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Lagiou, Pagona

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Lagiou, Pagona
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    Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European Prospective Investigation into Cancer and Nutrition Study (EPIC)123456
    (American Society for Nutrition, 2015) Ekelund, Ulf; Ward, Heather A; Norat, Teresa; Luan, Jian’an; May, Anne M; Weiderpass, Elisabete; Sharp, Stephen J; Overvad, Kim; Østergaard, Jane Nautrup; Tjønneland, Anne; Johnsen, Nina Føns; Mesrine, Sylvie; Fournier, Agnès; Fagherazzi, Guy; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Li, Kuanrong; Kaaks, Rudolf; Ferrari, Pietro; Licaj, Idlir; Jenab, Mazda; Bergmann, Manuela; Boeing, Heiner; Palli, Domenico; Sieri, Sabina; Panico, Salvatore; Tumino, Rosario; Vineis, Paolo; Peeters, Petra H; Monnikhof, Evelyn; Bueno-de-Mesquita, H Bas; Quirós, J Ramón; Agudo, Antonio; Sánchez, María-José; Huerta, José María; Ardanaz, Eva; Arriola, Larraitz; Hedblad, Bo; Wirfält, Elisabet; Sund, Malin; Johansson, Mattias; Key, Timothy J; Travis, Ruth C; Khaw, Kay-Tee; Brage, Søren; Wareham, Nicholas J; Riboli, Elio
    Background: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear. Objective: We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures. Design: This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m2) (>30), and WC (≥102 cm for men, ≥88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures. Results: Significant interactions (PA × BMI and PA × WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16–30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity. Conclusion: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health.
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    Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort
    (BioMed Central, 2015) Fages, Anne; Duarte-Salles, Talita; Stepien, Magdalena; Ferrari, Pietro; Fedirko, Veronika; Pontoizeau, Clément; Trichopoulou, Antonia; Aleksandrova, Krasimira; Tjønneland, Anne; Olsen, Anja; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Kaaks, Rudolf; Kuhn, Tilman; Floegel, Anna; Boeing, Heiner; Lagiou, Pagona; Bamia, Christina; Trichopoulos, Dimitrios; Palli, Domenico; Pala, Valeria; Panico, Salvatore; Tumino, Rosario; Vineis, Paolo; Bueno-de-Mesquita, H. Bas; Peeters, Petra H.; Weiderpass, Elisabete; Agudo, Antonio; Molina-Montes, Esther; Huerta, José María; Ardanaz, Eva; Dorronsoro, Miren; Sjöberg, Klas; Ohlsson, Bodil; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth C.; Schmidt, Julie A.; Cross, Amanda; Gunter, Marc; Riboli, Elio; Scalbert, Augustin; Romieu, Isabelle; Elena-Herrmann, Benedicte; Jenab, Mazda
    Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. Methods: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. Results: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. Conclusion: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0462-9) contains supplementary material, which is available to authorized users.
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    Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition; a cohort study
    (BioMed Central, 2015) Merritt, Melissa A.; Riboli, Elio; Murphy, Neil; Kadi, Mai; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Dossus, Laure; Dartois, Laureen; Clavel-Chapelon, Françoise; Fortner, Renée T.; Katzke, Verena A.; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Sacerdote, Carlotta; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Peeters, Petra H.; Lund, Eiliv; Nakamura, Aurelie; Weiderpass, Elisabete; Quirós, J. Ramón; Agudo, Antonio; Molina-Montes, Esther; Larrañaga, Nerea; Dorronsoro, Miren; Cirera, Lluís; Barricarte, Aurelio; Olsson, Åsa; Butt, Salma; Idahl, Annika; Lundin, Eva; Wareham, Nicholas J.; Key, Timothy J.; Brennan, Paul; Ferrari, Pietro; Wark, Petra A.; Norat, Teresa; Cross, Amanda J.; Gunter, Marc J.
    Background: Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation of reproductive characteristics with all-cause and cause-specific mortality risk. Methods: The analysis was performed within the European Investigation into Cancer and Nutrition prospective cohort study, which enrolled >500,000 women and men from 1992 to 2000, who were residing in a given town/geographic area in 10 European countries. The current analysis included 322,972 eligible women aged 25–70 years with 99 % complete follow-up for vital status. We assessed reproductive characteristics reported at the study baseline including parity, age at the first birth, breastfeeding, infertility, oral contraceptive use, age at menarche and menopause, total ovulatory years, and history of oophorectomy/hysterectomy. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality were determined using Cox proportional hazards regression models adjusted for menopausal status, body mass index, physical activity, education level, and smoking status/intensity and duration. Results: During a mean follow-up of 12.9 years, 14,383 deaths occurred. The HR (95 % CI) for risk of all-cause mortality was lower in parous versus nulliparous women (0.80; 0.76–0.84), in women who had ever versus never breastfed (0.92; 0.87–0.97), in ever versus never users of oral contraceptives (among non-smokers; 0.90; 0.86–0.95), and in women reporting a later age at menarche (≥15 years versus <12; 0.90; 0.85–0.96; P for trend = 0.038). Conclusions: Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes. These findings may contribute to the development of improved strategies to promote better long-term health in women. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0484-3) contains supplementary material, which is available to authorized users.
