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1. Dietary total antioxidant capacity and gastriccancer risk in the European prospective investigation into cancer and nutritionstudy

Author: Serafini M, Jakszyn P, Luján L, Agudo A, Bas Bueno de Mesquita H, van Duijnhoven FJ, Jenab M, Navarro C, Palli D, Boeing H, Wallström P, Regnér S, Numans ME, Carneiro F, Boutron Ruault MC, Clavel Chapelon F, Morois S, Grioni S, Tumino R, Sacerdote C, Ramon Quirós J, Molina Montes E, Huerta Castaño JM, Barricarte A, Amiano P, Khaw KT, Wareham N, Allen NE, Key TJ, Jeurnink SM, Peeters PH, Bamia C, Valanou E, Trichopoulou A, Kaaks R, Lukanova A, Bergmann MM, Lindkvist B, Stenling R, Johansson I, Dahm CC, Overvad K, Jensen M, Olsen A, Tjonneland A, Bakken K, Dumeaux V, Lund E, McCormack V, Rinaldi S, Michaud D, Mouw T, Riboli E, González C.A., PANICO, SALVATORE, Serafini, M, Jakszyn, P, Luján, L, Agudo, A, Bas Bueno de Mesquita, H, van Duijnhoven, Fj, Jenab, M, Navarro, C, Palli, D, Boeing, H, Wallström, P, Regnér, S, Numans, Me, Carneiro, F, Boutron Ruault, Mc, Clavel Chapelon, F, Morois, S, Grioni, S, Panico, Salvatore, Tumino, R, Sacerdote, C, Ramon Quirós, J, Molina Montes, E, Huerta Castaño, Jm, Barricarte, A, Amiano, P, Khaw, Kt, Wareham, N, Allen, Ne, Key, Tj, Jeurnink, Sm, Peeters, Ph, Bamia, C, Valanou, E, Trichopoulou, A, Kaaks, R, Lukanova, A, Bergmann, Mm, Lindkvist, B, Stenling, R, Johansson, I, Dahm, Cc, Overvad, K, Jensen, M, Olsen, A, Tjonneland, A, Bakken, K, Dumeaux, V, Lund, E, Mccormack, V, Rinaldi, S, Michaud, D, Mouw, T, Riboli, E, and González, C. A.
Published: 2012

2. Metabolic syndrome and risks ofcolon and rectal cancer: the European prospective investigation into cancer andnutrition study

Author: Aleksandrova K, Boeing H, Jenab M, Bas Bueno de Mesquita H, Jansen E, van Duijnhoven FJ, Fedirko V, Rinaldi S, Romieu I, Riboli E, Romaguera D, Overvad K, Østergaard JN, Olsen A, Tjønneland A, Boutron Ruault MC, Clavel Chapelon F, Morois S, Masala G, Agnoli C, Tumino R, Vineis P, Kaaks R, Lukanova A, Trichopoulou A, Naska A, Bamia C, Peeters PH, Rodríguez L, Buckland G, Sánchez MJ, Dorronsoro M, Huerta JM, Barricarte A, Hallmans G, Palmqvist R, Khaw KT, Wareham N, Allen NE, Tsilidis KK, Pischon T., PANICO, SALVATORE, Aleksandrova, K, Boeing, H, Jenab, M, Bas Bueno de Mesquita, H, Jansen, E, van Duijnhoven, Fj, Fedirko, V, Rinaldi, S, Romieu, I, Riboli, E, Romaguera, D, Overvad, K, Østergaard, Jn, Olsen, A, Tjønneland, A, Boutron Ruault, Mc, Clavel Chapelon, F, Morois, S, Masala, G, Agnoli, C, Panico, Salvatore, Tumino, R, Vineis, P, Kaaks, R, Lukanova, A, Trichopoulou, A, Naska, A, Bamia, C, Peeters, Ph, Rodríguez, L, Buckland, G, Sánchez, Mj, Dorronsoro, M, Huerta, Jm, Barricarte, A, Hallmans, G, Palmqvist, R, Khaw, Kt, Wareham, N, Allen, Ne, Tsilidis, Kk, and Pischon, T.
Published: 2011

3. Variety in vegetable and fruit consumption and risk of bladder cancer in theEuropean Prospective Investigation into Cancer and Nutrition

Author: Büchner FL, Bueno de Mesquita HB, Ros MM, Kampman E, Egevad L, Overvad K, Tjønneland A, Roswall N, Clavel Chapelon F, Boutron Ruault MC, Touillaud M, Kaaks R, Chang Claude J, Boeing H, Weikert S, Trichopoulou A, Naska A, Benetou V, Palli D, Sieri S, Vineis P, Tumino R, van Duijnhoven FJ, Peeters PH, van Gils CH, Lund E, Gram IT, Sánchez MJ, Jakszyn P, Larrañaga N, Ardanaz E, Navarro C, Rodríguez L, Manjer J, Ehrnström R, Hallmans G, Ljungberg B, Key TJ, Allen NE, Khaw KT, Wareham N, Slimani N, Jenab M, Boffetta P, Kiemeney LA, Riboli E., PANICO, SALVATORE, Büchner, Fl, Bueno de Mesquita, Hb, Ros, Mm, Kampman, E, Egevad, L, Overvad, K, Tjønneland, A, Roswall, N, Clavel Chapelon, F, Boutron Ruault, Mc, Touillaud, M, Kaaks, R, Chang Claude, J, Boeing, H, Weikert, S, Trichopoulou, A, Naska, A, Benetou, V, Palli, D, Sieri, S, Vineis, P, Tumino, R, Panico, Salvatore, van Duijnhoven, Fj, Peeters, Ph, van Gils, Ch, Lund, E, Gram, It, Sánchez, Mj, Jakszyn, P, Larrañaga, N, Ardanaz, E, Navarro, C, Rodríguez, L, Manjer, J, Ehrnström, R, Hallmans, G, Ljungberg, B, Key, Tj, Allen, Ne, Khaw, Kt, Wareham, N, Slimani, N, Jenab, M, Boffetta, P, Kiemeney, La, and Riboli, E.
Published: 2011

4. Prediagnosticcirculating parathyroid hormone concentration and colorectal cancer in theEuropean Prospective Investigation into Cancer and Nutrition cohort

Author: Fedirko V, Riboli E, Bueno de Mesquita HB, Rinaldi S, Pischon T, Norat T, Jansen EH, van Duijnhoven FJ, Tjønneland A, Olsen A, Overvad K, Boutron Ruault MC, Clavel Chapelon F, Engel P, Kaaks R, Teucher B, Boeing H, Buijsse B, Trichopoulou A, Trichopoulos D, Lagiou P, Sieri S, Vineis P, Palli D, Tumino R, van Gils CH, Peeters PH, Chirlaque MD, Gurrea AB, Rodríguez L, Molina Montes E, Dorronsoro M, Bonet C, Palmqvist R, Hallmans G, Key TJ, Tsilidis KK, Khaw KT, Romieu I, Straif K, Wark PA, Romaguera D, Jenab M., PANICO, SALVATORE, Fedirko, V, Riboli, E, Bueno de Mesquita, Hb, Rinaldi, S, Pischon, T, Norat, T, Jansen, Eh, van Duijnhoven, Fj, Tjønneland, A, Olsen, A, Overvad, K, Boutron Ruault, Mc, Clavel Chapelon, F, Engel, P, Kaaks, R, Teucher, B, Boeing, H, Buijsse, B, Trichopoulou, A, Trichopoulos, D, Lagiou, P, Sieri, S, Vineis, P, Panico, Salvatore, Palli, D, Tumino, R, van Gils, Ch, Peeters, Ph, Chirlaque, Md, Gurrea, Ab, Rodríguez, L, Molina Montes, E, Dorronsoro, M, Bonet, C, Palmqvist, R, Hallmans, G, Key, Tj, Tsilidis, Kk, Khaw, Kt, Romieu, I, Straif, K, Wark, Pa, Romaguera, D, and Jenab, M.
Published: 2011

5. Educational level and risk of colorectalcancer in EPIC with specific reference to tumor location

Author: Leufkens AM, Van Duijnhoven FJ, Boshuizen HC, Siersema PD, Kunst AE, Mouw T, Tjønneland A, Olsen A, Overvad K, Boutron Ruault MC, Clavel Chapelon F, Morois S, Krogh V, Tumino R, Polidoro S, Palli D, Kaaks R, Teucher B, Pischon T, Trichopoulou A, Orfanos P, Goufa I, Peeters PH, Skeie G, Braaten T, Rodríguez L, Lujan Barroso L, Sánchez Pérez MJ, Navarro C, Barricarte A, Zackrisson S, Almquist M, Hallmans G, Palmqvist R, Tsilidis KK, Khaw KT, Wareham N, Gallo V, Jenab M, Riboli E, Bueno de Mesquita H.B., PANICO, SALVATORE, Leufkens, Am, Van Duijnhoven, Fj, Boshuizen, Hc, Siersema, Pd, Kunst, Ae, Mouw, T, Tjønneland, A, Olsen, A, Overvad, K, Boutron Ruault, Mc, Clavel Chapelon, F, Morois, S, Krogh, V, Tumino, R, Panico, Salvatore, Polidoro, S, Palli, D, Kaaks, R, Teucher, B, Pischon, T, Trichopoulou, A, Orfanos, P, Goufa, I, Peeters, Ph, Skeie, G, Braaten, T, Rodríguez, L, Lujan Barroso, L, Sánchez Pérez, Mj, Navarro, C, Barricarte, A, Zackrisson, S, Almquist, M, Hallmans, G, Palmqvist, R, Tsilidis, Kk, Khaw, Kt, Wareham, N, Gallo, V, Jenab, M, Riboli, E, and Bueno de Mesquita, H. B.
Published: 2011

6. Dietary fat and breast cancer risk in the European ProspectiveInvestigation into Cancer and Nutrition

Author: Sieri S, Krogh V, Ferrari P, Berrino F, Pala V, Thiébaut AC, Tjønneland A, Olsen A, Overvad K, Jakobsen MU, Clavel Chapelon F, Chajes V, Boutron Ruault MC, Kaaks R, Linseisen J, Boeing H, Nöthlings U, Trichopoulou A, Naska A, Lagiou P, Palli D, Vineis P, Tumino R, Lund E, Kumle M, Skeie G, González CA, Ardanaz E, Amiano P, Tormo MJ, Martínez García C, Quirós JR, Berglund G, Gullberg B, Hallmans G, Lenner P, Bueno de Mesquita HB, van Duijnhoven FJ, Peeters PH, van Gils CH, Key TJ, Crowe FL, Bingham S, Khaw KT, Rinaldi S, Slimani N, Jenab M, Norat T, Riboli E., PANICO, SALVATORE, Sieri, S, Krogh, V, Ferrari, P, Berrino, F, Pala, V, Thiébaut, Ac, Tjønneland, A, Olsen, A, Overvad, K, Jakobsen, Mu, Clavel Chapelon, F, Chajes, V, Boutron Ruault, Mc, Kaaks, R, Linseisen, J, Boeing, H, Nöthlings, U, Trichopoulou, A, Naska, A, Lagiou, P, Panico, Salvatore, Palli, D, Vineis, P, Tumino, R, Lund, E, Kumle, M, Skeie, G, González, Ca, Ardanaz, E, Amiano, P, Tormo, Mj, Martínez García, C, Quirós, Jr, Berglund, G, Gullberg, B, Hallmans, G, Lenner, P, Bueno de Mesquita, Hb, van Duijnhoven, Fj, Peeters, Ph, van Gils, Ch, Key, Tj, Crowe, Fl, Bingham, S, Khaw, Kt, Rinaldi, S, Slimani, N, Jenab, M, Norat, T, and Riboli, E.
Published: 2008

7. N-acetyltransferase 2 polymorphisms, tobacco smoking, and breast cancer risk in the breast and prostate cancer cohort consortium

Author: Cox, Dg, Dostal, L, Hunter, Dj, Le Marchand, L, Hoover, R, Ziegler, Rg, Thun, Mj, Diver, Wr, Stevens, Vl, Amiano, P, Boutron Rualt MC, Campa, Daniele, van Duijnhoven FJ, Gram, It, Kaaks, R, Khaw, K. T., Riboli, E, Sund, M, Trichopoulos, D, Tumino, R, Vogel, U, Kraft, P, Buring, Je, Hankinson, Se, Lee, Im, Zhang, Sm, Lindstrom, S, Berg, Cd, Chanock, S, Isaacs, C, Mccarty, C, Haiman, Ca, Henderson, Be, Prostate Cancer Cohort Consortium, Equipe 6, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), DURHAM, Durham, University of Hawai‘i [Mānoa] (UHM), Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), and National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)
Subjects: Oncology, Male, single nucleotide, MESH: Menopause, Epidemiology, MESH: Logistic Models, arylamine N-acetyltransferase, polymorphism, Cohort Studies, Prostate cancer, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, breast neoplasms, Brief Original Contribution, MESH: Cohort Studies, 0303 health sciences, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, Middle Aged, MESH: Case-Control Studies, 3. Good health, NAT2 protein, human, polymorphism, single nucleotide, smoking, 030220 oncology & carcinogenesis, Cohort, Female, Menopause, Cohort study, MESH: Smoking, medicine.medical_specialty, NAT2 protein, [SDV.CAN]Life Sciences [q-bio]/Cancer, Polymorphism, Single Nucleotide, 03 medical and health sciences, Breast cancer, Internal medicine, medicine, Humans, human, 030304 developmental biology, MESH: Humans, Bladder cancer, business.industry, Case-control study, Cancer, Odds ratio, medicine.disease, MESH: Arylamine N-Acetyltransferase, MESH: Male, Logistic Models, Case-Control Studies, business, MESH: Female, MESH: Breast Neoplasms
Abstract: International audience; Common polymorphisms in the N-acetyltransferase 2 gene (NAT2) modify the association between cigarette smoking and bladder cancer and have been hypothesized to determine whether active cigarette smoking increases breast cancer risk. The authors sought to replicate the latter hypothesis in a prospective analysis of 6,900 breast cancer cases and 9,903 matched controls drawn from 6 cohorts (1989-2006) in the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. Standardized methods were used to genotype the 3 most common polymorphisms that define NAT2 acetylation phenotype (rs1799930, rs1799931, and rs1801280). In unconditional logistic regression analyses, breast cancer risk was higher in women with more than 20 pack-years of active cigarette smoking than in never smokers (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.17, 1.39), after controlling for established risk factors other than alcohol consumption and physical inactivity. However, associations were similar for the slow (OR = 1.25, 95% CI: 1.11, 1.39) and rapid/intermediate (OR = 1.24, 95% CI: 1.08, 1.42) acetylation phenotypes, with no evidence of interaction (P = 0.87). These results provide some support for the hypothesis that long-term cigarette smoking may be causally associated with breast cancer risk but underscore the need for caution when interpreting sparse data on gene-environment interactions.
Published: 2011
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8. Dietary patterns and colorectal adenomas in Lynch syndrome: The GEOLynch cohort study.

Author: Botma A, Vasen HF, van Duijnhoven FJ, Kleibeuker JH, Nagengast FM, and Kampman E
Published: 2013
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9. Serum vitamin D and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Travis RC, Crowe FL, Allen NE, Appleby PN, Roddam AW, Tjønneland A, Olsen A, Linseisen J, Kaaks R, Boeing H, Kröger J, Trichopoulou A, Dilis V, Trichopoulos D, Vineis P, Palli D, Tumino R, Sieri S, Bueno-de-Mesquita HB, and van Duijnhoven FJ
Abstract: Results from the majority of studies show little association between circulating concentrations of vitamin D and prostate cancer risk, a finding that has not been demonstrated in a wider European population, however. The authors examined whether vitamin D concentrations were associated with prostate cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (1994-2000). Serum concentrations of 25-hydroxyvitamin D were measured in 652 prostate cancer cases matched to 752 controls from 7 European countries after a median follow-up time of 4.1 years. Conditional logistic regression models were used to calculate odds ratios for prostate cancer risk in relation to serum 25-hydroxyvitamin D after standardizing for month of blood collection and adjusting for covariates. No significant association was found between 25-hydroxyvitamin D and risk of prostate cancer (highest vs. lowest quintile: odds ratio = 1.28, 95% confidence interval: 0.88, 1.88; P for trend = 0.188). Subgroup analyses showed no significant heterogeneity by cancer stage or grade, age at diagnosis, body mass index, time from blood collection to diagnosis, or calcium intake. In summary, the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer. [ABSTRACT FROM AUTHOR]
Published: 2009
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10. Postmenopausal hormone therapy and changes in mammographic density.

Author: van Duijnhoven FJ, Peeters PH, Warren RM, Bingham SA, van Noord PA, Monninkhof EM, Grobbee DE, van Gils CH, van Duijnhoven, Fränzel J B, Peeters, Petra H M, Warren, Ruth M L, Bingham, Sheila A, van Noord, Paulus A H, Monninkhof, Evelyn M, Grobbee, Diederick E, and van Gils, Carla H
Published: 2007

11. Plasma 25-hydroxyvitamin D concentration and lymphoma risk: results of the European Prospective Investigation into Cancer and Nutrition

Author: Magritt Brustad, Ruth C. Travis, Paolo Vineis, Rosario Tumino, Ann-Sofie Johansson, Elisabete Weiderpass, Beatrice Melin, Petra H.M. Peeters, Nicholas J. Wareham, Kim Overvad, José María Huerta, Martin Almquist, Fränzel J.B. Van Duijnhoven, Elisavet Valanou, Antonia Trichopoulou, H. Bas Bueno-de-Mesquita, Claudia Agnoli, Roel Vermeulen, Jakob Linseisen, Antonia Barmpitsioti, Johan Malm, Susen Becker, J. Ramón Quirós, Anna Łuczyńska, Eva Ardanaz, Carlos A. González, Mazda Jenab, Kay-Tee Khaw, Paula Jakszyn, Valentina Gallo, Giovanna Masala, Elio Riboli, Salvatore Panico, Isabelle Romieu, Guri Skeie, Brian Buijsse, Alexandra Nieters, Veronika Fedirko, Rudolf Kaaks, Sabine Rohrmann, María José Sánchez, University of Zurich, Nieters, Alexandra, uczy?ska, A, Kaaks, R, Rohrmann, S, Becker, S, Linseisen, J, Buijsse, B, Overvad, K, Trichopoulou, A, Valanou, E, Barmpitsioti, A, Masala, G, Agnoli, C, Tumino, R, Panico, Salvatore, Bueno de Mesquita, Hb, van Duijnhoven, Fj, Peeters, Ph, Vermeulen, R, Weiderpass, E, Brustad, M, Skeie, G, Gonz?lez, Ca, Jakszyn, P, Quir?s, Jr, S?nchez, Mj, Huerta, Jm, Ardanaz, E, Melin, B, Johansson, A, Almquist, M, Malm, J, Khaw, Kt, Wareham, N, Travis, Rc, Fedirko, V, Romieu, I, Jenab, M, Gallo, V, Riboli, E, Vineis, P, and Nieters, A.
Subjects: Male, Lymphoma, Nutrition and Disease, Chronic lymphocytic leukemia, Medicine (miscellaneous), Rate ratio, Gastroenterology, Cohort Studies, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Voeding en Ziekte, Medicine, infections, Vitamin D, 0303 health sciences, Nutrition and Dietetics, Incidence, Lymphoma, Non-Hodgkin, Incidence (epidemiology), 2701 Medicine (miscellaneous), Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 030220 oncology & carcinogenesis, vitamin-d status, 2916 Nutrition and Dietetics, Female, medicine.medical_specialty, 610 Medicine & health, 03 medical and health sciences, sun exposure, Internal medicine, Vitamin D and neurology, Humans, ddc:610, non-hodgkin-lymphoma, 030304 developmental biology, VLAG, subsequent risk, Global Nutrition, disease, Wereldvoeding, business.industry, Case-control study, association, Cancer, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), ultraviolet-radiation, medicine.disease, Diet, Leukemia, Lymphoid, Logistic Models, Case-Control Studies, Chronic Disease, Immunology, supplementation, business, chronic lymphocytic-leukemia, Follow-Up Studies
Abstract: Background: The relation between vitamin D status and lymphoma risk is inconclusive. Objective: We examined the association between prediagnostic plasma 25-hydroxyvitamin D [25(OH)D] and lymphoid cancer risk. Design: We conducted a study nested within the European Prospective Investigation into Cancer and Nutrition cohort of 1127 lymphoma cases and 1127 matched controls with a mean follow-up time of 7.1 y. Conditional logistic regression was used to estimate multivariable-adjusted incidence rate ratios of lymphoma risk in relation to plasma 25(OH)D. Season-standardized and season-specific 25(OH)D quartiles were used. We also analyzed 25(OH)D as a continuous variable and used predefined cutoffs. Results: No statistically significant association between plasma 25(OH)D and overall lymphoid cancer risk was observed. A positive association for B-cell non-Hodgkin lymphoma was noted only in those with a diagnosis made during the first 2 y of follow-up (P-heterogeneity = 0.03), which suggests the possibility of reverse causality. Further analysis restricted to participants with >= 2y of follow-up time showed a significant association between 25(OH)D and chronic lymphocytic leukemia (CLL) (n = 161): adjusted incidence rate ratios were 0.40 (95% CI: 0.18, 0.90; P-trend = 0.05) and 0.31 (95% CI: 0.13, 0.76; P-trend = 0.03) for the top compared with the bottom season-standardized and season-specific quartiles, respectively. Data on dietary vitamin D intake provided further support for the observed association (incidence rate ratio: 0.33; 95% CI = 0.12, 0.89; P-trend = 0.006). Conclusions: Our findings do not support a protective role of high 25(OH)D concentration in lymphoid cancers overall. However, they suggest that higher concentrations of 25(OH)D are associated with a reduced risk of CLL.
Published: 2013
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12. Obesity, inflammatory markers, and endometrial cancer risk: a prospective case-control study

Author: Jakob Stegger, Petra H.M. Peeters, Kay-Tee Khaw, Jone M. Altzibar, Kim Overvad, Nicholas J. Wareham, Anne Tjønneland, Göran Hallmans, María José Sánchez, Timothy J. Key, María Dolores Chirlaque, Carlotta Sacerdote, Sabina Rinaldi, Vassiliki Benetou, Fränzel J.B. Van Duijnhoven, N. Charlotte Onland-Moret, Sabine Rohrmann, Salvatore Panico, Laure Dossus, Eva Lundin, Maria Luisa Redondo, Madlen Schütze, Susen Becker, Birgit Teucher, Anja Olsen, Aida Jimenez-Corona, Rudolf Kaaks, Heiner Boeing, Dora Romaguera, Rosario Tumino, H. Bas Bueno-de-Mesquita, Franco Berrino, Teresa Norat, Naomi E. Allen, Domenico Palli, Nathalie Chabbert-Buffet, Eva Ardanaz, Pierre Hainaut, Nadia Slimani, Antonia Trichopoulou, Elio Riboli, Annekatrin Lukanova, Pagona Lagiou, Noémie Travier, Françoise Clavel-Chapelon, Dossus, L, Rinaldi, S, Becker, S, Lukanova, A, Tjonneland, A, Olsen, A, Stegger, J, Overvad, K, Chabbert Buffet, N, Jimenez Corona, A, Clavel Chapelon, F, Rohrmann, S, Teucher, B, Boeing, H, Schütze, M, Trichopoulou, A, Benetou, V, Lagiou, P, Palli, D, Berrino, F, Panico, Salvatore, Tumino, R, Sacerdote, C, Redondo, Ml, Travier, N, Sanchez, Mj, Altzibar, Jm, Chirlaque, Md, Ardanaz, E, Bueno de Mesquita, Hb, van Duijnhoven, Fj, Onland Moret, Nc, Peeters, Ph, Hallmans, G, Lundin, E, Khaw, Kt, Wareham, N, Allen, N, Key, Tj, Slimani, N, Hainaut, P, Romaguera, D, Norat, T, Riboli, E, and Kaaks, R.
Subjects: Risk, Cancer Research, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Gastroenterology, Body Mass Index, Endocrinology, Risk Factors, Internal medicine, Odds Ratio, medicine, Humans, Obesity, Prospective Studies, Risk factor, Prospective cohort study, Aged, Immunoassay, Inflammation, biology, Interleukin-6, business.industry, Endometrial cancer, C-reactive protein, Age Factors, Regular Papers, Case-control study, Odds ratio, Middle Aged, medicine.disease, Endometrial Neoplasms, European Prospective Investigation into Cancer and Nutrition, Interleukin 1 Receptor Antagonist Protein, C-Reactive Protein, Logistic Models, Oncology, Quartile, Case-Control Studies, biology.protein, Female, business, Biomarkers
Abstract: Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case–control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values Ptrend=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08–2.54, Ptrend=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22–2.73, Ptrend=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10–20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu.
Published: 2016
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13. Oral contraceptives, reproductive history and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition

Author: Yvoni Koumantaki, Eiliv Lund, Anne Tjønneland, Elio Riboli, Giovanna Tagliabue, F. J. B. van Duijnhoven, Paolo Vineis, M. C. Boutron-Ruault, Rudolf Kaaks, Salvatore Panico, M-J Sanchez, Aurelio Barricarte, B. Van Guelpen, V. Chajes, G. Stasinopoulou, Françoise Clavel-Chapelon, Teresa Norat, P. H. M. Peeters, Franco Berrino, M-D Chirlaque, Konstantinos K. Tsilidis, Graham Byrnes, Signe Borgquist, Domenico Palli, Kjersti Bakken, Kim Overvad, A. Olsen, M. Dorronsoro, Dora Romaguera, Jonas Manjer, Rosario Tumino, Timothy J. Key, Antonia Trichopoulou, M. Bergmann, L. Rodríguez, Agnès Fournier, Göran Hallmans, S. Rinaldi, K-T Khaw, Jenny Chang-Claude, C. H. van Gils, C. A. Gonzalez, H. B. Bueno-de-Mesquita, Heiner Boeing, Naomi E. Allen, Sheila A. Rodwell, Tsilidis, Kk, Allen, Ne, Key, Tj, Bakken, K, Lund, E, Berrino, F, Fournier, A, Olsen, A, Tjønneland, A, Overvad, K, Boutron Ruault, Mc, Clavel Chapelon, F, Byrnes, G, Chajes, V, Rinaldi, S, Chang Claude, J, Kaaks, R, Bergmann, M, Boeing, H, Koumantaki, Y, Stasinopoulou, G, Trichopoulou, A, Palli, D, Tagliabue, G, Panico, Salvatore, Tumino, R, Vineis, P, Bueno de Mesquita, Hb, van Duijnhoven, Fj, van Gils, Ch, Peeters, Ph, Rodríguez, L, González, Ca, Sánchez, Mj, Chirlaque, Md, Barricarte, A, Dorronsoro, M, Borgquist, S, Manjer, J, van Guelpen, B, Hallmans, G, Rodwell, Sa, Khaw, Kt, Norat, T, Romaguera, D, and Riboli, E.
Subjects: Cancer Research, Colorectal cancer, Epidemiology, medicine.medical_treatment, SERUM, 0302 clinical medicine, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, oral contraceptives, reproductive history, 2. Zero hunger, education.field_of_study, Obstetrics, Reproduction, COLON-CANCER, HORMONE-REPLACEMENT-THERAPY, WOMEN, Hormone replacement therapy (menopause), Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, LARGE BOWEL, Family planning, 030220 oncology & carcinogenesis, Female, Colorectal Neoplasms, Life Sciences & Biomedicine, Adult, Risk, medicine.medical_specialty, Population, UNITED-STATES, colorectal cancer, EXOGENOUS HORMONES, 03 medical and health sciences, ADENOMAS, medicine, cohort study, Humans, COHORT, Risk factor, education, Aged, Gynecology, Science & Technology, business.industry, Cancer, medicine.disease, ONCOLOGY, sense organs, business, Contraceptives, Oral
Abstract: Udgivelsesdato: 2010-Nov-2 Background:Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk.Methods:We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer.Results:After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83-1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74-0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk.Conclusion:Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk.British Journal of Cancer advance online publication, 2 November 2010; doi:10.1038/sj.bjc.6605965 www.bjcancer.com.
Published: 2016
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14. Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location

Author: Aurelio Barricarte, Konstantinos K. Tsilidis, Domenico Palli, Philippos Orfanos, Carmen Navarro, Petra H.M. Peeters, Göran Hallmans, Salvatore Panico, Maria Jose Sanchez-Perez, Martin Almquist, Fränzel J.B. Van Duijnhoven, Nicholas J. Wareham, Ioulia Goufa, Birgit Teucher, Tonje Braaten, Anja Olsen, Tobias Pischon, H. Bas Bueno-de-Mesquita, Leila Lujan-Barroso, Traci Mouw, Anke M. Leufkens, Silvia Polidoro, Françoise Clavel-Chapelon, Valentina Gallo, Kim Overvad, Anne Tjønneland, Laudina Rodríguez, Guri Skeie, Rudolf Kaaks, Hendriek C. Boshuizen, Anton E. Kunst, Peter D. Siersema, Sophie Morois, Kay-Tee Khaw, Vittorio Krogh, Antonia Trichopoulou, Rosario Tumino, Marie-Christine Boutron-Ruault, Richard Palmqvist, Mazda Jenab, Sophia Zackrisson, Elio Riboli, APH - Amsterdam Public Health, Public and occupational health, Leufkens, Am, Van Duijnhoven, Fj, Boshuizen, Hc, Siersema, Pd, Kunst, Ae, Mouw, T, Tj?nneland, A, Olsen, A, Overvad, K, Boutron Ruault, Mc, Clavel Chapelon, F, Morois, S, Krogh, V, Tumino, R, Panico, Salvatore, Polidoro, S, Palli, D, Kaaks, R, Teucher, B, Pischon, T, Trichopoulou, A, Orfanos, P, Goufa, I, Peeters, Ph, Skeie, G, Braaten, T, Rodr?guez, L, Lujan Barroso, L, S?nchez P?rez, Mj, Navarro, C, Barricarte, A, Zackrisson, S, Almquist, M, Hallmans, G, Palmqvist, R, Tsilidis, Kk, Khaw, Kt, Wareham, N, Gallo, V, Jenab, M, Riboli, E, and Bueno de Mesquita, Hb
Subjects: Gerontology, Male, Cancer Research, Nutrition and Disease, Colorectal cancer, Wiskundige en Statistische Methoden - Biometris, deprivation, Cohort Studies, 0302 clinical medicine, Risk Factors, Voeding en Ziekte, Medicine, rectum, 030212 general & internal medicine, Prospective Studies, socioeconomic-status, Hazard ratio, Confounding, health, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, nutrition, Oncology, 030220 oncology & carcinogenesis, Educational Status, Female, women, Colorectal Neoplasms, Adult, united-states, Lower risk, survival, 03 medical and health sciences, inequalities, Humans, Socioeconomic status, Mathematical and Statistical Methods - Biometris, VLAG, Aged, colon, business.industry, Proportional hazards model, medicine.disease, Confidence interval, digestive system diseases, Social Class, business, Demography, Follow-Up Studies
Abstract: Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational level and CRC. We studied data from 400,510 participants in the EPIC (European Prospective Investigation into Cancer and Nutrition) study, of whom 2,447 developed CRC (colon: 1,551, rectum: 896, mean follow-up 8.3 years). Cox proportional hazard regression analysis stratified by age, gender and center, and adjusted for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Relative indices of inequality (RII) for education were estimated using Cox regression models. We conducted separate analyses for tumor location, gender and geographical region. Compared with participants with college/university education, participants with vocational secondary education or less had a nonsignificantly lower risk of developing CRC. When further stratified for tumor location, adjusted risk estimates for the proximal colon were statistically significant for primary education or less (HR 0.73, 95% CI 0.57-0.94) and for vocational secondary education (HR 0.76, 95% CI 0.58-0.98). The inverse association between low education and CRC risk was particularly found in women and Southern Europe. These associations were statistically significant for CRC, for colon cancer and for proximal colon cancer. In conclusion, CRC risk, especially in the proximal colon, is lower in subjects with a lower educational level compared to those with a higher educational level. This association is most pronounced in women and Southern Europe
Published: 2012
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15. Menopausal Hormone Therapy and Risk of Endometrial Carcinoma Among Postmenopausal Women in the European Prospective Investigation into Cancer and Nutrition

Author: Kim Overvad, Konstantinos K. Tsilidis, Eiliv Lund, Timothy J. Key, N. Charlotte Onland-Moret, Benedetta Bendinelli, H. Bas Bueno-de-Mesquita, Agnès Fournier, Kay-Tee Khaw, Salvatore Panico, Eric J. Duell, Alban Fabre, Anja Olsen, Aurelio Barricarte, Maria-Dolores Chirlaque, Rudolf Kaaks, Madlen Schuetze, Pilar Amiano, Vittorio Krogh, Carla H. van Gils, Françoise Clavel-Chapelon, Nathalie Chabbert-Buffet, Veronika Fedirko, Kjersti Bakken, Manuela M. Bergmann, Maria-Esther Molina-Montes, Anne Tjønneland, Elio Riboli, Laure Dossus, Naomi E. Allen, Dominique S. Michaud, Nicholas J. Wareham, María-Luisa Redondo, Traci Mouw, Fränzel J. B. van Duijnhoven, Carlotta Sacerdote, Rosario Tumino, Oxana Gavrilyuk, Sabina Rinaldi, Allen, Ne, Tsilidis, Kk, Key, Tj, Dossus, L, Kaaks, R, Lund, E, Bakken, K, Gavrilyuk, O, Overvad, K, Tjønneland, A, Olsen, A, Fournier, A, Fabre, A, Clavel Chapelon, F, Chabbert Buffet, N, Sacerdote, C, Krogh, V, Bendinelli, B, Tumino, R, Panico, Salvatore, Bergmann, M, Schuetze, M, van Duijnhoven, Fj, Bueno de Mesquita, Hb, Onland Moret, Nc, van Gils, Ch, Amiano, P, Barricarte, A, Chirlaque, Md, Molina Montes, Me, Redondo, Ml, Duell, Ej, Khaw, Kt, Wareham, N, Rinaldi, S, Fedirko, V, Mouw, T, Michaud, D, and Riboli, E.
Subjects: Oncology, medicine.medical_specialty, Norpregnenes, Epidemiology, medicine.drug_class, medicine.medical_treatment, Tibolone, Body Mass Index, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Estrogen Receptor Modulators, Risk Factors, Internal medicine, medicine, Humans, Risk factor, Aged, Proportional Hazards Models, Retrospective Studies, Gynecology, 030219 obstetrics & reproductive medicine, business.industry, Incidence, Endometrial cancer, Estrogen Replacement Therapy, Age Factors, Cancer, Middle Aged, medicine.disease, Endometrial Neoplasms, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Postmenopause, Menopause, 030220 oncology & carcinogenesis, Female, Hormone therapy, business, Progestin, medicine.drug
Abstract: Udgivelsesdato: 2010-Oct-20 Estrogen-only menopausal hormone therapy (HT) increases the risk of endometrial cancer, but less is known about the association with other types of HT. Using Cox proportional hazards regression, the authors examined the association of various types of HT with the risk of endometrial cancer among 115,474 postmenopausal women recruited into the European Prospective Investigation into Cancer and Nutrition between 1992 and 2000. After a mean follow-up period of 9 years, 601 incident cases of endometrial cancer were identified. In comparison with never users of HT, risk of endometrial cancer was increased among current users of estrogen-only HT (hazard ratio (HR) = 2.52, 95% confidence interval (CI): 1.77, 3.57), tibolone (HR = 2.96, 95% CI: 1.67, 5.26), and, to a lesser extent, estrogen-plus-progestin HT (HR = 1.41, 95% CI: 1.08, 1.83), although risks differed according to regimen and type of progestin constituent. The association of HT use with risk was stronger among women who were older, leaner, or had ever smoked cigarettes. The finding of a strong increased risk of endometrial cancer with estrogen-only HT and a weaker association with combined HT supports the hypothesis that progestins have an attenuating effect on endometrial cancer risk. The increased risk associated with tibolone use requires further investigation.
Published: 2010
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16. Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study

Author: Aleksandrova, K., Drogan, D., Boeing, H., Jenab, M., Bueno-de-Mesquita, H.B., Jansen, E., van Duijnhoven, F.J.B., Rinaldi, S., Fedirko, V., Romieu, I., Kaaks, R., Riboli, E., Gunter, M.J., Romaguera, D., Westhpal, S., Overvad, K., Tjønneland, A., Halkjaer, J., Boutron-Ruault, M.C., Clavel-Chapelon, F., Lukanova, A., Trichopoulou, A., Trichopoulos, D., Vidalis, P., Panico, S., Agnoli, C., Palli, D., Tumino, R., Vineis, P., Buckland, G., Sánchez-Cruz, J.J., Dorronsoro, M., Tormo Díaz, M.J., Barricarte, A., Quiros, J.R., Peeters, P.H., May, A., Hallmans, G., Palmqvist, R., Crowe, F.L., Khaw, K.T., Wareham, N., Pischon, T., Aleksandrova, K, Drogan, D, Boeing, H, Jenab, M, Bas Bueno de Mesquita, H, Jansen, E, van Duijnhoven, Fj, Rinaldi, S, Fedirko, V, Romieu, I, Kaaks, R, Riboli, E, Gunter, Mj, Romaguera, D, Westhpal, S, Overvad, K, Tj?nneland, A, Halkjaer, J, Boutron Ruault, Mc, Clavel Chapelon, F, Lukanova, A, Trichopoulou, A, Trichopoulos, D, Vidalis, P, Panico, Salvatore, Agnoli, C, Palli, D, Tumino, R, Vineis, P, Buckland, G, S?nchez Cruz, Jj, Dorronsoro, M, D?az, Mj, Barricarte, A, Ramon Quiros, J, Peeters, Ph, May, Am, Hallmans, G, Palmqvist, R, Crowe, Fl, Khaw, Kt, Wareham, N, and Pischon, T.
Subjects: Male, Nutritional Status, Middle Aged, Europe, Cardiovascular and Metabolic Diseases, Risk Factors, Case-Control Studies, Colonic Neoplasms, Biomarkers, Tumor, Humans, Female, Prospective Studies, Adiposity, Aged
Abstract: Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which eleven biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analysed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk-sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CI-s were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs bottom tertile RR 1.68, 95% CI 1.06 - 2.65; Ptrend = 0.02) and in women (RR 1.67, 95% CI 1.09 - 2.56; Ptrend = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37 to 57%) of the association in men and 50% (95% CI 40 to 65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggests that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk. © 2013 Wiley Periodicals, Inc.
Published: 2014
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17. Colorectal cancer risk and dyslipidemia: a case-cohort study nested in an Italian multicentre cohort

Author: Sara Grioni, Leonardo Cattaneo, Sabina Sieri, Valeria Pala, Amalia De Curtis, Maria Concetta Giurdanella, Salvatore Panico, Paolo Vineis, Fränzel J.B. Van Duijnhoven, Licia Iacoviello, Amalia Mattiello, Carlotta Sacerdote, Vittorio Krogh, Claudia Agnoli, Rosario Tumino, Paolo Chiodini, Agnoli, C, Grioni, S, Sieri, S, Sacerdote, C, Vineis, P, Tumino, R, Giurdanella, Mc, Pala, V, Mattiello, A, Chiodini, Paolo, Iacoviello, L, De Curtis, A, Cattaneo, L, van Duijnhoven, Fjb, Panico, S, Krogh, V., Chiodini, P, van Duijnhoven, Fj, and Panico, Salvatore
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Nutrition and Disease, Epidemiology, Colorectal cancer, metabolic syndrome, Cohort Studies, lipids, Risk Factors, Voeding en Ziekte, Internal medicine, Humans, Medicine, triglyceride, Risk factor, glucose, Prospective cohort study, Dyslipidemias, VLAG, blood-cholesterol, business.industry, lipoprotein levels, association, Cancer, serum-cholesterol, Middle Aged, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Endocrinology, nutrition, Italy, Case-Control Studies, Cohort, Female, lipids (amino acids, peptides, and proteins), Colorectal Neoplasms, business, colon-cancer, Dyslipidemia, Cohort study
Abstract: Background: Dyslipidemia is an established risk factor for many diseases, but its effect on colorectal cancer risk is less clear. We investigated the association of colorectal cancer risk with plasma triglycerides, total, HDL, and LDL cholesterol in four Italian EPIC centers. Methods: We conducted a case-cohort study on participants recruited to four Italian EPIC centers (Turin, Varese, Naples, and Ragusa; 34,148 subjects). A random subcohort of 850 subjects was obtained and 286 colorectal cancer cases were diagnosed. Triglycerides, total and HDL cholesterol were determined in plasma samples obtained at baseline and stored at -196 degrees C; LDL cholesterol was calculated. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Cox regression models using the Prentice method. Results: The highest tertiles of total (HR 1.66, 95% CI 1.12-2.45) and LDL cholesterol (HR 1.87, 95% CI 1.27-2.76) were associated with increased colorectal cancer risk compared to lowest tertiles. Risks were greater for men than women, and for postmenopausal than premenopausal women. Highest tertiles of total and LDL cholesterol were also significantly associated with increased risks of colon cancer, distal colon cancer, and rectal cancer, but not proximal colon cancer. Conclusions: Our findings suggest that high levels of total and LDL cholesterol increase colorectal cancer risk, particularly in men and postmenopausal women. However additional studies are needed to clarify the role of plasma lipids in these cancers, particularly in view of the conflicting findings of previous studies. (C) 2014 Elsevier Ltd. All rights reserved.
Published: 2014

18. Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition

Author: Leenders, M., Leufkens, A.M., Siersema, P.D., Duijnhoven, F.J.B. van, Vrieling, A., Hulshof, P.J., Gils, C.H. van, Overvad, K., Roswall, N., Kyro, C., Boutron-Ruault, M.C., Fagerhazzi, G., Cadeau, C., Kuhn, T., Johnson, T., Boeing, H., Aleksandrova, K., Trichopoulou, A., Klinaki, E., Androulidaki, A., Palli, D., Grioni, S., Sacerdote, C., Tumino, R., Panico, S., Bakker, M.F., Skeie, G., Weiderpass, E., Jakszyn, P., Barricarte, A., Huerta, J. Maria, Molina-Montes, E., Arguelles, M., Johansson, I., Ljuslinder, I., Key, T.J., Bradbury, K.E., Khaw, K.T., Wareham, N.J., Ferrari, P., Duarte-Salles, T., Jenab, M., Gunter, M.J., Vergnaud, A.C., Wark, P.A., Bueno-De-Mesquita, H.B., Leenders, M, Leufkens, Am, Siersema, Pd, van Duijnhoven, Fj, Vrieling, A, Hulshof, Pj, van Gils, Ch, Overvad, K, Roswall, N, Kyr?, C, Boutron Ruault, Mc, Fagerhazzi, G, Cadeau, C, K?hn, T, Johnson, T, Boeing, H, Aleksandrova, K, Trichopoulou, A, Klinaki, E, Androulidaki, A, Palli, D, Grioni, S, Sacerdote, C, Tumino, R, Panico, Salvatore, Bakker, Mf, Skeie, G, Weiderpass, E, Jakszyn, P, Barricarte, A, Mar?a Huerta, J, Molina Montes, E, Arg?elles, M, Johansson, I, Ljuslinder, I, Key, Tj, Bradbury, Ke, Khaw, Kt, Wareham, Nj, Ferrari, P, Duarte Salles, T, Jenab, M, Gunter, Mj, Vergnaud, Ac, Wark, Pa, Bueno de Mesquita, Hb, LS IRAS EEPI GRA (Gezh.risico-analyse), IRAS RATIA2, and Risk Assessment of Toxic and Immunomodulatory Agents
Subjects: Adult, Male, Ascorbic Acid, Antioxidants, Fruits and vegetables, Body Mass Index, Risk Factors, Surveys and Questionnaires, Odds Ratio, Humans, Vitamin E, Vitamin A, Aged, Rectal Neoplasms, Incidence, Vitamins, Middle Aged, Colorectal cancer, Carotenoids, Diet, Europe, Oxidative Stress, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Case-Control Studies, Colonic Neoplasms, Multivariate Analysis, Female
Abstract: Item does not contain fulltext Carotenoids and vitamins A, C and E are possibly associated with a reduced colorectal cancer (CRC) risk through antioxidative properties. The association of prediagnostic plasma concentrations and dietary consumption of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer was examined in this case-control study, nested within the European Prospective Investigation into Cancer and Nutrition study. Plasma concentrations of carotenoids (alpha- and beta-carotene, canthaxanthin, beta-cryptoxanthin, lutein, lycopene, zeaxanthin) and vitamins A (retinol), C and E (alpha-, beta- and gamma- and delta-tocopherol) and dietary consumption of beta-carotene and vitamins A, C and E were determined in 898 colon cancer cases, 501 rectal cancer cases and 1,399 matched controls. Multivariable conditional logistic regression models were performed to estimate incidence rate ratios (IRR) and corresponding 95% confidence intervals (CIs). An association was observed between higher prediagnostic plasma retinol concentration and a lower risk of colon cancer (IRR for highest quartile = 0.63, 95% CI: 0.46, 0.87, p for trend = 0.01), most notably proximal colon cancer (IRR for highest quartile = 0.46, 95% CI: 0.27, 0.77, p for trend = 0.01). Additionally, inverse associations for dietary beta-carotene and dietary vitamins C and E with (distal) colon cancer were observed. Although other associations were suggested, there seems little evidence for a role of these selected compounds in preventing CRC through their antioxidative properties.
Published: 2014
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19. Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Anne Tjønneland, Christina Bamia, Aurelio Barricarte, Laure Dossus, Petra H.M. Peeters, Marc J. Gunter, Sabine Westhpal, Antonia Trichopoulou, Sabina Rinaldi, Ruth C. Travis, Veronika Fedirko, Fränzel J.B. Van Duijnhoven, J. Ramón Quirós, Kay-Tee Khaw, Philippos Orfanos, Rudolf Kaaks, Krasimira Aleksandrova, Richard Palmqvist, Neil Murphy, Esther Molina-Montes, Eric J. Duell, Eugene Jansen, Jytte Halkjær, Nicholas J. Wareham, Tobias Pischon, Mazda Jenab, Antoine Racine, María Dolores Chirlaque, Domenico Palli, Claudia Agnoli, Miren Dorronsoro, Pietro Ferrari, Heiner Boeing, Kim Overvad, Rosario Tumino, Elio Riboli, Ingrid Ljuslinder, Marie-Christine Boutron-Ruault, Salvatore Panico, Annekatrin Lukanova, H. Bas Bueno-de-Mesquita, Isabelle Romieu, Paolo Vineis, Aleksandrova, K, Jenab, M, Bueno de Mesquita, Hb, Fedirko, V, Kaaks, R, Lukanova, A, van Duijnhoven, Fj, Jansen, E, Rinaldi, S, Romieu, I, Ferrari, P, Murphy, N, Gunter, Mj, Riboli, E, Westhpal, S, Overvad, K, Tj?nneland, A, Halkj?r, J, Boutron Ruault, Mc, Dossus, L, Racine, A, Trichopoulou, A, Bamia, C, Orfanos, P, Agnoli, C, Palli, D, Panico, Salvatore, Tumino, R, Vineis, P, Peeters, Ph, Duell, Ej, Molina Montes, E, Quir?s, Jr, Dorronsoro, M, Chirlaque, Md, Barricarte, A, Ljuslinder, I, Palmqvist, R, Travis, Rc, Khaw, Kt, Wareham, N, Pischon, T, and Boeing, H.
Subjects: Oncology, Male, Nutrition and Disease, multiple imputation, Epidemiology, hdl-cholesterol, Rate ratio, adipose-tissue, Body Mass Index, chemistry.chemical_compound, c-reactive protein, Risk Factors, Voeding en Ziekte, plasma adiponectin, oxidative stress, Prospective Studies, Prospective cohort study, Incidence, density-lipoprotein cholesterol, Middle Aged, Prognosis, European Prospective Investigation into Cancer and Nutrition, Europe, C-Reactive Protein, Biomarker (medicine), Female, Colorectal Neoplasms, Metabolic Networks and Pathways, medicine.medical_specialty, binding-proteins, insulin-resistance, soluble leptin receptor, Adipokines, Internal medicine, medicine, Biomarkers, Tumor, Humans, Triglycerides, VLAG, Aged, Glycated Hemoglobin, Inflammation, Leptin receptor, Adiponectin, business.industry, Case-control study, Endocrinology, Logistic Models, chemistry, Socioeconomic Factors, Case-Control Studies, Glycated hemoglobin, business
Abstract: A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60% of the overall biomarker variance. In multi-variable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95% CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95% CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95% CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95% CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development. © Springer Science+Business Media 2014.
Published: 2013
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20. Mediterranean diet and colorectal cancer risk: results from a European cohort

Author: Timothy J. Key, Domenico Palli, Isabelle Romieu, Brian Buijsse, Alessio Naccarati, Veronika Fedirko, Pagona Lagiou, Miren Dorronsoro, Kay-Tee Khaw, Richard Palmqvist, Petra H.M. Peeters, Fränzel J.B. Van Duijnhoven, Anja Olsen, Eiliv Lund, Guri Skeie, Christina C. Dahm, Christina Bamia, Anne Tjønneland, Sara Grioni, Sophie Morois, Claudia Agnoli, Kim Overvad, Dimitrios Trichopoulos, George Adarakis, Dagrun Engeset, Nicholas J. Wareham, Verena A. Grote, Antonia Trichopoulou, Dora Romaguera, Rosario Tumino, María José Sánchez, Heiner Boeing, Genevieve Buckland, Salvatore Panico, Vanessa Cottet, Birgit Teucher, Aurelio Barricarte, Mazda Jenab, J. Ramón Quirós, Isabel Drake, José María Huerta, H. Bas Bueno-de-Mesquita, Teresa Norat, Marie-Christine Boutron-Ruault, Aliki J. Taylor, Ingrid Ljuslinder, Bamia, C, Lagiou, P, Buckland, G, Grioni, S, Agnoli, C, Taylor, Aj, Dahm, Cc, Overvad, K, Olsen, A, Tj?nneland, A, Cottet, V, Boutron Ruault, Mc, Morois, S, Grote, V, Teucher, B, Boeing, H, Buijsse, B, Trichopoulos, D, Adarakis, G, Tumino, R, Naccarati, A, Panico, Salvatore, Palli, D, Bueno de Mesquita, Hb, van Duijnhoven, Fj, Peeters, Ph, Engeset, D, Skeie, G, Lund, E, S?nchez, Mj, Barricarte, A, Huerta, Jm, Quir?s, Jr, Dorronsoro, M, Ljuslinder, I, Palmqvist, R, Drake, I, Key, Tj, Khaw, Kt, Wareham, N, Romieu, I, Fedirko, V, Jenab, M, Romaguera, D, Norat, T, and Trichopoulou, A.
Subjects: Gerontology, Mediterranean diet, Nutrition and Disease, Epidemiology, population, Diet, Mediterranean, 0302 clinical medicine, Risk Factors, Surveys and Questionnaires, Voeding en Ziekte, Medicine, Prospective Studies, 030212 general & internal medicine, adherence, Prospective cohort study, physical-activity, education.field_of_study, Incidence, Hazard ratio, health, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, nutrition, 030220 oncology & carcinogenesis, Cohort, Female, epic cohort, Colorectal Neoplasms, Cohort study, metaanalysis, Adult, Population, survival, White People, 03 medical and health sciences, rectal cancers, Confidence Intervals, Humans, patterns, Sex Distribution, education, Aged, Proportional Hazards Models, VLAG, business.industry, Proportional hazards model, Socioeconomic Factors, business, Follow-Up Studies, Demography
Abstract: The authors investigated the association of adherence to Mediterranean diet with colorectal cancer (CRC) risk in the European Prospective Investigation into Cancer and nutrition study. Adherence to Mediterranean diet was expressed through two 10-unit scales, the Modified Mediterranean diet score (MMDS) and the Centre-Specific MMDS (CSMMDS). Both scales share the same dietary components but differ in the cut-off values that were used for these components in the construction of the scales. Adjusted hazard ratios (HR) for the associations of these scales with CRC incidence were estimated. After 5,296,617 person-years of follow-up, 4,355 incident CRC cases were identified. A decreased risk of CRC, of 8 and 11 % was estimated when comparing the highest (scores 6-9) with the lowest (scores 0-3) adherence to CSMMDS and MMDS respectively. For MMDS the HR was 0.89 (95 % confidence interval (CI): 0.80, 0.99). A 2-unit increment in either Mediterranean scale was associated with a borderline statistically significant 3 to 4 % reduction in CRC risk (HR for MMDS: 0.96; 95 % CI: 0.92, 1.00). These associations were somewhat more evident, among women, were mainly manifested for colon cancer risk and their magnitude was not altered when alcohol was excluded from MMDS. These findings suggest that following a Mediterranean diet may have a modest beneficial effect on CRC risk.
Published: 2013
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21. Biomarkers of Oxidative Stress and Risk of Developing Colorectal Cancer:A Cohort-nested Case-Control Study in the European Prospective Investigation Into Cancer and Nutrition

Author: Kim Overvad, Elio Riboli, Krasimira Aleksandrova, Nicholas J. Wareham, Domenico Palli, Rosario Tumino, Miren Dorronsoro, Rudolf Kaaks, Valeria Pala, Petra H.M. Peeters, Françoise Clavel-Chapelon, Kay-Tee Khaw, María José Sánchez, Fränzel J.B. Van Duijnhoven, Francesca L. Crowe, Eva Ardanaz, Tobias Pischon, Anja Olsen, Veronika Fedirko, Peter D. Siersema, Heiner Boeing, Mazda Jenab, Paolo Vineis, Anne Tjønneland, José María Huerta, Annekatrin Lukanova, Sophie Morois, H. Bas Bueno-de-Mesquita, Dimitrios Trichopoulos, Teresa Norat, Carlos González, Göran Hallmans, Richard Palmqvist, Vardis Dilis, Eugene Jansen, Antonia Trichopoulou, Salvatore Panico, Sjoukje H.S. Woudt, Anke M. Leufkens, Guri Skeie, Naomi E. Allen, Marie-Christine Boutron-Ruault, Marcial Argüelles, Leufkens, Am, van Duijnhoven, Fj, Woudt, Sh, Siersema, Pd, Jenab, M, Jansen, Eh, Pischon, T, Tj?nneland, A, Olsen, A, Overvad, K, Boutron Ruault, Mc, Clavel Chapelon, F, Morois, S, Palli, D, Pala, V, Tumino, R, Vineis, P, Panico, Salvatore, Kaaks, R, Lukanova, A, Boeing, H, Aleksandrova, K, Trichopoulou, A, Trichopoulos, D, Dilis, V, Peeters, Ph, Skeie, G, Gonz?lez, Ca, Arg?elles, M, S?nchez, Mj, Dorronsoro, M, Huerta, Jm, Ardanaz, E, Hallmans, G, Palmqvist, R, Khaw, Kt, Wareham, N, Allen, Ne, Crowe, Fl, Fedirko, V, Norat, T, Riboli, E, and Bueno de Mesquita, Hb
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Epidemiology, Rate ratio, Risk Factors, Internal medicine, medicine, Humans, Risk factor, Aged, business.industry, Incidence, Case-control study, Cancer, Middle Aged, medicine.disease, Surgery, European Prospective Investigation into Cancer and Nutrition, Diet, Europe, Oxidative Stress, Logistic Models, Case-Control Studies, Cohort, Nested case-control study, population characteristics, Female, business, Colorectal Neoplasms, Reactive Oxygen Species, Biomarkers, Cohort study
Abstract: Oxidative stress has been shown to play an important role in carcinogenesis, but prospective evidence for an association between biomarkers of oxidative stress and colorectal cancer (CRC) risk is limited. The authors investigated the association between prediagnostic serum levels of oxidative stress indicators (i.e., reactive oxygen metabolites (ROM) and ferric reducing ability of plasma (FRAP)) and CRC risk. This was examined in a nested case-control study (1,064 CRC cases, 1,064 matched controls) in the European Prospective Investigation Into Cancer and Nutrition cohort (1992-2003). Incidence rate ratios and 95% confidence intervals were calculated using conditional logistic regression analyses. ROM were associated with overall CRC risk (highest tertile vs. lowest: adjusted incidence rate ratio (IRR(adj)) = 1.91, 95% confidence interval (CI): 1.47, 2.48), proximal (IRR(adj) = 1.89, 95% CI: 1.06, 3.36) and distal (IRR(adj) = 2.31, 95% CI: 1.37, 3.89) colon cancer, and rectal cancer (IRR(adj) = 1.69, 95% CI: 1.05, 2.72). When results were stratified by tertile of follow-up time, the association remained significant only in participants with less than 2.63 years of follow-up (IRR(adj) = 2.28, 95% CI: 1.78, 2.94; P-heterogeneity < 0.01). FRAP was not associated with CRC risk. In conclusion, prediagnostic serum ROM levels were associated with increased risk of CRC. However, this association was seen only in subjects with relatively short follow-up, suggesting that the association results from production of reactive oxygen species by preclinical tumors.
Published: 2012
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22. Prediagnostic 25-hydroxyvitamin D, VDR and CASR polymorphisms, and survival in patients with colorectal cancer in western European ppulations

