp Prevention 03/2014; · 4.56 Impact Factor
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    ABSTRACT: Epidemiological data regarding tea and coffee consumption and risk of esophageal cancer (EC) is still inconclusive. We examined the association of tea and coffee consumption with EC risk among 442,143 men and women without cancer at baseline from 9 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC). Tea and coffee intakes were recorded using country-specific validated dietary questionnaires. Cox regression models were used to analyze the relationships between tea and coffee intake and EC risk. During a mean follow-up of 11.1 years, 339 participants developed EC, of which 142 were esophageal adenocarcinoma (EAC) and 174 were esophageal squamous cell carcinoma (ESCC). In the multivariable models, no significant associations between tea (mostly black tea), and coffee intake and risk of EC, EAC and ESCC were observed. In stratified analyses, among men coffee consumption was inversely related to ESCC (HR for comparison of extreme tertiles 0.42, 95% CI 0.20-0.88; P-trend=0.022), but not among women. In current smokers, a significant and inverse association was observed between ESCC risk and tea (HR 0.46, 95% CI 0.23-0.93; P-trend=0.053) and coffee consumption (HR 0.37, 95% CI 0.19-0.73; P-trend=0.011). However, no statistically significant findings were observed using the continuous variable (per 100mL/d). These data did not show a significant association between tea and coffee consumption and EC, EAC and ESCC, although a decreased risk of ESCC among men and current smokers is suggested, but need to be confirmed in further prospective studies including more cases. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 02/2014; · 6.20 Impact Factor
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    ABSTRACT: In the prediction of time to menopause (TTM), what is the added value of anti-Müllerian hormone (AMH) when mother's age at natural menopause (ANM) is also known? AMH is a more accurate predictor of individual TTM than mother's age at menopause. Mother's ANM is considered a proxy for daughter's ANM although studies on its predictive accuracy are non-existent. AMH is a biomarker with a known capacity to predict ANM. However, its added value on top of known predictors, like mother's ANM, is unknown. Population-based cohort studies were used. To assess any additive predictive value of mother's ANM, 164 mother-daughter pairs were used (Group 1). To assess the added value of AMH, a second group of 150 women in whom AMH and mother's ANM were recorded prior to a 12-year follow-up period during which daughter's ANM was assessed was used (Group 2). Group 1 consisted of participants of the DOM cohort (an ongoing breast cancer study). Group 2 was a pooled cohort of women with regular menstrual cycles from two independent published studies. Cox proportional hazards analysis estimated uni- and multivariate regression coefficients for female age at study entry, mother's ANM and AMH in the prediction of TTM. Discrimination of models was assessed with C-statistics. Clinical added value of AMH was quantified with a net reclassification index (NRI). A model with female age and mother's ANM had a c-statistic of 79 and 85% in groups 1 and 2, respectively. Both age and mother's ANM were significantly associated with TTM (HR 1.54 and HR 0.93 for age and mother's ANM in Cohort 1 and HR 1.59 and HR 0.89 in Group 2, respectively. P-value for all <0.001). In Group 2, the multivariate model with age, mother's ANM and AMH had a c-statistic of 92%, and only female age and AMH remained significantly associated with TTM (HR 1.41 P < 0.0001; HR 0.93 P = 0.08 and HR 0.06 P < 0.0001 for age, mother's ANM and AMH, respectively). The mean weighted NRI suggests that a 47% improvement in predictive accuracy is offered by adding AMH to the model of age and mother's ANM. In conclusion, AMH and mother's ANM both have added value in forecasting TTM for the daughter based on her age. In comparison, AMH is a more accurate added predictor of TTM than mother's ANM. The cohort of women is relatively small and different cohorts of women were pooled. This study shows that AMH is a more accurate predictor of ANM than mother's ANM. However, before achieving clinical applicability, the certainty with which a woman's prediction is made must improve. The association between mother's ANM and TTM in daughters did not appear to be influenced by whether ANM was recorded by mothers or daughters-an important finding because in the clinical setting daughters usually provide this information. No funding was received and there were no competing interests in direct relation to this study.