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    Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study
    (BioMed Central, 2015) Tikk, Kaja; Sookthai, Disorn; Fortner, Renée T; Johnson, Theron; Rinaldi, Sabina; Romieu, Isabelle; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Clavel-Chapelon, Françoise; Baglietto, Laura; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Masala, Giovanna; Krogh, Vittorio; Tumino, Rosario; Ricceri, Fulvio; Mattiello, Amalia; Agudo, Antonio; Menéndez, Virginia; Sánchez, María-José; Amiano, Pilar; Chirlaque, Maria-Dolores; Barricarte, Aurelio; Bueno-de-Mesquita, HBas; Monninkhof, Evelyn M; Onland-Moret, N Charlotte; Andresson, Anne; Sund, Malin; Weiderpass, Elisabete; Khaw, Kay-Tee; Key, Timothy J; Travis, Ruth C; Merritt, Melissa A; Riboli, Elio; Dossus, Laure; Kaaks, Rudolf
    Introduction: The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention. Methods: We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects. Results: We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95% CI 1.04-1.76), Ptrend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (Phet = 0.98) or baseline HT use (Phet = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (Ptrend = 0.06 vs Ptrend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors <4 years compared to ≥4 years after blood donation (Ptrend = 0.01 vs Ptrend = 0.63; Phet = 0.04) and among nulliparous women compared to parous women (Ptrend = 0.03 vs Ptrend = 0.15; Phet = 0.07). Conclusions: Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.
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    Correction to: Early presence of anti-angiogenesis-related adverse events as a potential biomarker of antitumor efficacy in metastatic gastric cancer patients treated with apatinib: a cohort study
    (BioMed Central, 2018) Liu, Xinyang; Qin, Shukui; Wang, Zhichao; Xu, Jianming; Xiong, Jianping; Bai, Yuxian; Wang, Zhehai; Yang, Yan; Sun, Guoping; Wang, Liwei; Zheng, Leizhen; Xu, Nong; Cheng, Ying; Guo, Weijian; Yu, Hao; Liu, Tianshu; Lagiou, Pagona; Li, Jin
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    A Nested Case–Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
    (Public Library of Science, 2016) Murphy, Neil; Cross, Amanda J.; Abubakar, Mustapha; Jenab, Mazda; Aleksandrova, Krasimira; Boutron-Ruault, Marie-Christine; Dossus, Laure; Racine, Antoine; Kühn, Tilman; Katzke, Verena A.; Tjønneland, Anne; Petersen, Kristina E. N.; Overvad, Kim; Quirós, J. Ramón; Jakszyn, Paula; Molina-Montes, Esther; Dorronsoro, Miren; Huerta, José-María; Barricarte, Aurelio; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth C.; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Masala, Giovanna; Krogh, Vittorio; Tumino, Rosario; Vineis, Paolo; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Siersema, Peter D.; Peeters, Petra H.; Ohlsson, Bodil; Ericson, Ulrika; Palmqvist, Richard; Nyström, Hanna; Weiderpass, Elisabete; Skeie, Guri; Freisling, Heinz; Kong, So Yeon; Tsilidis, Kostas; Muller, David C.; Riboli, Elio; Gunter, Marc J
    Background: Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. Methods and Findings: The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10–2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01–1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65–1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49–0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of individuals as being hyperinsulinaemic—based on their C-peptide level—was arbitrary. However, when we used quartiles or the median of C-peptide, instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pattern of associations was observed. Conclusions: These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.