Author: Christina C. Dahm, Göran Hallmans, Mazda Jenab, Birgit Teucher, Sara Grioni, Guri Skeie, Eugene Jansen, Elio Riboli, Françoise Clavel-Chapelon, Antoine Racine, Miren Dorronsoro, Salvatore Panico, Vassiliki Benetou, Fränzel J.B. Van Duijnhoven, Francesca L. Crowe, Anja Olsen, Richard Palmqvist, Kim Overvad, Catalina Bonet, Petra H.M. Peeters, José Ramón Quirós, Nicholas J. Wareham, Pietro Ferrari, Antonia Trichopoulou, Magritt Brustad, Heiner Boeing, Aurelio Barricarte, Petra A. Wark, Marie-Christine Boutron-Ruault, Maria Dolores Chirlaque, María José Sánchez, Dora Romaguera, Rosario Tumino, Peter D. Siersema, Paolo Vineis, Dimitrios Trichopoulos, Anne Tjønneland, Veronika Fedirko, Annekatrin Lukanova, H. Bas Bueno-de-Mesquita, Teresa Norat, James McKay, Isabelle Romieu, Kay-Tee Khaw, Krasimira Aleksandrova, Timothy J. Key, Domenico Palli, Fedirko, V, Riboli, E, Tj?nneland, A, Ferrari, P, Olsen, A, Bueno de Mesquita, Hb, van Duijnhoven, Fj, Norat, T, Jansen, Eh, Dahm, Cc, Overvad, K, Boutron Ruault, Mc, Clavel Chapelon, F, Racine, A, Lukanova, A, Teucher, B, Boeing, H, Aleksandrova, K, Trichopoulou, A, Benetou, V, Trichopoulos, D, Grioni, S, Vineis, P, Panico, Salvatore, Palli, D, Tumino, R, Siersema, Pd, Peeters, Ph, Skeie, G, Brustad, M, Chirlaque, Md, Barricarte, A, Ram?n Quir?s, J, S?nchez, Mj, Dorronsoro, M, Bonet, C, Palmqvist, R, Hallmans, G, Key, Tj, Crowe, F, Khaw, Kt, Wareham, N, Romieu, I, Mckay, J, Wark, Pa, Romaguera, D, and Jenab, M.
Subjects: Oncology, Male, Nutrition and Disease, Epidemiology, Colorectal cancer, Calcitriol receptor, 25-dihydroxyvitamin d-3, Polymerase Chain Reaction, prostate-cancer, Prostate cancer, Risk Factors, Voeding en Ziekte, Prospective Studies, Vitamin D, Prospective cohort study, physical-activity, risk, 1,25-dihydroxyvitamin d-3, Middle Aged, Prognosis, Survival Rate, Female, serum 25-hydroxyvitamin-d, Colorectal Neoplasms, colon-cancer, medicine.medical_specialty, Genotype, Lower risk, Article, Internal medicine, vitamin-d-receptor, medicine, Vitamin D and neurology, Humans, supplement use, neoplasms, Survival rate, VLAG, calcium, Polymorphism, Genetic, business.industry, Case-control study, DNA, medicine.disease, cell lung-cancer, digestive system diseases, Endocrinology, Case-Control Studies, Receptors, Calcitriol, business, Receptors, Calcium-Sensing, Follow-Up Studies
Abstract: Background: Individuals with higher blood 25-hydroxyvitamin D [25(OH)D] levels have a lower risk of developing colorectal cancer (CRC), but the influence of 25(OH)D on mortality after CRC diagnosis is unknown. Methods: The association between prediagnostic 25(OH)D levels and CRC-specific (N = 444) and overall mortality (N = 541) was prospectively examined among 1,202 participants diagnosed with CRC between 1992 and 2003 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate HRs and corresponding 95% CIs according to 25(OH)D quintiles and genetic variation within the VDR and CASR genes. Potential dietary, lifestyle, and metabolic effect modifiers were also investigated. Results: There were 541 deaths, 444 (82%) due to CRC. Mean follow-up was 73 months. In multivariable analysis, higher 25(OH)D levels were associated with a statistically significant reduction in CRC-specific (Ptrend = 0.04) and overall mortality (Ptrend = 0.01). Participants with 25(OH)D levels in the highest quintile had an adjusted HR of 0.69 (95% CI: 0.50–0.93) for CRC-specific mortality and 0.67 (95% CI: 0.50–0.88) for overall mortality, compared with the lowest quintile. Except for a possible interaction by prediagnostic dietary calcium intake (Pinteraction = 0.01), no other potential modifying factors related to CRC survival were noted. The VDR (FokI and BsmI) and CASR (rs1801725) genotypes were not associated with survival. Conclusions: High prediagnostic 25(OH)D levels are associated with improved survival of patients with CRC. Impact: Our findings may stimulate further research directed at investigating the effects of blood vitamin D levels before, at, and after CRC diagnosis on outcomes in CRC patients. Cancer Epidemiol Biomarkers Prev; 21(4); 582–93. ©2012 AACR.
Published: 2012
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23. Blood lipid and lipoprotein concentrations and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition

Author: Amir F. Ayyobi, Mazda Jenab, Heiner Boeing, Richard Palmqvist, Kostas Tsilidis, Giovanna Tagliabue, Veronika Fedirko, Françoise Clavel-Chapelon, Elio Riboli, Vardis Dilis, Laudina Rodríguez, Kim Overvad, Anne Pernille Toft-Petersen, Peter D. Siersema, Kay-Tee Khaw, H. Bas Bueno-de-Mesquita, María José Tormo, Vanessa Cottet, Paolo Vineis, Teresa Norat, Göran Hallmans, Jiri Frohlich, Petra H.M. Peeters, Miren Dorronsoro, Birgit Teucher, Esther Molina-Montes, Dagmar Drogan, Aurelio Barricarte, Fränzel J.B. Van Duijnhoven, Francesca L. Crowe, Sabina Rinaldi, Pagona Lagiou, Marie-Christine Boutron-Ruault, Carlos A. González, Rosario Tumino, Salvatore Panico, Anne Tjønneland, Domenico Palli, Veronique Chajes, Antonia Trichopoulou, Louise Hansen, Eugene Jansen, Tobias Pischon, Rudolf Kaaks, Miriam Calligaro, [van Duijnhoven,FJB, Bueno-De-Mesquita,HB, Calligaro,M, Jansen,EHJM] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [van Duijnhoven,FJB] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Bueno-De-Mesquita,HB, Siersema,PD] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Jenab,M, Chajes,V, Fedirko,V, Rinaldi,S] Int Agcy Res Canc IARC WHO, Lyon, France. [Pischon,T, Boeing,H, Drogan,D] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany. [Frohlich,J, Ayyobi,A] Univ British Columbia, St Pauls Hosp, Vancouver, Canada. [Overvad,K] Aarhus Univ, Sch Publ Hlth, Dept Epidemiol, Aarhus, Denmark. [Overvad,K, Toft-Petersen,AP] Aarhus Univ Hosp, Aalborg Hosp, Dept Cardiol, Aalborg, Denmark. [Tjonneland,A, Hansen,L] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Boutron-Ruault,MC, Clavel-Chapelon,F, Cottet,V] INSERM, UMRS 1018, Team 9, Centre for Research in Epidemiology and Population Health, Paris S Univ, Inst Gustave Roussy, Ctr Res Epidemiol & Populat Hlth, Villejuif, France. [Palli,D] ISPO Canc Res & Prevent Inst, Mol & Nutr Epidemiol Unit, Florence, Italy. [Tagliabue, G] Fdn IRCCS Inst Nazl Tumori, Environm Epidemiol Unit, Milan, Italy. [Tagliabue, G] Fdn IRCCS Inst Nazl Tumori, Canc Registry, Milan, Italy. [Panico, S] Univ Naples Federico 2, Dept Clin & Expt Med, Naples, Italy. [Tumino,R] Civile MP Arezzo Hosp, Dept Oncol, Histopathol Unit, Ragusa, Italy. [Tumino, R] Civile MP Arezzo Hosp, Canc Registry, Ragusa, Italy. [Vineis, P] HuGeF Fdn Torino, Turin, Italy. [Vineis, P] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC HPA Ctr Environm & Hlth, London, England. [Kaaks, R, Teucher, B] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Trichopoulou, A, Lagiou, P] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, WHO Collaborating Ctr Food & Nutr Policies, GR-11527 Athens, Greece. [Trichopoulou,A, Dilis,V] Hellen Hlth Fdn, Athens, Greece. [Peeters,PHM, Norat,T, Riboli,E] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. [Rodriguez,L] Hlth & Hlth Care Serv Council, Publ Hlth & Participat Directorate, Asturias, Spain. [Gonzalez,CA] Catalan Inst Oncol, Unit Nutr Environm & Canc, Barcelona, Spain. [Molina-Montes,E] Andalusia Sch Publ Hlth, Granada, Spain. [Dorronsoro,M] Dept Publ Hlth Guipuzkoa, San Sebastian, Spain. [Tormo,MJ] Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain. [Barricarte,A] Publ Hlth Inst Navarra, Pamplona, Spain. [Palmqvist,R] Umea Univ, Dept Med Biosci, Umea, Sweden. [Hallmans,G] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Khaw,KT] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. [Tsilidis,KK, Crowe,FL] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England., This work was supported by the European Commission: Public Health and Consumer Protection Directorate 1993-2004, Research Directorate-General 2005-., Ligue contre le Cancer, Societé 3M, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany), Danish Cancer Society (Denmark), Health Research Fund (FIS) of the Spanish Ministry of Health, The participating regional governments and institutions (Spain), Cancer Research UK, Medical Research Council (UK), Hellenic Ministry of Health, the Stavros Niarchos Foundation and the Hellenic Health Foundation (Greece), Italian Association for Research on Cancer, National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands), Swedish Cancer Society, Swedish Scientific Council, Regional government of Västerbotten (Sweden), Norwegian Cancer Society (Norway)., van Duijnhoven, Fj, Bueno De Mesquita, Hb, Calligaro, M, Jenab, M, Pischon, T, Jansen, Eh, Frohlich, J, Ayyobi, A, Overvad, K, Toft Petersen, Ap, Tjønneland, A, Hansen, L, Boutron Ruault, Mc, Clavel Chapelon, F, Cottet, V, Palli, D, Tagliabue, G, Panico, Salvatore, Tumino, R, Vineis, P, Kaaks, R, Teucher, B, Boeing, H, Drogan, D, Trichopoulou, A, Lagiou, P, Dilis, V, Peeters, Ph, Siersema, Pd, Rodríguez, L, González, Ca, Molina Montes, E, Dorronsoro, M, Tormo, Mj, Barricarte, A, Palmqvist, R, Hallmans, G, Khaw, Kt, Tsilidis, Kk, Crowe, Fl, Chajes, V, Fedirko, V, Rinaldi, S, Norat, T, and Riboli, E.
Subjects: Male, medicine.medical_specialty, Colorectal cancer, Lipoproteins, Blood lipids, Chemicals and Drugs::Lipids::Lipoproteins [Medical Subject Headings], Gastroenterology, Colorectal neoplasms, Body Mass Index, chemistry.chemical_compound, Patient Education as Topic, Nephelometry and Turbidimetry, Risk Factors, Internal medicine, Surveys and Questionnaires, medicine, Biomarkers, Tumor, Humans, Cáncer colorrectal, Prospective Studies, Risk factor, Encuestas nutricionales, Prospective cohort study, Aged, Cholesterol, business.industry, Incidence, Cancer, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Middle Aged, medicine.disease, Prognosis, Nutrition Surveys, Lipids, European Prospective Investigation into Cancer and Nutrition, Europe, Endocrinology, chemistry, Lípidos, lipids (amino acids, peptides, and proteins), Colorimetry, Female, Geographical Locations::Geographic Locations::Europe [Medical Subject Headings], Metabolic syndrome, business, Colorectal Neoplasms, Follow-Up Studies, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Data Collection::Nutrition Assessment::Nutrition Surveys [Medical Subject Headings]
Abstract: Objective To examine the association between serum concentrations of total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B and the incidence of colorectal cancer (CRC). Design Nested case–control study. Setting The study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort of more than 520 000 participants from 10 western European countries. Participants 1238 cases of incident CRC, which developed after enrolment into the cohort, were matched with 1238 controls for age, sex, centre, follow-up time, time of blood collection and fasting status. Main outcome measures Serum concentrations were quantitatively determined by colorimetric and turbidimetric methods. Dietary and lifestyle data were obtained from questionnaires. Conditional logistic regression models were used to estimate incidence rate ratios (RRs) and 95% CIs which were adjusted for height, weight, smoking habits, physical activity, education, consumption of fruit, vegetables, meat, fish, alcohol, fibre and energy. Results After adjustments, the concentrations of HDL and apoA were inversely associated with the risk of colon cancer (RR for 1 SD increase of 16.6 mg/dl in HDL and 32.0 mg/dl in apoA of 0.78 (95% CI 0.68 to 0.89) and 0.82 (95% CI 0.72 to 0.94), respectively). No association was observed with the risk of rectal cancer. Additional adjustment for biomarkers of systemic inflammation, insulin resistance and oxidative stress or exclusion of the first 2 years of follow-up did not influence the association between HDL and risk of colon cancer. Conclusions These findings show that high concentrations of serum HDL are associated with a decreased risk of colon cancer. The mechanism behind this association needs further elucidation. Yes
Published: 2011
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24. Circulating C-reactive protein concentrations and risks of colon and rectal cancer: a nested case-control study within the European Prospective Investigation into Cancer and Nutrition

Author: Kim Overvad, Dora Romaguera, Rosario Tumino, Domenico Palli, Sabine Rohrmann, Vittorio Krogh, Anne Tjønneland, Marie-Christine Boutron-Ruault, Göran Hallmans, F. Clavel-Chapelon, Paolo Vineis, Sabina Rinaldi, Pagona Lagiou, Sophie Morois, María José Sánchez, Anke M. Leufkens, H. Bas Bueno-de-Mesquita, Laudina Rodríguez, Christina C. Dahm, Antonia Trichopoulou, Teresa Norat, Carmen Navarro, Richard Palmqvist, Rudolf Kaaks, Mazda Jenab, Salvatore Panico, Elizabeth A Spencer, Tobias Pischon, Nicholas J. Wareham, Catalina Bonet, Aurelio Barricarte, Miren Dorronsoro, Dimitrios Trichopoulos, Naomi E. Allen, Elio Riboli, Eugene Jansen, Heiner Boeing, Petra H.M. Peeters, Fränzel J.B. Van Duijnhoven, Anja Olsen, Krasimira Aleksandrova, Kay-Tee Khaw, Aleksandrova, K, Jenab, M, Boeing, H, Jansen, E, Bueno de Mesquita, Hb, Rinaldi, S, Riboli, E, Overvad, K, Dahm, Cc, Olsen, A, Tjønneland, A, Boutron Ruault, Mc, Clavel Chapelon, F, Morois, S, Palli, D, Krogh, V, Tumino, R, Vineis, P, Panico, Salvatore, Kaaks, R, Rohrmann, S, Trichopoulou, A, Lagiou, P, Trichopoulos, D, van Duijnhoven, Fj, Leufkens, Am, Peeters, Ph, Rodríguez, L, Bonet, C, Sánchez, Mj, Dorronsoro, M, Navarro, C, Barricarte, A, Palmqvist, R, Hallmans, G, Khaw, Kt, Wareham, N, Allen, Ne, Spencer, E, Romaguera, D, Norat, T, and Pischon, T.
Subjects: Adult, Male, medicine.medical_specialty, Epidemiology, Colorectal cancer, Gastroenterology, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Risk factor, 030304 developmental biology, Aged, 2. Zero hunger, Glycated Hemoglobin, 0303 health sciences, business.industry, Rectal Neoplasms, Incidence, Cholesterol, HDL, Cancer, Middle Aged, medicine.disease, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Menstrual cycle phase, Europe, Endocrinology, C-Reactive Protein, Logistic Models, 030220 oncology & carcinogenesis, Relative risk, Case-Control Studies, Nested case-control study, Colonic Neoplasms, Female, Metabolic syndrome, Waist Circumference, business, Biomarkers
Abstract: Udgivelsesdato: 2010-Jul-15 The authors investigated associations between serum C-reactive protein (CRP) concentrations and colon and rectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (1992-2003) among 1,096 incident cases and 1,096 controls selected using risk-set sampling and matched on study center, age, sex, time of blood collection, fasting status, menopausal status, menstrual cycle phase, and hormone replacement therapy. In conditional logistic regression with adjustment for education, smoking, nutritional factors, body mass index, and waist circumference, CRP showed a significant nonlinear association with colon cancer risk but not rectal cancer risk. Multivariable-adjusted relative risks for CRP concentrations of >/=3.0 mg/L versus
Published: 2010
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25. Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study

Author: Jakob Linseisen, Pierre Hainaut, Antonia Trichopoulou, Eiliv Lund, Pietro Ferrari, Sophie Morois, Kay-Tee Khaw, Kim Overvad, Philippe Autier, Gesthimani Misirli, Dimitrios Trichopoulos, Timothy J. Key, Andrew W. Roddam, Carla H. van Gils, Salvatore Panico, María J. Tormo, Paolo Vineis, Graham Byrnes, Eugene Jansen, Fränzel J.B. Van Duijnhoven, María José Sánchez, Martine M. Ros, Teresa Norat, Anja Olsen, Anne Tjønneland, Rudolf Kaaks, H. Bas Bueno-de-Mesquita, Tobias Pischon, Göran Hallmans, R. Palmqvist, Domenico Palli, Rosario Tumino, Sabina Rinaldi, Manuela M. Bergmann, Franco Berrino, Magritt Brustad, Eva Ardanaz, Heiner Boeing, Miren Dorronsoro, Nadia Slimani, Françoise Clavel-Chapelon, Petra H.M. Peeters, Elio Riboli, Mazda Jenab, Laudina Rodríguez, Marie-Christine Boutron-Ruault, Carlos A. González, [Jenab M, Ferrari P, Slimani N, Byrnes G, Rinaldi S, Autier P, Hainaut P] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Bueno-de-Mesquita HB, van Duijnhoven FJB, Jansen EHJM, Ros MM] National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands. [Ferrari P] Data Collection and Exposure Unit, European Food Safety Authority (EFSA), Parma, Italy. [van Duijnhoven FJB, van Gils CH, Peeters PH] Julius Centre for Health Sciences and Primary Care, University Medical Centre, Utrecht, Netherlands. [Norat T, Vineis P, Riboli E] School of Public Health, Imperial College, London, UK. [Pischon T, Boeing H, Bergmann MM] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Tjonneland A, Olsen A] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Overvad K] Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark. [Boutron-Ruault M-C, Clavel-Chapelon F, Morois S] Inserm (Institut National de la Santé et de la Recherche Médicale) ERI 20, EA. [Kaaks R, Linseisen J] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Trichopoulou A, Misirli G] Department of Hygiene and Epidemiology, University of Athens Medical School, Greece. [Trichopoulou A] Hellenic Health Foundation, Greece. [Trichopoulos D] Department of Epidemiology, Harvard School of Public Health, USA and Bureau of Epidemiologic Research, Academy of Athens, Greece. [Berrino F] Department of Preventive and Predictive Medicine, Etiologic Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (National Cancer Institute), Milan, Italy. [Vineis P] ISI Foundation, Turin, Italy. [Panico S] Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. [Palli D] Molecular and Nutritional Epidemiology Unit, ISPO (Cancer Research and Prevention Institute), Florence, Italy. [Tumino R] Ragusa Cancer Registry and Histopathology Unit, 'Civile M.P.Arezzo' Hospital, ASP 7 Ragusa, Italy. [Ros MM] Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. [Brustad M, Lund E] Centre for Sami Health Research, Institute of Community Medicine, University of Tromsø, Tromsø, Norway. [Tormo MJ] Epidemiology Service, Murcia Regional Health Authority, Spain. [Ardanaz E] Public Health Institute of Navarra, Pamplona, Spain. [Ardanaz E, Sánchez MJ] CIBER Epidemiología y Salud Pública (CIBERESP), Spain. [Rodríguez L] Health Information Section, Public Health and Participation Directorate, Health and Health Care Services Council, Asturias, Spain. [Sánchez MJ] Andalusian School of Public Health-Granada (Spain). [Dorronsoro M] Epidemiology Unit, Public Health Division of Guipuzkoa, San Sebastian, Spain. [Gonzalez CA] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Hallmans G] Department of Public Health and Clinical Medicine, Nutritional Research, Umeå, Sweden. [Palmqvist R] Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. [Roddam A, Key TJ] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. [Khaw KT] Clinical Gerontology Unit, University of Cambridge, Cambridge, UK. [Bueno-de-Mesquita HB] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands. [Linseisen J] Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany, We thank the World Cancer Research Fund (WCRF, London, UK, grant number 2005/12) for grant funding for the present study. The EPIC study was supported by the Europe Against Cancer Programme of the European Commission (SANCO), Ligue contre le Cancer (France), Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM), German Cancer Aid, German Cancer Research Center, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health (RETIC-RD06/0020), the participating regional governments and institutions of Spain, The ISCIII Red de Centro RCESP (C03/09), Cancer Research UK, Medical Research Council, UK, the Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, the Wellcome Trust, UK, Greek Ministry of Health and Social Solidarity, Hellenic Health Foundation and Stavros Niarchos Foundation, Greek Ministry of Education, Italian Association for Research on Cancer, Italian National Research Council, Compagnia di San Paolo, Dutch Ministry of Public Health, Welfare and Sports, Dutch Ministry of Health, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), Swedish Cancer Society, Swedish Scientific Council, Regional Governments of Skane and Vasterbotten, Sweden, and Norwegian Cancer Society., Jenab, M, Bueno de Mesquita, Hb, Ferrari, P, van Duijnhoven, Fj, Norat, T, Pischon, T, Jansen, Eh, Slimani, N, Byrnes, G, Rinaldi, S, Tjønneland, A, Olsen, A, Overvad, K, Boutron Ruault, Mc, Clavel Chapelon, F, Morois, S, Kaaks, R, Linseisen, J, Boeing, H, Bergmann, Mm, Trichopoulou, A, Misirli, G, Trichopoulos, D, Berrino, F, Vineis, P, Panico, Salvatore, Palli, D, Tumino, R, Ros, Mm, van Gils, Ch, Peeters, Ph, Brustad, M, Lund, E, Tormo, Mj, Ardanaz, E, Rodríguez, L, Sánchez, Mj, Dorronsoro, M, Gonzalez, Ca, Hallmans, G, Palmqvist, R, Roddam, A, Key, Tj, Khaw, Kt, Autier, P, Hainaut, P, Riboli, E., and University of Groningen
Subjects: Oncology, Male, Colorectal cancer, 0302 clinical medicine, Risk Factors, Neoplasias colorrectales, SERUM 25-HYDROXYVITAMIN-D, DIETARY-INTAKE, Epidemiology, 030212 general & internal medicine, Vitamin D, General Environmental Science, 2. Zero hunger, Colon Cancer, COLON-CANCER, Confounding, General Engineering, Estudios de Casos y Controles, Geographicals::Geographic Locations::Europe [Medical Subject Headings], General Medicine, Middle Aged, META-ANALYSIS, 3. Good health, Europe, 030220 oncology & carcinogenesis, Cohort, Female, Risk assessment, Colorectal Neoplasms, Europa, Life Sciences & Biomedicine, D SUPPLEMENTATION, medicine.medical_specialty, CALCIUM INTAKE, Vitamina D, Chemicals and Drugs::Polycyclic Compounds::Steroids::Secosteroids::Vitamin D [Medical Subject Headings], Enzyme-Linked Immunosorbent Assay, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Medicine, General & Internal, D-RECEPTOR, General & Internal Medicine, Internal medicine, Vitamin D and neurology, medicine, Humans, ddc:610, Life Style, Immunology (Including Allergy), Science & Technology, Dose-Response Relationship, Drug, 25-HYDROXYVITAMIN-D LEVELS, business.industry, Research, Case-control study, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], medicine.disease, RANDOMIZED-CONTROLLED-TRIALS, Diet, Epidemiologic Studies, Endocrinology, Cardiovascular and Metabolic Diseases, Case-Control Studies, Nested case-control study, General Earth and Planetary Sciences, Calcium, D METABOLITES, business
Abstract: Contains fulltext : 88351.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations. DESIGN: Nested case-control study. Setting The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries. PARTICIPANTS: 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls MAIN OUTCOME MEASURES: Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders. RESULTS: 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend or=100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P
Published: 2010
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26. Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk

Author: Yvoni Koumantaki, Elio Riboli, Bethany Van Guelpen, Nicholas J. Wareham, Paolo Vineis, Birgit Hoeft, Karin Jirström, Elizabeth A Spencer, Jonas Manjer, Göran Hallmans, H. B. Bueno-De-Mesquita, Ulla Vogel, Veronique Chajes, Carla H. van Gils, Paolo Boffetta, Heiner Boeing, Lars Beckmann, Kim Overvad, Rikke Dalgaard Hansen, Marianne Uhre Jakobsen, Laudina Rodríguez, Franco Berrino, Eiliv Lund, Mazda Jenab, Petra H.M. Peeters, Sophie Morois, Traci Mouw, Jakob Linseisen, Teresa Norat, Aurelio Barricarte, F. Clavel-Chapelon, Karin Müller-Decker, Fränzel J.B. Van Duijnhoven, Francesca L. Crowe, José María Huerta Castaño, Dimitrios Trichopoulos, Antonia Trichopoulou, Sven Knüppel, Rudolf Kaaks, Federico Canzian, Domenico Palli, Vanessa Dumeaux, Alexandra Nieters, Kay-Tee Khaw, Anika Hüsing, Xavier Muñoz, Rosario Tumino, Marie-Christine Boutron-Ruault, Salvatore Panico, Hoeft, B, Linseisen, J, Beckmann, L, Müller Decker, K, Canzian, F, Hüsing, A, Kaaksr, Vogel, U, Jakobsen, Mu, Overvad, K, Hansen, Rd, Knüppel, S, Boeing, H, Trichopoulou, A, Koumantaki, Y, Trichopoulos, D, Berrino, F, Palli, D, Panico, Salvatore, Tumino, R, Bueno de Mesquita, Hb, van Duijnhoven, Fj, van Gils, Ch, Peeters, Ph, Dumeaux, V, Lunde, Huerta Castaño, Jm, Muñoz, X, Rodriguez, L, Barricarte, A, Manjer, J, Jirström, K, Van Guelpen, B, Hallmans, G, Spencer, Ea, Crowe, Fl, Khaw, Kt, Wareham, N, Morois, S, Boutron Ruault, Mc, Clavel Chapelon, F, Chajes, V, Jenab, M, Boffetta, P, Vineis, P, Mouw, T, Norat, T, Riboli, E, Nieters, A., Hoeft, B., Linseisen, J., Beckmann, L., Müller-Decker, K., Canzian, F., Hüsing, A., Kaaks, R., Vogel, U., Jakobsen, M.U., Overvad, K., Hansen, R.D., Knüppel, S., Boeing, H., Trichopoulou, A., Koumantaki, Y., Trichopoulos, D., Berrino, F., Palli, D., Panico, S., Tumino, R., Buenode-Mesquita, H.B., van Duijnhoven, F.J.B., van Gils, C.H., Peeters, P.H., Dumeaux, V., Lund, E., Huerta Castaño, J.M., Muñoz, X., Rodriguez, L., Barricarte, A., Manjer, J., Jirström, K., van Guelpen, B., Hallmans, G., Spencer, E.A., Crowe, F.L., Khaw, K.-T., Wareham, N., Morois, S., Boutron-Ruault, M.-C., Clavel-Chapelon, F., Chajes, V., Jenab, M., Boffetta, P., Vineis, P., Mouw, T., Norat, T., and Riboli, E.
Subjects: Oncology, Male, Cancer Research, Colorectal cancer, Cohort Studies, 0302 clinical medicine, Genetics, 0303 health sciences, Group III Phospholipases A2, Fatty Acids, Smoking, General Medicine, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Neoplasm Proteins, Europe, 030220 oncology & carcinogenesis, Hydroxyprostaglandin Dehydrogenases, Female, Colorectal Neoplasms, medicine.medical_specialty, Genotype, TRPV Cation Channels, colorectal cancer, Single-nucleotide polymorphism, Biology, Adenocarcinoma, Polymorphism, Single Nucleotide, Group VI Phospholipases A2, 03 medical and health sciences, Internal medicine, medicine, Humans, Receptors, Prostaglandin E, ddc:610, Polymorphism, Allele frequency, Alleles, Genetic Association Studies, 030304 developmental biology, Haplotype, Cancer, Odds ratio, Receptors, Prostaglandin E, EP2 Subtype, medicine.disease, Minor allele frequency, Haplotypes, Case-Control Studies, fatty acid, metabolism
Abstract: Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. Three hundred and ninety two single-nucleotide polymorphisms were selected using pairwise tagging with an r2 cutoff of 0.8 and a minor allele frequency of >5%. Conditional logistic regression models were used to estimate odds ratios and corresponding 95% confidence intervals. Haplotype analysis was performed using a generalized linear model framework. On the genotype level, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), phospholipase A2 group VI (PLA2G6) and transient receptor potential vanilloid 3 were associated with higher risk for CRC, whereas prostaglandin E receptor 2 (PTGER2) was associated with lower CRC risk. A significant inverse association (P < 0.006) was found for PTGER2 GGG haplotype, whereas HPGD AGGAG and PLA2G3 CT haplotypes were significantly (P < 0.001 and P = 0.003, respectively) associated with higher risk of CRC. Based on these data, we present for the first time the association of HPGD variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk. © The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org.
Published: 2010
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27. Plasma vitamins B2, B6, B12, and related genetic variants as predictors of colorectal cancer risk

Author: Simone J. P. M. Eussen, Øivind Midttun, Kim Overvad, Elio Riboli, Tobias Pischon, Ole Thorlacius-Ussing, Paolo Vineis, Rudolf Kaaks, Laudina Rodríguez, Domenico Palli, Bethany VanGuelpen, Mazda Jenab, Per Magne Ueland, Ulrika Ericson, Cornelia Weikert, Åse Fredriksen, Anne Tjønneland, Carmen Enid Martínez, Petra H.M. Peeters, Paolo Boffetta, Klaus Meyer, Carmen Navarro, H. Bas Bueno-de-Mesquita, Jonas Manjer, Valeria Pala, Françoise Clavel-Chapelon, Teresa Norat, Sophie Morois, Fränzel J.B. Van Duijnhoven, Anja Olsen, Rosario Tumino, Kay-Tee Khaw, Steinar Hustad, Jakob Linseisen, Michael Katsoulis, Richard Palmqvist, Stein Emil Vollset, Sheila Bingham, Antonia Trichopoulou, Guri Skeie, Miren Dorronsoro, Demosthenes Zilis, Nadia Slimani, Eva Ardanaz, Salvatore Panico, Xavier Muñoz, Marie-Christine Boutron-Ruault, Eussen, Sj, Vollset, Se, Hustad, S, Midttun, Ø, Meyer, K, Fredriksen, A, Ueland, Pm, Jenab, M, Slimani, N, Boffetta, P, Overvad, K, Thorlacius Ussing, O, Tjønneland, A, Olsen, A, Clavel Chapelon, F, Boutron Ruault, Mc, Morois, S, Weikert, C, Pischon, T, Linseisen, J, Kaaks, R, Trichopoulou, A, Zilis, D, Katsoulis, M, Palli, D, Pala, V, Vineis, P, Tumino, R, Panico, Salvatore, Peeters, Ph, Bueno de Mesquita, Hb, van Duijnhoven, Fj, Skeie, G, Muñoz, X, Martínez, C, Dorronsoro, M, Ardanaz, E, Navarro, C, Rodríguez, L, Vanguelpen, B, Palmqvist, R, Manjer, J, Ericson, U, Bingham, S, Khaw, Kt, Norat, T, Riboli, E., Eussen, S.J.P.M., Vollset, S.E., Hustad, S., Midttun, Ø., Meyer, K., Fredriksen, Å., Ueland, P.M., Jenab, M., Slimani, N., Boffetta, P., Overvad, K., Thorlacius-Ussing, O., Tjønneland, A., Olsen, A., Clavel-Chapelon, F., Boutron-Ruault, M.-C., Morois, S., Weikert, C., Pischon, T., Linseisen, J., Kaaks, R., Trichopoulou, A., Zilis, D., Katsoulis, M., Palli, D., Pala, V., Vineis, P., Tumino, R., Panico, S., Peeters, P.H.M., Bueno-de-Mesquita, H.B., Van Duijnhoven, F.J.B., Skeie, G., Muñoz, X., Martínez, C., Dorronsoro, M., Ardanaz, E., Navarro, C., Rodríguez, L., VanGuelpen, B., Palmqvist, R., Manjer, J., Ericson, U., Bingham, S., Khaw, K.-T., and Norat, T.
Subjects: Oncology, Male, medicine.medical_specialty, Epidemiology, Colorectal cancer, Riboflavin, Polymorphism, Single Nucleotide, Article, Cohort Studies, Folic Acid, Risk Factors, Internal medicine, Genotype, medicine, Humans, Vitamin B12, ONE-CARBON METABOLISM, METHIONINE SYNTHASE GENE, METHYLENETETRAHYDROFOLATE REDUCTASE, FOLATE METABOLISM, MASS-SPECTROMETRY, HOMOCYSTEINE METABOLISM, DNA METHYLATION, DIETARY-INTAKE, RAT-LIVER, POLYMORPHISMS, B12, biology, colorectal cancer risk, business.industry, Case-control study, Cancer, Middle Aged, medicine.disease, Vitamin B 6, B vitamins, Vitamin B 12, Endocrinology, Methylenetetrahydrofolate reductase, Case-Control Studies, biology.protein, B6, Female, B2, business, Colorectal Neoplasms, Cohort study
Abstract: Background: B-vitamins are essential for one-carbon metabolism and have been linked to colorectal cancer. Although associations with folate have frequently been studied, studies on other plasma vitamins B2, B6, and B12 and colorectal cancer are scarce or inconclusive. Methods: We carried out a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, including 1,365 incident colorectal cancer cases and 2,319 controls matched for study center, age, and sex. We measured the sum of B2 species riboflavin and flavin mononucleotide, and the sum of B6 species pyridoxal 5′-phosphate, pyridoxal, and 4-pyridoxic acid as indicators for vitamin B2 and B6 status, as well as vitamin B12 in plasma samples collected at baseline. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for colorectal cancer were estimated using conditional logistic regression, adjusted for smoking, education, physical activity, body mass index, alcohol consumption, and intakes of fiber and red and processed meat. Results: The relative risks comparing highest to lowest quintile were 0.71 [95% confidence interval (95% CI), 0.56-0.91; Ptrend = 0.02] for vitamin B2, 0.68 (95% CI, 0.53-0.87; Ptrend Conclusions: Higher plasma concentrations of vitamins B2 and B6 are associated with a lower colorectal cancer risk. Impact: This European population-based study is the first to indicate that vitamin B2 is inversely associated with colorectal cancer, and is in agreement with previously suggested inverse associations of vitamin B6 with colorectal cancer. Cancer Epidemiol Biomarkers Prev; 19(10); 2549–61. ©2010 AACR.
Published: 2010
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28. Plasma folate, related genetic variants, and colorectal cancer risk in EPIC

Author: Elio Riboli, Klaus Meyer, Rudolf Kaaks, Eiliv Lund, Salvatore Panico, Françoise Clavel-Chapelon, Åse Fredriksen, Laudina Rodríguez, H. Bas Bueno-de-Mesquita, Sophie Morois, Richard Palmqvist, Guri Skeie, Teresa Norat, Carmen Navarro, Inger T. Gram, Kim Overvad, Jakob Linseisen, Stein Emil Vollset, Jannicke Igland, Miren Dorronsoro, Demosthenes Zilis, Nadia Slimani, Mazda Jenab, Bethany Van Guelpen, Paolo Vineis, Paolo Boffetta, Ulrika Ericson, Carlos A. González, Petra H.M. Peeters, Marie-Christine Boutron-Ruault, Franco Berrino, Eva Ardanaz, Fränzel J.B. Van Duijnhoven, Sheila Bingham, Anja Olsen, Antonia Trichopoulou, Rosario Tumino, Jonas Manjer, Kay-Tee Khaw, Cornelia Weikert, Carmen Enid Martínez, Simone J. P. M. Eussen, Tobias Pischon, Domenico Palli, Per Magne Ueland, Michael Katsoulis, Anne Tjønneland, Eussen, Sj, Vollset, Se, Igland, J, Meyer, K, Fredriksen, A, Ueland, Pm, Jenab, M, Slimani, N, Boffetta, P, Overvad, K, Tjønneland, A, Olsen, A, Clavel Chapelon, F, Boutron Ruault, Mc, Morois, S, Weikert, C, Pischon, T, Linseisen, J, Kaaks, R, Trichopoulou, A, Zilis, D, Katsoulis, M, Palli, D, Berrino, F, Vineis, P, Tumino, R, Panico, Salvatore, Peeters, Ph, Bueno de Mesquita, Hb, van Duijnhoven, Fj, Gram, It, Skeie, G, Lund, E, González, Ca, Martínez, C, Dorronsoro, M, Ardanaz, E, Navarro, C, Rodríguez, L, Van Guelpen, B, Palmqvist, R, Manjer, J, Ericson, U, Bingham, S, Khaw, Kt, Norat, T, Riboli, E., Eussen, S.J.P.M., Vollset, S.E., Igland, J., Meyer, K., Fredriksen, Å., Ueland, P.M., Jenab, M., Slimani, N., Boffetta, P., Overvad, K., Tjønneland, A., Olsen, A., Clavel-Chapelon, F., Boutron-Ruault, M.-C., Morois, S., Weikert, C., Pischon, T., Linseisen, J., Kaaks, R., Trichopoulou, A., Zilis, D., Katsoulis, M., Palli, D., Berrino, F., Vineis, P., Tumino, R., Panico, S., Peeters, P.H.M., Bueno-de-Mesquita, H.B., Van Duijnhoven, F.J.B., Gram, I.T., Skeie, G., Lund, E., González, C.A., Martínez, C., Dorronsoro, M., Ardanaz, E., Navarro, C., Rodríguez, L., Van Guelpen, B., Palmqvist, R., Manjer, J., Ericson, U., Bingham, S., Khaw, K.-T., and Norat, T.
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Epidemiology, Colorectal cancer, colorectal cancer, Biology, medicine.disease_cause, Polymorphism, Single Nucleotide, Article, Methylenetetrahydrofolate reductase polymorphism, Nested case-control, Human methionine synthase, Carbon metabolic pathway, C677T MTHFR polymorphism, Colon-cancer, Folic-acid, Mass-spectrometry, Dietary patterns, Common mutation, Folic Acid, Risk Factors, Molecular genetics, Internal medicine, Genetic variation, medicine, Humans, Genetic Predisposition to Disease, Prospective Studies, Prospective cohort study, Methylenetetrahydrofolate Reductase (NADPH2), Aged, Aged, 80 and over, Genetics, Plasma folate, Case-control study, Middle Aged, Prognosis, medicine.disease, digestive system diseases, Survival Rate, Case-Control Studies, Methylenetetrahydrofolate reductase, Nested case-control study, biology.protein, Female, EPIC, Colorectal Neoplasms, Carcinogenesis
Abstract: Background: A potential dual role of folate in colorectal cancer (CRC) is currently subject to debate. We investigate the associations between plasma folate, several relevant folate-related polymorphisms, and CRC risk within the large European Prospective Investigation into Cancer and Nutrition cohort.Methods: In this nested case-control study, 1,367 incident CRC cases were matched to 2,325 controls for study center, age, and sex. Risk ratios (RR) were estimated with conditional logistic regression and adjusted for smoking, education, physical activity, and intake of alcohol and fiber.Results: Overall analyses did not reveal associations of plasma folate with CRC. The RR (95% confidence interval; Ptrend) for the fifth versus the first quintile of folate status was 0.94 (0.74-1.20; 0.44). The polymorphisms MTHFR677C→T, MTHFR1298A→C, MTR2756A→G, MTRR66A→G, and MTHFD11958G→A were not associated with CRC risk. However, in individuals with the lowest plasma folate concentrations, the MTHFR 677TT genotype showed a statistically nonsignificant increased CRC risk [RR (95% CI; Ptrend) TT versus CC = 1.39 (0.87-2.21); 0.12], whereas those with the highest folate concentrations showed a nonsignificant decreased CRC risk [RR TT versus CC = 0.74 (0.39-1.37); 0.34]. The SLC19A180G→A showed a positive association with CRC risk [RR AA versus GG 1.30 (1.06-1.59); Conclusions: This large European prospective multicenter study did not show an association of CRC risk with plasma folate status nor with MTHFR polymorphisms.Impact: Findings of the present study tend to weaken the evidence that folate plays an important role in CRC carcinogenesis. However, larger sample sizes are needed to adequately address potential gene-environment interactions. Cancer Epidemiol Biomarkers Prev; 19(5); 1328–40. ©2010 AACR.
Published: 2010
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29. Fruit, vegetables, and colorectal cancer risk: the European Prospective Investigation into Cancer and Nutrition

Author: Petra H.M. Peeters, Domenico Palli, Carmen Navarro, Carla H. van Gils, Jonas Manjer, Corinne Casagrande, Mazda Jenab, Jakob Linseisen, Ute Nöthlings, Paolo Vineis, Martine M. Ros, Sheila Bingham, Anja Olsen, Miren Dorronsoro, Elio Riboli, Göran Berglund, Pietro Ferrari, Aurelio Barricarte, Nadia Slimani, Antonia Trichopoulou, Marie-Christine Boutron-Ruault, Dagrun Engeset, Salvatore Panico, Marga C. Ocké, Françoise Clavel-Chapelon, Sabina Sieri, Ole Thorlacius-Ussing, Dimitrios Trichopoulos, Sophie Morois, Timothy J. Key, Kim Overvad, Valentina Gallo, Carlos A. González, Rosario Tumino, Paolo Boffetta, Heiner Boeing, H. Bas Bueno-de-Mesquita, Kay-Tee Khaw, Anne Tjønneland, Teresa Norat, Laudina Rodríguez Suárez, Fränzel J. B. van Duijnhoven, Guri Skeie, Naomi E. Allen, Eiliv Lund, Rudolf Kaaks, Richard Palmqvist, Gesthimani Misirli, María José Sánchez, Göran Hallmans, Hendriek C. Boshuizen, Sabina Rinaldi, Van Duijnhoven, F.J.B., Bueno-De-Mesquita, H.B., Ferrari, P., Jenab, M., Boshuizen, H.C., Ros, M.M., Casagrande, C., Tjønneland, A., Olsen, A., Overvad, K., Thorlacius-Ussing, O., Clavel-Chapelon, F., Boutron-Ruault, M.-C., Morois, S., Kaaks, R., Linseisen, J., Boeing, H., Nöthlings, U., Trichopoulou, A., Trichopoulos, D., Misirli, G., Palli, D., Sieri, S., Panico, S., Tumino, R., Vineis, P., Peeters, P.H.M., Van Gils, C.H., Ocké, M.C., Lund, E., Engeset, D., Skeie, G., Suárez, L.R., González, C.A., Sánchez, M.-J., Dorronsoro, M., Navarro, C., Barricarte, A., Berglund, G., Manjer, J., Hallmans, G., Palmqvist, R., Bingham, S.A., Khaw, K.-T., Key, T.J., Allen, N.E., Boffetta, P., Slimani, N., Rinaldi, S., Gallo, V., Norat, T., Riboli, E., van Duijnhoven, Fj, Bueno De Mesquita, Hb, Ferrari, P, Jenab, M, Boshuizen, Hc, Ros, Mm, Casagrande, C, Tjønneland, A, Olsen, A, Overvad, K, Thorlacius Ussing, O, Clavel Chapelon, F, Boutron Ruault, Mc, Morois, S, Kaaks, R, Linseisen, J, Boeing, H, Nöthlings, U, Trichopoulou, A, Trichopoulos, D, Misirli, G, Palli, D, Sieri, S, Panico, Salvatore, Tumino, R, Vineis, P, Peeters, Ph, van Gils, Ch, Ocké, Mc, Lund, E, Engeset, D, Skeie, G, Suárez, Lr, González, Ca, Sánchez, Mj, Dorronsoro, M, Navarro, C, Barricarte, A, Berglund, G, Manjer, J, Hallmans, G, Palmqvist, R, Bingham, Sa, Khaw, Kt, Key, Tj, Allen, Ne, Boffetta, P, Slimani, N, Rinaldi, S, Gallo, V, and Norat, T
Subjects: Questionnaires, Oncology, Male, medicine.medical_specialty, Time Factors, Colorectal cancer, Medicine (miscellaneous), Environment, Gastroenterology, 03 medical and health sciences, Fruit vegetables colorectal cancer risk The European Prospective Investigation Cancer Nutrition, 0302 clinical medicine, Risk Factors, Internal medicine, Surveys and Questionnaires, Vegetables, medicine, Humans, ddc:610, Prospective Studies, Risk factor, Life Style, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, Nutrition and Dietetics, Proportional hazards model, business.industry, Incidence (epidemiology), Incidence, Patient Selection, Hazard ratio, Smoking, Cancer, Reproducibility of Results, Colonoscopy, medicine.disease, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Diet, Europe, 030220 oncology & carcinogenesis, Fruit, Cohort, Female, business, Colorectal Neoplasms, Demography, Follow-Up Studies
Abstract: Background: A high consumption of fruit and vegetables is possibly associated with a decreased risk of colorectal cancer (CRC). However, the findings to date are inconsistent. Objective: We examined the relation between self-reported usual consumption of fruit and vegetables and the incidence of CRC. Design: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 452,755 subjects (131,985 men and 320,770 women) completed a dietary questionnaire in 1992-2000 and were followed up for cancer incidence and mortality until 2006. A multivariate Cox proportional hazard model was used to estimate adjusted hazard ratios (HRs) and 95% CIs. Results: After an average follow-up of 8.8 y, 2,819 incident CRC cases were reported. Consumption of fruit and vegetables was inversely associated with CRC in a comparison of the highest with the lowest EPIC-wide quintile of consumption (HR: 0.86; 95% CI: 0.75, 1.00; P for trend = 0.04), particularly with colon cancer risk (HR: 0.76; 95% CI: 0.63, 0.91; P for trend < 0.01). Only after exclusion of the first 2 y of follow-up were these findings corroborated by calibrated continuous analyses for a 100-g increase in consumption: HRs of 0.95 (95% CI: 0.91, 1.00; P = 0.04) and 0.94 (95% CI: 0.89, 0.99; P = 0.02), respectively. The association between fruit and vegetable consumption and CRC risk was inverse in never and former smokers, but positive in current smokers. This modifying effect was found for fruit and vegetables combined and for vegetables alone (P for interaction < 0.01 for both). Conclusions: These findings suggest that a high consumption of fruit and vegetables is associated with a reduced risk of CRC, especially of colon cancer. This effect may depend on smoking status. © 2009 American Society for Nutrition.
Published: 2009
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30. Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Timothy J. Key, Carlotta Sacerdote, Göran Berglund, Sabina Rinaldi, Anne Tjønneland, Naomi E. Allen, Franco Berrino, Eho Riboli, Veronique Chajes, Eva Lundin, Heiner Boeing, Jakob Linseisen, Eiliv Lund, Nerea Larrañaga, Marianne Uhre Jakobsen, Anne E. Cust, Inger T. Gram, Noémie Travier, Petra H.M. Peeters, Salvatore Panico, Dimitrios Trichopoulos, Annekatrin Lukanova, Bamia Christina, H. Bas Bueno-de-Mesquita, Nadia Slimani, Martine Laville, Fränzel J.B. Van Duijnhoven, Anja Olsen, Rudolf Kaaks, Christine M. Friedenreich, Eva Ardanaz, Kim Overvad, Sheila Bingham, Antonia Trichopoulou, J. R. Quirós, Rosario Tumino, Carmen Martinez-Garcia, María Dolores Chirlaque, Marie-Christine Boutron-Ruault, Kay-Tee Khaw, Tobias Pischon, Fabrice Bonnet, Françoise Clavel-Chapelon, Domenico Palli, Pietro Ferrari, Cust, Ae, Kaaks, R, Friedenreich, C, Bonnet, F, Laville, M, Tjonneland, A, Olsen, A, Overvad, K, Jakobsen, Mu, Chajes, V, CLAVEL CHAPELON, F, BOUTRON RUAULT, Mc, Linseisen, J, Lukanova, A, Boeing, H, Pischon, T, Trichopoulou, A, Christina, B, Trichopoulos, D, Palli, D, Berrino, F, Panico, Salvatore, Tumino, R, Sacerdote, C, Gram, It, Lund, E, Quiros, Jr, Travier, N, MARTINEZ GARCIA, C, Larranaga, N, Chirlaque, Md, Ardanaz, E, Berglund, G, Lundin, E, BUENO DE MESQUITA, Hb, VAN DUIJNHOVEN, Fj, Peeters, Ph, Bingham, S, Khaw, Kt, Allen, N, Key, T, Ferrari, P, Rinaldi, S, Slimani, N, and Riboli, E.
Subjects: Adult, Blood Glucose, Cancer Research, medicine.medical_specialty, Waist, Endocrinology, Diabetes and Metabolism, Lipoproteins, Physiology, Adenocarcinoma, Endocrinology, Risk Factors, Internal medicine, Medicine, Humans, Nutritional Physiological Phenomena, Prospective Studies, ddc:610, Prospective cohort study, Metabolic Syndrome, business.industry, Endometrial cancer, Metabolic Syndrome X, Case-control study, Middle Aged, medicine.disease, Lipids, European Prospective Investigation into Cancer and Nutrition, Endometrial Neoplasms, Europe, Oncology, Relative risk, Case-Control Studies, Female, Metabolic syndrome, business, Body mass index
Abstract: To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS; a cluster of metabolic factors) and endometrial cancer risk. Among pre- and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set sampling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (RR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38–0.97), Ptrend = 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% CI 0.99–2.90), Ptrend = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% CI 1.46–4.66), Ptrend = 0.0006, Pheterogeneity = 0.13) and never-users of exogenous hormones (Pheterogeneity = 0.005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51–2.97)), which increased with the number of MetS factors (Ptrend = 0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median (Pinteraction = 0.01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk.
Published: 2007
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31. Characterization of additive gene-environment interactions for colorectal cancer risk.

Author: Thomas CE, Lin Y, Kim M, Kawaguchi ES, Qu C, Um CY, Lynch BM, Van Guelpen B, Tsilidis K, Carreras-Torres R, van Duijnhoven FJ, Sakoda LC, Campbell PT, Tian Y, Chang-Claude J, Bézieau S, Budiarto A, Palmer JR, Newcomb PA, Casey G, Le Marchand L, Giannakis M, Li CI, Gsur A, Newton C, Obón-Santacana M, Moreno V, Vodicka P, Brenner H, Hoffmeister M, Pellatt AJ, Schoen RE, Dimou N, Murphy N, Gunter MJ, Castellví-Bel S, Figueiredo JC, Chan AT, Song M, Li L, Bishop DT, Gruber SB, Baurley JW, Bien SA, Conti DV, Huyghe JR, Kundaje A, Su YR, Wang J, Keku TO, Woods MO, Berndt SI, Chanock SJ, Tangen CM, Wolk A, Burnett-Hartman A, Wu AH, White E, Devall MA, Díez-Obrero V, Drew DA, Giovannucci E, Hidaka A, Kim AE, Lewinger JP, Morrison J, Ose J, Papadimitriou N, Pardamean B, Peoples AR, Ruiz-Narvaez EA, Shcherbina A, Stern MC, Chen X, Thomas DC, Platz EA, Gauderman WJ, Peters U, and Hsu L
Abstract: Background: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure., Methods: Using resources from colorectal cancer consortia including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score including 141 variants associated with CRC risk., Results: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking [RERI = 0.24, 95% confidence interval, CI, (0.13, 0.36)], ever smoking [0.11 (0.05, 0.16)], high BMI [female 0.09 (0.05, 0.13), male 0.10 (0.05, 0.14)], or high red meat intake [highest versus lowest quartile 0.18 (0.09, 0.27)] was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/NSAID use [-0.16 (-0.20, -0.11)] or higher intake of fruit, fiber, or calcium [highest quartile versus lowest quartile -0.12 (-0.18, -0.050); -0.16 (-0.23, -0.09); -0.11 (-0.18, -0.05), respectively] than those with average genetic susceptibility., Conclusions: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention., Competing Interests: Conflict of Interest: SB Gruber: Brogent International LLC, co-founder, not related to submitted work. All other authors do not have any conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2024
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32. Intake and biomarkers of folate and folic acid as determinants of chemotherapy-induced toxicities in patients with colorectal cancer: a cohort study.

Author: Kok DE, van Duijnhoven FJ, Lubberman FJ, McKay JA, Lanen AV, Winkels RM, Wesselink E, van Halteren HK, de Wilt JH, Ulrich CM, Ulvik A, Ueland PM, and Kampman E
Subjects: Humans, Folic Acid, Cohort Studies, Capecitabine adverse effects, Prospective Studies, Quality of Life, Chromatography, Liquid, Tandem Mass Spectrometry, Dietary Supplements adverse effects, Biomarkers, Colorectal Neoplasms drug therapy, Colorectal Neoplasms pathology, Antineoplastic Agents
Abstract: Background: Capecitabine is an oral chemotherapeutic drug showing antitumor activity through inhibition of thymidylate synthase, an enzyme involved in folate metabolism. There are concerns about the high intake of certain vitamins, and specifically folate, during chemotherapy with capecitabine. Whether folate or folic acid, the synthetic variant of the vitamin, impact treatment toxicity remains unclear., Objective: We studied associations between intake and biomarkers of folate as well as folic acid and toxicities in patients with colorectal cancer (CRC) receiving capecitabine., Methods: Within the prospective COLON (Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that influence recurrence, survival, and quality of life) cohort, 290 patients with stage II to III CRC receiving capecitabine were identified. Dietary and supplemental intake of folate and folic acid were assessed at diagnosis and during chemotherapy using questionnaires (available for 280 patients). Plasma folate and folic acid levels were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) and were available for 212 patients. Toxicities were defined as toxicity-related modifications of treatment, including dose reductions, regimen switches, and early discontinuation. Associations of intake and biomarkers of folate and folic acid with toxicities were determined using Cox proportional hazards regression adjusted for age and sex., Results: In total, 153 (53%) patients experienced toxicities leading to modification of capecitabine treatment. Folate intake and plasma folate levels were not associated with risk of toxicities. However, use of folic acid-containing supplements during treatment (hazard ratio (HR) 1.81 and 95% confidence interval (CI) 1.15-2.85) and presence of folic acid in plasma at diagnosis (HR 2.09, 95% CI: 1.24, 3.52) and during treatment (HR 2.31, 95% CI: 1.29, 4.13) were associated with an increased risk of toxicities., Conclusions: This study suggests a potential association between folic acid and capecitabine-induced toxicities, providing a rationale to study diet-drug interactions and raise further awareness of the use of dietary supplements during oncological treatment., Clinical Trial Details: This trial was registered at clinicaltrials.gov as NCT03191110., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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33. Genome-wide interaction analysis of folate for colorectal cancer risk.

Author: Bouras E, Kim AE, Lin Y, Morrison J, Du M, Albanes D, Barry EL, Baurley JW, Berndt SI, Bien SA, Bishop TD, Brenner H, Budiarto A, Burnett-Hartman A, Campbell PT, Carreras-Torres R, Casey G, Cenggoro TW, Chan AT, Chang-Claude J, Conti DV, Cotterchio M, Devall M, Diez-Obrero V, Dimou N, Drew DA, Figueiredo JC, Giles GG, Gruber SB, Gunter MJ, Harrison TA, Hidaka A, Hoffmeister M, Huyghe JR, Joshi AD, Kawaguchi ES, Keku TO, Kundaje A, Le Marchand L, Lewinger JP, Li L, Lynch BM, Mahesworo B, Männistö S, Moreno V, Murphy N, Newcomb PA, Obón-Santacana M, Ose J, Palmer JR, Papadimitriou N, Pardamean B, Pellatt AJ, Peoples AR, Platz EA, Potter JD, Qi L, Qu C, Rennert G, Ruiz-Narvaez E, Sakoda LC, Schmit SL, Shcherbina A, Stern MC, Su YR, Tangen CM, Thomas DC, Tian Y, Um CY, van Duijnhoven FJ, Van Guelpen B, Visvanathan K, Wang J, White E, Wolk A, Woods MO, Ulrich CM, Hsu L, Gauderman WJ, Peters U, and Tsilidis KK
Subjects: Humans, Risk Factors, Case-Control Studies, Dietary Supplements, Folic Acid metabolism, Colorectal Neoplasms genetics
Abstract: Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC., Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk., Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO)., Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10 -8 ) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10 -8 ). No interactions were observed for dietary and total folate., Conclusions: Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2023
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34. A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk.

Author: Aglago EK, Kim A, Lin Y, Qu C, Evangelou M, Ren Y, Morrison J, Albanes D, Arndt V, Barry EL, Baurley JW, Berndt SI, Bien SA, Bishop DT, Bouras E, Brenner H, Buchanan DD, Budiarto A, Carreras-Torres R, Casey G, Cenggoro TW, Chan AT, Chang-Claude J, Chen X, Conti DV, Devall M, Diez-Obrero V, Dimou N, Drew D, Figueiredo JC, Gallinger S, Giles GG, Gruber SB, Gsur A, Gunter MJ, Hampel H, Harlid S, Hidaka A, Harrison TA, Hoffmeister M, Huyghe JR, Jenkins MA, Jordahl K, Joshi AD, Kawaguchi ES, Keku TO, Kundaje A, Larsson SC, Marchand LL, Lewinger JP, Li L, Lynch BM, Mahesworo B, Mandic M, Obón-Santacana M, Moreno V, Murphy N, Nan H, Nassir R, Newcomb PA, Ogino S, Ose J, Pai RK, Palmer JR, Papadimitriou N, Pardamean B, Peoples AR, Platz EA, Potter JD, Prentice RL, Rennert G, Ruiz-Narvaez E, Sakoda LC, Scacheri PC, Schmit SL, Schoen RE, Shcherbina A, Slattery ML, Stern MC, Su YR, Tangen CM, Thibodeau SN, Thomas DC, Tian Y, Ulrich CM, van Duijnhoven FJ, Van Guelpen B, Visvanathan K, Vodicka P, Wang J, White E, Wolk A, Woods MO, Wu AH, Zemlianskaia N, Hsu L, Gauderman WJ, Peters U, Tsilidis KK, and Campbell PT
Subjects: Humans, Body Mass Index, Risk Factors, Genetic Loci, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Genome-Wide Association Study, Intercellular Signaling Peptides and Proteins genetics, Obesity complications, Obesity genetics, Colorectal Neoplasms genetics
Abstract: Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer., Significance: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies., (©2023 The Authors; Published by the American Association for Cancer Research.)
Published: 2023
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35. Longitudinal associations of fast foods, red and processed meat, alcohol and sugar-sweetened drinks with quality of life and symptoms in colorectal cancer survivors up to 24 months post-treatment.

Author: Kenkhuis MF, Mols F, van Roekel EH, Breedveld-Peters JJL, Breukink S, Janssen-Heijnen M, Keulen E, van Duijnhoven FJ, Weijenberg MP, and Bours M
Subjects: Humans, Fast Foods, Quality of Life, Sugars, Prospective Studies, Meat, Carbohydrates, Ethanol, Fatigue, Sugar-Sweetened Beverages, Colorectal Neoplasms, Cancer Survivors
Abstract: Unhealthy dietary habits can contribute to the development of colorectal cancer (CRC). Such habits may also be associated with post-treatment symptoms experienced by CRC survivors. Therefore, we aimed to assess longitudinal associations of post-treatment unhealthy dietary habits, i.e. intake of ultra-processed foods (UPF), red and processed meat, alcohol and sugar-sweetened drinks, with health-related quality of life (HRQoL), fatigue and chemotherapy-induced peripheral neuropathy (CIPN) in CRC survivors from 6 weeks up to 24 months post-treatment. In a prospective cohort among stage I-III CRC survivors ( n 396), five repeated home visits from diagnosis up to 24 months post-treatment were executed. Dietary intake was measured by 7-d dietary records to quantify consumption of UPF, red and processed meat, alcohol and sugar-sweetened drinks. HRQoL, fatigue and CIPN were measured by validated questionnaires. We applied confounder-adjusted linear mixed models to analyse longitudinal associations from 6 weeks until 24 months post-treatment. We applied a post hoc time-lag analysis for alcohol to explore the directionality. Results showed that higher post-treatment intake of UPF and sugar-sweetened drinks was longitudinally associated with worsened HRQoL and more fatigue, while higher intake of UPF and processed meat was associated with increased CIPN symptoms. In contrast, post-treatment increases in alcohol intake were longitudinally associated with better HRQoL and less fatigue; however, time-lag analysis attenuated these associations. In conclusion, unhealthy dietary habits are longitudinally associated with lower HRQoL and more symptoms, except for alcohol. Results from time-lag analysis suggest no biological effect of alcohol; hence, the longitudinal association for alcohol should be interpreted with caution.
Published: 2023
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36. Postdiagnostic intake of a more proinflammatory diet is associated with a higher risk of recurrence and all-cause mortality in colorectal cancer survivors.

Author: Wesselink E, Valk AW, Kok DE, Lanen AV, de Wilt JH, van Kouwenhoven EA, Schrauwen RW, van Halteren HK, Winkels RM, Balvers MG, Kampman E, and van Duijnhoven FJ
Subjects: Humans, Prospective Studies, Diet, Survivors, Risk Factors, Neoplasm Recurrence, Local, Colorectal Neoplasms
Abstract: Background: The inflammatory potential of the diet has been associated with colorectal cancer (CRC) risk, but its association with CRC prognosis is unclear., Objective: To investigate the inflammatory potential of the diet in relation to recurrence and all-cause mortality among persons diagnosed with stage I to III CRC., Methods: Data of the COLON study, a prospective cohort among CRC survivors were used. Dietary intake, 6 mo after diagnosis, was assessed by using a food frequency questionnaire and was available for 1631 individuals. The empirical dietary inflammatory pattern (EDIP) score was used as a proxy for the inflammatory potential of the diet. The EDIP score was created by using reduced rank regression and stepwise linear regression to identify food groups that explained most of the variations in plasma inflammatory markers (IL6, IL8, C-reactive protein, and tumor necrosis factor-α) measured in a subgroup of survivors (n = 421). Multivariable Cox proportional hazard models with restricted cubic splines were used to investigate the relation between the EDIP score and CRC recurrence and all-cause mortality. Models were adjusted for age, sex, BMI, PAL, smoking status, stage of disease, and tumor location., Results: The median follow-up time was 2.6 y (IQR: 2.1) for recurrence and 5.6 y (IQR: 3.0) for all-cause mortality, during which 154 and 239 events occurred, respectively. A nonlinear positive association between the EDIP score and recurrence and all-cause mortality was observed. For example, a more proinflammatory diet (EDIP score +0.75) compared with the median (EDIP score 0) was associated with a higher risk of CRC recurrence (HR: 1.15; 95% CI: 1.03, 1.29) and all-cause mortality (HR: 1.23; 95% CI: 1.12, 1.35)., Conclusions: A more proinflammatory diet was associated with a higher risk of recurrence and all-cause mortality in CRC survivors. Further intervention studies should investigate whether a switch to a more anti-inflammatory diet improves CRC prognosis., (Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)
Published: 2023
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37. Combining Asian-European Genome-Wide Association Studies of Colorectal Cancer Improves Risk Prediction Across Race and Ethnicity.

Author: Thomas M, Su YR, Rosenthal EA, Sakoda LC, Schmit SL, Timofeeva MN, Chen Z, Fernandez-Rozadilla C, Law PJ, Murphy N, Carreras-Torres R, Diez-Obrero V, van Duijnhoven FJ, Jiang S, Shin A, Wolk A, Phipps AI, Burnett-Hartman A, Gsur A, Chan AT, Zauber AG, Wu AH, Lindblom A, Um CY, Tangen CM, Gignoux C, Newton C, Haiman CA, Qu C, Bishop DT, Buchanan DD, Crosslin DR, Conti DV, Kim DH, Hauser E, White E, Siegel E, Schumacher FR, Rennert G, Giles GG, Hampel H, Brenner H, Oze I, Oh JH, Lee JK, Schneider JL, Chang-Claude J, Kim J, Huyghe JR, Zheng J, Hampe J, Greenson J, Hopper JL, Palmer JR, Visvanathan K, Matsuo K, Matsuda K, Jung KJ, Li L, Marchand LL, Vodickova L, Bujanda L, Gunter MJ, Matejcic M, Jenkins MA, Slattery ML, D'Amato M, Wang M, Hoffmeister M, Woods MO, Kim M, Song M, Iwasaki M, Du M, Udaltsova N, Sawada N, Vodicka P, Campbell PT, Newcomb PA, Cai Q, Pearlman R, Pai RK, Schoen RE, Steinfelder RS, Haile RW, Vandenputtelaar R, Prentice RL, Küry S, Castellví-Bel S, Tsugane S, Berndt SI, Lee SC, Brezina S, Weinstein SJ, Chanock SJ, Jee SH, Kweon SS, Vadaparampil S, Harrison TA, Yamaji T, Keku TO, Vymetalkova V, Arndt V, Jia WH, Shu XO, Lin Y, Ahn YO, Stadler ZK, Van Guelpen B, Ulrich CM, Platz EA, Potter JD, Li CI, Meester R, Moreno V, Figueiredo JC, Casey G, Vogelaar IL, Dunlop MG, Gruber SB, Hayes RB, Pharoah PDP, Houlston RS, Jarvik GP, Tomlinson IP, Zheng W, Corley DA, Peters U, and Hsu L
Abstract: Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expanded PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS were 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1,681-3,651 cases and 8,696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They were significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values<0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
Published: 2023
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38. Cohort profile: Biomarkers related to folate-dependent one-carbon metabolism in colorectal cancer recurrence and survival - the FOCUS Consortium.

Author: Gigic B, van Roekel E, Holowatyj AN, Brezina S, Geijsen AJMR, Ulvik A, Ose J, Koole JL, Damerell V, Kiblawi R, Gumpenberger T, Lin T, Kvalheim G, Koelsch T, Kok DE, van Duijnhoven FJ, Bours MJ, Baierl A, Li CI, Grady W, Vickers K, Habermann N, Schneider M, Kampman E, Ueland PM, Ulrich A, Weijenberg M, Gsur A, and Ulrich C
Subjects: Male, Humans, Female, Prospective Studies, Quality of Life, Biomarkers, Carbon metabolism, Folic Acid, Colorectal Neoplasms metabolism
Abstract: Purpose: The overarching goal of the FOCUS (biomarkers related to folate-dependent one-carbon metabolism in colorectal cancer (CRC) recurrence and survival) Consortium is to unravel the effect of folate and folate-mediated one-carbon metabolism (FOCM) biomarkers on CRC prognosis to provide clinically relevant advice on folate intake to cancer patients and define future tertiary prevention strategies., Participants: The FOCUS Consortium is an international, prospective cohort of 2401 women and men above 18 years of age who were diagnosed with a primary invasive non-metastatic (stages I-III) CRC. The consortium comprises patients from Austria, two sites from the Netherlands, Germany and two sites from the USA. Patients are recruited after CRC diagnosis and followed at 6 and 12 months after enrolment. At each time point, sociodemographic data, data on health behaviour and clinical data are collected, blood samples are drawn., Findings to Date: An increased risk of cancer recurrences was observed among patients with higher compared with lower circulating folic acid concentrations. Furthermore, specific folate species within the FOCM pathway were associated with both inflammation and angiogenesis pathways among patients with CRC. In addition, higher vitamin B 6 status was associated with better quality of life at 6 months post-treatment., Future Plans: Better insights into the research on associations between folate and FOCM biomarkers and clinical outcomes in patients with CRC will facilitate the development of guidelines regarding folate intake in order to provide clinically relevant advice to patients with cancer, health professionals involved in patient care, and ultimately further tertiary prevention strategies in the future. The FOCUS Consortium offers an excellent infrastructure for short-term and long-term research projects and for combining additional biomarkers and data resulting from the individual cohorts within the next years, for example, microbiome data, omics and multiomics data or CT-quantified body composition data., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)
Published: 2022
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39. Editorial: Diet, Inflammation and Colorectal Cancer.

Author: Gessani S, Van Duijnhoven FJ, and Moreno-Aliaga MJ
Subjects: Humans, Colorectal Neoplasms etiology, Diet, Inflammation complications
Published: 2019
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40. Inflammatory potential of the diet and colorectal tumor risk in persons with Lynch syndrome.

Author: Brouwer JG, Makama M, van Woudenbergh GJ, Vasen HF, Nagengast FM, Kleibeuker JH, Kampman E, and van Duijnhoven FJ
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Colorectal Neoplasms etiology, Colorectal Neoplasms, Hereditary Nonpolyposis complications, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, DNA Mismatch Repair genetics, Dietary Carbohydrates administration & dosage, Dietary Fats administration & dosage, Dietary Proteins administration & dosage, Exercise, Female, Follow-Up Studies, Humans, Life Style, Male, Micronutrients administration & dosage, Middle Aged, Mutation, Netherlands, Nutrition Assessment, Proportional Hazards Models, Prospective Studies, Risk Factors, Surveys and Questionnaires, Young Adult, Colorectal Neoplasms prevention & control, Colorectal Neoplasms, Hereditary Nonpolyposis diet therapy, Diet
Abstract: Background: Persons with Lynch syndrome (LS) have high lifetime risk of developing colorectal tumors (CRTs) because of a germline mutation in one of their mismatch repair (MMR) genes. An important process in the development of CRTs is inflammation, which has been shown to be modulated by diet. Objective: We aimed to investigate the association between the inflammatory potential of the diet and the risk of CRTs in persons with LS. Design: We used the dietary intake of 457 persons with LS from a prospective cohort study to calculate the adapted dietary inflammatory index (ADII). The ADII was split into tertiles in which the highest tertile reflects the most proinflammatory potential of the diet. Cox proportional hazard models, with robust sandwich variance estimates to adjust for dependency within families, were used to calculate HRs and 95% CIs of CRTs by ADII tertile. HRs were adjusted for age, smoking status, and education level, and number of colonoscopies as a time-dependent variable. A potential effect measure modification was explored by stratifying the results by mutated MMR gene, sex, and a history of CRTs. We performed sensitivity analyses by repeating the analyses in non-nonsteroidal anti-inflammatory drug (NSAID) users ( n = 315). Results: During a median follow-up time of 59 mo, 200 participants (43.8%) developed CRTs. No significant association was shown between highest compared with lowest ADII tertiles (HR for highest compared with lowest tertiles: 1.37; 95% CI: 0.80, 2.34). Stratification by mutated MMR gene, sex, and CRT history did not show significantly differential associations ( P -interactions ≥ 0.64). In non-NSAID users, an HR of 1.60 (95% CI: 0.88, 2.93) for highest compared with lowest tertiles was shown. No significant effect modification was shown in this group either ( P -interactions ≥ 0.24). Conclusion: A proinflammatory potential of the diet does not seem to be significantly associated with CRT risk in persons with LS., (© 2017 American Society for Nutrition.)
Published: 2017
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41. An increase in physical activity after colorectal cancer surgery is associated with improved recovery of physical functioning: a prospective cohort study.

Author: van Zutphen M, Winkels RM, van Duijnhoven FJ, van Harten-Gerritsen SA, Kok DE, van Duijvendijk P, van Halteren HK, Hansson BM, Kruyt FM, Bilgen EJ, de Wilt JH, Dronkers JJ, and Kampman E
Subjects: Aged, Colorectal Neoplasms epidemiology, Colorectal Neoplasms physiopathology, Female, Humans, Male, Middle Aged, Quality of Life, Risk Factors, Surveys and Questionnaires, Colorectal Neoplasms rehabilitation, Colorectal Neoplasms surgery, Colorectal Surgery rehabilitation, Exercise
Abstract: Background: The influence of physical activity on patient-reported recovery of physical functioning after colorectal cancer (CRC) surgery is unknown. Therefore, we studied recovery of physical functioning after hospital discharge by (a) a relative increase in physical activity level and (b) absolute activity levels before and after surgery., Methods: We included 327 incident CRC patients (stages I-III) from a prospective observational study. Patients completed questionnaires that assessed physical functioning and moderate-to-vigorous physical activity shortly after diagnosis and 6 months later. Cox regression models were used to calculate prevalence ratios (PRs) of no recovery of physical functioning. All PRs were adjusted for age, sex, physical functioning before surgery, stage of disease, ostomy and body mass index., Results: At 6 months post-diagnosis 54% of CRC patients had not recovered to pre-operative physical functioning. Patients who increased their activity by at least 60 min/week were 43% more likely to recover physical function (adjusted PR 0.57 95%CI 0.39-0.82), compared with those with stable activity levels. Higher post-surgery levels of physical activity were also positively associated with recovery (P for trend = 0.01). In contrast, activity level before surgery was not associated with recovery (P for trend = 0.24)., Conclusions: At 6 month post-diagnosis, about half of CRC patients had not recovered to preoperative functioning. An increase in moderate-to-vigorous physical activity after CRC surgery was associated with enhanced recovery of physical functioning. This benefit was seen regardless of physical activity level before surgery. These associations provide evidence to further explore connections between physical activity and recovery from CRC surgery after discharge from the hospital.
Published: 2017
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42. Adherence to the World Cancer Research Fund/American Institute for Cancer Research lifestyle recommendations in colorectal cancer survivors: results of the PROFILES registry.

Author: Winkels RM, van Lee L, Beijer S, Bours MJ, van Duijnhoven FJ, Geelen A, Hoedjes M, Mols F, de Vries J, Weijenberg MP, and Kampman E
Subjects: Aged, Aged, 80 and over, Colorectal Neoplasms pathology, Comorbidity, Female, Humans, Male, Middle Aged, Neoplasm Staging, Netherlands epidemiology, Outcome Assessment, Health Care, Population Surveillance, Registries, Risk Factors, Socioeconomic Factors, Colorectal Neoplasms epidemiology, Life Style, Patient Acceptance of Health Care, Survivors
Abstract: We examined adherence to the eight The World Cancer Research Foundation/American Institute for Cancer Research (WCRF/AICR) recommendations on diet, physical activity, and body weight among colorectal cancer survivors, and whether adherence was associated with intention to eat healthy and with the need for dietary advice. Adherence to these recommendations may putatively reduce the risk of recurrence and death. Studies on adherence to these recommendations in colorectal cancer (CRC) survivors are lacking. Adherence was assessed in a cross-sectional study among 1196 CRC survivors and could range between 0 (no adherence) and 8 points (complete adherence). Participants completed questionnaires on dietary intake, physical activity, and body weight. Prevalence Ratios were calculated to assess whether adherence to recommendations were associated with dietary intentions and needs. Twelve percentage of the survivors adhered to 6 or more recommendations; 65% had a score between >4 and 6 points; 23% scored no more than 4 points. The recommendation for to be modest with consumption of meat showed lowest adherence: 8% adhered; whereas the recommendation not to use dietary supplements showed highest adherence (75%). 18% reported a need for dietary advice, but this was not associated with adherence to recommendations. Survivors with higher adherence reported less often that they had received dietary advice, were less likely to have the intention to eat healthier, but reported more often that they had changed their diet since diagnosis. There is ample room for improvement of lifestyle recommendations in virtually all CRC survivors. A minor part of CRC survivors expressed a need for dietary advice which was not associated with adherence to the recommendations., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Published: 2016
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43. Pre-diagnostic meat and fibre intakes in relation to colorectal cancer survival in the European Prospective Investigation into Cancer and Nutrition.

Author: Ward HA, Norat T, Overvad K, Dahm CC, Bueno-de-Mesquita HB, Jenab M, Fedirko V, van Duijnhoven FJ, Skeie G, Romaguera-Bosch D, Tjønneland A, Olsen A, Carbonnel F, Affret A, Boutron-Ruault MC, Katzke V, Kühn T, Aleksandrova K, Boeing H, Trichopoulou A, Lagiou P, Bamia C, Palli D, Sieri S, Tumino R, Naccarati A, Mattiello A, Peeters PH, Weiderpass E, Åsli LA, Jakszyn P, Ramón Quirós J, Sánchez MJ, Dorronsoro M, Huerta JM, Barricarte A, Jirström K, Ericson U, Johansson I, Gylling B, Bradbury KE, Khaw KT, Wareham NJ, Stepien M, Freisling H, Murphy N, Cross AJ, and Riboli E
Subjects: Adult, Aged, Animals, Europe epidemiology, Female, Humans, Life Style, Male, Middle Aged, Nutrition Policy, Poultry, Proportional Hazards Models, Prospective Studies, Red Meat adverse effects, Sex Factors, White People, Colorectal Neoplasms mortality, Diet, Dietary Fiber therapeutic use, Feeding Behavior, Meat adverse effects
Abstract: Improvements in colorectal cancer (CRC) detection and treatment have led to greater numbers of CRC survivors, for whom there is limited evidence on which to provide dietary guidelines to improve survival outcomes. Higher intake of red and processed meat and lower intake of fibre are associated with greater risk of developing CRC, but there is limited evidence regarding associations with survival after CRC diagnosis. Among 3789 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, pre-diagnostic consumption of red meat, processed meat, poultry and dietary fibre was examined in relation to CRC-specific mortality (n 1008) and all-cause mortality (n 1262) using multivariable Cox regression models, adjusted for CRC risk factors. Pre-diagnostic red meat, processed meat or fibre intakes (defined as quartiles and continuous grams per day) were not associated with CRC-specific or all-cause mortality among CRC survivors; however, a marginal trend across quartiles of processed meat in relation to CRC mortality was detected (P 0·053). Pre-diagnostic poultry intake was inversely associated with all-cause mortality among women (hazard ratio (HR)/20 g/d 0·92; 95 % CI 0·84, 1·00), but not among men (HR 1·00; 95 % CI 0·91, 1·09) (P for heterogeneity=0·10). Pre-diagnostic intake of red meat or fibre is not associated with CRC survival in the EPIC cohort. There is suggestive evidence of an association between poultry intake and all-cause mortality among female CRC survivors and between processed meat intake and CRC-specific mortality; however, further research using post-diagnostic dietary data is required to confirm this relationship.
Published: 2016
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44. Candidate Predictors of Health-Related Quality of Life of Colorectal Cancer Survivors: A Systematic Review.

Author: Bours MJ, van der Linden BW, Winkels RM, van Duijnhoven FJ, Mols F, van Roekel EH, Kampman E, Beijer S, and Weijenberg MP
Subjects: Colorectal Neoplasms pathology, Colorectal Neoplasms psychology, Depression pathology, Depression psychology, Health Status, Humans, Quality of Life, Social Class, Surveys and Questionnaires, Survivors psychology, Colorectal Neoplasms epidemiology, Prognosis
Abstract: Unlabelled: The population of colorectal cancer (CRC) survivors is growing and many survivors experience deteriorated health-related quality of life (HRQoL) in both early and late post-treatment phases. Identification of CRC survivors at risk for HRQoL deterioration can be improved by using prediction models. However, such models are currently not available for oncology practice. As a starting point for developing prediction models of HRQoL for CRC survivors, a comprehensive overview of potential candidate HRQoL predictors is necessary. Therefore, a systematic literature review was conducted to identify candidate predictors of HRQoL of CRC survivors. Original research articles on associations of biopsychosocial factors with HRQoL of CRC survivors were searched in PubMed, Embase, and Google Scholar. Two independent reviewers assessed eligibility and selected articles for inclusion (N = 53). Strength of evidence for candidate HRQoL predictors was graded according to predefined methodological criteria. The World Health Organization's International Classification of Functioning, Disability and Health (ICF) was used to develop a biopsychosocial framework in which identified candidate HRQoL predictors were mapped across the main domains of the ICF: health condition, body structures and functions, activities, participation, and personal and environmental factors. The developed biopsychosocial ICF framework serves as a basis for selecting candidate HRQoL predictors, thereby providing conceptual guidance for developing comprehensive, evidence-based prediction models of HRQoL for CRC survivors. Such models are useful in clinical oncology practice to aid in identifying individual CRC survivors at risk for HRQoL deterioration and could also provide potential targets for a biopsychosocial intervention aimed at safeguarding the HRQoL of at-risk individuals., Implications for Practice: More and more people now survive a diagnosis of colorectal cancer. The quality of life of these cancer survivors is threatened by health problems persisting for years after diagnosis and treatment. Early identification of survivors at risk of experiencing low quality of life in the future is thus important for taking preventive measures. Clinical prediction models are tools that can help oncologists identify at-risk individuals. However, such models are currently not available for clinical oncology practice. This systematic review outlines candidate predictors of low quality of life of colorectal cancer survivors, providing a firm conceptual basis for developing prediction models., (©AlphaMed Press.)
Published: 2016
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45. Vitamin D, Inflammation, and Colorectal Cancer Progression: A Review of Mechanistic Studies and Future Directions for Epidemiological Studies.

Author: van Harten-Gerritsen AS, Balvers MG, Witkamp RF, Kampman E, and van Duijnhoven FJ
Subjects: Animals, Colorectal Neoplasms pathology, Disease Progression, Humans, Inflammation pathology, Colorectal Neoplasms epidemiology, Colorectal Neoplasms metabolism, Inflammation metabolism, Vitamin D metabolism
Abstract: Survival from colorectal cancer is positively associated with vitamin D status. However, whether this association is causal remains unclear. Inflammatory processes may link vitamin D to colorectal cancer survival, and therefore investigating inflammatory markers as potential mediators may be a valuable next step. This review starts with an overview of inflammatory processes suggested to be involved in colorectal cancer progression and regulated by vitamin D. Next, we provide recommendations on how to study inflammatory markers in future epidemiologic studies on vitamin D and colorectal cancer survival. Mechanistic studies have shown that calcitriol-active form of vitamin D-influences inflammatory processes involved in cancer progression, including the enzyme cyclooxygenase 2, the NF-κB pathway, and the expression of the cytokines TNFα, IL1β, IL6, IL8, IL17, and TGFβ1. Based on this and taking into account methodologic issues, we recommend to include analysis of specific soluble peptides and proteins, such as cytokines, in future epidemiologic studies on this issue. Vitamin D and the markers should preferably be measured at multiple time points during disease progression or recovery and analyzed using mediation analysis. Including these markers in epidemiologic studies may help answer whether inflammation mediates a causal relationship between vitamin D and colorectal cancer survival., (©2015 American Association for Cancer Research.)
Published: 2015
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46. Dietary changes and dietary supplement use, and underlying motives for these habits reported by colorectal cancer survivors of the Patient Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship (PROFILES) registry.

Author: Bours MJ, Beijer S, Winkels RM, van Duijnhoven FJ, Mols F, Breedveld-Peters JJ, Kampman E, Weijenberg MP, and van de Poll-Franse LV
Subjects: Aged, Cross-Sectional Studies, Diet, Female, Health Behavior, Humans, Life Style, Logistic Models, Male, Micronutrients administration & dosage, Middle Aged, Motivation, Registries, Socioeconomic Factors, Treatment Outcome, Colorectal Neoplasms epidemiology, Dietary Supplements, Feeding Behavior, Survivors
Abstract: In the present study, we aimed to describe dietary changes made post-diagnosis and current dietary supplement use by survivors of colorectal cancer (CRC), and explore the underlying motives for these lifestyle habits. Cross-sectional analyses were performed for 1458 stage I-IV CRC survivors of the Patient Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship (PROFILES) registry, diagnosed between 2000 and 2009. Lifestyle, sociodemographic and clinical information was collected. Prevalence of and motivations for dietary changes and supplement use were assessed. Associations between lifestyle, sociodemographic and clinical variables were analysed by multivariable logistic regression. CRC survivors (57% male) were on average 70 (SD 9) years of age and diagnosed 7 (SD 3) years ago. Dietary changes post-diagnosis were reported by 36% of the survivors and current supplement use by 32%. Motivations for dietary changes were mostly cancer-related (44% reported 'prevention of cancer recurrence' as the main reason), while motivations for supplement use were less frequently related to the cancer experience (38% reported 'to improve health and prevent disease in general' as the main reason). Dietary changes were significantly associated with dietary supplement use (OR 1.5, 95% CI 1.1, 2.1). Survivors who had received dietary advice, were non-smokers, under 65 years of age, and had no stoma were more likely to have changed their diet. Survivors who were female, had multiple co-morbidities, and no overweight or obesity were more likely to use supplements. In conclusion, many CRC survivors alter their diet post-diagnosis and use dietary supplements, in part for different reasons. Insights into motivations behind these lifestyle habits and characteristics of CRC survivors adopting these habits can improve the tailoring of lifestyle counselling strategies.
Published: 2015
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47. Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: a nested case-control study: plasma micronutrients and pancreatic cancer risk.

Author: Jeurnink SM, Ros MM, Leenders M, van Duijnhoven FJ, Siersema PD, Jansen EH, van Gils CH, Bakker MF, Overvad K, Roswall N, Tjønneland A, Boutron-Ruault MC, Racine A, Cadeau C, Grote V, Kaaks R, Aleksandrova K, Boeing H, Trichopoulou A, Benetou V, Valanou E, Palli D, Krogh V, Vineis P, Tumino R, Mattiello A, Weiderpass E, Skeie G, Castaño JM, Duell EJ, Barricarte A, Molina-Montes E, Argüelles M, Dorronsoro M, Johansen D, Lindkvist B, Sund M, Crowe FL, Khaw KT, Jenab M, Fedirko V, Riboli E, and Bueno-de-Mesquita HB
Subjects: Adult, Aged, Case-Control Studies, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms blood, Prospective Studies, Risk, Tocopherols blood, Ascorbic Acid blood, Carotenoids blood, Micronutrients blood, Pancreatic Neoplasms prevention & control, Vitamin A blood
Abstract: Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (α- and β-carotene, lycopene, β-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), α- and γ-tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma β-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend = 0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend = 0.06) and α-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend = 0.08. For α- and β-carotene, lutein, sum of carotenoids and γ-tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of β-carotene, zeaxanthin and α-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted., (© 2014 UICC.)
Published: 2015
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48. Coffee and tea consumption and risk of pre- and postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study.

Author: Bhoo-Pathy N, Peeters PH, Uiterwaal CS, Bueno-de-Mesquita HB, Bulgiba AM, Bech BH, Overvad K, Tjønneland A, Olsen A, Clavel-Chapelon F, Fagherazzi G, Perquier F, Teucher B, Kaaks R, Schütze M, Boeing H, Lagiou P, Orfanos P, Trichopoulou A, Agnoli C, Mattiello A, Palli D, Tumino R, Sacerdote C, van Duijnhoven FJ, Braaten T, Lund E, Skeie G, Redondo ML, Buckland G, Pérez MJ, Chirlaque MD, Ardanaz E, Amiano P, Wirfält E, Wallström P, Johansson I, Nilsson LM, Khaw KT, Wareham N, Allen NE, Key TJ, Rinaldi S, Romieu I, Gallo V, Riboli E, and van Gils CH
Subjects: Adult, Aged, Biomarkers, Tumor metabolism, Breast Neoplasms metabolism, Cohort Studies, Europe epidemiology, Female, Follow-Up Studies, Humans, Middle Aged, Registries, Risk Assessment, Risk Factors, Surveys and Questionnaires, Breast Neoplasms epidemiology, Breast Neoplasms etiology, Coffee, Menopause, Tea
Abstract: Introduction: Specific coffee subtypes and tea may impact risk of pre- and post-menopausal breast cancer differently. We investigated the association between coffee (total, caffeinated, decaffeinated) and tea intake and risk of breast cancer., Methods: A total of 335,060 women participating in the European Prospective Investigation into Nutrition and Cancer (EPIC) Study, completed a dietary questionnaire from 1992 to 2000, and were followed-up until 2010 for incidence of breast cancer. Hazard ratios (HR) of breast cancer by country-specific, as well as cohort-wide categories of beverage intake were estimated., Results: During an average follow-up of 11 years, 1064 premenopausal, and 9134 postmenopausal breast cancers were diagnosed. Caffeinated coffee intake was associated with lower risk of postmenopausal breast cancer: adjusted HR=0.90, 95% confidence interval (CI): 0.82 to 0.98, for high versus low consumption; Ptrend=0.029. While there was no significant effect modification by hormone receptor status (P=0.711), linear trend for lower risk of breast cancer with increasing caffeinated coffee intake was clearest for estrogen and progesterone receptor negative (ER-PR-), postmenopausal breast cancer (P=0.008). For every 100 ml increase in caffeinated coffee intake, the risk of ER-PR- breast cancer was lower by 4% (adjusted HR: 0.96, 95% CI: 0.93 to 1.00). Non-consumers of decaffeinated coffee had lower risk of postmenopausal breast cancer (adjusted HR=0.89; 95% CI: 0.80 to 0.99) compared to low consumers, without evidence of dose-response relationship (Ptrend=0.128). Exclusive decaffeinated coffee consumption was not related to postmenopausal breast cancer risk, compared to any decaffeinated-low caffeinated intake (adjusted HR=0.97; 95% CI: 0.82 to 1.14), or to no intake of any coffee (HR: 0.96; 95%: 0.82 to 1.14). Caffeinated and decaffeinated coffee were not associated with premenopausal breast cancer. Tea intake was neither associated with pre- nor post-menopausal breast cancer., Conclusions: Higher caffeinated coffee intake may be associated with lower risk of postmenopausal breast cancer. Decaffeinated coffee intake does not seem to be associated with breast cancer.
Published: 2015
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49. Dietary B vitamin and methionine intake and MTHFR C677T genotype on risk of colorectal tumors in Lynch syndrome: the GEOLynch cohort study.

Author: Jung AY, van Duijnhoven FJ, Nagengast FM, Botma A, Heine-Bröring RC, Kleibeuker JH, Vasen HF, Harryvan JL, Winkels RM, and Kampman E
Subjects: Adult, Case-Control Studies, Cohort Studies, Colorectal Neoplasms, Hereditary Nonpolyposis blood, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Netherlands, Proportional Hazards Models, Prospective Studies, Riboflavin administration & dosage, Risk Factors, Surveys and Questionnaires, White People genetics, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Diet, Methionine administration & dosage, Methylenetetrahydrofolate Reductase (NADPH2) genetics, Vitamin B Complex administration & dosage
Abstract: Purpose: Dietary intake of B vitamins and methionine, essential components of DNA synthesis and methylation pathways, may influence colorectal tumor (CRT) development. The impact of B vitamins on colorectal carcinogenesis in individuals with Lynch syndrome (LS) is unknown but is important given their high lifetime risk of developing neoplasms. The role of MTHFR C677T genotype in modifying these relationships in LS individuals is also unclear. We investigated associations between dietary intakes of folate, vitamins B2, B6, B12, and methionine and CRT development in a prospective cohort study of 470 mismatch repair gene mutation carriers., Methods: Dietary intakes were assessed by food frequency questionnaire. Cox regression models with robust sandwich covariance estimation, adjusted for age, sex, physical activity, number of colonoscopies during person-time, NSAID use, and mutual vitamins were used to calculate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs). Analyses were also stratified by MTHFR C677T genotype., Results: During a median person-time of 28.0 months, 131 persons developed a CRT. Fifty-one of these persons developed an incident colorectal adenoma, while there were four persons who developed an incident colorectal carcinoma. Compared to the lowest tertile of intake, adjusted HRs (95 % CIs) for CRT development in the highest tertile were 1.06 (0.59-1.91) for folate, 0.77 (0.39-1.51) for vitamin B2, 0.98 (0.59-1.62) for vitamin B6, 1.24 (0.77-2.00) for vitamin B12, and 1.36 (0.83-2.20) for methionine. Low vitamin B2 and low methionine intake were statistically significantly associated with an increased risk of CRT in MTHFR 677TT individuals compared to a combined reference of persons with low intake and CC genotype., Conclusions: There was no suggestion that intake of any dietary B vitamin or methionine was associated with CRT development among those with LS.
Published: 2014
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50. Coffee and tea consumption, genotype-based CYP1A2 and NAT2 activity and colorectal cancer risk-results from the EPIC cohort study.

Author: Dik VK, Bueno-de-Mesquita HB, Van Oijen MG, Siersema PD, Uiterwaal CS, Van Gils CH, Van Duijnhoven FJ, Cauchi S, Yengo L, Froguel P, Overvad K, Bech BH, Tjønneland A, Olsen A, Boutron-Ruault MC, Racine A, Fagherazzi G, Kühn T, Campa D, Boeing H, Aleksandrova K, Trichopoulou A, Peppa E, Oikonomou E, Palli D, Grioni S, Vineis P, Tumino R, Panico S, Peeters PH, Weiderpass E, Engeset D, Braaten T, Dorronsoro M, Chirlaque MD, Sánchez MJ, Barricarte A, Zamora-Ros R, Argüelles M, Jirström K, Wallström P, Nilsson LM, Ljuslinder I, Travis RC, Khaw KT, Wareham N, Freisling H, Licaj I, Jenab M, Gunter MJ, Murphy N, Romaguera-Bosch D, and Riboli E
Subjects: Adult, Aged, Caffeine metabolism, Case-Control Studies, Coffee metabolism, Cohort Studies, Colorectal Neoplasms epidemiology, Female, Genetic Predisposition to Disease genetics, Genotype, Humans, Incidence, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Proportional Hazards Models, Risk Factors, Surveys and Questionnaires, Tea metabolism, Arylamine N-Acetyltransferase genetics, Coffee adverse effects, Colorectal Neoplasms genetics, Cytochrome P-450 CYP1A2 genetics, Tea adverse effects
Abstract: Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.7 ± 8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84-1.11) and tea (HR 0.97, 95% CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC., (© 2013 UICC.)
Published: 2014
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