Carla H van Gils

Publications (128)777.77 Total impact

• Source

  Available from: Sabine Rohrmann

  Article: Plasma adiponectin levels and endometrial cancer risk in pre-and postmenopausal women

  Anne E Cust, Rudolf Kaaks, Christine Friedenreich, Fabrice Bonnet, Martine Laville, Annekatrin Lukanova, Sabina Rinaldi, Laure Dossus, Nadia Slimani, Eva Lundin, [......], H Bas, Bueno-De -Mesquita, Petra H M Peeters, Carla H Van Gils, Kay-Tee Khaw, Sheila Bingham, Naomi Allen, Tim Key, Mazda Jenab, Elio Riboli
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  ABSTRACT: Background: Adiponectin, an adipocytokine secreted by adipose tis-sue, is decreased in obesity, insulin resistance, type 2 diabetes, and polycystic ovary syndrome, all of which are well-established risk fac-tors for endometrial cancer.
  Epidemiology Unit (F.Be.), Istituto Nazionale Tumori Cancer Registry Julius Center for Health Sciences and Primary Care The Netherlands Clinical Gerontology. ; 69372(3508).
• Article: Fruit and Vegetable Consumption and Mortality: European Prospective Investigation Into Cancer and Nutrition.

  Max Leenders, Ivonne Sluijs, Martine M Ros, Hendriek C Boshuizen, Peter D Siersema, Pietro Ferrari, Cornelia Weikert, Anne Tjønneland, Anja Olsen, Marie-Christine Boutron-Ruault, [......], Kay-Tee Khaw, Nicholas J Wareham, Timothy J Key, Francesca L Crowe, Isabelle Romieu, Marc J Gunter, Valentina Gallo, Kim Overvad, Elio Riboli, H Bas Bueno-de-Mesquita
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  ABSTRACT: In this study, the relation between fruit and vegetable consumption and mortality was investigated within the European Prospective Investigation Into Cancer and Nutrition. Survival analyses were performed, including 451,151 participants from 10 European countries, recruited between 1992 and 2000 and followed until 2010. Hazard ratios, rate advancement periods, and preventable proportions to respectively compare risk of death between quartiles of consumption, to estimate the period by which the risk of death was postponed among high consumers, and to estimate proportions of deaths that could be prevented if all participants would shift their consumption 1 quartile upward. Consumption of fruits and vegetables was inversely associated with all-cause mortality (for the highest quartile, hazard ratio = 0.90, 95% confidence interval (CI): 0.86, 0.94), with a rate advancement period of 1.12 years (95% CI: 0.70, 1.54), and with a preventable proportion of 2.95%. This association was driven mainly by cardiovascular disease mortality (for the highest quartile, hazard ratio = 0.85, 95% CI: 0.77, 0.93). Stronger inverse associations were observed for participants with high alcohol consumption or high body mass index and suggested in smokers. Inverse associations were stronger for raw than for cooked vegetable consumption. These results support the evidence that fruit and vegetable consumption is associated with a lower risk of death.
  American journal of epidemiology 04/2013; · 5.59 Impact Factor
• Article: Adherence to the World Cancer Research Fund/American Institute for Cancer Research guidelines and risk of death in Europe: results from the European Prospective Investigation into Nutrition and Cancer cohort study.