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    Early presence of anti-angiogenesis-related adverse events as a potential biomarker of antitumor efficacy in metastatic gastric cancer patients treated with apatinib: a cohort study
    (BioMed Central, 2017) Liu, Xinyang; Qin, Shukui; Wang, Zhichao; Xu, Jianming; Xiong, Jianping; Bai, Yuxian; Wang, Zhehai; Yang, Yan; Sun, Guoping; Wang, Liwei; Zheng, Leizhen; Xu, Nong; Cheng, Ying; Guo, Weijian; Yu, Hao; Liu, Tianshu; Lagiou, Pagona; Li, Jin
    Background: Reliable biomarkers of apatinib response in gastric cancer (GC) are lacking. We investigated the association between early presence of common adverse events (AEs) and clinical outcomes in metastatic GC patients. Patients and methods We conducted a retrospective cohort study using data on 269 apatinib-treated GC patients in two clinical trials. AEs were assessed at baseline until 28 days after the last dose of apatinib. Clinical outcomes were compared between patients with and without hypertension (HTN), proteinuria, or hand and foot syndrome (HFS) in the first 4 weeks. Time-to-event variables were assessed using Kaplan–Meier methods and Cox proportional hazard regression models. Binary endpoints were assessed using logistic regression models. Landmark analyses were performed as sensitivity analyses. Predictive model was analyzed, and risk scores were calculated to predict overall survival. Results: Presence of AEs in the first 4 weeks was associated with prolonged median overall survival (169 vs. 103 days, log-rank p = 0.0039; adjusted hazard ratio (HR) 0.64, 95% confidence interval [CI] 0.64–0.84, p = 0.001), prolonged median progression-free survival (86.5 vs. 62 days, log-rank p = 0.0309; adjusted HR 0.69, 95% CI 0.53–0.91, p = 0.007), and increased disease control rate (54.67 vs. 32.77%; adjusted odds ratio 2.67, p < 0.001). Results remained significant in landmark analyses. The onset of any single AE or any combinations of the AEs were all statistically significantly associated with prolonged OS, except for the presence of proteinuria. An AE-based prediction model and subsequently derived scoring system showed high calibration and discrimination in predicting overall survival. Conclusion: Presence of HTN, proteinuria, or HFS during the first cycle of apatinib treatment was a viable biomarker of antitumor efficacy in metastatic GC patients. Electronic supplementary material The online version of this article (10.1186/s13045-017-0521-0) contains supplementary material, which is available to authorized users.
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    Methylome Analysis and Epigenetic Changes Associated with Menarcheal Age
    (Public Library of Science, 2013) Demetriou, Christiana A.; Chen, Jia; Polidoro, Silvia; van Veldhoven, Karin; Cuenin, Cyrille; Campanella, Gianluca; Brennan, Kevin; Clavel-Chapelon, Françoise; Dossus, Laure; Kvaskoff, Marina; Drogan, Dagmar; Boeing, Heiner; Kaaks, Rudolf; Risch, Angela; Trichopoulos, Dimitrios; Lagiou, Pagona; Masala, Giovanna; Sieri, Sabina; Tumino, Rosario; Panico, Salvatore; Quirós, J. Ramón; Sánchez Perez, María-José; Amiano, Pilar; Huerta Castaño, José María; Ardanaz, Eva; Onland-Moret, Charlotte; Peeters, Petra; Khaw, Kay-Tee; Wareham, Nick; Key, Timothy J.; Travis, Ruth C.; Romieu, Isabelle; Gallo, Valentina; Gunter, Marc; Herceg, Zdenko; Kyriacou, Kyriacos; Riboli, Elio; Flanagan, James M.; Vineis, Paolo
    Reproductive factors have been linked to both breast cancer and DNA methylation, suggesting methylation as an important mechanism by which reproductive factors impact on disease risk. However, few studies have investigated the link between reproductive factors and DNA methylation in humans. Genome-wide methylation in peripheral blood lymphocytes of 376 healthy women from the prospective EPIC study was investigated using LUminometric Methylation Assay (LUMA). Also, methylation of 458877 CpG sites was additionally investigated in an independent group of 332 participants of the EPIC-Italy sub-cohort, using the Infinium HumanMethylation 450 BeadChip. Multivariate logistic regression and linear models were used to investigate the association between reproductive risk factors and genome wide and CpG-specific DNA methylation, respectively. Menarcheal age was inversely associated with global DNA methylation as measured with LUMA. For each yearly increase in age at menarche, the risk of having genome wide methylation below median level was increased by 32% (OR:1.32, 95%CI:1.14–1.53). When age at menarche was treated as a categorical variable, there was an inverse dose-response relationship with LUMA methylation levels (OR12–14vs.≤11 yrs:1.78, 95%CI:1.01–3.17 and OR≥15vs.≤11 yrs:4.59, 95%CI:2.04–10.33; P for trend<0.0001). However, average levels of global methylation as measured by the Illumina technology were not significantly associated with menarcheal age. In locus by locus comparative analyses, only one CpG site had significantly different methylation depending on the menarcheal age category examined, but this finding was not replicated by pyrosequencing in an independent data set. This study suggests a link between age at menarche and genome wide DNA methylation, and the difference in results between the two arrays suggests that repetitive element methylation has a role in the association. Epigenetic changes may be modulated by menarcheal age, or the association may be a mirror of other important changes in early life that have a detectable effect on both methylation levels and menarcheal age.