    Human Reproduction 01/2014; · 4.67 Impact Factor
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    ABSTRACT: Cigarette smoking is the best established modifiable risk factor for pancreatic cancer. Genetic factors that underlie smoking-related pancreatic cancer have previously not been examined at the genome-wide level. Taking advantage of the existing GWAS genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study in 2,028 cases and 2,109 controls to examine gene-smoking interactions at pathway/gene/SNP level. Using the likelihood ratio test (LRT) nested in logistic regression models and Ingenuity Pathway Analysis (IPA), we examined 172 KEGG pathways, 3 manually curated gene sets, 3 nicotine-dependency GO pathways, 17,912 genes and 486,114 SNPs. None of the individual pathway/gene/SNP showed significant interaction with smoking after adjusting for multiple comparisons. Six KEGG pathways showed nominal interactions (P <0.05) with smoking, and the top two are the pancreatic secretion and salivary secretion pathways (major contributing genes: RAB8A, PLCB, and CTRB1). Nine genes, i.e. ZBED2, EXO1, PSG2, SLC36A1, CLSTN1, MTHFSD, FAT2, IL10RB, and ATXN2 had Pinteraction <0.0005. Five inter-genic region SNPs and two SNPs of the EVC and KCNIP4 genes had Pinteraction <0.00003. In IPA analysis of genes with nominal interactions with smoking, axonal guidance signaling (P=2.12×10(-7)) and α-adrenergic signaling (P=2.52×10(-5)) genes were significantly overrepresented canonical pathways. Genes contributing to the axon guidance signaling pathway included the SLIT/ROBO signaling genes that were frequently altered in pancreatic cancer. These observations need to be confirmed in additional dataset. Once confirmed, it will open a new avenue to unveiling the etiology of smoking-associated pancreatic cancer.
    Carcinogenesis 01/2014; · 5.64 Impact Factor
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    ABSTRACT: To investigate the added diagnostic value of 3.0 Tesla breast MRI over conventional breast imaging in the diagnosis of in situ and invasive breast cancer and to explore the role of routine versus expert reading. We evaluated MRI scans of patients with nonpalpable BI-RADS 3-5 lesions who underwent dynamic contrast-enhanced 3.0 Tesla breast MRI. Initially, MRI scans were read by radiologists in a routine clinical setting. All histologically confirmed index lesions were re-evaluated by two dedicated breast radiologists. Sensitivity and specificity for the three MRI readings were determined, and the diagnostic value of breast MRI in addition to conventional imaging was assessed. Interobserver reliability between the three readings was evaluated. MRI examinations of 207 patients were analyzed. Seventy-eight of 207 (37.7%) patients had a malignant lesion, of which 33 (42.3%) patients had pure DCIS and 45 (57.7%) invasive breast cancer. Sensitivity of breast MRI was 66.7% during routine, and 89.3% and 94.7% during expert reading. Specificity was 77.5% in the routine setting, and 61.0% and 33.3% during expert reading. In the routine setting, MRI provided additional diagnostic information over clinical information and conventional imaging, as the Area Under the ROC Curve increased from 0.76 to 0.81. Expert MRI reading was associated with a stronger improvement of the AUC to 0.87. Interobserver reliability between the three MRI readings was fair and moderate. 3.0 T breast MRI of nonpalpable breast lesions is of added diagnostic value for the diagnosis of in situ and invasive breast cancer.
    PLoS ONE 01/2014; 9(4):e94233. · 3.53 Impact Factor
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    ABSTRACT: Background: Imbalances in tryptophan metabolism have been linked to cancer related immune escape and implicated in several cancers, including lung cancer. Methods: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) that included 893 incident lung cancer cases and 1,748 matched controls. Circulating levels of tryptophan and six of its metabolites were measured and evaluated in relation to lung cancer risk. Results: Tryptophan (Ptrend=2x10-5) and the kynurenine/tryptophan ratio (KTR) (Ptrend=4x10-5) were associated with lung cancer risk overall after adjusting for established risk factors. The odds ratios comparing the fifth and first quintiles (OR5thvs.1st) were 0.52 (95% CI: 0.37-0.74) for tryptophan and 1.74 (95% CI: 1.24-2.45) for KTR. After adjusting for plasma methionine (available from previous work, which was strongly correlated with tryptophan), the associations of tryptophan (adjusted Ptrend=0.13) and KTR (Ptrend=0.009) were substantially attenuated. KTR was positively associated with squamous cell carcinoma, the OR5thvs.1st being 2.83 (95% CI: 1.62-4.94, Ptrend=3x10-5) that was only marginally affected by adjusting for methionine. Conclusions: This study indicates that biomarkers of tryptophan metabolism are associated with subsequent lung cancer risk. While this result would seem consistent with the immune system having a role in lung cancer development, the overall associations were dependent on methionine, and further studies are warranted to further elucidate the importance of these metabolites in lung cancer etiology. Impact: This is the first prospective study investigating the tryptophan pathway in relation to lung cancer risk.
    Cancer Epidemiology Biomarkers &amp Prevention 12/2013; · 4.56 Impact Factor
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    ABSTRACT: Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95%-confidence intervals (95%-CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.7±8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95%-CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95%-CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95%-CI 0.84-1.11) and tea (HR 0.97, 95%-CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggest that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 12/2013; · 6.20 Impact Factor
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    ABSTRACT: Background: Obesity and diabetes are potentially alterable risk factors for pancreatic cancer. Genetic factors that modify the associations of obesity and diabetes with pancreatic cancer have previously not been examined at the genome-wide level. Methods: Using GWAS genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study of 2,028 cases and 2,109 controls to examine gene-obesity and gene-diabetes interactions in relation to pancreatic cancer risk by employing the likelihood ratio test (LRT) nested in logistic regression models and Ingenuity Pathway Analysis (IPA). Results: After adjusting for multiple comparisons, a significant interaction of the chemokine signaling pathway with obesity (P=3.29×10^(-6)) and a near significant interaction of calcium signaling pathway with diabetes (P=1.57×10^(-4)) in modifying the risk of pancreatic cancer was observed. These findings were supported by results from IPA analysis of the top genes with nominal interactions. The major contributing genes to the two top pathways include GNGT2, RELA, TIAM1 and GNAS. None of the individual genes or SNPs except one SNP remained significant after adjusting for multiple testing. Notably, SNP rs10818684 of the PTGS1 gene showed an interaction with diabetes (P = 7.91×10^(-7)) at a false discovery rate of 6%. Conclusions: Genetic variations in inflammatory response and insulin resistance may affect the risk of obesity and diabetes-related pancreatic cancer. These observations should be replicated in additional large datasets. Impact: Gene-environment interaction analysis may provide new insights into the genetic susceptibility and molecular mechanisms of obesity- and diabetes-related pancreatic cancer.
    Cancer Epidemiology Biomarkers &amp Prevention 10/2013; · 4.56 Impact Factor
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    ABSTRACT: To investigate the diagnostic value of 3-Tesla (T) breast MRI in patients presenting with microcalcifications on mammography. Between January 2006 and May 2009, 123 patients with mammographically detected BI-RADS 3-5 microcalcifications underwent 3-T breast MRI before undergoing breast biopsy. All MRIs of the histopathologically confirmed index lesions were reviewed by two breast radiologists. The detection rate of invasive carcinoma and ductal carcinoma in situ (DCIS) was evaluated, as well as the added diagnostic value of MRI over mammography and breast ultrasound. At pathology, 40/123 (33 %) lesions proved malignant; 28 (70 %) DCIS and 12 (30 %) invasive carcinoma. Both observers detected all invasive malignancies at MRI, as well as 79 % (observer 1) and 86 % (observer 2) of in situ lesions. MRI in addition to conventional imaging led to a significant increase in area under the receiver operating characteristic (ROC) curve from 0.67 (95 % CI 0.56-0.79) to 0.79 (95 % CI 0.70-0.88, observer 1) and to 0.80 (95 % CI 0.71-0.89, observer 2), respectively. 3-T breast MRI was shown to add significant value to conventional imaging in patients presenting with suspicious microcalcifications on mammography. • 3-T MRI is increasingly used for breast imaging in clinical practice. • On 3-T breast MRI up to 86 % of DCIS lesions are detected. • 3-T MRI increases the diagnostic value in patients with mammographically detected microcalcifications.
    European Radiology 09/2013; · 4.34 Impact Factor
  • Anne-Claire Vergnaud, Dora Romaguera, Petra H M Peeters
    American Journal of Clinical Nutrition 08/2013; 98(2):507. · 6.50 Impact Factor
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    ABSTRACT: Increasing evidence suggests that oral microbiota play a pivotal role in chronic diseases, in addition to the well-established role in periodontal disease. Moreover, recent studies suggest that oral bacteria may also be involved in carcinogenesis; periodontal disease has been linked to several cancers. In this study, we examined whether lifestyle factors have an impact on antibody levels to oral bacteria. Data on demographic characteristics, lifestyle factors, and medical conditions were obtained at the time of blood sample collection. For the current analysis, we measured antibody levels to 25 oral bacteria in 395 cancer-free individuals using an immunoblot array. Combined total immunoglobin G (IgG) levels were obtained by summing concentrations for all oral bacteria measured. IgG antibody levels were substantially lower among current and former smokers (1,697 and 1,677 ng/mL, respectively) than never smokers (1,960 ng/mL; p trend = 0.01), but did not vary by other factors, including body mass index, diabetes, physical activity, or by dietary factors, after adjusting for age, sex, education, country, and smoking status. The highest levels of total IgG were found among individuals with low education (2,419 ng/mL). Our findings on smoking are consistent with previous studies and support the notion that smokers have a compromised humoral immune response. Moreover, other major factors known to be associated with inflammatory markers, including obesity, were not associated with antibody levels to a large number of oral bacteria.
    Cancer Causes and Control 07/2013; · 3.20 Impact Factor

Publication Stats

13k Citations
2,525.54 Total Impact Points


  • 2001–2014
    • University Medical Center Utrecht
      • • Julius Center for Health Sciences and Primary Care
      • • Department of Surgery
      Utrecht, Utrecht, Netherlands
  • 2013
    • University of Malaya
      Kuala Lumpor, Kuala Lumpur, Malaysia
    • Umeå University
      Umeå, Västerbotten, Sweden
    • Brown University
      • Department of Epidemiology
      Providence, RI, United States
  • 2009–2013
    • National and Kapodistrian University of Athens
      • Division of Hygiene - Epidemiology
      Athens, Attiki, Greece
    • University of Cambridge
      • Department of Public Health and Primary Care
      Cambridge, ENG, United Kingdom
    • Universität Bremen
      • Bremen Institute for Prevention Research and Social Medicine (BIPS)
      Bremen, Bremen, Germany
  • 2008–2013
    • Imperial College London
      • • Department of Epidemiology and Biostatistics
      • • School of Public Health
      Londinium, England, United Kingdom
    • VU University Medical Center
      • Department of Pathology
      Amsterdam, North Holland, Netherlands
    • University of Groningen
      • Laboratory for Medical Microbiology
      Groningen, Province of Groningen, Netherlands
  • 2002–2013
    • National Institute for Public Health and the Environment (RIVM)
      • Centre for Nutrition and Health
      Utrecht, Utrecht, Netherlands
    • Catalan Institute of Oncology
      • • Cancer Epidemiology Research Programme (PREC)
      • • Translational Research Laboratory
      Badalona, Catalonia, Spain
  • 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
  • 2003–2012
    • 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
    • CRO Centro di Riferimento Oncologico di Aviano
      Aviano, Friuli Venezia Giulia, Italy
    • Lund University
      Lund, Skåne, Sweden
  • 2011
    • 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
    • University of São Paulo
      • Faculdade de Saúde Pública (FSP) (São Paulo)
      Ribeirão Preto, Estado de Sao Paulo, Brazil
    • IDIBELL Bellvitge Biomedical Research Institute
      Barcino, Catalonia, Spain
    • Harvard University
      • Department of Epidemiology
      Cambridge, MA, United States
  • 2008–2011
    • Hellenic Health Foundation
      Athínai, Attica, Greece
  • 2004–2011
    • University of Oxford
      • Nuffield Department of Clinical Medicine
      Oxford, ENG, United Kingdom
    • Netherlands Cancer Institute
      • Division of Experimental Therapy
      Amsterdamo, North Holland, Netherlands
  • 2003–2011
    • International Agency for Research on Cancer
      Lyons, Rhône-Alpes, France
  • 2002–2011
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Potsdam, Brandenburg, Germany
  • 1997–2011
    • Universiteit Utrecht
      • • Julius Centre for Health Sciences and Primary Care
      • • University Medical Center Utrecht
      Utrecht, Provincie Utrecht, Netherlands
  • 2010
    • Mayo Clinic - Rochester
      • Department of Health Science Research
      Rochester, MN, United States
  • 2007–2010
    • University of Bergen
      • Institute of Medicine
      Bergen, Hordaland Fylke, Norway
    • University of Southern California
      • Department of Preventive Medicine
      Los Angeles, CA, United States
    • Athens State University
      Athens, Alabama, 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
    • 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