  Anne-Claire Vergnaud, Dora Romaguera, Petra H Peeters, Carla H van Gils, Doris Sm Chan, Isabelle Romieu, Heinz Freisling, Pietro Ferrari, Françoise Clavel-Chapelon, Guy Fagherazzi, [......], Anne May, Elisabet Wirfält, Emily Sonestedt, Ingegerd Johansson, Göran Hallmans, Eiliv Lund, Elisabete Weiderpass, Christine L Parr, Elio Riboli, Teresa Norat
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  ABSTRACT: BACKGROUND: In 2007, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) issued recommendations on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE: We investigated whether concordance with WCRF/AICR recommendations is related to risk of death. DESIGN: The current study included 378,864 participants from 9 European countries enrolled in the European Prospective Investigation into Cancer and Nutrition study. At recruitment (1992-1998), dietary, anthropometric, and lifestyle information was collected. A WCRF/AICR score, which incorporated 6 of the WCRF/AICR recommendations for men [regarding body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, and alcoholic drinks (score range: 0-6)] and 7 WCRF/AICR recommendations for women [plus breastfeeding (score range: 0-7)], was constructed. Higher scores indicated greater concordance with WCRF/AICR recommendations. Associations between the WCRF/AICR score and risks of total and cause-specific death were estimated by using Cox regression analysis. RESULTS: After a median follow-up time of 12.8 y, 23,828 deaths were identified. Participants within the highest category of the WCRF/AICR score (5-6 points in men; 6-7 points in women) had a 34% lower hazard of death (95% CI: 0.59, 0.75) compared with participants within the lowest category of the WCRF/AICR score (0-2 points in men; 0-3 points in women). Significant inverse associations were observed in all countries. The WCRF/AICR score was also significantly associated with a lower hazard of dying from cancer, circulatory disease, and respiratory disease. CONCLUSION: Results of this study suggest that following WCRF/AICR recommendations could significantly increase longevity.
  American Journal of Clinical Nutrition 04/2013; · 6.67 Impact Factor
• Source

  Available from: Valeria Troncoso Baltar

  Article: A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk.

  Valéria Troncoso Baltar, Wei W Xun, Mattias Johansson, Pietro Ferrari, Shu-Chun Chuang, Caroline Relton, Per Magne Ueland, Oivind Midttun, Nadia Slimani, Mazda Jenab, [......], Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Torgny Rasmuson, Göran Hallmans, Nina Roswall, Anne Tjønneland, Elio Riboli, Paul Brennan, Paolo Vineis
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  ABSTRACT: The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms.
  European Journal of Epidemiology 03/2013; · 4.71 Impact Factor
• Article: Plasma 25(OH)vitamin D and the risk of breast cancer in the european prospective investigation into cancer and nutrition (EPIC): A nested case-control study.

  Tilman Kühn, Rudolf Kaaks, Susen Becker, Piia-Piret Eomois, Françoise Clavel-Chapelon, Marina Kvaskoff, Laure Dossus, Anne Tjønneland, Anja Olsen, Kim Overvad, [......], Nick Wareham, Kay Tee Khaw, Ruth C Travis, Julie A Schmidt, Sabina Rinaldi, Isabelle Romieu, Valentina Gallo, Neil Murphy, Elio Riboli, Jakob Linseisen
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  ABSTRACT: Experimental evidence suggests that vitamin D might play a role in the development of breast cancer. While the results of case-control studies indicate that circulating 25-hydroxyvitamin D (25(OH)D) is inversely associated with the risk of breast cancer, the results of prospective studies are inconsistent. A case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) was carried out comprising 1391 incident breast cancer cases and 1391 controls. Multivariable conditional logistic regression models did not reveal a significant overall association between season-standardized 25(OH)D levels and the risk of breast cancer (ORQ4- Q1 [95% CI]: 1.07 [0.85-1.36], ptrend =0.67). Moreover, 25(OH)D levels were not related to the risks of ER+ tumors (ORQ4- Q1 [95% CI]: 0.97 [0.67-1.38], ptrend =0.90) and ER- tumors (ORQ4- Q1 [95% CI]: 0.97 [0.66-1.42], ptrend =0.98). In HRT users, 25(OH)D was significantly inversely associated with incident breast cancer (ORlog2 [95% CI]: 0.62 [0.42-0.90], p=0.01), whereas no significant association was found in HRT non-users (ORlog2 [95% CI]: 1.14 [0.80-1.62], p=0.48). Further, a non-significant inverse association was found in women with BMIs <25 kg/m(2) (ORlog2 [95% CI]: 0.83 [0.67-1.03], p=0.09), as opposed to a borderline significant positive association in women with BMIs ≥25 kg/m(2) (ORlog2 [95% CI]: 1.30 [1.0-1.69], p=0.05). Overall, pre-diagnostic levels of circulating 25(OH)D were not related to the risk of breast cancer in the EPIC study. This result is in line with findings in the majority of prospective studies and does not support a role of vitamin D in the development of breast cancer. © 2013 Wiley Periodicals, Inc.
  International Journal of Cancer 03/2013; · 5.44 Impact Factor
• Article: Plasma carotenoid- and retinol-weighted gene scores and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.

  Sara J Hendrickson, Sara Lindström, A Heather Eliassen, Bernard A Rosner, Constance Chen, Myrto Barrdahl, Louise A Brinton, Julie E Buring, Federico Canzian, Stephen J Chanock, [......], Carlotta Sacerdote, Maria-Jose Sanchez, Anne Tjonneland, Dimitrios Trichopoulos, Carla H van Gils, Meredith Yeager, Peter Kraft, David J Hunter, Regina G Ziegler, Walter C Willett
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  ABSTRACT: BACKGROUND: Dietary and circulating carotenoids have been inversely associated with breast cancer risk, but observed associations may be due to confounding. Single nucleotide polymorphisms (SNPs) in β-carotene 15,15'-monooxygenase 1 (BCMO1), a gene encoding the enzyme involved in the first step of synthesizing vitamin A from dietary carotenoids, have been associated with circulating carotenoid concentrations and may serve as unconfounded surrogates for those biomarkers. We determined associations between variants in BCMO1 and breast cancer risk in a large cohort consortium. METHODS: We used unconditional logistic regression to test four SNPs in BCMO1 for associations with breast cancer risk in 9,226 cases and 10,420 controls from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also tested weighted multi-SNP scores composed of the two SNPs with strong, confirmed associations with circulating carotenoid concentrations. RESULTS: Neither the individual SNPs nor the weighted multi-SNP scores were associated with breast cancer risk (odds ratio (95% confidence interval) comparing extreme quintiles of weighted multi-SNP scores =1.04 (0.94-1.16) for β-carotene, 1.08 (0.98-1.20) for α-carotene, 1.04 (0.94-1.16) for β-cryptoxanthin, 0.95 (0.87-1.05) for lutein/zeaxanthin, and 0.92 (0.83-1.02) for retinol). Furthermore, no associations were observed when stratifying by estrogen receptor status, but power was limited. CONCLUSIONS: Our results do not support an association between SNPs associated with circulating carotenoid concentrations and breast cancer risk. Impact: Future studies will need additional genetic surrogates and/or sample sizes at least three times larger to contribute evidence of a causal link between carotenoids and breast cancer.
  Cancer Epidemiology Biomarkers &amp Prevention 03/2013; · 4.12 Impact Factor
• Article: Reliability of Selected Antioxidants and Compounds Involved in One-Carbon Metabolism in Two Dutch Cohorts.

  Max Leenders, Martine M Ros, Ivonne Sluijs, Hendriek C Boshuizen, Carla H van Gils, Eugène H J M Jansen, H Bas Bueno-de-Mesquita
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  ABSTRACT: Many epidemiological studies assess nutritional status based on single blood measurements, without verifying if these remain reliable over repeated measurements. This study assessed the reliability over a period of 2 to 5 yr of plasma carotenoids, vitamin C, retinol, tocopherols, and serum compounds involved in 1-carbon metabolism in a subsample of Dutch participants of European Prospective Investigation into Cancer and Nutrition (EPIC). Blood samples from 38 men from MORGEN-EPIC and 35 women from Prospect-EPIC were collected between 1993 and 1997 and again after 2 to 5 yr. The reliability of plasma carotenoids, retinol, vitamin C, and tocopherols, and of serum folate, homocysteine, and vitamins B6 and B12 was estimated using an intraclass correlation coefficient (ICC). Serum homocysteine and vitamin B12 were highly reliable biomarkers, with ICCs of 0.91 and 0.75, respectively. All other analyzed biomarkers had a slight or fair reliability over several years (ICCs ranged from 0.17 to 0.56). Most examined biomarkers showed reliability values that may lead to considerable attenuation of the risk estimate when used as exposure assessment in a risk model. If multiple measurements are not available, the risk estimates can be adjusted for the regression dilution using the ICC as adjustment coefficient.
  Nutrition and Cancer 01/2013; 65(1):17-24. · 2.78 Impact Factor
• Article: Dietary fiber intake and risk of hormonal receptor defined breast cancer in the European Prospective Investigation into Cancer and Nutrition study.

  Pietro Ferrari, Sabina Rinaldi, Mazda Jenab, Annekatrin Lukanova, Anja Olsen, Anne Tjønneland, Kim Overvad, Françoise Clavel-Chapelon, Guy Fagherazzi, Marina Touillaud, [......], Tim Key, Kay-Tee Khaw, Nicholas J Wareham, Malin Sund, Per Lenner, Nadia Slimani, Teresa Norat, Dagfinn Aune, Elio Riboli, Isabelle Romieu
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  ABSTRACT: BACKGROUND: Limited scientific evidence has characterized the association between dietary fiber intake and risk of breast cancer (BC) by menopausal status and hormone receptor expression in tumors. OBJECTIVE: We investigated the relation between total dietary fiber and its main food sources (vegetables, fruit, cereals, and legumes) and BC risk by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: A total of 11,576 invasive BC cases in 334,849 EPIC women mostly aged 35-70 y at baseline were identified over a median follow up of 11.5 y. Dietary fiber was estimated from country-specific dietary questionnaires. Multivariable Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk with energy adjustment by using the residual method. Subgroup analyses were performed by menopausal status and estrogen receptor (ER) and progesterone receptor (PR) expression in tumors. RESULTS: BC risk was inversely associated with intakes of total dietary fiber (HR(Q5-Q1): 0.95; 95% CI: 0.89, 1.01; P-trend = 0.03) and fiber from vegetables (0.90; 0.84, 0.96; P-trend < 0.01) but not with fiber from fruit, cereals, or legumes. Overall, associations were homogeneous by menopausal status and ER and PR expression in tumors. For vegetable fiber, stronger associations were observed for estrogen receptor-negative and progesterone receptor-negative (HR(Q5-Q1):0.74; 95% CI: 0.59, 0.93; P-trend = 0.01) than for estrogen receptor-positive and progesterone receptor-positive tumors (0.92: 0.81, 1.03; P-trend = 0.05), with P-heterogeneity = 0.09. CONCLUSION: Diets rich in dietary fiber and, particularly, fiber from vegetables may be associated with a small reduction in risk of BC, independently of menopausal status.
  American Journal of Clinical Nutrition 12/2012; · 6.67 Impact Factor
• Article: Height, age at menarche and risk of hormone receptor positive and negative breast cancer: A cohort study.

  Rebecca Ritte, Annekatrin Lukanova, Anne Tjønneland, Anja Olsen, Kim Overvad, Sylvie Mesrine, Guy Fagherazzi, Laure Dossus, Birgit Teucher, Karen Steindorf, [......], Sanda Krum-Hansen, Inger Torhild Gram, Eiliv Lund, Malin Sund, Anne Andersson, Isabelle Romieu, Sabina Rinaldi, Valerie McCormack, Elio Riboli, Rudolf Kaaks
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  ABSTRACT: Associations of breast cancer overall with indicators of exposures during puberty are reasonably well characterized; however, uncertainty remains regarding the associations of height, leg length, sitting height and menarcheal age with hormone-receptor defined malignancies. Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of adult height, leg length and sitting height and age at menarche with risk of ER-PR- (n=990) and ER+PR+ (n=3,524) breast tumors. Height as a single risk factor was compared to a model combining leg length and sitting height. The possible interactions of height, leg length and sitting height with menarche were also analyzed. Risk of both ER-PR- and ER+PR+ malignancies was positively associated with standing height, leg length and sitting height and inversely associated with increasing age at menarche. For ER+PR+ disease, sitting height (HR: 1.14[95%CI 1.08-1.20]) had a stronger risk association than leg length (1.05[1.00-1.11]). In comparison, for ER-PR- disease, no distinct differences were observed between leg length and sitting height. Women who were tall and had an early menarche (≤13 years), showed an almost two-fold increase in risk of ER+PR+ tumors but no such increase in risk was observed for ER-PR- disease. Indicators of exposures during rapid growth periods were associated with risks of both HR-defined breast cancers. Exposures during childhood promoting faster development may establish risk associations for both HR-positive and negative malignancies. The stronger associations of the components of height with ER+PR+ tumors among older women suggest possible hormonal links that could be specific for postmenopausal women. © 2012 Wiley Periodicals, Inc.
  International Journal of Cancer 10/2012; · 5.44 Impact Factor
• Article: A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11.

  Afshan Siddiq, Fergus J Couch, Gary K Chen, Sara Lindström, Diana Eccles, Robert C Millikan, Kyriaki Michailidou, Daniel O Stram, Lars Beckmann, Suhn Kyong Rhie, [......], Elad Ziv, Heli Nevanlinna, Douglas F Easton, David J Hunter, Brian E Henderson, Stephen J Chanock, Montserrat Garcia-Closas, Peter Kraft, Christopher A Haiman, Celine M Vachon
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  ABSTRACT: Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10(-8)) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10(-6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10(-9)), and with both ER-positive (OR = 1.09; P = 1.5 × 10(-5)) and ER-negative (OR = 1.16, P = 2.5 × 10(-7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.
  Human Molecular Genetics 09/2012; · 7.64 Impact Factor
• Article: Plasma carotenoids and vitamin C concentrations and risk of urothelial cell carcinoma in the European Prospective Investigation into Cancer and Nutrition.

  Martine M Ros, H Bas Bueno-de-Mesquita, Ellen Kampman, Katja Kh Aben, Frederike L Büchner, Eugene Hjm Jansen, Carla H van Gils, Lars Egevad, Kim Overvad, Anne Tjønneland, [......], Peter Wallström, Börje Ljungberg, Göran Hallmans, Timothy J Key, Naomi E Allen, Kay-Tee Khaw, Nick Wareham, Paul Brennan, Elio Riboli, Lambertus A Kiemeney
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  ABSTRACT: Published associations between dietary carotenoids and vitamin C and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. We investigated the association between plasma carotenoids and vitamin C and risk of urothelial cell carcinoma (UCC) in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 856 patients with newly diagnosed UCC were matched with 856 cohort members by sex, age at baseline, study center, date and time of blood collection, and fasting status. Plasma carotenoids (α- and β-carotene, β-cryptoxanthin, lycopene, lutein, and zeaxanthin) were measured by using reverse-phase HPLC, and plasma vitamin C was measured by using a colorimetric assay. Incidence rate ratios (IRRs) were estimated by using conditional logistic regression with adjustment for smoking status, duration, and intensity. UCC risk decreased with higher concentrations of the sum of plasma carotenoids (IRR for the highest compared with the lowest quartile: 0.64; 95% CI: 0.44, 0.93; P-trend = 0.04). Plasma β-carotene was inversely associated with aggressive UCC (IRR: 0.51; 95% CI: 0.30, 0.88; P-trend = 0.02). Plasma lutein was inversely associated with risk of nonaggressive UCC (IRR: 0.56; 95% CI: 0.32, 0.98; P-trend = 0.05). No association was observed between plasma vitamin C and risk of UCC. Although residual confounding by smoking or other factors cannot be excluded, higher concentrations of plasma carotenoids may reduce risk of UCC, in particular aggressive UCC. Plasma lutein may reduce risk of nonaggressive UCC.
  American Journal of Clinical Nutrition 09/2012; 96(4):902-10. · 6.67 Impact Factor
• Article: Fruit and vegetable consumption and risk of aggressive and non-aggressive urothelial cell carcinomas in the European Prospective Investigation into Cancer and Nutrition.

  Martine M Ros, H Bas Bueno-de-Mesquita, Ellen Kampman, Frederike L Büchner, Katja K H Aben, Lars Egevad, Kim Overvad, Anne Tjønneland, Nina Roswall, Francoise Clavel-Chapelon, [......], Roy Ernström, Börje Ljungberg, Naomi E Allen, Timothy J Key, Kee-Tee Khaw, Nick Wareham, Nadia Slimani, Isabelle Romieu, Lambertus A Kiemeney, Elio Riboli
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  ABSTRACT: BACKGROUND: Many epidemiological studies have examined fruit and vegetable consumption in relation to the risk of urothelial cell carcinoma (UCC) of the bladder, but results are inconsistent. The association between fruit and vegetable consumption and UCC risk may vary by bladder tumour aggressiveness. Therefore, we examined the relation between fruit and vegetable consumption and the risk of aggressive and non-aggressive UCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: After 8.9years of follow-up, 947UCC were diagnosed among 468,656 EPIC participants. Of these, 421 could be classified as aggressive UCC and 433 as non-aggressive UCC cases. At recruitment, fruit and vegetable consumption was assessed by validated dietary questionnaires. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for smoking status, duration and intensity of smoking, and energy intake. RESULTS: Total consumption of fruits and vegetables was not associated with aggressive UCC nor with non-aggressive UCC. A 25g/day increase in leafy vegetables and grapes consumption was associated with a reduced risk of non-aggressive UCC (hazard ratio (HR) 0.88; 95%confidence interval (CI) 0.78-1.00 and HR 0.87; 95%CI 0.77-0.98, respectively), while the intake of root vegetables was inversely associated with risk of aggressive UCC (HR 0.87; 95%CI 0.77-0.98). CONCLUSION: Our study did not confirm a protective effect of total fruit and/or vegetable consumption on aggressive or non-aggressive UCC. High consumption of certain types of vegetables and of fruits may reduce the risk of aggressive or non-aggressive UCC; however chance findings cannot be excluded.
  European journal of cancer (Oxford, England: 1990) 08/2012; · 4.12 Impact Factor
• Article: Effect of compression paddle tilt correction on volumetric breast density estimation.

  Michiel G J Kallenberg, Carla H van Gils, Mariëtte Lokate, Gerard J den Heeten, Nico Karssemeijer
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  ABSTRACT: For the acquisition of a mammogram, a breast is compressed between a compression paddle and a support table. When compression is applied with a flexible compression paddle, the upper plate may be tilted, which results in variation in breast thickness from the chest wall to the breast margin. Paddle tilt has been recognized as a major problem in volumetric breast density estimation methods. In previous work, we developed a fully automatic method to correct the image for the effect of compression paddle tilt. In this study, we investigated in three experiments the effect of paddle tilt and its correction on volumetric breast density estimation. Results showed that paddle tilt considerably affected accuracy of volumetric breast density estimation, but that effect could be reduced by tilt correction. By applying tilt correction, a significant increase in correspondence between mammographic density estimates and measurements on MRI was established. We argue that in volumetric breast density estimation, tilt correction is both feasible and essential when mammographic images are acquired with a flexible compression paddle.
  Physics in Medicine and Biology 07/2012; 57(16):5155-68. · 2.83 Impact Factor
• Article: Dietary glycemic index and glycemic load and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

  Isabelle Romieu, Pietro Ferrari, Sabina Rinaldi, Nadia Slimani, Mazda Jenab, Anja Olsen, Anne Tjonneland, Kim Overvad, Marie-Christine Boutron-Ruault, Martin Lajous, [......], Elisabet Wirfält, Göran Hallmans, Ingegerd Johansson, Timothy J Key, Naomi E Allen, Kay-Tee Khaw, Nicholas J Wareham, Teresa Norat, Elio Riboli, Françoise Clavel-Chapelon
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  ABSTRACT: The glycemic potential of a diet is associated with chronically elevated insulin concentrations, which may augment breast cancer (BC) risk by stimulating insulin receptor or by affecting insulin-like growth factor I (IGF-I)-mediated mitogenesis. It is unclear whether this effect differs by BC phenotype. The objective was to investigate the relation between glycemic index (GI), glycemic load (GL), and total carbohydrate intake with BC by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). We identified 11,576 women with invasive BC among 334,849 EPIC women aged 34-66 y (5th to 95th percentiles) at baseline over a median follow-up of 11.5 y. Dietary GI and GL were calculated from country-specific dietary questionnaires. We used multivariable Cox proportional hazards models to quantify the association between GI, GL, and carbohydrate intake and BC risk. BC tumors were classified by receptor status. Overall GI, GL, and carbohydrates were not related to BC. Among postmenopausal women, GL and carbohydate intake were significantly associated with an increased risk of estrogen receptor-negative (ER(-)) BC when extreme quintiles (Q) were compared [multivariable HR(Q5-Q1) (95% CI) = 1.36 (1.02, 1.82; P-trend = 0.010) and HR(Q5-Q1) = 1.41 (1.05, 1.89; P-trend = 0.009), respectively]. Further stratification by progesterone receptor (PR) status showed slightly stronger associations with ER(-)/PR(-) BC [HR(Q5-Q1) (95% CI) = 1.48 (1.07, 2.05; P-trend = 0.010) for GL and HR(Q5-Q1) = 1.62 (1.15, 2.30; P-trend = 0.005) for carbohydrates]. No significant association with ER-positive BC was observed. Our results indicate that a diet with a high GL and carbohydrate intake is positively associated with an increased risk of developing ER(-) and ER(-)/PR(-) BC among postmenopausal women.
  American Journal of Clinical Nutrition 07/2012; 96(2):345-55. · 6.67 Impact Factor
• Source

  Available from: Alexander Teumer

  Article: A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.

  Andrea D Coviello, Robin Haring, Melissa Wellons, Dhananjay Vaidya, Terho Lehtimäki, Sarah Keildson, Kathryn L Lunetta, Chunyan He, Myriam Fornage, Vasiliki Lagou, [......], Timothy M Frayling, Anna Murray, Steve Franks, Marjo-Riitta Järvelin, Frank H de Jong, Olli Raitakari, Alexander Teumer, Claes Ohlsson, Joanne M Murabito, John R B Perry
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  ABSTRACT: Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8 × 10(-106)), PRMT6 (rs17496332, 1p13.3, p = 1.4 × 10(-11)), GCKR (rs780093, 2p23.3, p = 2.2 × 10(-16)), ZBTB10 (rs440837, 8q21.13, p = 3.4 × 10(-09)), JMJD1C (rs7910927, 10q21.3, p = 6.1 × 10(-35)), SLCO1B1 (rs4149056, 12p12.1, p = 1.9 × 10(-08)), NR2F2 (rs8023580, 15q26.2, p = 8.3 × 10(-12)), ZNF652 (rs2411984, 17q21.32, p = 3.5 × 10(-14)), TDGF3 (rs1573036, Xq22.3, p = 4.1 × 10(-14)), LHCGR (rs10454142, 2p16.3, p = 1.3 × 10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7 × 10(-08)), and UGT2B15 (rs293428, 4q13.2, p = 5.5 × 10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5 × 10(-08), women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ~15.6% and ~8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
  PLoS Genetics 07/2012; 8(7):e1002805. · 8.69 Impact Factor
• Article: Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk of cancer? Results from the EPIC study.

  Dora Romaguera, Anne-Claire Vergnaud, Petra H Peeters, Carla H van Gils, Doris S M Chan, Pietro Ferrari, Isabelle Romieu, Mazda Jenab, Nadia Slimani, Françoise Clavel-Chapelon, [......], Frederike L Büchner, Elisabet Wirfält, Jonas Manjer, Ingegerd Johansson, Göran Hallmans, Guri Skeie, Kristin Benjaminsen Borch, Christine L Parr, Elio Riboli, Teresa Norat
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  ABSTRACT: In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models. Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers. Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer.
  American Journal of Clinical Nutrition 05/2012; 96(1):150-63. · 6.67 Impact Factor
• Article: Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study.

  Rebecca Ritte, Annekatrin Lukanova, Franco Berrino, Laure Dossus, Anne Tjønneland, Anja Olsen, Thure Filskov Overvad, Kim Overvad, Françoise Clavel-Chapelon, Agnès Fournier, [......], Kay-Tee Khaw, Nick Wareham, Naomi E Allen, Timothy J Key, Isabelle Romieu, Sabina Rinaldi, Afshan Siddiq, David Cox, Elio Riboli, Rudolf Kaaks
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  ABSTRACT: Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use. Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed. For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime. An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors.
  Breast cancer research: BCR 05/2012; 14(3):R76. · 5.24 Impact Factor
• Article: Prognostic value of estrogen receptor α and progesterone receptor conversion in distant breast cancer metastases.

  Laurien D C Hoefnagel, Cathy B Moelans, S L Meijer, Henk-Jan van Slooten, Pieter Wesseling, Jelle Wesseling, Pieter J Westenend, Joost Bart, Cornelis A Seldenrijk, Iris D Nagtegaal, Joost Oudejans, Paul van der Valk, Carla H van Gils, Elsken van der Wall, Paul J van Diest
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  ABSTRACT: Changes in the receptor profile of primary breast cancers to their metastases (receptor conversion) have been described for the estrogen receptor α (ERα) and progesterone receptor (PR). The purpose of this study was to evaluate the impact of receptor conversion for ERα and PR on survival in a large group of distant non-bone breast cancer metastases. Receptor conversion was studied by immunohistochemistry in a group of 233 metastatic breast cancer patients. Kaplan-Meier overall survival curves were plotted, and differences between the curves were analyzed by log-rank analysis. The additional prognostic value of conversion to established prognosticators was studied by Cox regression. Overall survival of patients showing conversion from positive to negative ERα or PR, or from negative to positive ERα or PR, or remaining receptor negative was comparable, and significantly worse than patients remaining receptor positive. ERα or PR receptor conversion from positive in the primary breast tumor to negative in distant metastases has independent negative prognostic value. ERα or PR receptor conversion from positive in the primary breast cancer to negative in distant metastases has negative prognostic value. Cancer 2012. © 2012 American Cancer Society.
  Cancer 03/2012; 118(20):4929-35. · 4.77 Impact Factor
• Source

  Available from: Jerome I Rotter

  Article: Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

  Lisette Stolk, John R B Perry, Daniel I Chasman, Chunyan He, Massimo Mangino, Patrick Sulem, Maja Barbalic, Linda Broer, Enda M Byrne, Florian Ernst, [......], Elizabeth A Streeten, Unnur Thorsteinsdottir, Manuela Uda, G Uitterlinden, Cornelia M van Duijn, Henry, Anna Murray, Joanne M Murabito, Jenny A Visser, Kathryn L Lunetta
  Nature Genetics 01/2012; 44(3):260-268. · 35.53 Impact Factor
• Article: A bead-based multiplexed immunoassay to evaluate breast cancer biomarkers for early detection in pre-diagnostic serum.

  Annemieke W J Opstal-van Winden, Wendy Rodenburg, Jeroen L A Pennings, Conny T M van Oostrom, Jos H Beijnen, Petra H M Peeters, Carla H van Gils, Annemieke de Vries
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  ABSTRACT: This study investigates whether a set of ten potential breast cancer serum biomarkers and cancer antigens (osteopontin (OPN), haptoglobin, cancer antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125), prolactin, cancer antigen 19-9 (CA19-9), α-fetoprotein (AFP), leptin and migration inhibitory factor (MIF)) can predict early stage breast cancer in samples collected before clinical diagnosis (phase III samples). We performed a nested case-control study within the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort. We examined to what extent the biomarker panel could discriminate between 68 women diagnosed with breast cancer up to three years after enrollment and 68 matched healthy controls (all 56-64 years at baseline). Using a quantitative bead-based multiplexed assay, we determined protein concentrations in serum samples collected at enrollment. Principal Component Analysis (PCA) and Random Forest (RF) analysis revealed that on the basis of all ten proteins, early cases could not be separated from controls. When we combined serum protein concentrations and subject characteristics related to breast cancer risk in the RF analysis, this did not result in classification accuracy scores that could correctly classify the samples (sensitivity: 50%, specificity: 50%). Our findings indicate that this panel of selected tumor markers cannot be used for diagnosis of early breast cancer.
  International Journal of Molecular Sciences 01/2012; 13(10):13587-604. · 2.60 Impact Factor