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    Consumption of Dairy Products and Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
    (Public Library of Science, 2013) Murphy, Neil; Norat, Teresa; Ferrari, Pietro; Jenab, Mazda; Bueno-de-Mesquita, Bas; Skeie, Guri; Olsen, Anja; Tjønneland, Anne; Dahm, Christina C.; Overvad, Kim; Boutron-Ruault, Marie Christine; Clavel-Chapelon, Françoise; Nailler, Laura; Kaaks, Rudolf; Teucher, Birgit; Boeing, Heiner; Bergmann, Manuela M.; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Pala, Valeria; Tumino, Rosario; Vineis, Paolo; Panico, Salvatore; Peeters, Petra H. M.; Dik, Vincent K.; Weiderpass, Elisabete; Lund, Eiliv; Garcia, Jose Ramon Quiros; Zamora-Ros, Raul; Pérez, Maria José Sánchez; Dorronsoro, Miren; Navarro, Carmen; Ardanaz, Eva; Manjer, Jonas; Almquist, Martin; Johansson, Ingegerd; Palmqvist, Richard; Khaw, Kay-Tee; Wareham, Nick; Key, Timothy J.; Crowe, Francesca L.; Fedirko, Veronika; Gunter, Marc J.; Riboli, Elio
    Background: Prospective studies have consistently reported lower colorectal cancer risks associated with higher intakes of total dairy products, total milk and dietary calcium. However, less is known about whether the inverse associations vary for individual dairy products with differing fat contents. Materials and Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between intakes of total milk and milk subtypes (whole-fat, semi-skimmed and skimmed), yoghurt, cheese, and dietary calcium with colorectal cancer risk amongst 477,122 men and women. Dietary questionnaires were administered at baseline. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for relevant confounding variables. Results: During the mean 11 years of follow-up, 4,513 incident cases of colorectal cancer occurred. After multivariable adjustments, total milk consumption was inversely associated with colorectal cancer risk (HR per 200 g/day 0.93, 95% CI: 0.89–0.98). Similar inverse associations were observed for whole-fat (HR per 200 g/day 0.90, 95% CI: 0.82–0.99) and skimmed milk (HR per 200 g/day 0.90, 95% CI: 0.79–1.02) in the multivariable models. Inverse associations were observed for cheese and yoghurt in the categorical models; although in the linear models, these associations were non-significant. Dietary calcium was inversely associated with colorectal cancer risk (HR per 200 mg/day 0.95, 95% CI: 0.91–0.99); this association was limited to dairy sources of calcium only (HR per 200 mg/day 0.95, 95% CI: 0.91–0.99), with no association observed for non-dairy calcium sources (HR per 200 mg/day 1.00, 95% CI: 0.81–1.24). Conclusions: Our results strengthen the evidence for a possible protective role of dairy products on colorectal cancer risk. The inverse associations we observed did not differ by the fat content of the dairy products considered.
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    Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study
    (BioMed Central, 2013) Ritte, Rebecca; Tikk, Kaja; Lukanova, Annekatrin; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Dossus, Laure; Fournier, Agnès; Clavel-Chapelon, Françoise; Grote, Verena; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Berrino, Franco; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Quirós, José Ramón; Buckland, Genevieve; Molina-Montes, Esther; Chirlaque, María-Dolores; Ardanaz, Eva; Amiano, Pilar; Bueno-de-Mesquita, H Bas; van Gils, Carla H; Peeters, Petra HM; Wareham, Nick; Khaw, Kay-Tee; Key, Timothy J; Travis, Ruth C; Weiderpass, Elisabete; Dumeaux, Vanessa; Lund, Eliv; Sund, Malin; Andersson, Anne; Romieu, Isabelle; Rinaldi, Sabina; Vineis, Paulo; Merritt, Melissa A; Riboli, Elio; Kaaks, Rudolf
    Background: The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain. Methods: Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) breast tumors. Results: A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors (≥35 vs. ≤19 years HR: 1.47 [95% CI 1.15-1.88] ptrend < 0.001 for ER+PR+ tumors; ≥35 vs. ≤19 years HR: 0.93 [95% CI 0.53-1.65] ptrend = 0.96 for ER-PR- tumors; P het = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (phet = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age- and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk. Conclusion: Our study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant.