Petra H Peeters

National Cancer Institute (USA), 베서스다, Maryland, United States

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Publications (399)1761.7 Total impact

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    ABSTRACT: Physical inactivity and overweight are risk factors for postmenopausal breast cancer. The effect of physical activity may be partially mediated by concordant weight loss. We studied the effect on serum sex hormones, which are known to be associated with postmenopausal breast cancer risk, that is attributable to exercise by comparing randomly obtained equivalent weight loss by following a hypocaloric diet only or mainly by exercise. Overweight, insufficiently active women were randomised to a diet (N = 97), mainly exercise (N = 98) or control group (N = 48). The goal of both interventions was to achieve 5-6 kg of weight loss by following a calorie-restricted diet or an intensive exercise programme combined with only a small caloric restriction. Primary outcomes after 16 weeks were serum sex hormones and sex hormone-binding globulin (SHBG). Body fat and lean mass were measured by dual-energy X-ray absorptiometry. Both the diet (-4.9 kg) and mainly exercise (-5.5 kg) groups achieved the target weight loss. Loss of body fat was significantly greater with exercise versus diet (difference -1.4 kg, P < 0.001). In the mainly exercise arm, the reduction in free testosterone was statistically significantly greater than that of the diet arm (treatment effect ratio [TER] 0.92, P = 0.043), and the results were suggestive of a difference for androstenedione (TER 0.90, P = 0.064) and SHBG (TER 1.05, P = 0.070). Compared with the control arm, beneficial effects were seen with both interventions, diet and mainly exercise, respectively, on oestradiol (TER 0.86, P = 0.025; TER 0.83, P = 0.007), free oestradiol (TER 0.80, P = 0.002; TER 0.77, P < 0.001), SHBG (TER 1.14; TER 1.21, both P < 0.001) and free testosterone (TER 0.91, P = 0.069; TER = 0.84, P = 0.001). After adjustment for changes in body fat, intervention effects attenuated or disappeared. Weight loss with both interventions resulted in favourable effects on serum sex hormones, which have been shown to be associated with a decrease in postmenopausal breast cancer risk. Weight loss induced mainly by exercise additionally resulted in maintenance of lean mass, greater fitness, greater fat loss and a larger effect on (some) sex hormones. The greater fat loss likely explains the observed larger effects on sex hormones. identifier: NCT01511276 . Registered on 12 January 2012.
    Breast cancer research: BCR 09/2015; 17(1):120. DOI:10.1186/s13058-015-0633-9 · 5.49 Impact Factor
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    ABSTRACT: Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean=0, SD=1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which 7 metabolites and 4 ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development. This article is protected by copyright. All rights reserved. © 2015 UICC.
    International Journal of Cancer 08/2015; DOI:10.1002/ijc.29718 · 5.09 Impact Factor
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    ABSTRACT: Although it seems biologically plausible for iron to be associated with gastric carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body iron status and gastric cancer risk, we conducted a nested case-control study in the multi-centric European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured pre-diagnostic serum iron, ferritin, transferrin, and C-reactive protein, and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (OR) and 95% confidence intervals (CI) for the risk of gastric cancer by iron metrics were estimated from multivariable conditional logistic regression models. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2 =0.80, 95% CI=0.72-0.88; and OR10%increment =0.87, 95% CI=0.78-0.97, respectively). These associations seem to be restricted to noncardia gastric cancer (ferritin showed a P for heterogeneity=0.04 and TS had a P for heterogeneity=0.02), and no differences were found by histological type. TIBC increased risk of overall gastric cancer (OR50µg/dl =1.13, 95% CI=1.02-1.2) and also with noncardia gastric cancer (P for heterogeneity=0.04). Additional analysis suggests that time between blood draw and gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of gastric cancer related to higher body iron stores as measured by serum iron and ferritin. Further investigation is needed to clarify the role of iron in gastric carcinogenesis. This article is protected by copyright. All rights reserved. © 2015 UICC.
    International Journal of Cancer 07/2015; DOI:10.1002/ijc.29669 · 5.09 Impact Factor
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    Dataset: IJC2015
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    ABSTRACT: The role of amount and type of dietary fat consumption in the aetiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-h diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95%CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC=122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/d, HR=0.80, 95%CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/d, HR=0.71, 95%CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/d, HR=0.92, 95%CI: 0.68-1.25). There was no association between saturated fats (HR=1.08, 95%CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR=0.86, 95%CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk. This article is protected by copyright. All rights reserved. © 2015 UICC.
    International Journal of Cancer 06/2015; 137(11). DOI:10.1002/ijc.29643 · 5.09 Impact Factor
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    ABSTRACT: Breast cancer in situ (BCIS) diagnoses, a precursor lesion for invasive breast cancer, comprise about 20 % of all breast cancers (BC) in countries with screening programs. Family history of BC is considered one of the strongest risk factors for BCIS. To evaluate the association of BC susceptibility loci with BCIS risk, we genotyped 39 single nucleotide polymorphisms (SNPs), associated with risk of invasive BC, in 1317 BCIS cases, 10,645 invasive BC cases, and 14,006 healthy controls in the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3). Using unconditional logistic regression models adjusted for age and study, we estimated the association of SNPs with BCIS using two different comparison groups: healthy controls and invasive BC subjects to investigate whether BCIS and BC share a common genetic profile. We found that five SNPs (CDKN2BAS-rs1011970, FGFR2-rs3750817, FGFR2-rs2981582 TNRC9-rs3803662, 5p12-rs10941679) were significantly associated with BCIS risk (p-value adjusted for multiple comparisons <0.0016). Comparing invasive BC and BCIS, the largest difference was for CDKN2BAS-rs1011970 which showed a positive association with BCIS (OR = 1.24, 95 % CI: 1.11-1.38, P = 1.27x10(-4)) and no association with invasive BC (OR = 1.03, 95 % CI: 0.99-1.07, P = 0.06), with a p-value for case-case comparison of 0.006. Subgroup analyses investigating associations with ductal carcinoma in situ (DCIS) found similar associations, albeit less significant (OR = 1.25, 95 % CI: 1.09-1.42, P = 1.07x10(-3)). Additional risk analyses showed significant associations with invasive disease at the 0.05-level for 28 of the alleles and the OR estimates were consistent with those reported by other studies. Our study adds to the knowledge that several of the known BC susceptibility loci are risk factors for both BCIS and invasive BC, with the possible exception of rs1011970, a putatively functional SNP situated in the CDKN2BAS gene that may be a specific BCIS susceptibility locus.
    Breast cancer research: BCR 06/2015; 17(1):82. DOI:10.1186/s13058-015-0596-x · 5.49 Impact Factor
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    ABSTRACT: We aimed to estimate the proportion of Dutch postmenopausal breast cancer cases in 2010 that is attributable to lifestyle-related risk factors. We calculated population attributable fractions (PAFs) of potentially modifiable risk factors for postmenopausal breast cancer in Dutch women aged >50 in 2010. First, age-specific PAFs were calculated for each risk factor, based on their relative risks for postmenopausal breast cancer (from meta-analyses) and age-specific prevalence in the population (from national surveys) around the year 2000, assuming a latency period of 10 years. To obtain the overall PAF, age-specific PAFs were summed in a weighted manner, using the age-specific breast cancer incidence rates (2010) as weights. 95 % confidence intervals for PAF estimates were derived by Monte Carlo simulations. Of Dutch women >40 years, in 2000, 51 % were overweight/obese, 55 % physically inactive (<5 days/week 30 min activity), 75 % regularly consumed alcohol, 42 % ever smoked cigarettes and 79 % had a low-fibre intake (<3.4 g/1000 kJ/day). These factors combined had a PAF of 25.7 % (95 % CI 24.2-27.2), corresponding to 2,665 Dutch postmenopausal breast cancer cases in 2010. PAFs were 8.8 % (95 % CI 6.3-11.3) for overweight/obesity, 6.6 % (95 % CI 5.2-8.0) for alcohol consumption, 5.5 % (95 % CI 4.0-7.0) for physical inactivity, 4.6 % (95 % CI 3.3-6.0) for smoking and 3.2 % (95 % CI 1.6-4.8) for low-fibre intake. Our findings imply that modifiable risk factors are jointly responsible for approximately one out of four Dutch postmenopausal breast cancer cases. This suggests that incidence rates can be lowered substantially by living a more healthy lifestyle.
    Breast Cancer Research and Treatment 06/2015; 152(1). DOI:10.1007/s10549-015-3447-7 · 3.94 Impact Factor
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    ABSTRACT: This study investigates the effect of a modest weight loss either by a calorie restricted diet or mainly by increased physical exercise on health related quality of life (HRQoL) in overweight-to-obese and inactive postmenopausal women. We hypothesize that HRQoL improves with weight loss, and that exercise-induced weight loss is more effective for this than diet-induced weight loss. The SHAPE-2 trial was primarily designed to evaluate any additional effect of weight loss by exercise compared with a comparable amount of weight loss by diet on biomarkers relevant for breast cancer risk. In the present analysis we focus on HRQoL. We randomly assigned 243 eligible women to a diet (n = 97), exercise (n = 98), or control group (n = 48). Both interventions aimed for 5-6 kg weight loss. HRQoL was measured at baseline and after 16 weeks by the SF-36 questionnaire. Data of 214 women were available for analysis. Weight loss was 4.9 kg (6.1%) and 5.5 kg (6.9%) with diet and exercise, respectively. Scores of the SF-36 domain 'health change' increased significantly by 8.8 points (95% CI 1.6;16.1) with diet, and by 20.5 points (95% CI 13.2;27.7) with exercise when compared with control. Direct comparison of diet and exercise showed a statistically significantly stronger improvement with exercise. Both intervention groups showed a tendency towards improvements in most other domains, which were more pronounced in the exercise group, but not statistically different from control or each other. In a randomized trial in overweight-to-obese and inactive postmenopausal women a comparable 6%-7% weight loss was achieved by diet-only or mainly by exercise and showed improvements in physical and mental HRQoL domains, but results were not statistically significant in either the diet or exercise group. However, a modest weight loss does lead to a positive change in self-perceived health status. This effect was significantly larger with exercise-induced weight loss than with comparable diet-induced weight loss. NCT01511276.
    PLoS ONE 06/2015; 10(6):e0127520. DOI:10.1371/journal.pone.0127520 · 3.23 Impact Factor
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    ABSTRACT: Despite an extensive screening programme in The Netherlands, some cases of cervical cancer are still diagnosed in late stages of disease. The aim of the present study was to investigate which elements in the diagnostic process of cervical cancer may be improved. This is a retrospective study of 120 patients with cervical cancer diagnosed between January 1st 2008 and June 1st 2010 at the University Medical Center Utrecht. Patient charts, referral information and pathology results were analysed. 39.1% of cancer cases were screen or interval detected; the other 60.9% of patients had not been screened, either due to non-attendance or because they fell outside the age range for screening. The final diagnosis of cervical cancer was established by biopsy in 77 (64.2%) and by excision of the cervical transformation zone in 35 (29.2%) of the patients. Fifteen (43%) of these excisions could have been avoided if biopsies would have been taken at the first examination, and had shown invasive cancer. Cervical cancer screening aims at early detection of precursor lesions to decrease the incidence of cancer. This in-depth analysis suggests that improvement of quality of care is to be expected from correct recognition of cervical cancer by physicians and adjustments of the screening programme to reach younger women and non-responders. Copyright © 2015. Published by Elsevier Inc.
    Gynecologic Oncology 05/2015; 138(2). DOI:10.1016/j.ygyno.2015.05.037 · 3.77 Impact Factor
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    ABSTRACT: Purpose: All Dutch hospitals are obliged to report their 5-year ipsilateral breast tumor recurrence (IBTR) rate after breast cancer surgery. Experts decided that these rates should not exceed 5 %. This study determined the value of IBTR as an indicator to compare quality of care between hospitals. Methods: All patients with breast cancer (pT1-3, any N, M0) who underwent surgery in 1 of 92 Dutch hospitals from 2003 to 2006 were identified in the Netherlands Cancer Registry. Data of recurrence was retrieved from hospital records. Five-year IBTR rates for breast-conserving surgery (BCS) and mastectomy were calculated by using the Kaplan-Meier method. Hospital variation was presented in funnel plots. Multivariate analysis was used to assess hospital characteristics associated with IBTR rates. Results: A total of 40,892 breast cancer patients were included. The overall 5-year IBTR rate was 2.85 % (95 % confidence interval 2.68-3.03) and was significantly lower for BCS than for mastectomy (2.38 vs. 3.45 %, p < 0.001). IBTR rates decreased over time in both groups. Rates varied between 0.77 and 5.70 % between hospitals. When random variation is taken into account, only extremely high IBTR rates can be detected as deviant from the target value of 5 %. Adjusting for tumor and patient characteristics, analyses showed that a higher volume of mastectomies is associated with lower IBTR rates. Conclusions: Our population-based findings show that IBTR rates in the Netherlands are low and have improved over time. The 5-year IBTR rate as an indicator for quality of care of individual hospitals is of limited value.
    Annals of Surgical Oncology 05/2015; DOI:10.1245/s10434-015-4626-9 · 3.93 Impact Factor
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    ABSTRACT: The associations of circulating 25-hydroxyvitamin D [25(OH)D] concentrations with total and site-specific cancer incidence have been examined in several epidemiological studies with overall inconclusive findings. Very little is known about the association of vitamin D with cancer incidence in older populations. We assessed the association of pre-diagnostic serum 25(OH)D levels with incidence of all cancers combined and incidence of lung, colorectal, breast, prostate and lymphoid malignancies among older adults. Pre-diagnostic 25(OH)D concentrations and cancer incidence were available in total for 15,486 older adults (mean age 63, range 50-84 years) participating in two cohort studies: ESTHER (Germany) and TROMSØ (Norway); and a subset of previously published nested-case control data from a another cohort study: EPIC-Elderly (Greece, Denmark, Netherlands, Spain and Sweden) from the CHANCES consortium on health and aging. Cox proportional hazards or logistic regression were used to derive multivariable adjusted hazard and odds ratios, respectively, and their 95 % confidence intervals across 25(OH)D categories. Meta-analyses with random effects models were used to pool study-specific risk estimates. Overall, lower 25(OH)D concentrations were not significantly associated with increased incidence of most of the cancers assessed. However, there was some evidence of increased breast cancer and decreased lymphoma risk with higher 25(OH)D concentrations. Our meta-analyses with individual participant data from three large European population-based cohort studies provide at best limited support for the hypothesis that vitamin D may have a major role in cancer development and prevention among European older adults.
    European Journal of Epidemiology 05/2015; DOI:10.1007/s10654-015-0040-7 · 5.34 Impact Factor
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    ABSTRACT: Endometrial cancer (EC) is the fourth most frequent cancer in women in Europe, and as its incidence is increasing, prevention strategies gain further pertinence. Risk prediction models can be a useful tool for identifying women likely to benefit from targeted prevention measures. On the basis of data from 201,811 women (mostly aged 30-65 years) including 855 incident EC cases from eight countries in the European Prospective Investigation into Cancer and Nutrition cohort, a model to predict EC was developed. A step-wise model selection process was used to select confirmed predictive epidemiologic risk factors. Piece-wise constant hazard rates in 5-year age-intervals were estimated in a cause-specific competing risks model, five-fold-cross-validation was applied for internal validation. Risk factors included in the risk prediction model were body-mass index (BMI), menopausal status, age at menarche and at menopause, oral contraceptive use, overall and by different BMI categories and overall duration of use, parity, age at first full-term pregnancy, duration of menopausal hormone therapy and smoking status (specific for pre, peri- and post-menopausal women). These variables improved the discriminating capacity to predict risk over 5 years from 71 % for a model based on age alone to 77 % (overall C statistic), and the model was well-calibrated (ratio of expected to observed cases = 0.99). Our model could be used for the identification of women at increased risk of EC in Western Europe. To achieve an EC-risk model with general validity, a large-scale cohort-consortium approach would be needed to assess and adjust for population variation.
    European Journal of Epidemiology 05/2015; DOI:10.1007/s10654-015-0030-9 · 5.34 Impact Factor
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    ABSTRACT: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend <0.0001), compared to participants with the lowest concordance with the recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall mortality were observed (P for trend 0.004). Meeting the recommendations on body fatness and plant food consumption were associated with improved survival among CRC cases in mutually adjusted models. Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.
    BMC Medicine 05/2015; 13(1):107. DOI:10.1186/s12916-015-0332-5 · 7.25 Impact Factor
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    ABSTRACT: The timing of the sentinel lymph node biopsy (SNB) is controversial in clinically node negative patients receiving neoadjuvant chemotherapy (NAC). We studied variation in the timing of axillary staging in breast cancer patients who received NAC and the subsequent axillary treatment in The Netherlands. Patients diagnosed with clinically node negative primary breast cancer between 1st January 2010 and 30th June 2013 who received NAC and SNB were selected from the Netherlands Cancer Registry. Data on patient and tumour characteristics, axillary staging and treatment were analysed. Two groups were defined: (1) patients with SNB before NAC (N = 980) and (2) patients with SNB after NAC (N = 203). Eighty-three percent of patients underwent SNB before NAC, with large regional variation (35-99%). The SN identification rate differed for SNBs conducted before and after NAC (98% versus 95%; p = 0.032). A lower proportion of patients had a negative SNB when assessed before NAC compared to after (54% versus 67%; p = 0.001). The proportion of patients receiving any axillary treatment was higher for those with SNB before NAC than after (45% versus 33%; p = 0.006). In conclusion, variation exists in the timing of SNB in clinical practice in The Netherlands for clinically node negative breast cancer patients receiving NAC. The post-NAC SN procedure is, despite some lower SN identification rate, associated with a significantly less frequent axillary treatment and thus with less expected morbidity. The effect on recurrence rate is not yet clear. Patients in this registry will be followed prospectively for long-term outcome.
    European journal of cancer (Oxford, England: 1990) 05/2015; 51(8):915-921. DOI:10.1016/j.ejca.2015.03.014 · 5.42 Impact Factor
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    ABSTRACT: Menopause has been hypothesized to occur when the non-growing follicle (NGF) number falls below a critical threshold. Age at natural menopause (ANM) can be predicted using NGF numbers and this threshold. These predictions support the use of ovarian reserve tests, reflective of the ovarian follicle pool, in menopause forecasting. To investigate the hypothesis that age-specific NGF numbers reflect age at natural menopause. Histologically derived NGF numbers obtained from published literature (n=218) and distribution of menopausal ages derived from the population based Prospect-EPIC cohort (n=4037) were combined. NGF data were from single ovaries that had been obtained post-natally for various reasons, such as elective surgery or autopsy. From the Prospect-EPIC cohort, women aged 58 years and older with a known ANM were selected. None Main Outcome Measure(s): Conformity between observed age at menopause in the Prospect-EPIC cohort and NGF-predicted age at menopause from a model for age-related NGF decline constructed using a robust regression analysis. A critical threshold for NGF number was estimated by comparing the probability distribution of age at which NGF numbers fall below this threshold with the observed distribution of ANM from the Prospect-EPIC cohort. The distributions of observed age at natural menopause and predicted age at natural menopause showed close conformity. The close conformity observed between NGF-predicted and actual age at natural menopause supports the hypothesis that that the size of the primordial follicle pool is an important determinant for the length of the individual ovarian lifespan and supports the concept of menopause prediction using ovarian reserve tests, such as anti-Müllerian hormone and antral follicle count, as derivatives of the true ovarian reserve.
    The Journal of Clinical Endocrinology and Metabolism 04/2015; 100(6):jc20151298. DOI:10.1210/jc.2015-1298 · 6.21 Impact Factor
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    ABSTRACT: Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 through to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n = 931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment versus the light drinkers category were 0.78 (0.62–0.99), 0.82 (0.64–1.04), 0.70 (0.55–0.90), 0.91 (0.63–1.30), respectively, (ptrend = 0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer.
    International Journal of Cancer 04/2015; 137(8). DOI:10.1002/ijc.29559. · 5.09 Impact Factor
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    ABSTRACT: Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse. We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), interleukin-6 (IL-6), and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n=1,497) were matched per case. We used multivariable conditional logistic regression to assess associations. CRP and IL-6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 vs. CRP ≤1 mg/L was associated with higher overall EOC risk (OR=1.67 [1.03 - 2.70]). We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference: (e.g., IL-6: waist <80: ORlog2=0.97 [0.81 - 1.16]; waist >88: ORlog2=1.78 [1.28 - 2.48], pheterogeneity ≤0.01). Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL-6 and CRP may be associated with EOC risk among women with higher adiposity. Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu. Copyright © 2015, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 04/2015; DOI:10.1158/1055-9965.EPI-14-1279-T · 4.13 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.
    Nature Genetics 03/2015; DOI:10.1038/ng.3242 · 29.35 Impact Factor
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    ABSTRACT: Background: Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents. Methods: We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202,206 women in the European Prospective Investigation into Cancer and Nutrition study. Results: Older age at menopause, longer duration of hormone replacement therapy, and higher body mass index were included as increasing ovarian cancer risk, whereas unilateral ovariectomy, longer duration of oral contraceptive use, and higher number of full-term pregnancies were decreasing risk. The discriminatory power (overall concordance index) of this model, as examined with five-fold cross-validation, was 0.64 (95% confidence interval (CI): 0.57, 0.70). The ratio of the expected to observed number of ovarian cancer cases occurring in the first 5 years of follow-up was 0.90 (293 out of 324, 95% CI: 0.81-1.01), in general there was no evidence for miscalibration. Conclusion: Our ovarian cancer risk model containing only epidemiological data showed modest discriminatory power for a Western European population. Future studies should consider adding informative biomarkers to possibly improve the predictive ability of the model.
    British Journal of Cancer 03/2015; 112(7). DOI:10.1038/bjc.2015.22 · 4.84 Impact Factor
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    ABSTRACT: Background: Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations. Methods: In 486,799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes. Results: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11. Conclusions: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.
    British Journal of Cancer 03/2015; 112(7). DOI:10.1038/bjc.2014.654 · 4.84 Impact Factor

Publication Stats

11k Citations
1,761.70 Total Impact Points


  • 2015
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      베서스다, Maryland, United States
  • 2005–2015
    • Imperial College London
      • Department of Epidemiology and Biostatistics
      Londinium, England, United Kingdom
  • 1998–2015
    • University Medical Center Utrecht
      • • Department of Epidemiology
      • • Julius Center for Health Sciences and Primary Care
      • • Department of Surgery
      Utrecht, Utrecht, Netherlands
  • 2013
    • German Cancer Research Center
      • Division of Cancer Epidemiology
      Heidelberg, Baden-Wuerttemberg, Germany
  • 1995–2013
    • Utrecht University
      • Department of Epidemiology
      Utrecht, Utrecht, Netherlands
  • 2012
    • Umeå University
      • Department of Clinical Sciences
      Umeå, Västerbotten, Sweden
    • Wageningen University
      Wageningen, Gelderland, Netherlands
    • Council for Public Health and Health Care, Netherlands
      's-Gravenhage, South Holland, Netherlands
  • 2011
    • Catalan Institute of Oncology
      • Cancer Epidemiology Research Programme (PREC)
      Badalona, Catalonia, Spain
  • 2003–2011
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Potsdam, Brandenburg, Germany
    • University of Oslo
      • Department of Biostatistics
      Kristiania (historical), Oslo County, Norway
    • CRO Centro di Riferimento Oncologico di Aviano
      Aviano, Friuli Venezia Giulia, Italy
  • 2010
    • Icahn School of Medicine at Mount Sinai
      • Institute for Translational Epidemiology
      Borough of Manhattan, New York, United States
    • International Agency for Research on Cancer
      Lyons, Rhône-Alpes, France
  • 2009
    • IDIBELL Bellvitge Biomedical Research Institute
      Barcino, Catalonia, Spain
    • National Institute for Public Health and the Environment (RIVM)
      • Centre for Nutrition and Health
      Utrecht, Utrecht, Netherlands
  • 2005–2007
    • University of Naples Federico II
      Napoli, Campania, Italy
  • 1990
    • Sociaal en Cultureel Planbureau
      's-Gravenhage, South Holland, Netherlands
  • 1987–1989
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands
  • 1984–1989
    • Radboud University Nijmegen
      Nymegen, Gelderland, Netherlands