Author: "Bueno-de-Mesquita, H.B." / Database: OpenAIRE - Searchworks@Jio Institute Digital Library Search Results

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263 results on '"Bueno-de-Mesquita, H.B."'

1. Using multiple imputation methods to estimate relative risks in small EPIC lung cancer subsets

Author: Altenburg, H.P., Agudo, A., Berrino, F., Boshuizen, H.C., Bueno-de-Mesquita, H.B., Janzon, L., Le Marchand, L., Linseisen, Jakob, Lukanova, A., Rasmuson, T., Vineis, P., Riboli, E., and Miller, A.
Subjects: ddc:610
Published: 2021

2. Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study

Author: Stepien, M., Keski-Rahkonen, P., Kiss, A., Robinot, N., Duarte-Salles, T., Murphy, N., Perlemuter, G., Viallon, V., Tjønneland, A., Rostgaard-Hansen, A.L., Dahm, C.C., Overvad, K., Boutron-Ruault, M.-C., Mancini, F.R., Mahamat-Saleh, Y., Aleksandrova, K., Kaaks, R., Kühn, T., Trichopoulou, A., Karakatsani, A., Panico, S., Tumino, R., Palli, D., Tagliabue, G., Naccarati, A., Vermeulen, R.C.H., Bueno-de-Mesquita, H.B., Weiderpass, E., Skeie, G., Ramón Quirós, J., Ardanaz, E., Mokoroa, O., Sala, N., Sánchez, M.-J., Huerta, J.M., Winkvist, A., Harlid, S., Ohlsson, B., Sjöberg, K., Wareham, N., Khaw, K.-T., Ferrari, P., Rothwell, J.A., Gunter, M., Riboli, E., Scalbert, A., Jenab, M., IRAS OH Epidemiology Chemical Agents, and dIRAS RA-2
Subjects: untargeted metabolomics, Cancer Research, prospective observational cohort, Oncology, hepatocellular carcinoma
Abstract: Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.
Published: 2021

3. Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score

Author: Aleksandrova, K. Reichmann, R. Kaaks, R. Jenab, M. Bueno-de-Mesquita, H.B. Dahm, C.C. Eriksen, A.K. Tjønneland, A. Artaud, F. Boutron-Ruault, M.-C. Severi, G. Hüsing, A. Trichopoulou, A. Karakatsani, A. Peppa, E. Panico, S. Masala, G. Grioni, S. Sacerdote, C. Tumino, R. Elias, S.G. May, A.M. Borch, K.B. Sandanger, T.M. Skeie, G. Sánchez, M.-J. Huerta, J.M. Sala, N. Gurrea, A.B. Quirós, J.R. Amiano, P. Berntsson, J. Drake, I. van Guelpen, B. Harlid, S. Key, T. Weiderpass, E. Aglago, E.K. Cross, A.J. Tsilidis, K.K. Riboli, E. Gunter, M.J.
Abstract: Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level. © 2020, The Author(s).
Published: 2021

4. Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study

Author: Stepien, M. Keski-Rahkonen, P. Kiss, A. Robinot, N. Duarte-Salles, T. Murphy, N. Perlemuter, G. Viallon, V. Tjønneland, A. Rostgaard-Hansen, A.L. Dahm, C.C. Overvad, K. Boutron-Ruault, M.-C. Mancini, F.R. Mahamat-Saleh, Y. Aleksandrova, K. Kaaks, R. Kühn, T. Trichopoulou, A. Karakatsani, A. Panico, S. Tumino, R. Palli, D. Tagliabue, G. Naccarati, A. Vermeulen, R.C.H. Bueno-de-Mesquita, H.B. Weiderpass, E. Skeie, G. Ramón Quirós, J. Ardanaz, E. Mokoroa, O. Sala, N. Sánchez, M.-J. Huerta, J.M. Winkvist, A. Harlid, S. Ohlsson, B. Sjöberg, K. Schmidt, J.A. Wareham, N. Khaw, K.-T. Ferrari, P. Rothwell, J.A. Gunter, M. Riboli, E. Scalbert, A. Jenab, M.
Subjects: digestive system diseases
Abstract: Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development. © 2020 UICC
Published: 2021

5. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Iurilli, M.L.C. Zhou, B. Bennett, J.E. Carrillo-Larco, R.M. Sophiea, M.K. Rodriguez-Martinez, A. Bixby, H. Solomon, B.D. Taddei, C. Danaei, G. Di Cesare, M. Stevens, G.A. Riley, L.M. Savin, S. Cowan, M.J. Bovet, P. Damasceno, A. Chirita-Emandi, A. Hayes, A.J. Ikeda, N. Jackson, R.T. Khang, Y.-H. Laxmaiah, A. Liu, J. Miranda, J.J. Saidi, O. Sebert, S. Sorić, M. Starc, G. Gregg, E.W. Abarca-Gómez, L. Abdeen, Z.A. Abdrakhmanova, S. Ghaffar, S.A. Rahim, H.F.A. Abu-Rmeileh, N.M. Garba, J.A. Acosta-Cazares, B. Adams, R.J. Aekplakorn, W. Afsana, K. Afzal, S. Agdeppa, I.A. Aghazadeh-Attari, J. Aguilar-Salinas, C.A. Agyemang, C. Ahmad, M.H. Ahmad, N.A. Ahmadi, A. Ahmadi, N. Ahmed, S.H. Ahrens, W. Aitmurzaeva, G. Ajlouni, K. Al-Hazzaa, H.M. Al-Lahou, B. Al-Raddadi, R. Alarouj, M. AlBuhairan, F. AlDhukair, S. Ali, M.M. Alkandari, A. Alkerwi, A. Allin, K. Alvarez-Pedrerol, M. Aly, E. Amarapurkar, D.N. Amiri, P. Amougou, N. Amouyel, P. Andersen, L.B. Anderssen, S.A. Ängquist, L. Anjana, R.M. Ansari-Moghaddam, A. Aounallah-Skhiri, H. Araújo, J. Ariansen, I. Aris, T. Arku, R.E. Arlappa, N. Aryal, K.K. Aspelund, T. Assah, F.K. Assunção, M.C.F. Aung, M.S. Auvinen, J. Mária Avdicová Avi, S. Azevedo, A. Azimi-Nezhad, M. Azizi, F. Azmin, M. Babu, B.V. Bæksgaard Jørgensen, M. Baharudin, A. Bahijri, S. Baker, J.L. Balakrishna, N. Bamoshmoosh, M. Banach, M. Bandosz, P. Banegas, J.R. Baran, J. Barbagallo, C.M. Barceló, A. Barkat, A. Barros, A.J.D. Barros, M.V.G. Basit, A. Bastos, J.L.D. Bata, I. Batieha, A.M. Batista, R.L. Battakova, Z. Batyrbek, A. Baur, L.A. Beaglehole, R. Bel-Serrat, S. Belavendra, A. Romdhane, H.B. Benedics, J. Benet, M. Bergh, I.H. Berkinbayev, S. Bernabe-Ortiz, A. Bernotiene, G. Bettiol, H. Bezerra, J. Bhagyalaxmi, A. Bharadwaj, S. Bhargava, S.K. Bhutta, Z.A. Bi, H. Bi, Y. Bia, D. Lele, E.C.B. Bikbov, M.M. Bista, B. Bjelica, D.J. Bjerregaard, P. Bjertness, E. Bjertness, M.B. Björkelund, C. Bloch, K.V. Blokstra, A. Bo, S. Bobak, M. Boddy, L.M. Boehm, B.O. Boeing, H. Boggia, J.G. Bogova, E. Boissonnet, C.P. Bojesen, S.E. Bonaccio, M. Bongard, V. Bonilla-Vargas, A. Bopp, M. Borghs, H. Braeckevelt, L. Braeckman, L. Bragt, M.C.E. Brajkovich, I. Branca, F. Breckenkamp, J. Breda, J. Brenner, H. Brewster, L.M. Brian, G.R. Brinduse, L. Brophy, S. Bruno, G. Bueno-de-Mesquita, H.B. Bugge, A. Buoncristiano, M. Burazeri, G. Burns, C. de León, A.C. Cacciottolo, J. Cai, H. Cama, T. Cameron, C. Camolas, J. Can, G. Candido, A.P.C. Cañete, F. Capanzana, M.V. Capková, N. Capuano, E. Capuano, V. Cardol, M. Cardoso, V.C. Carlsson, A.C. Carmuega, E. Carvalho, J. Casajús, J.A. Casanueva, F.F. Celikcan, E. Censi, L. Cervantes-Loaiza, M. Cesar, J.A. Chamukuttan, S. Chan, A.W. Chan, Q. Chaturvedi, H.K. Chaturvedi, N. Rahim, N.C.A. Chee, M.L. Chen, C.-J. Chen, F. Chen, H. Chen, S. Chen, Z. Cheng, C.-Y. Cheraghian, B. Chetrit, A. Chikova-Iscener, E. Chiolero, A. Chiou, S.-T. Chirlaque, M.-D. Cho, B. Christensen, K. Christofaro, D.G. Chudek, J. Cifkova, R. Cilia, M. Cinteza, E. Claessens, F. Clarke, J. Clays, E. Cohen, E. Concin, H. Confortin, S.C. Cooper, C. Coppinger, T.C. Corpeleijn, E. Costanzo, S. Cottel, D. Cowell, C. Craig, C.L. Crampin, A.C. Crujeiras, A.B. Csilla, S. Cucu, A.M. Cui, L. Cureau, F.V. Czenczek-Lewandowska, E. D’Arrigo, G. d’Orsi, E. Dacica, L. Dal Re Saavedra, M.A. Dallongeville, J. Damsgaard, C.T. Dankner, R. Dantoft, T.M. Dasgupta, P. Dastgiri, S. Dauchet, L. Davletov, K. De Backer, G. De Bacquer, D. de Gaetano, G. De Henauw, S. de Oliveira, P.D. De Ridder, D. De Ridder, K. de Rooij, S.R. De Smedt, D. Deepa, M. Deev, A.D. DeGennaro, V., Jr Dehghan, A. Delisle, H. Delpeuch, F. Demarest, S. Dennison, E. Dereń, K. Deschamps, V. Dhimal, M. Di Castelnuovo, A.F. Dias-da-Costa, J.S. Díaz-Sánchez, M.E. Diaz, A. Dika, Z. Djalalinia, S. Djordjic, V. Do, H.T.P. Dobson, A.J. Donati, M.B. Donfrancesco, C. Donoso, S.P. Döring, A. Dorobantu, M. Dorosty, A.R. Doua, K. Dragano, N. Drygas, W. Duan, J.L. Duante, C.A. Duboz, P. Duda, R.B. Duleva, V. Dulskiene, V. Dumith, S.C. Dushpanova, A. Dzerve, V. Dziankowska-Zaborszczyk, E. Eddie, R. Eftekhar, E. Egbagbe, E.E. Eggertsen, R. Eghtesad, S. Eiben, G. Ekelund, U. El-Khateeb, M. Ati, J.E. Eldemire-Shearer, D. Eliasen, M. Elliott, P. Engle-Stone, R. Enguerran, M. Erasmus, R.T. Erbel, R. Erem, C. Eriksen, L. Eriksson, J.G. Escobedo-de la Peña, J. Eslami, S. Esmaeili, A. Evans, A. Faeh, D. Fakhretdinova, A.A. Fall, C.H. Faramarzi, E. Farjam, M. Sant’Angelo, V.F. Farzadfar, F. Fattahi, M.R. Fawwad, A. Felix-Redondo, F.J. Ferguson, T.S. Fernandes, R.A. Fernández-Bergés, D. Ferrante, D. Ferrao, T. Ferrari, M. Ferrario, M.M. Ferreccio, C. Ferrer, E. Ferrieres, J. Figueiró, T.H. Fijalkowska, A. Fink, G. Fischer, K. Foo, L.H. Forsner, M. Fouad, H.M. Francis, D.K. Maria do Carmo Franco Frikke-Schmidt, R. Frontera, G. Fuchs, F.D. Fuchs, S.C. Fujiati, I.I. Fujita, Y. Fumihiko, M. Furusawa, T. Gaciong, Z. Gafencu, M. Galbarczyk, A. Galenkamp, H. Galeone, D. Galfo, M. Galvano, F. Gao, J. Garcia-de-la-Hera, M. García-Solano, M. Gareta, D. Garnett, S.P. Gaspoz, J.-M. Gasull, M. Gaya, A.C.A. Gaya, A.R. Gazzinelli, A. Gehring, U. Geiger, H. Geleijnse, J.M. Ghanbari, A. Ghasemi, E. Gheorghe-Fronea, O.-F. Giampaoli, S. Gianfagna, F. Gill, T.K. Giovannelli, J. Gironella, G. Giwercman, A. Gkiouras, K. Godos, J. Gogen, S. Goldberg, M. Goldsmith, R.A. Goltzman, D. Gómez, S.F. Gomula, A. da Silva, B.G.C. Gonçalves, H. Gonzalez-Chica, D.A. Gonzalez-Gross, M. González-Leon, M. González-Rivas, J.P. González-Villalpando, C. González-Villalpando, M.-E. Gonzalez, A.R. Gottrand, F. Graça, A.P. Graff-Iversen, S. Grafnetter, D. Grajda, A. Grammatikopoulou, M.G. Gregor, R.D. Grodzicki, T. Grøholt, E.K. Grøntved, A. Grosso, G. Gruden, G. Gu, D. Gualdi-Russo, E. Guallar-Castillón, P. Gualtieri, A. Gudmundsson, E.F. Gudnason, V. Guerrero, R. Guessous, I. Guimaraes, A.L. Gulliford, M.C. Gunnlaugsdottir, J. Gunter, M.J. Guo, X.-H. Guo, Y. Gupta, P.C. Gupta, R. Gureje, O. Gurzkowska, B. Gutiérrez-González, E. Gutierrez, L. Gutzwiller, F. Ha, S. Hadaegh, F. Hadjigeorgiou, C.A. Haghshenas, R. Hakimi, H. Halkjær, J. Hambleton, I.R. Hamzeh, B. Hange, D. Hanif, A.A.M. Hantunen, S. Hao, J. Kumar, R.H. Hashemi-Shahri, S.M. Hassapidou, M. Hata, J. Haugsgjerd, T. He, J. He, Y. He, Y. Heidinger-Felso, R. Heinen, M. Hejgaard, T. Hendriks, M.E. dos Santos Henrique, R. Henriques, A. Cadena, L.H. Herrala, S. Herrera, V.M. Herter-Aeberli, I. Heshmat, R. Hill, A.G. Ho, S.Y. Ho, S.C. Hobbs, M. Holdsworth, M. Homayounfar, R. Homs, C. Hopman, W.M. Horimoto, A.R.V.R. Hormiga, C.M. Horta, B.L. Houti, L. Howitt, C. Htay, T.T. Htet, A.S. Htike, M.M.T. Hu, Y. Huerta, J.M. Huhtaniemi, I.T. Huiart, L. Petrescu, C.H. Huisman, M. Husseini, A. Huu, C.N. Huybrechts, I. Hwalla, N. Hyska, J. Iacoviello, L. Ibarluzea, J.M. Ibrahim, M.M. Wong, N.I. Ikram, M.A. Iotova, V. Irazola, V.E. Ishida, T. Islam, M. Islam, S.M.S. Iwasaki, M. Jacobs, J.M. Jaddou, H.Y. Jafar, T. James, K. Jamil, K.M. Jamrozik, K. Janszky, I. Janus, E. Jarani, J. Jarvelin, M.-R. Jasienska, G. Jelakovic, A. Jelakovic, B. Jennings, G. Jha, A.K. Jiang, C.Q. Jimenez, R.O. Jöckel, K.-H. Joffres, M. Johansson, M. Jokelainen, J.J. Jonas, J.B. Jonnagaddala, J. Jørgensen, T. Joshi, P. Joukar, F. Jovic, D.P. Jóźwiak, J.J. Juolevi, A. Jurak, G. Simina, I.J. Juresa, V. Kaaks, R. Kaducu, F.O. Kafatos, A. Kajantie, E.O. Kalmatayeva, Z. Kalter-Leibovici, O. Kameli, Y. Kampmann, F.B. Kanala, K.R. Kannan, S. Kapantais, E. Karakosta, A. Kårhus, L.L. Karki, K.B. Katibeh, M. Katz, J. Katzmarzyk, P.T. Kauhanen, J. Kaur, P. Kavousi, M. Kazakbaeva, G.M. Keil, U. Boker, L.K. Keinänen-Kiukaanniemi, S. Kelishadi, R. Kelleher, C. Kemper, H.C.G. Kengne, A.P. Keramati, M. Kerimkulova, A. Kersting, M. Key, T. Khader, Y.S. Khalili, D. Khaw, K.-T. Kheiri, B. Kheradmand, M. Khosravi, A. Khouw, I.M.S.L. Kiechl-Kohlendorfer, U. Kiechl, S. Killewo, J. Kim, D.W. Kim, H.C. Kim, J. Kindblom, J.M. Klakk, H. Klimek, M. Klimont, J. Klumbiene, J. Knoflach, M. Koirala, B. Kolle, E. Kolsteren, P. König, J. Korpelainen, R. Korrovits, P. Korzycka, M. Kos, J. Koskinen, S. Kouda, K. Kovacs, V.A. Kowlessur, S. Koziel, S. Kratenova, J. Kratzer, W. Kriemler, S. Kristensen, P.L. Krokstad, S. Kromhout, D. Kruger, H.S. Kubinova, R. Kuciene, R. Kujala, U.M. Kujundzic, E. Kulaga, Z. Kumar, R.K. Kunešová, M. Kurjata, P. Kusuma, Y.S. Kuulasmaa, K. Kyobutungi, C. La, Q.N. Laamiri, F.Z. Laatikainen, T. Lachat, C. Laid, Y. Lam, T.H. Lambrinou, C.-P. Landais, E. Lanska, V. Lappas, G. Larijani, B. Latt, T.S. Lauria, L. Lazo-Porras, M. Le Coroller, G. Bao, K.L.N. Le Port, A. Le, T.D. Lee, J. Lee, J. Lee, P.H. Lehmann, N. Lehtimäki, T. Lemogoum, D. Levitt, N.S. Li, Y. Liivak, M. Lilly, C.L. Lim, W.-Y. Lima-Costa, M.F. Lin, H.-H. Lin, X. Lin, Y.-T. Lind, L. Linneberg, A. Lissner, L. Litwin, M. Liu, L. Lo, W.-C. Loit, H.-M. Long, K.Q. Lopes, L. Lopes, O. Lopez-Garcia, E. Lopez, T. Lotufo, P.A. Lozano, J.E. Lukrafka, J.L. Luksiene, D. Lundqvist, A. Lundqvist, R. Lunet, N. Lunogelo, C. Lustigová, M. Łuszczki, E. Ma, G. Ma, J. Ma, X. Machado-Coelho, G.L.L. Machado-Rodrigues, A.M. Macieira, L.M. Madar, A.A. Maggi, S. Magliano, D.J. Magnacca, S. Magriplis, E. Mahasampath, G. Maire, B. Majer, M. Makdisse, M. Mäki, P. Malekzadeh, F. Malekzadeh, R. Malhotra, R. Rao, K.M. Malyutina, S.K. Maniego, L.V. Manios, Y. Mann, J.I. Mansour-Ghanaei, F. Manzato, E. Margozzini, P. Markaki, A. Markey, O. Ioannidou, E.M. Marques-Vidal, P. Marques, L.P. Marrugat, J. Martin-Prevel, Y. Martin, R. Martorell, R. Martos, E. Maruszczak, K. Marventano, S. Mascarenhas, L.P. Masoodi, S.R. Mathiesen, E.B. Mathur, P. Matijasevich, A. Matsha, T.E. Mavrogianni, C. Mazur, A. Mbanya, J.C.N. McFarlane, S.R. McGarvey, S.T. McKee, M. McLachlan, S. McLean, R.M. McLean, S.B. McNulty, B.A. Benchekor, S.M. Medzioniene, J. Mehdipour, P. Mehlig, K. Mehrparvar, A.H. Meirhaeghe, A. Meisfjord, J. Meisinger, C. Menezes, A.M.B. Menon, G.R. Mensink, G.B.M. Menzano, M.T. Mereke, A. Meshram, I.I. Metspalu, A. Meyer, H.E. Mi, J. Michaelsen, K.F. Michels, N. Mikkel, K. Milkowska, K. Miller, J.C. Minderico, C.S. Mini, G.K. Miquel, J.F. Mirjalili, M.R. Mirkopoulou, D. Mirrakhimov, E. Mišigoj-Durakovic, M. Mistretta, A. Mocanu, V. Modesti, P.A. Moghaddam, S.S. Mohajer, B. Mohamed, M.K. Mohamed, S.F. Mohammad, K. Mohammadi, Z. Mohammadifard, N. Mohammadpourhodki, R. Mohan, V. Mohanna, S. Yusoff, M.F.M. Mohebbi, I. Mohebi, F. Moitry, M. Molbo, D. Møllehave, L.T. Møller, N.C. Molnár, D. Momenan, A. Mondo, C.K. Monroy-Valle, M. Monterrubio-Flores, E. Monyeki, K.D.K. Moon, J.S. Moosazadeh, M. Moreira, L.B. Morejon, A. Moreno, L.A. Morgan, K. Morin, S.N. Mortensen, E.L. Moschonis, G. Mossakowska, M. Mostafa, A. Mota-Pinto, A. Mota, J. Motlagh, M.E. Motta, J. Moura-dos-Santos, M.A. Mridha, M.K. Msyamboza, K.P. Mu, T.T. Muc, M. Mugoša, B. Muiesan, M.L. Mukhtorova, P. Müller-Nurasyid, M. Murphy, N. Mursu, J. Murtagh, E.M. Musa, K.I. Milanovic, S.M. Musil, V. Mustafa, N. Nabipour, I. Naderimagham, S. Nagel, G. Naidu, B.M. Najafi, F. Nakamura, H. Námešná, J. Nang, E.E.K. Nangia, V.B. Nankap, M. Narake, S. Nardone, P. Nauck, M. Neal, W.A. Nejatizadeh, A. Nekkantti, C. Nelis, K. Nelis, L. Nenko, I. Neovius, M. Nervi, F. Nguyen, C.T. Nguyen, N.D. Nguyen, Q.N. Nieto-Martínez, R.E. Nikitin, Y.P. Ning, G. Ninomiya, T. Nishtar, S. Noale, M. Noboa, O.A. Nogueira, H. Norat, T. Nordendahl, M. Nordestgaard, B.G. Noto, D. Nowak-Szczepanska, N. Al Nsour, M. Nuhoglu, I. Nurk, E. O’Neill, T.W. O’Reilly, D. Obreja, G. Ochimana, C. Ochoa-Avilés, A.M. Oda, E. Oh, K. Ohara, K. Ohlsson, C. Ohtsuka, R. Olafsson, O. Olinto, M.T.A. Oliveira, I.O. Omar, M.A. Onat, A. Ong, S.K. Ono, L.M. Ordunez, P. Ornelas, R. Ortiz, A.P. Ortiz, P.J. Osler, M. Osmond, C. Ostojic, S.M. Ostovar, A. Otero, J.A. Overvad, K. Owusu-Dabo, E. Paccaud, F.M. Padez, C. Pagkalos, I. Pahomova, E. de Paiva, K.M. Pajak, A. Palli, D. Palloni, A. Palmieri, L. Pan, W.-H. Panda-Jonas, S. Pandey, A. Panza, F. Papandreou, D. Park, S.-W. Park, S. Parnell, W.R. Parsaeian, M. Pascanu, I.M. Pasquet, P. Patel, N.D. Pecin, I. Pednekar, M.S. Peer, N. Pei, G. Peixoto, S.V. Peltonen, M. Pereira, A.C. Peres, M.A. Pérez-Farinós, N. Pérez, C.M. Peterkova, V. Peters, A. Petersmann, A. Petkeviciene, J. Petrauskiene, A. Pettenuzzo, E. Peykari, N. Pham, S.T. Pichardo, R.N. Pierannunzio, D. Pigeot, I. Pikhart, H. Pilav, A. Pilotto, L. Pistelli, F. Pitakaka, F. Piwonska, A. Pizarro, A.N. Plans-Rubió, P. Poh, B.K. Pohlabeln, H. Pop, R.M. Popovic, S.R. Porta, M. Posch, G. Poudyal, A. Poulimeneas, D. Pouraram, H. Pourfarzi, F. Pourshams, A. Poustchi, H. Pradeepa, R. Price, A.J. Price, J.F. Providencia, R. Puder, J.J. Pudule, I. Puhakka, S.E. Puiu, M. Punab, M. Qasrawi, R.F. Qorbani, M. Bao, T.Q. Radic, I. Radisauskas, R. Rahimikazerooni, S. Rahman, M. Rahman, M. Raitakari, O. Raj, M. Rakhimova, E. Rakhmatulloev, S. Rakovac, I. Rao, S.R. Ramachandran, A. Ramke, J. Ramos, E. Ramos, R. Rampal, L. Rampal, S. Rarra, V. Rascon-Pacheco, R.A. Rasmussen, M. Rech, C.R. Redon, J. Reganit, P.F.M. Regecová, V. Revilla, L. Rezaianzadeh, A. Ribas-Barba, L. Ribeiro, R. Riboli, E. Richter, A. Rigo, F. Rinaldo, N. de Wit, T.F.R. Rito, A. Ritti-Dias, R.M. Rivera, J.A. Robitaille, C. Roccaldo, R. Rodrigues, D. Rodríguez-Artalejo, F. del Cristo Rodriguez-Perez, M. Rodríguez-Villamizar, L.A. Roggenbuck, U. Rojas-Martinez, R. Rojroongwasinkul, N. Romaguera, D. Romeo, E.L. Rosario, R.V. Rosengren, A. Rouse, I. Roy, J.G.R. Rubinstein, A. Rühli, F.J. Ruidavets, J.-B. Ruiz-Betancourt, B.S. Ruiz-Castell, M. Moreno, E.R. Rusakova, I.A. Jonsson, K.R. Russo, P. Rust, P. Rutkowski, M. Sabanayagam, C. Sacchini, E. Sachdev, H.S. Sadjadi, A. Safarpour, A.R. Safiri, S. Saki, N. Salanave, B. Martinez, E.S. Salmerón, D. Salomaa, V. Salonen, J.T. Salvetti, M. Samoutian, M. Sánchez-Abanto, J. Sans, S. Marina, L.S. Santos, D.A. Santos, I.S. Santos, L.C. Santos, M.P. Santos, O. Santos, R. Sanz, S.S. Saramies, J.L. Sardinha, L.B. Sarrafzadegan, N. Sathish, T. Saum, K.-U. Savva, S. Savy, M. Sawada, N. Sbaraini, M. Scazufca, M. Schaan, B.D. Rosario, A.S. Schargrodsky, H. Schienkiewitz, A. Schipf, S. Schmidt, C.O. Schmidt, I.M. Schnohr, P. Schöttker, B. Schramm, S. Schramm, S. Schröder, H. Schultsz, C. Schutte, A.E. Sein, A.A. Selamat, R. Sember, V. Sen, A. Senbanjo, I.O. Sepanlou, S.G. Sequera, V. Serra-Majem, L. Servais, J. Ševcíková, L. Shalnova, S.A. Shamah-Levy, T. Shamshirgaran, M. Shanthirani, C.S. Sharafkhah, M. Sharma, S.K. Shaw, J.E. Shayanrad, A. Shayesteh, A.A. Shengelia, L. Shi, Z. Shibuya, K. Shimizu-Furusawa, H. Shin, D.W. Shirani, M. Shiri, R. Shrestha, N. Si-Ramlee, K. Siani, A. Siantar, R. Sibai, A.M. Silva, A.M. Silva, D.A.S. Simon, M. Simons, J. Simons, L.A. Sjöberg, A. Sjöström, M. Skodje, G. Slowikowska-Hilczer, J. Slusarczyk, P. Smeeth, L. So, H.-K. Soares, F.C. Sobek, G. Sobngwi, E. Sodemann, M. Söderberg, S. Soekatri, M.Y.E. Soemantri, A. Sofat, R. Solfrizzi, V. Somi, M.H. Sonestedt, E. Song, Y. Sørensen, T.I.A. Sørgjerd, E.P. Jérome, C.S. Soto-Rojas, V.E. Soumaré, A. Sovic, S. Sparboe-Nilsen, B. Sparrenberger, K. Spinelli, A. Spiroski, I. Staessen, J.A. Stamm, H. Stathopoulou, M.G. Staub, K. Stavreski, B. Steene-Johannessen, J. Stehle, P. Stein, A.D. Stergiou, G.S. Stessman, J. Stevanovic, R. Stieber, J. Stöckl, D. Stocks, T. Stokwiszewski, J. Stoyanova, E. Stratton, G. Stronks, K. Strufaldi, M.W. Sturua, L. Suárez-Medina, S. Suka, M. Sun, C.-A. Sundström, J. Sung, Y.-T. Sunyer, J. Suriyawongpaisal, P. Swinburn, B.A. Sy, R.G. Syddall, H.E. Sylva, R.C. Szklo, M. Szponar, L. Tai, E.S. Tammesoo, M.-L. Tamosiunas, A. Tan, E.J. Tang, X. Tanrygulyyeva, M. Tanser, F. Tao, Y. Tarawneh, M.R. Tarp, J. Tarqui-Mamani, C.B. Braunerová, R.T. Taylor, A. Taylor, J. Tchibindat, F. Tebar, W.R. Tell, G.S. Tello, T. Tham, Y.C. Thankappan, K.R. Theobald, H. Theodoridis, X. Thijs, L. Thomas, N. Thuesen, B.H. Tichá, L. Timmermans, E.J. Tjonneland, A. Tolonen, H.K. Tolstrup, J.S. Topbas, M. Topór-Madry, R. Torheim, L.E. Tormo, M.J. Tornaritis, M.J. Torrent, M. Torres-Collado, L. Toselli, S. Touloumi, G. Traissac, P. Tran, T.T.-H. Trichopoulos, D. Trichopoulou, A. Trinh, D.T.H. Trivedi, A. Tshepo, L. Tsigga, M. Tsugane, S. Tuliakova, A.M. Tulloch-Reid, M.K. Tullu, F. Tuomainen, T.-P. Tuomilehto, J. Turley, M.L. Twig, G. Tynelius, P. Tzotzas, T. Tzourio, C. Ueda, P. Ugel, E. Ukoli, F.A.M. Ulmer, H. Unal, B. Usupova, Z. Uusitalo, H.M.T. Uysal, N. Vaitkeviciute, J. Valdivia, G. Vale, S. Valvi, D. van Dam, R.M. Van der Heyden, J. van der Schouw, Y.T. Van Herck, K. Van Minh, H. Van Schoor, N.M. van Valkengoed, I.G.M. Vanderschueren, D. Vanuzzo, D. Varbo, A. Varela-Moreiras, G. Varona-Pérez, P. Vasan, S.K. Vega, T. Veidebaum, T. Velasquez-Melendez, G. Velika, B. Veronesi, G. Verschuren, W.M.M. Victora, C.G. Viegi, G. Viet, L. Villalpando, S. Vineis, P. Vioque, J. Virtanen, J.K. Visser, M. Visvikis-Siest, S. Viswanathan, B. Vladulescu, M. Vlasoff, T. Vocanec, D. Vollenweider, P. Völzke, H. Voutilainen, A. Voutilainen, S. Vrijheid, M. Vrijkotte, T.G.M. Wade, A.N. Wagner, A. Waldhör, T. Walton, J. Wambiya, E.O.A. Bebakar, A.M.W. Mohamud, W.N.W. de Souza Wanderley Júnior, R. Wang, M.-D. Wang, N. Wang, Q. Wang, X. Wang, Y.X. Wang, Y.-W. Wannamethee, S.G. Wareham, N. Weber, A. Wedderkopp, N. Weerasekera, D. Weghuber, D. Wei, W. Weres, A. Werner, B. Whincup, P.H. Widhalm, K. Widyahening, I.S. Wiecek, A. Wilks, R.J. Willeit, J. Willeit, P. Williams, J. Wilsgaard, T. Wojtyniak, B. Wong-McClure, R.A. Wong, A. Wong, J.E. Wong, T.Y. Woo, J. Woodward, M. Wu, F.C. Wu, J. Wu, L.J. Wu, S. Xu, H. Xu, L. Yaacob, N.A. Yamborisut, U. Yan, W. Yang, L. Yang, X. Yang, Y. Yardim, N. Yaseri, M. Yasuharu, T. Ye, X. Yiallouros, P.K. Yoosefi, M. Yoshihara, A. You, Q.S. You, S.-L. Younger-Coleman, N.O. Yusof, S.M. Yusoff, A.F. Zaccagni, L. Zafiropulos, V. Zainuddin, A.A. Zakavi, S.R. Zamani, F. Zambon, S. Zampelas, A. Zamrazilová, H. Zapata, M.E. Zargar, A.H. Zaw, K.K. Zdrojewski, T. Zejglicova, K. Vrkic, T.Z. Zeng, Y. Zhang, L. Zhang, Z.-Y. Zhao, D. Zhao, M.-H. Zhao, W. Zhen, S. Zheng, W. Zheng, Y. Zholdin, B. Zhou, M. Zhu, D. Zins, M. Zitt, E. Zocalo, Y. Cisneros, J.Z. Zuziak, M. Ezzati, M. Filippi, S. NCD Risk Factor Collaboration (NCD-RisC)
Subjects: nutritional and metabolic diseases, sense organs, skin and connective tissue diseases
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions. © Copyright.
Published: 2021

6. Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Zamora-Ros, R., Cayssials, V., Franceschi, S., Kyrø, C., Weiderpass, E., Hennings, J., Sandström, M., Tjønneland, A., Olsen, A., Overvad, K., Boutron-Ruault, M.-C., Truong, T., Mancini, F.R., Katzke, V., Kühn, T., Boeing, H., Trichopoulou, A., Karakatsani, A., Martimianaki, G., Palli, D., Krogh, V., Panico, S., Tumino, R., Sacerdote, C., Lasheras, C., Rodríguez-Barranco, M., Amiano, P., Colorado-Yohar, S.M., Ardanaz, E., Almquist, M., Ericson, U., Bueno-de-Mesquita, H.B., Vermeulen, R., Byrnes, G., Scalbert, A., Agudo, A., Rinaldi, S., IRAS OH Epidemiology Chemical Agents, and dIRAS RA-2
Subjects: flavonoids, thyroid cancer, cohort, EPIC, intake, polyphenols
Abstract: Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77–1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80–1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55–2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.
Published: 2020

7. Healthy lifestyle and the risk of pancreatic cancer in the EPIC study

Author: Naudin, S. Viallon, V. Hashim, D. Freisling, H. Jenab, M. Weiderpass, E. Perrier, F. McKenzie, F. Bueno-de-Mesquita, H.B. Olsen, A. Tjønneland, A. Dahm, C.C. Overvad, K. Mancini, F.R. Rebours, V. Boutron-Ruault, M.-C. Katzke, V. Kaaks, R. Bergmann, M. Boeing, H. Peppa, E. Karakatsani, A. Trichopoulou, A. Pala, V. Masala, G. Panico, S. Tumino, R. Sacerdote, C. May, A.M. van Gils, C.H. Rylander, C. Borch, K.B. Chirlaque López, M.D. Sánchez, M.-J. Ardanaz, E. Quirós, J.R. Amiano Exezarreta, P. Sund, M. Drake, I. Regnér, S. Travis, R.C. Wareham, N. Aune, D. Riboli, E. Gunter, M.J. Duell, E.J. Brennan, P. Ferrari, P.
Abstract: Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants’ shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e−09) and 0.77 (0.72, 0.82; ptrend = 1.7e−15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e−04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence. © 2019, Springer Nature B.V.
Published: 2020

8. Gallbladder disease, cholecystectomy, and pancreatic cancer risk in the International Pancreatic Cancer Case-Control Consortium (PanC4)

Author: Rosato, V. Negri, E. Bosetti, C. Malats, N. Gomez-Rubio, P. Consortium, P. Maisonneuve, P. Miller, A.B. Bueno-De-Mesquita, H.B. Baghurst, P.A. Zatonski, W. Petersen, G.M. Scelo, G. Holcatova, I. Fabianova, E. Serraino, D. Olson, S.H. Vioque, J. Lagiou, P. Duell, E.J. Boffetta, P. La Vecchia, C.
Abstract: Background The association among gallbladder disease, cholecystectomy, and pancreatic cancer is unclear. Moreover, time interval between gallbladder disease or cholecystectomy and pancreatic cancer diagnosis is not considered in most previous studies. Aim To quantify the association among gallbladder disease, cholecystectomy, and pancreatic cancer, considering time since first diagnosis of gallbladder disease or cholecystectomy. Methods We used data from nine case-control studies within the Pancreatic Cancer Case-Control Consortium, including 5760 cases of adenocarcinoma of the exocrine pancreas and 8437 controls. We estimated pooled odds ratios and the corresponding 95% confidence intervals by estimating study-specific odds ratios through multivariable unconditional logistic regression models, and then pooling the obtained estimates using fixed-effects models. Results Compared with patients with no history of gallbladder disease, the pooled odds ratio of pancreatic cancer was 1.69 (95% confidence interval, 1.51-1.88) for patients reporting a history of gallbladder disease. The odds ratio was 4.90 (95% confidence interval, 3.45-6.97) for gallbladder disease diagnosed
Published: 2020

9. Intake of individual fatty acids and risk of prostate cancer in the European prospective investigation into cancer and nutrition

Author: Perez-Cornago, A. Huybrechts, I. Appleby, P.N. Schmidt, J.A. Crowe, F.L. Overvad, K. Tjønneland, A. Kühn, T. Katzke, V. Trichopoulou, A. Karakatsani, A. Peppa, E. Grioni, S. Palli, D. Sacerdote, C. Tumino, R. Bueno-de-Mesquita, H.B. Larrañaga, N. Sánchez, M.-J. Quirós, J.R. Ardanaz, E. Chirlaque, M.-D. Agudo, A. Bjartell, A. Wallström, P. Chajes, V. Tsilidis, K.K. Aune, D. Riboli, E. Travis, R.C. Key, T.J.
Abstract: The associations of individual dietary fatty acids with prostate cancer risk have not been examined comprehensively. We examined the prospective association of individual dietary fatty acids with prostate cancer risk overall, by tumor subtypes, and prostate cancer death. 142,239 men from the European Prospective Investigation into Cancer and Nutrition who were free from cancer at recruitment were included. Dietary intakes of individual fatty acids were estimated using center-specific validated dietary questionnaires at baseline and calibrated with 24-h recalls. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow-up of 13.9 years, 7,036 prostate cancer cases and 936 prostate cancer deaths were ascertained. Intakes of individual fatty acids were not related to overall prostate cancer risk. There was evidence of heterogeneity in the association of some short chain saturated fatty acids with prostate cancer risk by tumor stage (pheterogeneity < 0.015), with a positive association with risk of advanced stage disease for butyric acid (4:0; HR1SD = 1.08; 95%CI = 1.01–1.15; p-trend = 0.026). There were no associations with fatal prostate cancer, with the exception of a slightly higher risk for those who consumed more eicosenoic acid (22:1n-9c; HR1SD = 1.05; 1.00–1.11; p-trend = 0.048) and eicosapentaenoic acid (20:5n-3c; HR1SD = 1.07; 1.00–1.14; p-trend = 0.045). There was no evidence that dietary intakes of individual fatty acids were associated with overall prostate cancer risk. However, a higher intake of butyric acid might be associated with a higher risk of advanced, whereas intakes of eicosenoic and eicosapentaenoic acids might be positively associated with fatal prostate cancer risk. © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
Published: 2020

10. Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Zamora-Ros, R. Cayssials, V. Franceschi, S. Kyrø, C. Weiderpass, E. Hennings, J. Sandström, M. Tjønneland, A. Olsen, A. Overvad, K. Boutron-Ruault, M.-C. Truong, T. Mancini, F.R. Katzke, V. Kühn, T. Boeing, H. Trichopoulou, A. Karakatsani, A. Martimianaki, G. Palli, D. Krogh, V. Panico, S. Tumino, R. Sacerdote, C. Lasheras, C. Rodríguez-Barranco, M. Amiano, P. Colorado-Yohar, S.M. Ardanaz, E. Almquist, M. Ericson, U. Bueno-de-Mesquita, H.B. Vermeulen, R. Schmidt, J.A. Byrnes, G. Scalbert, A. Agudo, A. Rinaldi, S.
Subjects: food and beverages
Abstract: Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77–1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80–1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55–2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals. © 2019 UICC
Published: 2020

11. Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations

Author: Duijnhoven, F.J. van, Jenab, M., Hveem, Kristian, Siersema, P.D., Fedirko, V., Duell, Eric J., Kampman, E., Riboli, Elio, and Bueno-de-Mesquita, H.B.
Subjects: Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], All institutes and research themes of the Radboud University Medical Center
Abstract: Contains fulltext : 189766.pdf (Publisher’s version ) (Open Access)
Published: 2018

12. Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author: Zamora-Ros, R. Alghamdi, M.A. Cayssials, V. Franceschi, S. Almquist, M. Hennings, J. Sandström, M. Tsilidis, K.K. Weiderpass, E. Boutron-Ruault, M.-C. Hammer Bech, B. Overvad, K. Tjønneland, A. Petersen, K.E.N. Mancini, F.R. Mahamat-Saleh, Y. Bonnet, F. Kühn, T. Fortner, R.T. Boeing, H. Trichopoulou, A. Bamia, C. Martimianaki, G. Masala, G. Grioni, S. Panico, S. Tumino, R. Fasanelli, F. Skeie, G. Braaten, T. Lasheras, C. Salamanca-Fernández, E. Amiano, P. Chirlaque, M.-D. Barricarte, A. Manjer, J. Wallström, P. Bueno-de-Mesquita, H.B. Peeters, P.H. Khaw, K.-T. Wareham, N.J. Schmidt, J.A. Aune, D. Byrnes, G. Scalbert, A. Agudo, A. Rinaldi, S.
Abstract: Purpose: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study. Methods: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires. Results: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97–1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95–1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95–1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81–0.99), but this association was based on a sub-analysis with a small number of cancer cases. Conclusions: In this large prospective study, coffee and tea consumptions were not associated with TC risk. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
Published: 2019

13. Haem iron intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Ward, H.A. Whitman, J. Muller, D.C. Johansson, M. Jakszyn, P. Weiderpass, E. Palli, D. Fanidi, A. Vermeulen, R. Tjønneland, A. Hansen, L. Dahm, C.C. Overvad, K. Severi, G. Boutron-Ruault, M.-C. Affret, A. Kaaks, R. Fortner, R. Boeing, H. Trichopoulou, A. La Vecchia, C. Kotanidou, A. Berrino, F. Krogh, V. Tumino, R. Ricceri, F. Panico, S. Bueno-de-Mesquita, H.B. Peeters, P.H. Nøst, T.H. Sandanger, T.M. Quirós, J.R. Agudo, A. Rodríguez-Barranco, M. Larrañaga, N. Huerta, J.M. Ardanaz, E. Drake, I. Brunnström, H. Johansson, M. Grankvist, K. Travis, R.C. Freisling, H. Stepien, M. Merritt, M.A. Riboli, E. Cross, A.J.
Abstract: Background: Epidemiological studies suggest that haem iron, which is found predominantly in red meat and increases endogenous formation of carcinogenic N-nitroso compounds, may be positively associated with lung cancer. The objective was to examine the relationship between haem iron intake and lung cancer risk using detailed smoking history data and serum cotinine to control for potential confounding. Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 416,746 individuals from 10 countries completed demographic and dietary questionnaires at recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident lung cancer (n = 3731) risk relative to haem iron, non-haem iron, and total dietary iron intake. A corresponding analysis was conducted among a nested subset of 800 lung cancer cases and 1489 matched controls for whom serum cotinine was available. Results: Haem iron was associated with lung cancer risk, including after adjustment for details of smoking history (time since quitting, number of cigarettes per day): as a continuous variable (HR per 0.3 mg/1000 kcal 1.03, 95% CI 1.00–1.07), and in the highest versus lowest quintile (HR 1.16, 95% CI 1.02–1.32; trend across quintiles: P = 0.035). In contrast, non-haem iron intake was related inversely with lung cancer risk; however, this association attenuated after adjustment for smoking history. Additional adjustment for serum cotinine did not considerably alter the associations detected in the nested case–control subset. Conclusions: Greater haem iron intake may be modestly associated with lung cancer risk. © 2018, Springer Nature Limited.
Published: 2019

14. Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition

Author: Bradbury, K.E. Appleby, P.N. Tipper, S.J. Travis, R.C. Allen, N.E. Kvaskoff, M. Overvad, K. Tjønneland, A. Halkjær, J. Cervenka, I. Mahamat-Saleh, Y. Bonnet, F. Kaaks, R. Fortner, R.T. Boeing, H. Trichopoulou, A. La Vecchia, C. Stratigos, A.J. Palli, D. Grioni, S. Matullo, G. Panico, S. Tumino, R. Peeters, P.H. Bueno-de-Mesquita, H.B. Ghiasvand, R. Veierød, M.B. Weiderpass, E. Bonet, C. Molina, E. Huerta, J.M. Larrañaga, N. Barricarte, A. Merino, S. Isaksson, K. Stocks, T. Ljuslinder, I. Hemmingsson, O. Wareham, N. Khaw, K.-T. Gunter, M.J. Rinaldi, S. Tsilidis, K.K. Aune, D. Riboli, E. Key, T.J.
Abstract: Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case–control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma. © 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
Published: 2019

15. CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer: a prospective evaluation

Author: Honda, K. Katzke, V.A. Hüsing, A. Okaya, S. Shoji, H. Onidani, K. Olsen, A. Tjønneland, A. Overvad, K. Weiderpass, E. Vineis, P. Muller, D. Tsilidis, K. Palli, D. Pala, V. Tumino, R. Naccarati, A. Panico, S. Aleksandrova, K. Boeing, H. Bueno-de-Mesquita, H.B. Peeters, P.H. Trichopoulou, A. Lagiou, P. Khaw, K.-T. Wareham, N. Travis, R.C. Merino, S. Duell, E.J. Rodríguez-Barranco, M. Chirlaque, M.D. Barricarte, A. Rebours, V. Boutron-Ruault, M.-C. Romana Mancini, F. Brennan, P. Scelo, G. Manjer, J. Sund, M. Öhlund, D. Canzian, F. Kaaks, R.
Subjects: digestive system diseases
Abstract: Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. Our study provides a first prospective evaluation of an ApoA2 isoform (“ApoA2-ATQ/AT”), alone and in combination with carbohydrate antigen 19–9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6–18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6–18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤ 18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6–18 or ≤ 18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging. © 2018 UICC
Published: 2019

16. Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study

Author: Naudin, S. Li, K. Jaouen, T. Assi, N. Kyrø, C. Tjønneland, A. Overvad, K. Boutron-Ruault, M.-C. Rebours, V. Védié, A.-L. Boeing, H. Kaaks, R. Katzke, V. Bamia, C. Naska, A. Trichopoulou, A. Berrino, F. Tagliabue, G. Palli, D. Panico, S. Tumino, R. Sacerdote, C. Peeters, P.H. Bueno-de-Mesquita, H.B. Weiderpass, E. Gram, I.T. Skeie, G. Chirlaque, M.-D. Rodríguez-Barranco, M. Barricarte, A. Quirós, J.R. Dorronsoro, M. Johansson, I. Sund, M. Sternby, H. Bradbury, K.E. Wareham, N. Riboli, E. Gunter, M. Brennan, P. Duell, E.J. Ferrari, P.
Abstract: Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In our study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1,283 incident PC (57% women) were diagnosed from 476,106 cancer-free participants, followed up for 14 years. Amounts of lifetime and baseline alcohol were estimated through lifestyle and dietary questionnaires, respectively. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and their 95% confidence interval (CI). Alcohol intake was positively associated with PC risk in men. Associations were mainly driven by extreme alcohol levels, with HRs comparing heavy drinkers (>60 g/day) to the reference category (0.1–4.9 g/day) equal to 1.77 (95% CI: 1.06, 2.95) and 1.63 (95% CI: 1.16, 2.29) for lifetime and baseline alcohol, respectively. Baseline alcohol intakes from beer (>40 g/day) and spirits/liquors (>10 g/day) showed HRs equal to 1.58 (95% CI: 1.07, 2.34) and 1.41 (95% CI: 1.03, 1.94), respectively, compared to the reference category (0.1–2.9 g/day). In women, HR estimates did not reach statistically significance. The alcohol and PC risk association was not modified by smoking status. Findings from a large prospective study suggest that baseline and lifetime alcohol intakes were positively associated with PC risk, with more apparent risk estimates for beer and spirits/liquors than wine intake. © 2018 IARC/WHO
Published: 2018

17. Consumption of fruits, vegetables and fruit juices and differentiated thyroid carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author: Zamora-Ros, R. Béraud, V. Franceschi, S. Cayssials, V. Tsilidis, K.K. Boutron-Ruault, M.-C. Weiderpass, E. Overvad, K. Tjønneland, A. Eriksen, A.K. Bonnet, F. Affret, A. Katzke, V. Kühn, T. Boeing, H. Trichopoulou, A. Valanou, E. Karakatsani, A. Masala, G. Grioni, S. Santucci de Magistris, M. Tumino, R. Ricceri, F. Skeie, G. Parr, C.L. Merino, S. Salamanca-Fernández, E. Chirlaque, M.-D. Ardanaz, E. Amiano, P. Almquist, M. Drake, I. Hennings, J. Sandström, M. Bueno-de-Mesquita, H.B. Peeters, P.H. Khaw, K.-T. Wareham, N.J. Schmidt, J.A. Perez-Cornago, A. Aune, D. Riboli, E. Slimani, N. Scalbert, A. Romieu, I. Agudo, A. Rinaldi, S.
Abstract: Fruit and vegetable (F&V) intake is considered as probably protective against overall cancer risk, but results in previous studies are not consistent for thyroid cancer (TC). The purpose of this study is to examine the association between the consumption of fruits, vegetables, fruit juices and differentiated thyroid cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The EPIC study is a cohort including over half a million participants, recruited between 1991 and 2000. During a mean follow-up of 14 years, 748 incident first primary differentiated TC cases were identified. F&V and fruit juice intakes were assessed through validated country-specific dietary questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounding factors. Comparing the highest versus lowest quartile of intake, differentiated TC risk was not associated with intakes of total F&V (HR: 0.89; 95% CI: 0.68–1.15; p-trend = 0.44), vegetables (HR: 0.89; 95% CI: 0.69–1.14; p-trend = 0.56), or fruit (HR: 1.00; 95% CI: 0.79–1.26; p-trend = 0.64). No significant association was observed with any individual type of vegetable or fruit. However, there was a positive borderline trend with fruit juice intake (HR: 1.23; 95% CI: 0.98–1.53; p-trend = 0.06). This study did not find any significant association between F&V intakes and differentiated TC risk; however a positive trend with fruit juice intake was observed, possibly related to its high sugar content. © 2017 UICC
Published: 2018

18. Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels: Results from the EPIC cohort

Author: Fortner, R.T. Schock, H. Le Cornet, C. Hüsing, A. Vitonis, A.F. Johnson, T.S. Fichorova, R.N. Fashemi, T. Yamamoto, H.S. Tjønneland, A. Hansen, L. Overvad, K. Boutron-Ruault, M.-C. Kvaskoff, M. Severi, G. Boeing, H. Trichopoulou, A. Papatesta, E.-M. La Vecchia, C. Palli, D. Sieri, S. Tumino, R. Sacerdote, C. Mattiello, A. Onland-Moret, N.C. Peeters, P.H. Bueno-de-Mesquita, H.B. Weiderpass, E. Quirós, J.R. Duell, E.J. Sánchez, M.-J. Navarro, C. Ardanaz, E. Larrañaga, N. Nodin, B. Jirström, K. Idahl, A. Lundin, E. Khaw, K.-T. Travis, R.C. Gunter, M. Johansson, M. Dossus, L. Merritt, M.A. Riboli, E. Terry, K.L. Cramer, D.W. Kaaks, R.
Subjects: endocrine system diseases, female genital diseases and pregnancy complications
Abstract: CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case–control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed
Published: 2018

19. Prospective evaluation of antibody response to Streptococcus gallolyticus and risk of colorectal cancer

Author: Butt, J. Jenab, M. Willhauck-Fleckenstein, M. Michel, A. Pawlita, M. Kyrø, C. Tjønneland, A. Boutron-Ruault, M.-C. Carbonnel, F. Severi, G. Kaaks, R. Kühn, T. Boeing, H. Trichopoulou, A. la Vecchia, C. Karakatsani, A. Panico, S. Tumino, R. Agnoli, C. Palli, D. Sacerdote, C. Bueno-de-Mesquita, H.B. Weiderpass, E. Sánchez, M.-J. Bonet Bonet, C. Huerta, J.M. Ardanaz, E. Bradbury, K. Gunter, M. Murphy, N. Freisling, H. Riboli, E. Tsilidis, K. Aune, D. Waterboer, T. Hughes, D.J.
Subjects: digestive system diseases
Abstract: The gut microbiome is increasingly implicated in colorectal cancer (CRC) development. A subgroup of patients diagnosed with CRC show high antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG). However, it is unclear whether the association is also present pre-diagnostically. We assessed the association of antibody responses to SGG proteins in pre-diagnostic serum samples with CRC risk in a case–control study nested within a prospective cohort. Pre-diagnostic serum samples from 485 first incident CRC cases (mean time between blood draw and diagnosis 3.4 years) and 485 matched controls in the European Prospective Investigation into Nutrition and Cancer (EPIC) study were analyzed for antibody responses to 11 SGG proteins using multiplex serology. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable conditional logistic regression models. Antibody positivity for any of the 11 SGG proteins was significantly associated with CRC risk with 56% positive controls compared to 63% positive cases (OR: 1.36, 95% CI: 1.04–1.77). Positivity for two or more proteins of a previously identified SGG 6-marker panel with greater CRC-specificity was also observed among 9% of controls compared to 17% of CRC cases, corresponding to a significantly increased CRC risk (OR: 2.17, 95% CI: 1.44–3.27). In this prospective nested case–control study, we observed a positive association between antibody responses to SGG and CRC development in serum samples taken before evident disease onset. Further work is required to establish the possibly etiological significance of these observations and whether SGG serology may be applicable for CRC risk stratification. © 2018 UICC
Published: 2018

20. Nut intake and 5-year changes in body weight and obesity risk in adults: results from the EPIC-PANACEA study

Author: Freisling, H. Noh, H. Slimani, N. Chajès, V. May, A.M. Peeters, P.H. Weiderpass, E. Cross, A.J. Skeie, G. Jenab, M. Mancini, F.R. Boutron-Ruault, M.-C. Fagherazzi, G. Katzke, V.A. Kühn, T. Steffen, A. Boeing, H. Tjønneland, A. Kyrø, C. Hansen, C.P. Overvad, K. Duell, E.J. Redondo-Sánchez, D. Amiano, P. Navarro, C. Barricarte, A. Perez-Cornago, A. Tsilidis, K.K. Aune, D. Ward, H. Trichopoulou, A. Naska, A. Orfanos, P. Masala, G. Agnoli, C. Berrino, F. Tumino, R. Sacerdote, C. Mattiello, A. Bueno-de-Mesquita, H.B. Ericson, U. Sonestedt, E. Winkvist, A. Braaten, T. Romieu, I. Sabaté, J.
Subjects: food and beverages
Abstract: Purpose: There is inconsistent evidence regarding the relationship between higher intake of nuts, being an energy-dense food, and weight gain. We investigated the relationship between nut intake and changes in weight over 5 years. Methods: This study includes 373,293 men and women, 25–70 years old, recruited between 1992 and 2000 from 10 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Habitual intake of nuts including peanuts, together defined as nut intake, was estimated from country-specific validated dietary questionnaires. Body weight was measured at recruitment and self-reported 5 years later. The association between nut intake and body weight change was estimated using multilevel mixed linear regression models with center/country as random effect and nut intake and relevant confounders as fixed effects. The relative risk (RR) of becoming overweight or obese after 5 years was investigated using multivariate Poisson regressions stratified according to baseline body mass index (BMI). Results: On average, study participants gained 2.1 kg (SD 5.0 kg) over 5 years. Compared to non-consumers, subjects in the highest quartile of nut intake had less weight gain over 5 years (−0.07 kg; 95% CI −0.12 to −0.02) (P trend = 0.025) and had 5% lower risk of becoming overweight (RR 0.95; 95% CI 0.92–0.98) or obese (RR 0.95; 95% CI 0.90–0.99) (both P trend
Published: 2018

21. Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

Author: Ezzati, M. and Zhou, B. and Bentham, J. and Di Cesare, M. and Bixby, H. and Danaei, G. and Hajifathalian, K. and Taddei, C. and Carrillo-Larco, R.M. and Djalalinia, S. and Khatibzadeh, S. and Lugero, C. and Peykari, N. and Zhang, W.Z. and Bennett, J. and Bilano, V. and Stevens, G.A. and Cowan, M.J. and Riley, L.M. and Chen, Z. and Hambleton, I.R. and Jackson, R.T. and Kengne, A.P. and Khang, Y.-H. and Laxmaiah, A. and Liu, J. and Malekzadeh, R. and Neuhauser, H.K. and Sorić, M. and Starc, G. and Sundström, J. and Woodward, M. and Abarca-Gómez, L. and Abdeen, Z.A. and Abu-Rmeileh, N.M. and Acosta-Cazares, B. and Adams, R.J. and Aekplakorn, W. and Afsana, K. and Aguilar-Salinas, C.A. and Agyemang, C. and Ahmad, N.A. and Ahmadvand, A. and Ahrens, W. and Ajlouni, K. and Akhtaeva, N. and Al-Raddadi, R. and Ali, M.M. and Ali, O. and Alkerwi, A. and Aly, E. and Amarapurkar, D.N. and Amouyel, P. and Amuzu, A. and Andersen, L.B. and Anderssen, S.A. and Ängquist, L.H. and Anjana, R.M. and Ansong, D. and Aounallah-Skhiri, H. and Araújo, J. and Ariansen, I. and Aris, T. and Arlappa, N. and Arveiler, D. and Aryal, K.K. and Aspelund, T. and Assah, F.K. and Assunção, M.C.F. and Avdicová, M. and Azevedo, A. and Azizi, F. and Babu, B.V. and Bahijri, S. and Balakrishna, N. and Bamoshmoosh, M. and Banach, M. and Bandosz, P. and Banegas, J.R. and Barbagallo, C.M. and Barceló, A. and Barkat, A. and Barros, A.J.D. and Barros, M.V. and Bata, I. and Batieha, A.M. and Batyrbek, A. and Baur, L.A. and Beaglehole, R. and Romdhane, H.B. and Benet, M. and Benson, L.S. and Bernabe-Ortiz, A. and Bernotiene, G. and Bettiol, H. and Bhagyalaxmi, A. and Bharadwaj, S. and Bhargava, S.K. and Bi, Y. and Bikbov, M. and Bista, B. and Bjerregaard, P. and Bjertness, E. and Bjertness, M.B. and Björkelund, C. and Blokstra, A. and Bo, S. and Bobak, M. and Boeing, H. and Boggia, J.G. and Boissonnet, C.P. and Bongard, V. and Borchini, R. and Bovet, P. and Braeckman, L. and Brajkovich, I. and Branca, F. and Breckenkamp, J. and Brenner, H. and Brewster, L.M. and Bruno, G. and Bueno-de-Mesquita, H.B. and Bugge, A. and Burns, C. and Bursztyn, M. and de León, A.C. and Cacciottolo, J. and Cai, H. and Cameron, C. and Can, G. and Cândido, A.P.C. and Capuano, V. and Cardoso, V.C. and Carlsson, A.C. and Carvalho, M.J. and Casanueva, F.F. and Casas, J.-P. and Caserta, C.A. and Chamukuttan, S. and Chan, A.W. and Chan, Q. and Chaturvedi, H.K. and Chaturvedi, N. and Chen, C.-J. and Chen, F. and Chen, H. and Chen, S. and Cheng, C.-Y. and Dekkaki, I.C. and Chetrit, A. and Chiolero, A. and Chiou, S.-T. and Chirita-Emandi, A. and Chirlaque, M.-D. and Cho, B. and Cho, Y. and Christofaro, D.G. and Chudek, J. and Cifkova, R. and Cinteza, E. and Claessens, F. and Clays, E. and Concin, H. and Cooper, C. and Cooper, R. and Coppinger, T.C. and Costanzo, S. and Cottel, D. and Cowell, C. and Craig, C.L. and Crujeiras, A.B. and Cruz, J.J. and D'Arrigo, G. and d'Orsi, E. and Dallongeville, J. and Damasceno, A. and Dankner, R. and Dantoft, T.M. and Dauchet, L. and Davletov, K. and De Backer, G. and De Bacquer, D. and de Gaetano, G. and De Henauw, S. and de Oliveira, P.D. and De Smedt, D. and Deepa, M. and Dehghan, A. and Delisle, H. and Deschamps, V. and Dhana, K. and Di Castelnuovo, A.F. and Dias-da-Costa, J.S. and Diaz, A. and Dickerson, T.T. and Do, H.T.P. and Dobson, A.J. and Donfrancesco, C. and Donoso, S.P. and Döring, A. and Dorobantu, M. and Doua, K. and Drygas, W. and Dulskiene, V. and Džakula, A. and Dzerve, V. and Dziankowska-Zaborszczyk, E. and Eggertsen, R. and Ekelund, U. and El Ati, J. and Elliott, P. and Elosua, R. and Erasmus, R.T. and Erem, C. and Eriksen, L. and Eriksson, J.G. and Escobedo-de la Peña, J. and Evans, A. and Faeh, D. and Fall, C.H. and Farzadfar, F. and Felix-Redondo, F.J. and Ferguson, T.S. and Fernandes, R.A. and Fernández-Bergés, D. and Ferrante, D. and Ferrari, M. and Ferreccio, C. and Ferrieres, J. and Finn, J.D. and Fischer, K. and Föger, B. and Foo, 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Association, Iceland, Universidad Icesi, Colombia, King's College London, United Kingdom, International Agency for Research on Cancer, France, Healis-Sekhsaria Institute for Public Health, India, Eternal Heart Care Centre and Research Institute, India, University of Ibadan, Nigeria, Children's Memorial Health Institute, Poland, Institute for Clinical Effectiveness and Health Policy, Argentina, Danish Cancer Society Research Centre, Denmark, Kyushu University, Japan, Tulane University, United States, Chinese Center for Disease Control and Prevention, China, Academic Medical Center of University of Amsterdam, Netherlands, National Institute of Public Health, Mexico, Oulu University Hospital, Finland, Chronic Diseases Research Center, Iran, University of Hong Kong, Hong Kong, The Chinese University of Hong Kong, Hong Kong, University of Western Australia, Australia, Celal Bayar University, Turkey, Heart Institute, Brazil, Fundación Oftalmológica de Santander, Colombia, University of Oran 1, Algeria, Independent Public Health Specialist, Myanmar, Ministry of Health, Myanmar, Peking University, China, VU University Medical Center and VU University, Netherlands, American University of Beirut, Lebanon, Cairo University, Egypt, National Institute of Health and Nutrition, Japan, Aga Khan University, Pakistan, UHC Zagreb, Croatia, Niigata University, Japan, Hadassah University Medical Center, Israel, Duke- NUS Medical School, Singapore, Norwegian University of Science and Technology, Norway, University of Zagreb School of Medicine, Croatia, Heart Foundation, Australia, National Health Insurance Service, South Korea, Guangzhou 12th Hospital, China, Simon Fraser University, Canada, Ruprecht-Karls- University of Heidelberg, Germany, Research Centre for Prevention and Health, Denmark, World Health Organization Country Office, India, Czestochowa University of Technology, Poland, University of Crete, Greece, Universiti Kebangsaan Malaysia, Malaysia, Johns Hopkins Bloomberg School of Public Health, United States, University of Eastern Finland, Finland, National Institute of Epidemiology, India, University of Münster, Germany, Israel Center for Disease Control, Israel, Research Institute for Primordial Prevention of Noncommunicable Disease, Iran, VU University Medical Center, Netherlands, Kyrgyz State Medical Academy, Kyrgyzstan, Research Institute of Child Nutrition, Germany, University of Cambridge, United Kingdom, Medical University of Innsbruck, Austria, Muhimbili University of Health and Allied Sciences, Tanzania, National Cancer Center, South Korea, Institute of Tropical Medicine, Belgium, Tartu University Clinics, Estonia, Ministry of Health and Quality of Life, Mauritius, Polish Academy of Sciences Anthropology Unit in Wroclaw, Poland, University of Zürich, Switzerland, University of Groningen, Netherlands, North-West University, South Africa, National Institute of Public Health, Czech Republic, University of Jyväskylä, Finland, Amrita Institute of Medical Sciences, India, All India Institute of Medical Sciences, India, African Population and Health Research Center, Kenya, Ministerio de Salud Pública, Cuba, Sahlgrenska Academy, Sweden, Endocrinology and Metabolism Research Center, Iran, Food and Agriculture Organization of the United Nations, Italy, National University of Singapore, Singapore, Tampere University Hospital, Finland, University of Cape Town, South Africa, West Virginia University, United States, Oswaldo Cruz Foundation Rene Rachou Research Institute, Brazil, National Taiwan University, Taiwan, University of Chinese Academy of Sciences, China, University Medicine Greifswald, Germany, Consejería de Sanidad Junta de Castilla y León, Spain, University of Uppsala, Sweden, Universidade Federal de Ouro Preto, Brazil, The Jikei University School of Medicine, Japan, National Research Council, Italy, Baker Heart and Diabetes Institute, Australia, Agricultural University of Athens, Greece, Hospital Israelita Albert Einstein, Brazil, Shiraz University of Medical Sciences, Iran, Institute of Internal and Preventive Medicine, Russian Federation, Harokopio University, Greece, University of Otago, New Zealand, University of Padova, Italy, Lausanne University Hospital, Switzerland, CIBERCV, Spain, Emory University, United States, UiT The Arctic University of Norway, Norway, Cape Peninsula University of Technology, South Africa, Gorgas Memorial Institute of Health Studies, Panama, Brown University, United States, University of Edinburgh, United Kingdom, Statistics Canada, Canada, University College Dublin, Ireland, Institut National de la Santé et de la Recherche Médicale, France, Lusófona University, Portugal, Universita' degli Studi di Firenze, Italy, Ain Shams University, Egypt, Hypertension Research Center, Iran, University of Pécs, Hungary, Seoul National University Children's Hospital, South Korea, University Medical Science, Cuba, Universidad de Zaragoza, Spain, RCSI Dublin, Ireland, La Trobe University, Australia, International Institute of Molecular and Cell Biology, Poland, Ahvaz Jundishapur University of Medical Sciences, Iran, Gorgas Memorial Institute of Public Health, Panama, World Health Organization Country Office, Malawi, Department of Public Health, Myanmar, University of Brescia, Italy, Bushehr University of Medical Sciences, Iran, Ulm University, Germany, Kobe University, Japan, Suraj Eye Institute, India, University Medicine of Greifswald, Germany, INSERM, France, National Institute of Hygiene and Epidemiology, Viet Nam, The University of Pharmacy and Medicine of Ho Chi Minh City, Viet Nam, Hanoi Medical University, Viet Nam, National Hospital of Endocrinology, Viet Nam, Miami Veterans Affairs Healthcare System, United States, University of Turku Tyks, Finland, Heartfile, Pakistan, Eastern Mediterranean Public Health Network, Jordan, Tachikawa General Hospital, Japan, Academic Hospital of Paramaribo, Suriname, Ministry of Health, Brunei Darussalam, University of Madeira, Portugal, MRC Lifecourse Epidemiology Unit, United Kingdom, Aarhus University, Denmark, Kwame Nkrumah University of Science and Technology, Ghana, Institute for Social and Preventive Medicine, Switzerland, University of Coimbra, Portugal, Cancer Prevention and Research Institute, Italy, Ruprecht-Karls-University of Heidelberg, Germany, IRCCS Casa Sollievo della Sofferenza, Italy, Zayed University, United Arab Emirates, Catholic University of Daegu, South Korea, Jivandeep Hospital, India, University Hospital Centre Zagreb, Croatia, University Medical Center Utrecht, Netherlands, Vietnam National Heart Institute, Viet Nam, University of Sarajevo, Bosnia and Herzegovina, Cardiovascular Prevention Centre Udine, Italy, Ministry of Health and Medical Services, Solomon Islands, Public Health Agency of Catalonia, Spain, University of Split, Croatia, Digestive Oncology Research Center, Iran, Digestive Disease Research Institute, Iran, Alborz University of Medical Sciences, Iran, Ministry of Health, Viet Nam, University of Turku, Finland, Universiti Putra Malaysia, Malaysia, University of Malaya, Malaysia, University of Valencia, Spain, University of the Philippines, Philippines, Minas Gerais State Secretariat for Health, Brazil, Health Center San Agustín, Spain, PharmAccess Foundation, Netherlands, Universidade Nove de Julho, Brazil, Public Health Agency of Canada, Canada, Canarian Health Service, Spain, Universidad Industrial de Santander, Colombia, Instituto Nacional de Salud Pública, Mexico, Sitaram Bhartia Institute of Science and Research, India, Marmara University, Turkey, CIBER de Epidemiología y Salud Pública, Spain, University of Helsinki, Finland, National Institute of Health, Peru, Catalan Department of Health, Spain, Universidade de Lisboa, Portugal, University of Sao Paulo Clinics Hospital, Brazil, South Karelia Social and Health Care District, Finland, Isfahan Cardiovascular Research Center, Iran, Research and Education Institute of Child Health, Cyprus, Hospital Italiano de Buenos Aires, Argentina, Lagos State University College of Medicine, Nigeria, The University of Tokyo, Japan, Samsung Medical Center, South Korea, Federal University of Santa Catarina, Brazil, St Vincent's Hospital, Australia, Academic Medical Center Amsterdam, Netherlands, University of Bari, Italy, Lund University, Sweden, University of Copenhagen, Denmark, Institut Régional de Santé Publique, Benin, University of Bordeaux, France, University of Leuven, Belgium, Bonn University, Germany, Sotiria Hospital, Greece, National Institute of Public Health- National Institute of Hygiene, Poland, Fu Jen Catholic University, Taiwan, Ministry of Health, Jordan, Health Service of Murcia, Spain, IB-SALUT Area de Salut de Menorca, Spain, Institut de Recherche pour le Développement, France, Hellenic Health Foundation, Greece, GovernmentMedical College, India, Sefako Makgatho Health Science University, South Africa, Addis Ababa University, Ethiopia, Dasman Diabetes Institute, Kuwait, Ministry of Health, New Zealand, Universidad Centro-Occidental Lisandro Alvarado, Venezuela, University of Tampere Tays Eye Center, Finland, Utrecht University, Netherlands, Hanoi University of Public Health, Viet Nam, Amsterdam Public Health Research Institute, Netherlands, Universidade Federal de Minas Gerais, Brazil, Finnish Institute of Occupational Health, Finland, Universidad Miguel Hernandez, Spain, North Karelian Center for Public Health, Finland, University of the Witwatersrand, South Africa, University of Strasbourg, France, Institute for Medical Research, Malaysia, Xinjiang Medical University, China, Capital Medical University, China, St George's, University of London, United Kingdom, Medical University of Vienna, Austria, Universitas Indonesia, Indonesia, National Institute of Public Health-National Institute of Hygiene, Poland, Institute of Food and Nutrition Development of Ministry of Agriculture, China, Children's Hospital of Fudan University, China, University of Cyprus, Cyprus, Universiti Teknologi MARA, Malaysia, Inner Mongolia Medical University, China, Universidad Politécnica de Madrid, Spain, State University of Montes Claros, Brazil, and University of Limpopo, South Africa
Subjects: sense organs
Abstract: Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups. © The Author(s) 2018.
Published: 2018

22. A prospective evaluation of plasma polyphenol levels and colon cancer risk

Author: Murphy, N. Achaintre, D. Zamora-Ros, R. Jenab, M. Boutron-Ruault, M.-C. Carbonnel, F. Savoye, I. Kaaks, R. Kühn, T. Boeing, H. Aleksandrova, K. Tjønneland, A. Kyrø, C. Overvad, K. Quirós, J.R. Sánchez, M.-J. Altzibar, J.M. María Huerta, J. Barricarte, A. Khaw, K.-T. Bradbury, K.E. Perez-Cornago, A. Trichopoulou, A. Karakatsani, A. Peppa, E. Palli, D. Grioni, S. Tumino, R. Sacerdote, C. Panico, S. Bueno-de-Mesquita, H.B. Peeters, P.H. Rutegård, M. Johansson, I. Freisling, H. Noh, H. Cross, A.J. Vineis, P. Tsilidis, K. Gunter, M.J. Scalbert, A.
Abstract: Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre-diagnostic plasma polyphenols and colon cancer risk in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (q values ) was computed to control for multiple comparisons. All statistical tests were two-sided. After false discovery rate correction and in continuous log 2 -transformed multivariable models, equol (odds ratio [OR] per log 2 -value, 0.86, 95% confidence interval [95% CI] = 0.79–0.93; q value = 0.01) and homovanillic acid (OR per log 2 -value, 1.46, 95% CI = 1.16–1.84; q value = 0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR = 0.61, 95% CI = 0.41–0.91, p trend = 0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR = 1.72, 95% CI = 1.17–2.53, p trend < 0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis. © 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
Published: 2018

23. Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation

Author: Campa, D. Pastore, M. Capurso, G. Hackert, T. Di Leo, M. Izbicki, J.R. Khaw, K.-T. Gioffreda, D. Kupcinskas, J. Pasquali, C. Macinga, P. Kaaks, R. Stigliano, S. Peeters, P.H. Key, T.J. Talar-Wojnarowska, R. Vodicka, P. Valente, R. Vashist, Y.K. Salvia, R. Papaconstantinou, I. Shimizu, Y. Valsuani, C. Zambon, C.F. Gazouli, M. Valantiene, I. Niesen, W. Mohelnikova-Duchonova, B. Hara, K. Soucek, P. Malecka-Panas, E. Bueno-de-Mesquita, H.B. Johnson, T. Brenner, H. Tavano, F. Fogar, P. Ito, H. Sperti, C. Butterbach, K. Latiano, A. Andriulli, A. Cavestro, G.M. Busch, O.R.C. Dijk, F. Greenhalf, W. Matsuo, K. Lombardo, C. Strobel, O. König, A.-K. Cuk, K. Strothmann, H. Katzke, V. Cantore, M. Mambrini, A. Oliverius, M. Pezzilli, R. Landi, S. Canzian, F.
Subjects: endocrine system diseases, digestive system diseases
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous = 1.19, 95% CI 1.02–1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous = 0.51, 95% CI 0.39–0.67, p = 1.10 × 10−6) and MORC4-rs 12837024 (ORhomozygous = 2.07 (1.55–2.77, ptrend = 0.7 × 10−11). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants. © 2017 UICC
Published: 2018

24. Consumption of fish is not associated with risk of differentiated thyroid carcinoma in the European prospective investigation into cancer and nutrition (EPIC) study

Author: Zamora-Ros, R. Castañeda, J. Rinaldi, S. Cayssials, V. Slimani, N. Weiderpass, E. Tsilidis, K.K. Boutron-Ruault, M.-C. Overvad, K. Eriksen, A.K. Tjønneland, A. Kühn, T. Katzke, V. Boeing, H. Trichopoulou, A. La Vecchia, C. Kotanidou, A. Palli, D. Grioni, S. Mattiello, A. Tumino, R. Sciannameo, V. Lund, E. Merino, S. Salamanca-Fernández, E. Amiano, P. Huerta, J.M. Barricarte, A. Ericson, U. Almquist, M. Hennings, J. Sandström, M. Bueno-de-Mesquita, H.B. Peeters, P.H. Khaw, K.-T. Wareham, N.J. Schmidt, J.A. Cross, A.J. Riboli, E. Scalbert, A. Romieu, I. Agudo, A. Franceschi, S.
Abstract: Background: Differentiated thyroid cancer (TC) is the most common endocrine cancer. Fish can be an important source of iodine and other micronutrients and contaminants that may affect the thyroid gland and TC risk. Objective: We prospectively evaluated the relations between the consumption of total fish and different fish types and shellfish and TC risk in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Methods: EPIC is a cohort of > 500,000 men and women, mostly aged 35-70 y, who were recruited in 10 European countries. After a mean follow-up of 14 y, 748 primary differentiated TC cases were diagnosed; 666 were in women and 601 were papillary TC. Data on intakes of lean fish, fatty fish, fish products, and shellfish were collected by using countryspecific validated dietary questionnaires at recruitment. Multivariable Cox regression was used to calculate HRs and 95% CIs adjusted for many potential confounders, including dietary and nondietary factors. Results: No significant association was observed between total fish consumption and differentiated TC risk for the highest compared with the lowest quartile (HR: 1.03; 95% CI: 0.81, 1.32; P-trend = 0.67). Likewise, no significant association was observed with the intake of any specific type of fish, fish product, or shellfish. No significant heterogeneity was found by TC subtype (papillary or follicular tumors), by sex, or between countries with low and high TC incidence. Conclusion: This large study shows that the intake of fish and shellfish was not associated with differentiated TC risk in Europe, a region in which iodine deficiency or excess is rare. © 2017 American Society for Nutrition.
Published: 2017

25. Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Author: Stepien, M. Jenab, M. Freisling, H. Becker, N.-P. Czuban, M. Tjønneland, A. Olsen, A. Overvad, K. Boutron-Ruault, M.-C. Mancini, F.R. Savoye, I. Katzke, V. Kühn, T. Boeing, H. Iqbal, K. Trichopoulou, A. Bamia, C. Orfanos, P. Palli, D. Sieri, S. Tumino, R. Naccarati, A. Panico, S. Bueno-de-Mesquita, H.B. Peeters, P.H. Weiderpass, E. Merino, S. Jakszyn, P. Sanchez, M.-J. Dorronsoro, M. Huerta, J.M. Barricarte, A. Boden, S. van Guelpen, B. Wareham, N. Khaw, K.-T. Bradbury, K.E. Cross, A.J. Schomburg, L. Hughes, D.J.
Abstract: Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels in relation to zinc (copper to zinc ratio) become imbalanced in the process of CRC development. Mechanistic studies into the underlying mechanisms of regulation and action are required to further examine a possible role for higher copper and copper/zinc ratio levels in CRC development and progression. © The Author 2017. Published by Oxford University Press.
Published: 2017

26. Pre-diagnostic metabolite concentrations and prostate cancer risk in 1077 cases and 1077 matched controls in the European Prospective Investigation into Cancer and Nutrition

Author: Schmidt, J.A. Fensom, G.K. Rinaldi, S. Scalbert, A. Appleby, P.N. Achaintre, D. Gicquiau, A. Gunter, M.J. Ferrari, P. Kaaks, R. Kühn, T. Floegel, A. Boeing, H. Trichopoulou, A. Lagiou, P. Anifantis, E. Agnoli, C. Palli, D. Trevisan, M. Tumino, R. Bueno-de-Mesquita, H.B. Agudo, A. Larrañaga, N. Redondo-Sánchez, D. Barricarte, A. Huerta, J.M. Quirós, J.R. Wareham, N. Khaw, K.-T. Perez-Cornago, A. Johansson, M. Cross, A.J. Tsilidis, K.K. Riboli, E. Key, T.J. Travis, R.C.
Abstract: Background: Little is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer. Methods: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition, pre-diagnostic plasma concentrations of 122 metabolites (including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit) and compared between 1077 prostate cancer cases and 1077 matched controls. Risk of prostate cancer associated with metabolite concentrations was estimated by multi-variable conditional logistic regression, and multiple testing was accounted for by using a false discovery rate controlling procedure. Results: Seven metabolite concentrations, i.e. acylcarnitine C18:1, amino acids citrulline and trans-4-hydroxyproline, glycerophospholipids PC aa C28:1, PC ae C30:0 and PC ae C30:2, and sphingolipid SM (OH) C14:1, were associated with prostate cancer (p < 0.05), but none of the associations were statistically significant after controlling for multiple testing. Citrulline was associated with a decreased risk of prostate cancer (odds ratio (OR1SD) = 0.73; 95% confidence interval (CI) 0.62-0.86; p trend = 0.0002) in the first 5 years of follow-up after taking multiple testing into account, but not after longer follow-up; results for other metabolites did not vary by time to diagnosis. After controlling for multiple testing, 12 glycerophospholipids were inversely associated with advanced stage disease, with risk reduction up to 46% per standard deviation increase in concentration (OR1SD = 0.54; 95% CI 0.40-0.72; p trend = 0.00004 for PC aa C40:3). Death from prostate cancer was associated with higher concentrations of acylcarnitine C3, amino acids methionine and trans-4-hydroxyproline, biogenic amine ADMA, hexose and sphingolipid SM (OH) C14:1 and lower concentration of glycerophospholipid PC aa C42:4. Conclusions: Several metabolites, i.e. C18:1, citrulline, trans-4-hydroxyproline, three glycerophospholipids and SM (OH) C14:1, might be related to prostate cancer. Analyses by time to diagnosis indicated that citrulline may be a marker of subclinical prostate cancer, while other metabolites might be related to aetiology. Several glycerophospholipids were inversely related to advanced stage disease. More prospective data are needed to confirm these associations. © 2017 The Author(s).
Published: 2017

27. Alcohol consumption and risk of urothelial cell bladder cancer in the European prospective investigation into cancer and nutrition cohort

Author: Botteri, E. Ferrari, P. Roswall, N. Tjønneland, A. Hjartåker, A. Huerta, J.M. Fortner, R.T. Trichopoulou, A. Karakatsani, A. La Vecchia, C. Pala, V. Perez-Cornago, A. Sonestedt, E. Liedberg, F. Overvad, K. Sánchez, M.J. Gram, I.T. Stepien, M. Trijsburg, L. Börje, L. Johansson, M. Kühn, T. Panico, S. Tumino, R. Bueno-de-Mesquita, H.B. Weiderpass, E.
Abstract: Findings on the association between alcohol consumption and bladder cancer are inconsistent. We investigated that association in the European Prospective Investigation into Cancer and Nutrition cohort. We included 476,160 individuals mostly aged 35–70 years, enrolled in ten countries and followed for 13.9 years on average. Hazard ratios (HR) for developing urothelial cell carcinoma (UCC; 1,802 incident cases) were calculated using Cox proportional hazards models. Alcohol consumption at baseline and over the life course was analyzed, as well as different types of beverages (beer, wine, spirits). Baseline alcohol intake was associated with a statistically nonsignificant increased risk of UCC (HR 1.03; 95% confidence interval (CI) 1.00–1.06 for each additional 12 g/day). HR in smokers was 1.04 (95% CI 1.01–1.07). Men reporting high baseline intakes of alcohol (>96 g/day) had an increased risk of UCC (HR 1.57; 95% CI 1.03–2.40) compared to those reporting moderate intakes (6 to 24 g/day). Average lifelong alcohol intake was not associated with the risk of UCC, however intakes of spirits > 24 g/day were associated with an increased risk of UCC in men (1.38; 95% CI 1.01–1.91) and smokers (1.39; 95% CI 1.01–1.92), compared to moderate intakes. We found no association between alcohol and UCC in women and never smokers. In conclusion, we observed some associations between alcohol and UCC in men and in smokers, possibly because of residual confounding by tobacco smoking. © 2017 UICC
Published: 2017

28. Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: Meta-analysis of individual participant data of seven prospective cohorts in Europe

Author: Freisling, H. Arnold, M. Soerjomataram, I. O'Doherty, M.G. Ordóñez-Mena, J.M. Bamia, C. Kampman, E. Leitzmann, M. Romieu, I. Kee, F. Tsilidis, K. Tjønneland, A. Trichopoulou, A. Boffetta, P. Benetou, V. Bueno-De-Mesquita, H.B. Huerta, J.M. Brenner, H. Wilsgaard, T. Jenab, M.
Abstract: Background:We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence.Methods:This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models.Results:After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02-1.21) for BMI, 1.13 (95% CI 1.04-1.23) for WC, 1.09 (95% CI 0.98-1.21) for HC, and 1.15 (95% CI 1.00-1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone therapy (HT) use was observed for postmenopausal breast cancer (P interaction
Published: 2017

29. Hepcidin levels and gastric cancer risk in the EPIC-EurGast study

Author: Jakszyn, P. Fonseca-Nunes, A. Lujan-Barroso, L. Aranda, N. Tous, M. Arija, V. Cross, A. Bueno-de-Mesquita, H.B. Weiderpass, E. Kühn, T. Kaaks, R. Sjöberg, K. Ohlsson, B. Tumino, R. Palli, D. Ricceri, F. Fasanelli, F. Krogh, V. Mattiello, A. Jenab, M. Gunter, M. Perez-Cornago, A. Khaw, K.-T. Tjønneland, A. Olsen, A. Overvad, K. Trichopoulou, A. Peppa, E. Vasilopoulou, E. Boeing, H. Sánchez-Cantalejo, E. Huerta, J.M. Dorronsoro, M. Barricarte, A. Quirós, J.M. Peeters, P.H. Agudo, A.
Subjects: hemic and lymphatic diseases, nutritional and metabolic diseases
Abstract: Hepcidin is the main regulator of iron homeostasis and dysregulation of proteins involved in iron metabolism has been associated with tumorogenesis. However, to date, no epidemiological study has researched the association between hepcidin levels and gastric cancer risk. To further investigate the relationship between hepcidin levels and gastric cancer risk, we conducted a nested case-control study (EURGAST) within the multicentric European Prospective Investigation into Cancer and Nutrition study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured serum levels of hepcidin-25, iron, ferritin, transferrin and C-reactive protein. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by hepcidin levels were estimated from multivariable conditional logistic regression models. Mediation effect of the ferritin levels on the hepcidin-gastric cancer pathway was also evaluated. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and hepcidin levels (OR 5 ng/l = 0.96, 95% CI = 0.93–0.99). No differences were found by tumor localization or histological type. In mediation analysis, we found that the direct effect of hepcidin only represents a nonsignificant 38% (95% CI: −69%, 91%). In summary, these data suggest that the inverse association of hepcidin levels and gastric cancer risk was mostly accounted by ferritin levels. Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis. © 2017 UICC
Published: 2017

30. Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

Author: Duell, E.J. Lujan-Barroso, L. Sala, N. Deitz McElyea, S. Overvad, K. Tjonneland, A. Olsen, A. Weiderpass, E. Busund, L.-T. Moi, L. Muller, D. Vineis, P. Aune, D. Matullo, G. Naccarati, A. Panico, S. Tagliabue, G. Tumino, R. Palli, D. Kaaks, R. Katzke, V.A. Boeing, H. Bueno-de-Mesquita, H.B. Peeters, P.H. Trichopoulou, A. Lagiou, P. Kotanidou, A. Travis, R.C. Wareham, N. Khaw, K.-T. Ramon Quiros, J. Rodríguez-Barranco, M. Dorronsoro, M. Chirlaque, M.-D. Ardanaz, E. Severi, G. Boutron-Ruault, M.-C. Rebours, V. Brennan, P. Gunter, M. Scelo, G. Cote, G. Sherman, S. Korc, M.
Abstract: Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155 and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status and age/date/time of blood collection. MiR levels in prediagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 years of blood collection compared to matched controls (all p-values
Published: 2017

31. Circulating RANKL and RANKL/OPG and breast cancer risk by ER and PR subtype: Results from the EPIC cohort

Author: Sarink, D. Schock, H. Johnson, T. Overvad, K. Holm, M. Tjønneland, A. Boutron-Ruault, M.-C. His, M. Kvaskoff, M. Boeing, H. Lagiou, P. Papatesta, E.-M. Trichopoulou, A. Palli, D. Pala, V. Mattiello, A. Tumino, R. Sacerdote, C. Bueno-De-Mesquita, H.B. Van Gils, C.H. Peeters, P.H. Weiderpass, E. Agudo, A. Sánchez, M.-J. Chirlaque, M.-D. Ardanaz, E. Amiano, P. Khaw, K.T. Travis, R. Dossus, L. Gunter, M. Rinaldi, S. Merritt, M. Riboli, E. Kaaks, R. Fortner, R.T.
Abstract: Receptor activator of nuclear factor-kappa B (RANK)-RANK ligand (RANKL) signaling promotes mammary tumor development in experimental models. Circulating concentrations of soluble RANKL (sRANKL) may influence breast cancer risk via activation of RANK signaling; this may be modulated by osteoprotegerin (OPG), the decoy receptor for RANKL. sRANKL and breast cancer risk by hormone receptor subtype has not previously been investigated. A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. This study included 1, 976 incident invasive breast cancer cases [estrogen receptor positive (ER+), n=1, 598], matched 1:1 to controls. Women were pre- or postmenopausal at blood collection. Serum sRANKL was quantified using an ELISA, serum OPG using an electrochemiluminescent assay. Risk ratios (RR) and95% confidence intervals (95% CI) were calculated using conditional logistic regression. Associations between sRANKL and breast cancer risk differed by tumor hormone receptor status (Phet = 0.05). Higher concentrations of sRANKL were positively associated with risk of ER+ breast cancer [5th vs. 1st quintile RR 1.28 (95% CI, 1.01-1.63); Ptrend=0.20], but not ER-disease. For both ER+and estrogen and progesterone receptor positive (ER+PR+) breast cancer, results considering the sRANKL/OPG ratio were similar to those for sRANKL; we observed a suggestive inverse association between the ratio and ER-PR-disease [5th vs. 1st quintile RR = 0.60 (0.31-1.14); Ptrend=0.03]. This study provides the first largescale prospective data on circulating sRANKLand breast cancer. We observed limited evidence for an association between sRANKLand breast cancer risk. Cancer Prev Res; 10(9); 525-34. © 2017 American Association for Cancer Research.
Published: 2017

32. Self-rated health and all-cause and cause-specific mortality of older adults: Individual data meta-analysis of prospective cohort studies in the CHANCES Consortium

Author: Bamia, C. Orfanos, P. Juerges, H. Schöttker, B. Brenner, H. Lorbeer, R. Aadahl, M. Matthews, C.E. Klinaki, E. Katsoulis, M. Lagiou, P. Bueno-de-mesquita, H.B. Eriksson, S. Mons, U. Saum, K.-U. Kubinova, R. Pajak, A. Tamosiunas, A. Malyutina, S. Gardiner, J. Peasey, A. de Groot, L.C. Wilsgaard, T. Boffetta, P. Trichopoulou, A. Trichopoulos, D.
Abstract: Objectives To evaluate, among the elderly, the association of self-rated health (SRH) with mortality, and to identify determinants of self-rating health as “at-least-good”. Study design Individual data on SRH and important covariates were obtained for 424,791 European and United States residents, ≥60 years at recruitment (1982–2008), in eight prospective studies in the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES). In each study, adjusted mortality ratios (hazard ratios, HRs) in relation to SRH were calculated and subsequently combined with random-effect meta-analyses. Main outcome measures All-cause, cardiovascular and cancer mortality. Results Within the median 12.5 years of follow-up, 93,014 (22%) deaths occurred. SRH “fair” or “poor” vs. “at-least-good” was associated with increased mortality: HRs 1.46 (95% CI 1·23–1.74) and 2.31 (1.79–2.99), respectively. These associations were evident: for cardiovascular and, to a lesser extent, cancer mortality, and within-study, within-subgroup analyses. Accounting for lifestyle, sociodemographic, somatometric factors and, subsequently, for medical history explained only a modest amount of the unadjusted associations. Factors favourably associated with SRH were: sex (males), age (younger-old), education (high), marital status (married/cohabiting), physical activity (active), body mass index (non-obese), alcohol consumption (low to moderate) and previous morbidity (absence). Conclusion SRH provides a quick and simple tool for assessing health and identifying groups of elders at risk of early mortality that may be useful also in clinical settings. Modifying determinants of favourably rating health, e.g. by increasing physical activity and/or by eliminating obesity, may be important for older adults to “feel healthy” and “be healthy”. © 2017
Published: 2017

33. Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort

Author: Matejcic, M. de Batlle, J. Ricci, C. Biessy, C. Perrier, F. Huybrechts, I. Weiderpass, E. Boutron-Ruault, M.C. Cadeau, C. His, M. Cox, D.G. Boeing, H. Fortner, R.T. Kaaks, R. Lagiou, P. Trichopoulou, A. Benetou, V. Tumino, R. Panico, S. Sieri, S. Palli, D. Ricceri, F. Bueno-de-Mesquita, H.B. Skeie, G. Amiano, P. Sánchez, M.J. Chirlaque, M.D. Barricarte, A. Quirós, J.R. Buckland, G. van Gils, C.H. Peeters, P.H. Key, T.J. Riboli, E. Gylling, B. Zeleniuch-Jacquotte, A. Gunter, M.J. Romieu, I. Chajès, V.
Abstract: Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1 = 1.26; 95% CI 1.00–1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1 = 1.29; 95% CI 1.02–1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation. © 2016 UICC
Published: 2017

34. Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants

Author: Zhou, B. and Bentham, J. and Di Cesare, M. and Bixby, H. and Danaei, G. and Cowan, M.J. and Paciorek, C.J. and Singh, G. and Hajifathalian, K. and Bennett, J.E. and Taddei, C. and Bilano, V. and Carrillo-Larco, R.M. and Djalalinia, S. and Khatibzadeh, S. and Lugero, C. and Peykari, N. and Zhang, W.Z. and Lu, Y. and Stevens, G.A. and Riley, L.M. and Bovet, P. and Elliott, P. and Gu, D. and Ikeda, N. and Jackson, R.T. and Joffres, M. and Kengne, A.P. and Laatikainen, T. and Lam, T.H. and Laxmaiah, A. and Liu, J. and Miranda, J.J. and Mondo, C.K. and Neuhauser, H.K. and Sundström, J. and Smeeth, L. and Sorić, M. and Woodward, M. and Ezzati, M. and Abarca-Gómez, L. and Abdeen, Z.A. and Rahim, H.A. and Abu-Rmeileh, N.M. and Acosta-Cazares, B. and Adams, R. and Aekplakorn, W. and Afsana, K. and Aguilar-Salinas, C.A. and Agyemang, C. and Ahmadvand, A. and Ahrens, W. and Al Raddadi, R. and Al Woyatan, R. and Ali, M.M. and Alkerwi, A. and Aly, E. and Amouyel, P. and Amuzu, A. and Andersen, L.B. and Anderssen, S.A. and Ängquist, L. and Anjana, R.M. and Ansong, D. and Aounallah-Skhiri, H. and Araújo, J. and Ariansen, I. and Aris, T. and Arlappa, N. and Aryal, K. and Arveiler, D. and Assah, F.K. and Assunção, M.C.F. and Avdicová, M. and Azevedo, A. and Azizi, F. and Babu, B.V. and Bahijri, S. and Balakrishna, N. and Bandosz, P. and Banegas, J.R. and Barbagallo, C.M. and Barceló, A. and Barkat, A. and Barros, A.J.D. and Barros, M.V. and Bata, I. and Batieha, A.M. and Baur, L.A. and Beaglehole, R. and Romdhane, H.B. and Benet, M. and Benson, L.S. and Bernabe-Ortiz, A. and Bernotiene, G. and Bettiol, H. and Bhagyalaxmi, A. and Bharadwaj, S. and Bhargava, S.K. and Bi, Y. and Bikbov, M. and Bjerregaard, P. and Bjertness, E. and Björkelund, C. and Blokstra, A. and Bo, S. and Bobak, M. and Boeing, H. and Boggia, J.G. and Boissonnet, C.P. and Bongard, V. and Braeckman, L. and Brajkovich, I. and Branca, F. and Breckenkamp, J. and Brenner, H. and Brewster, L.M. and Bruno, G. and Bueno-de-Mesquita, H.B. and Bugge, A. and Burns, C. and Bursztyn, M. and de León, A.C. and Cacciottolo, J. and Cameron, C. and Can, G. and Cândido, A.P.C. and Capuano, V. and Cardoso, V.C. and Carlsson, A.C. and Carvalho, M.J. and Casanueva, F.F. and Casas, J.-P. and Caserta, C.A. and Chamukuttan, S. and Chan, A.W. and Chan, Q. and Chaturvedi, H.K. and Chaturvedi, N. and Chen, C.-J. and Chen, F. and Chen, H. and Chen, S. and Chen, Z. and Cheng, C.-Y. and Dekkaki, I.C. and Chetrit, A. and Chiolero, A. and Chiou, S.-T. and Chirita-Emandi, A. and Cho, B. and Cho, Y. and Chudek, J. and Cifkova, R. and Claessens, F. and Clays, E. and Concin, H. and Cooper, C. and Cooper, R. and Coppinger, T.C. and Costanzo, S. and Cottel, D. and Cowell, C. and Craig, C.L. and Crujeiras, A.B. and Cruz, J.J. and D'Arrigo, G. and d'Orsi, E. and Dallongeville, J. and Damasceno, A. and Dankner, R. and Dantoft, T.M. and Dauchet, L. and De Backer, G. and De Bacquer, D. and de Gaetano, G. and De Henauw, S. and De Smedt, D. and Deepa, M. and Dehghan, A. and Delisle, H. and Deschamps, V. and Dhana, K. and Di Castelnuovo, A.F. and Dias-da-Costa, J.S. and Diaz, A. and Dickerson, T.T. and Do, H.T.P. and Donfrancesco, C. and Dobson, A.J. and Donoso, S.P. and Döring, A. and Doua, K. and Drygas, W. and Dulskiene, V. and Džakula, A. and Dzerve, V. and Dziankowska-Zaborszczyk, E. and Ekelund, U. and El Ati, J. and Ellert, U. and Elosua, R. and Erasmus, R.T. and Erem, C. and Eriksen, L. and Escobedo-de la Peña, J. and Evans, A. and Faeh, D. and Fall, C.H. and Farzadfar, F. and Felix-Redondo, F.J. and Ferguson, T.S. and Fernández-Bergés, D. and Ferrante, D. and Ferrari, M. and Ferreccio, C. and Ferrieres, J. and Finn, J.D. and Fischer, K. and Föger, B. and Foo, L.H. and Forslund, A.-S. and Forsner, M. and Fortmann, S.P. and Fouad, H.M. and Francis, D.K. and do Carmo Franco, M. and Franco, O.H. and Frontera, G. and Fuchs, F.D. and Fuchs, S.C. and Fujita, Y. and Furusawa, T. and Gaciong, Z. and Gareta, D. and Garnett, S.P. and Gaspoz, J.-M. and Gasull, M. and Gates, L. and Gavrila, D. and Geleijnse, J.M. and Ghasemian, A. and Ghimire, A. and Giampaoli, S. and Gianfagna, F. and Giovannelli, J. and Goldsmith, R.A. and Gonçalves, H. and Gross, M.G. and González Rivas, J.P. and Gottrand, F. and Graff-Iversen, S. and Grafnetter, D. and Grajda, A. and Gregor, R.D. and Grodzicki, T. and Grøntved, A. and Gruden, G. and Grujic, V. and Guan, O.P. and Gudnason, V. and Guerrero, R. and Guessous, I. and Guimaraes, A.L. and Gulliford, M.C. and Gunnlaugsdottir, J. and Gunter, M. and Gupta, P.C. and Gureje, O. and Gurzkowska, B. and Gutierrez, L. and Gutzwiller, F. and Hadaegh, F. and Halkjær, J. and Hambleton, I.R. and Hardy, R. and Harikumar, R. and Hata, J. and Hayes, A.J. and He, J. and Hendriks, M.E. and Henriques, A. and Cadena, L.H. and Herqutanto and Herrala, S. and Heshmat, R. and Hihtaniemi, I.T. and Ho, S.Y. and Ho, S.C. and Hobbs, M. and Hofman, A. and Dinc, G.H. and Hormiga, C.M. and Horta, B.L. and Houti, L. and Howitt, C. and Htay, T.T. and Htet, A.S. and Hu, Y. and Huerta, J.M. and Husseini, A.S. and Huybrechts, I. and Hwalla, N. and Iacoviello, L. and Iannone, A.G. and Ibrahim, M.M. and Ikram, M.A. and Irazola, V.E. and Islam, M. and Ivkovic, V. and Iwasaki, M. and Jacobs, J.M. and Jafar, T. and Jamrozik, K. and Janszky, I. and Jasienska, G. and Jelakovic, B. and Jiang, C.Q. and Johansson, M. and Jonas, J.B. and Jørgensen, T. and Joshi, P. and Juolevi, A. and Jurak, G. and Jureša, V. and Kaaks, R. and Kafatos, A. and Kalter-Leibovici, O. and Kamaruddin, N.A. and Kasaeian, A. and Katz, J. and Kauhanen, J. and Kaur, P. and Kavousi, M. and Kazakbaeva, G. and Keil, U. and Boker, L.K. and Keinänen-Kiukaanniemi, S. and Kelishadi, R. and Kemper, H.C.G. and Kersting, M. and Key, T. and Khader, Y.S. and Khalili, D. and Khang, Y.-H. and Khaw, K.-T. and Kiechl, S. and Killewo, J. and Kim, J. and Klumbiene, J. and Kolle, E. and Kolsteren, P. and Korrovits, P. and Koskinen, S. and Kouda, K. and Koziel, S. and Kristensen, P.L. and Krokstad, S. and Kromhout, D. and Kruger, H.S. and Kubinova, R. and Kuciene, R. and Kuh, D. and Kujala, U.M. and Kula, K. and Kulaga, Z. and Krishna Kumar, R. and Kurjata, P. and Kusuma, Y.S. and Kuulasmaa, K. and Kyobutungi, C. and Lachat, C. and Landrove, O. and Lanska, V. and Lappas, G. and Larijani, B. and Laugsand, L.E. and Le Nguyen Bao, K. and Le, T.D. and Leclercq, C. and Lee, J. and Lee, J. and Lehtimäki, T. and Rampal, L. and León-Muñoz, L.M. and Levitt, N.S. and Li, Y. and Lilly, C.L. and Lim, W.-Y. and Lima-Costa, M.F. and Lin, H.-H. and Lin, X. and Linneberg, A. and Lissner, L. and Litwin, M. and Lorbeer, R. and Lotufo, P.A. and Lozano, J.E. and Luksiene, D. and Lundqvist, A. and Lunet, N. and Lytsy, P. and Ma, G. and Ma, J. and Machado-Coelho, G.L.L. and Machi, S. and Maggi, S. and Magliano, D.J. and Majer, M. and Makdisse, M. and Malekzadeh, R. and Malhotra, R. and Rao, K.M. and Malyutina, S. and Manios, Y. and Mann, J.I. and Manzato, E. and Margozzini, P. and Marques-Vidal, P. and Marrugat, J. and Martorell, R. and Mathiesen, E.B. and Matijasevich, A. and Matsha, T.E. and Mbanya, J.C.N. and McDonald Posso, A.J. and McFarlane, S.R. and McGarvey, S.T. and McLachlan, S. and McLean, R.M. and McNulty, B.A. and MdKhir, A.S. and Mediene-Benchekor, S. and Medzioniene, J. and Meirhaeghe, A. and Meisinger, C. and Menezes, A.M.B. and Menon, G.R. and Meshram, I.I. and Metspalu, A. and Mi, J. and Mikkel, K. and Miller, J.C. and Miquel, J.F. and Mišigoj-Durakovic, M. and Mohamed, M.K. and Mohammad, K. and Mohammadifard, N. and Mohan, V. and Mohd Yusoff, M.F. and Møller, N.C. and Molnár, D. and Momenan, A. and Monyeki, K.D.K. and Moreira, L.B. and Morejon, A. and Moreno, L.A. and Morgan, K. and Moschonis, G. and Mossakowska, M. and Mota, J. and Mostafa, A. and Motlagh, M.E. and Motta, J. and Muiesan, M.L. and Müller-Nurasyid, M. and Murphy, N. and Mursu, J. and Musil, V. and Nagel, G. and Naidu, B.M. and Nakamura, H. and Námešná, J. and Nang, E.E.K. and Nangia, V.B. and Narake, S. and Navarrete-Muñoz, E.M. and Ndiaye, N.C. and Neal, W.A. and Nenko, I. and Nervi, F. and Nguyen, N.D. and Nguyen, Q.N. and Nieto-Martínez, R.E. and Niiranen, T.J. and Ning, G. and Ninomiya, T. and Nishtar, S. and Noale, M. and Noboa, O.A. and Noorbala, A.A. and Norat, T. and Noto, D. and Al Nsour, M. and O'Reilly, D. and Oh, K. and Olinto, M.T.A. and Oliveira, I.O. and Omar, M.A. and Onat, A. and Ordunez, P. and Osmond, C. and Ostojic, S.M. and Otero, J.A. and Overvad, K. and Owusu-Dabo, E. and Paccaud, F.M. and Padez, C. and Pahomova, E. and Pajak, A. and Palli, D. and Palmieri, L. and Panda-Jonas, S. and Panza, F. and Papandreou, D. and Parnell, W.R. and Parsaeian, M. and Pecin, I. and Pednekar, M.S. and Peer, N. and Peeters, P.H. and Peixoto, S.V. and Pelletier, C. and Peltonen, M. and Pereira, A.C. and Pérez, R.M. and Peters, A. and Petkeviciene, J. and Pham, S.T. and Pigeot, I. and Pikhart, H. and Pilav, A. and Pilotto, L. and Pitakaka, F. and Plans-Rubió, P. and Polakowska, M. and Polašek, O. and Porta, M. and Portegies, M.L.P. and Pourshams, A. and Pradeepa, R. and Prashant, M. and Price, J.F. and Puiu, M. and Punab, M. and Qasrawi, R.F. and Qorbani, M. and Radic, I. and Radisauskas, R. and Rahman, M. and Raitakari, O. and Raj, M. and Rao, S.R. and Ramachandran, A. and Ramos, E. and Rampal, S. and Rangel Reina, D.A. and Rasmussen, F. and Redon, J. and Reganit, P.F.M. and Ribeiro, R. and Riboli, E. and Rigo, F. and Rinke de Wit, T.F. and Ritti-Dias, R.M. and Robinson, S.M. and Robitaille, C. and Rodríguez-Artalejo, F. and del Cristo Rodriguez-Perez, M. and Rodríguez-Villamizar, L.A. and Rojas-Martinez, R. and Rosengren, A. and Rubinstein, A. and Rui, O. and Ruiz-Betancourt, B.S. and Russo Horimoto, A.R.V. and Rutkowski, M. and Sabanayagam, C. and Sachdev, H.S. and Saidi, O. and Sakarya, S. and Salanave, B. and Martinez, E.S. and Salmerón, D. and Salomaa, V. and Salonen, 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E. and Cisneros, J.Z. and Zhu, D. and Eggertsen, R. and NCD Risk Factor Collaboration (NCD-RisC), Imperial College London, United Kingdom, Middlesex University, United Kingdom, World Health Organization, Switzerland, University of California, Berkeley, United States, Tufts University, United States, Universidad Peruana Cayetano Heredia, Peru, Tehran University of Medical Sciences, Iran, Brandeis University, United States, Mulago Hospital, Uganda, Yale University, United States, University of Lausanne, Switzerland, Ministry of Health, Seychelles, National Center for Cardiovascular Diseases, China, National Institute of Health and Nutrition, Japan, University of Auckland, New Zealand, Simon Fraser University, Canada, South African Medical Research Council, South Africa, National Institute for Health and Welfare, Finland, University of Hong Kong, Hong Kong, National Institute of Nutrition, India, Capital Medical University Beijing An Zhen Hospital, China, Robert Koch Institute, Germany, Uppsala University, Sweden, London School of Hygiene and Tropical Medicine, United Kingdom, University of Zagreb, Croatia, University of Sydney, Australia, University of Oxford, United Kingdom, Caja Costarricense de Seguro Social, Costa Rica, Al-Quds University, Palestine, Qatar University, Qatar, Birzeit University, Palestine, Instituto Mexicano del Seguro Social, Mexico, The University of Adelaide, Australia, Mahidol University, Thailand, BRAC, Bangladesh, Instituto Nacional de Ciencias Médicas y Nutricion, Mexico, University of Amsterdam, Netherlands, Non-Communicable Diseases Research Center, Iran, Leibniz Institute for Prevention Research and Epidemiology—BIPS, Germany, Ministry of Health, Saudi Arabia, Ministry of Health, Kuwait, World Health Organization Regional Office for the Eastern Mediterranean, Egypt, Luxembourg Institute of Health, Luxembourg, Lille University and Hospital, France, Sogn and Fjordane University College, Norway, Norwegian School of Sport Sciences, Norway, Bispebjerg and Frederiksberg Hospitals, Denmark, Madras Diabetes Research Foundation, India, Komfo Anokye Teaching Hospital, Ghana, National Institute of Public Health, Tunisia, University of Porto, Portugal, Norwegian Institute of Public Health, Norway, Ministry of Health Malaysia, Malaysia, Nepal Health Research Council, Nepal, Strasbourg University and Hospital, France, University of Yaoundé 1, Cameroon, Federal University of Pelotas, Brazil, Regional Authority of Public Health, Banska Bystrica, Slovakia, University of Porto Medical School, Portugal, Shahid Beheshti University of Medical Sciences, Iran, Indian Council of Medical Research, India, King Abdulaziz University, Saudi Arabia, Medical University of Gdansk, Poland, Universidad Autónoma de Madrid, Spain, University of Palermo, Italy, Pan American Health Organization, United States, Université Mohammed V de Rabat, Morocco, University of Pernambuco, Brazil, Dalhousie University, Canada, Jordan University of Science and Technology, Jordan, University Tunis El Manar, Tunisia, University Medical Science, Cuba, University of Utah School of Medicine, United States, Lithuanian University of Health Sciences, Lithuania, University of São Paulo, Brazil, B J Medical College, India, Chirayu Medical College, India, SL Jain Hospital, India, Shanghai Jiao-Tong University School of Medicine, China, Ufa Eye Research Institute, Russian Federation, University of Southern Denmark, Denmark, University of Greenland, Greenland, University of Oslo, Norway, University of Gothenburg, Sweden, National Institute for Public Health and the Environment, Netherlands, University of Turin, Italy, University College London, United Kingdom, German Institute of Human Nutrition, Germany, Universidad de la República, Uruguay, CEMIC, Argentina, Toulouse University School of Medicine, France, Ghent University, Belgium, Universidad Central de Venezuela, Venezuela, Bielefeld University, Germany, German Cancer Research Center, Germany, Cork Institute of Technology, Ireland, Hadassah-Hebrew University Medical Center, Israel, Universidad de La Laguna, Spain, University of Malta, Malta, Canadian Fitness and Lifestyle Research Institute, Canada, Istanbul University, Turkey, Universidade Federal de Juiz de Fora, Brazil, Cardiologia di Mercato S Severino, Italy, Karolinska Institutet, Sweden, Santiago de Compostela University, Spain, Associazione Calabrese di Epatologia, Italy, India Diabetes Research Foundation, India, Duke-NUS Medical School, Singapore, National Institute of Medical Statistics, India, Academia Sinica, Taiwan, Capital Institute of Pediatrics, China, Duke University, United States, Kailuan General Hospital, China, The Gertner Institute for Epidemiology and Health Policy Research, Israel, Lausanne University Hospital, Switzerland, Ministry of Health and Welfare, Taiwan, Victor Babeș University of Medicine and Pharmacy Timisoara, Romania, Seoul National University College of Medicine, South Korea, Korea Centers for Disease Control and Prevention, South Korea, Medical University of Silesia, Poland, Charles University in Prague, Czech Republic, Katholieke Universiteit Leuven, Belgium, Agency for Preventive and Social Medicine, Austria, University of Southampton, United Kingdom, IRCCS Istituto Neurologico Mediterraneo Neuromed, Italy, Institut Pasteur de Lille, France, Westmead University of Sydney, Australia, CIBEROBN, Spain, National Council of Research, Italy, Federal University of Santa Catarina, Brazil, Eduardo Mondlane University, Mozambique, Research Centre for Prevention and Health, Denmark, Lille University Hospital, France, Erasmus Medical Center Rotterdam, Netherlands, University of Montreal, Canada, French Public Health Agency, France, Universidade do Vale do Rio dos Sinos, Brazil, National Council of Scientific and Technical Research, Argentina, National Institute of Nutrition, Viet Nam, University of Queensland, Australia, Istituto Superiore di Sanità, Italy, Universidad de Cuenca, Ecuador, Helmholtz Zentrum München, Germany, Ministère de la Santé et de la Lutte Contre le Sida, Cote d'Ivoire, The Cardinal Wyszynski Institute of Cardiology, Poland, University of Latvia, Latvia, Medical University of Łodz, Poland, National Institute of Nutrition and Food Technology, Tunisia, Institut Hospital del Mar d'Investigacions Mèdiques, Spain, University of Stellenbosch, South Africa, Karadeniz Technical University, Turkey, The Queen's University of Belfast, United Kingdom, University of Zurich, Switzerland, Centro de Salud Villanueva Norte, Spain, The University of the West Indies, Jamaica, Hospital Don Benito-Villanueva de la Serena, Spain, Ministry of Health, Argentina, Council for Agricultural Research and Economics, Italy, Pontificia Universidad Católica de Chile, Chile, University of Manchester, United Kingdom, University of Tartu, Estonia, Universiti Sains Malaysia, Malaysia, Umeå University, Sweden, Dalarna University, Sweden, Stanford University, United States, Federal University of São Paulo, Brazil, Hospital Universitario Son Espases, Spain, Hospital de Clinicas de Porto Alegre, Brazil, Universidade Federal do Rio Grande do Sul, Brazil, Kindai University, Japan, Kyoto University, Japan, Medical University of Warsaw, Poland, University of KwaZulu-Natal, South Africa, Geneva University Hospitals, Switzerland, CIBER en Epidemiología y Salud Pública, Spain, Australian Bureau of Statistics, Australia, Murcia Regional Health Council, Spain, Wageningen University, Netherlands, Endocrinology and Metabolism Research Institute, Iran, B P Koirala Institute of Health Sciences, Nepal, University of Insubria, Italy, Ministry of Health, Israel, Universidad Politécnica de Madrid, Spain, The Andes Clinic of Cardio-Metabolic Studies, Venezuela, Université de Lille 2, France, Institute for Clinical and Experimental Medicine, Czech Republic, The Children's Memorial Health Institute, Poland, Jagiellonian University Medical College, Poland, University of Novi Sad, Serbia, Singapore Eye Research Institute, Singapore, University of Iceland, Iceland, Universidad Icesi, Colombia, State University of Montes Claros, Brazil, King's College London, United Kingdom, Icelandic Heart Association, Iceland, Healis-Sekhsaria Institute for Public Health, India, University of Ibadan, Nigeria, Institute for Clinical Effectiveness and Health Policy, Argentina, Danish Cancer Society Research Centre, Denmark, The University of the West Indies, Barbados, Kyushu University, Japan, Tulane University, United States, Academic Medical Center Amsterdam, Netherlands, National Institute of Public Health, Mexico, Universitas Indonesia, Indonesia, Oulu University Hospital, Finland, Chronic Diseases Research Center, Iran, The Chinese University of Hong Kong, Hong Kong, University of Western Australia, Australia, Celal Bayar University, Turkey, Fundación Oftalmológica de Santander, Colombia, Universidade Federal de Pelotas, Brazil, University of Oran 1, Algeria, University of Public Health, Myanmar, Ministry of Health, Myanmar, Peking University, China, International Agency for Research on Cancer, France, American University of Beirut, Lebanon, Cairo University, Egypt, Aga Khan University, Pakistan, UHC Zagreb, Croatia, Niigata University, Japan, Hadassah University Medical Center, Israel, Norwegian University of Science and Technology, Norway, University of Zagreb School of Medicine, Croatia, Guangzhou 12th Hospital, China, Ruprecht-Karls-University of Heidelberg, Germany, World Health Organization Country Office, India, University of Ljubljana, Slovenia, University of Crete, Greece, Universiti Kebangsaan Malaysia, Malaysia, Johns Hopkins Bloomberg School of Public Health, United States, University of Eastern Finland, Finland, National Institute of Epidemiology, India, University of Münster, Germany, Israel Center for Disease Control, Israel, Research Institute for Primordial Prevention of Non-Communicable Disease, Iran, VU University Medical Center, Netherlands, Research Institute of Child Nutrition, Germany, Seoul National University, South Korea, University of Cambridge, United Kingdom, Medical University of Innsbruck, Austria, Muhimbili University of Health and Allied Sciences, Tanzania, National Cancer Center, South Korea, Institute of Tropical Medicine, Belgium, Tartu University Clinics, Estonia, Polish Academy of Sciences Anthropology Unit in Wroclaw, Poland, University of Groningen, Netherlands, North-West University, South Africa, National Institute of Public Health, Czech Republic, University of Jyväskylä, Finland, Amrita Institute of Medical Sciences, India, All India Institute of Medical Sciences, India, African Population and Health Research Center, Kenya, Ministerio de Salud Pública, Cuba, Sahlgrenska Academy, Sweden, Endocrinology and Metabolism Research Center, Iran, Food and Agriculture Organization, Italy, National University of Singapore, Singapore, Tampere University Hospital, Finland, Universiti Putra Malaysia, Malaysia, University of Cape Town, South Africa, West Virginia University, United States, Oswaldo Cruz Foundation Rene Rachou Research Institute, Brazil, National Taiwan University, Taiwan, University of Chinese Academy of Sciences, China, University Medicine Greifswald, Germany, Consejería de Sanidad Junta de Castilla y León, Spain, Universidade do Porto, Portugal, University of Uppsala, Sweden, Universidade Federal de Ouro Preto, Brazil, The Jikei University School of Medicine, Japan, National Research Council, Italy, Baker IDI Heart and Diabetes Institute, Australia, Hospital Israelita Albert Einstein, Brazil, Institute of Internal and Preventive Medicine, Russian Federation, Harokopio University, Greece, University of Otago, New Zealand, University of Padova, Italy, Emory University, United States, UiT The Arctic University of Norway, Norway, Cape Peninsula University of Technology, South Africa, Gorgas Memorial Institute of Health Studies, Panama, Brown University, United States, University of Edinburgh, United Kingdom, University College Dublin, Ireland, Penang Medical College, Malaysia, Institut National de la Santé et de la Recherche Médicale, France, Ain Shams University, Egypt, Hypertension Research Center, Iran, University of Pécs, Hungary, University of Limpopo, South Africa, Universidad de Zaragoza, Spain, RCSI Dublin, Ireland, International Institute of Molecular and Cell Biology, Poland, Ahvaz Jundishapur University of Medical Sciences, Iran, Gorgas Memorial Institute of Public Health, Panama, University of Brescia, Italy, Ulm University, Germany, Institute of Public Health, Malaysia, Kobe University, Japan, Suraj Eye Institute, India, INSERM, France, The University of Pharmacy and Medicine of Ho Chi Minh City, Viet Nam, Hanoi Medical University, Viet Nam, Universidad Centro-Occidental Lisandro Alvarado, Venezuela, Heartfile, Pakistan, Eastern Mediterranean Public Health Network, Jordan, Aarhus University, Denmark, Kwame Nkrumah University of Science and Technology, Ghana, Institute for Social and Preventive Medicine, Switzerland, University of Coimbra, Portugal, Cancer Prevention and Research Institute, Italy, University of Bari, Italy, Zayed University, United Arab Emirates, University Medical Center Utrecht, Netherlands, Public Health Agency of Canada, Canada, Heart Institute, Brazil, National Institute of Hygiene, Epidemiology and Microbiology, Cuba, Vietnam National Heart Institute, Viet Nam, Federal Ministry of Health, Bosnia and Herzegovina, Cardiovascular Prevention Centre Udine, Italy, University of New South Wales, Australia, Public Health Agency of Catalonia, Spain, University of Split, Croatia, Alborz University of Medical Sciences, Iran, Turku University Hospital, Finland, Julius Centre University of Malaya, Malaysia, University of Valencia, Spain, University of the Philippines, Philippines, Minas Gerais State Secretariat for Health, Brazil, Health Center San Agustín, Spain, PharmAccess Foundation, Netherlands, Canarian Health Service, Spain, Universidad Industrial de Santander, Colombia, Instituto Nacional de Salud Pública, Mexico, University of Madeira, Portugal, Sitaram Bhartia Institute of Science and Research, India, Marmara University, Turkey, University of Helsinki, Finland, National Institute of Health, Peru, Catalan Department of Health, Spain, Universidade de Lisboa, Portugal, University of Sao Paulo Clinics Hospital, Brazil, South Karelia Social and Health Care District, Finland, Robert Koch Institut, Germany, Isfahan Cardiovascular Research Center, Iran, Research and Education Institute of Child Health, Cyprus, Hospital Italiano de Buenos Aires, Argentina, Lagos State University College of Medicine, Nigeria, Digestive Diseases Research Institute, Iran, The University of Tokyo, Japan, St Vincent's Hospital, Australia, Lund University, Sweden, University of Copenhagen, Denmark, Institut Régional de Santé Publique, Benin, University of Bordeaux, France, University of Leuven, Belgium, Heart Foundation, Australia, Bonn University, Germany, Sotiria Hospital, Greece, National Institute of Public Health-National Institute of Hygiene, Poland, Fu Jen Catholic University, Taiwan, Ministry of Health, Jordan, IB-SALUT Area de Salut de Menorca, Spain, Institut de Recherche pour le Développement, France, Harvard T H Chan School of Public Health, United States, Hellenic Health Foundation, Greece, Government Medical College, India, Sefako Makgatho Health Science University, South Africa, Dasman Diabetes Institute, Kuwait, Ministry of Health, New Zealand, University of Tampere Tays Eye Center, Finland, Centro di Prevenzione Cardiovascolare Udine, Italy, Universidade Federal de Minas Gerais, Brazil, Finnish Institute of Occupational Health, Finland, Universidad Miguel Hernandez, Spain, Centre for Research in Environmental Epidemiology, Spain, University of the Witwatersrand, South Africa, University of Strasbourg, France, University College Cork, Ireland, Institute for Medical Research, Malaysia, Xinjiang Medical University, China, Beijing Tongren Hospital, China, St George's, University of London, United Kingdom, Medical University of Vienna, Austria, Institute of Food and Nutrition Development of Ministry of Agriculture, China, Children's Hospital of Fudan University, China, Chinese Center for Disease Control and Prevention, China, University of Cyprus, Cyprus, Ministry of Health, Malaysia, and Inner Mongolia Medical University, China
Abstract: Background Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher. Methods For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure. Findings We pooled 1479 studies that had measured the blood pressures of 19·1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127·0 mm Hg (95% credible interval 125·7–128·3) in men and 122·3 mm Hg (121·0–123·6) in women; age-standardised mean diastolic blood pressure was 78·7 mm Hg (77·9–79·5) for men and 76·7 mm Hg (75·9–77·6) for women. Global age-standardised prevalence of raised blood pressure was 24·1% (21·4–27·1) in men and 20·1% (17·8–22·5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence. Interpretation During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe. Funding Wellcome Trust. © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license
Published: 2017

35. Helicobacter pylori infection, chronic corpus atrophic gastritis and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: A nested case-control study

Author: Huang, J. Zagai, U. Hallmans, G. Nyrén, O. Engstrand, L. Stolzenberg-Solomon, R. Duell, E.J. Overvad, K. Katzke, V.A. Kaaks, R. Jenab, M. Park, J.Y. Murillo, R. Trichopoulou, A. Lagiou, P. Bamia, C. Bradbury, K.E. Riboli, E. Aune, D. Tsilidis, K.K. Capellá, G. Agudo, A. Krogh, V. Palli, D. Panico, S. Weiderpass, E. Tjønneland, A. Olsen, A. Martínez, B. Redondo-Sanchez, D. Chirlaque, M.-D. HM Peeters, P. Regnér, S. Lindkvist, B. Naccarati, A. Ardanaz, E. Larrañaga, N. Boutron-Ruault, M.-C. Rebours, V. Barré, A. Bueno-de-Mesquita, H.B. Ye, W.
Abstract: The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction < 0.01). Our findings provided evidence supporting the null association between H. pylori infection and pancreatic cancer risk in western European populations. However, the suggested association between chronic corpus atrophic gastritis and pancreatic cancer risk warrants independent verification in future studies, and, if confirmed, further studies on the underlying mechanisms. © 2016 UICC
Published: 2017

36. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Author: Lu, L. (Lingeng), Lissowska, J. (Jolanta), Liu, J. (Jianjun), Lin, D. (Dongxin), Liao, L. (Linda), Liang, X. (Xiaolin), Li, D. (Donghui), Le-Marchand, L. (Loic), Landi, M.T. (María Teresa), Lan, Q. (Qing), LaCroix, A. (Andrea), Kurtz, R.C. (Robert C.), Krogh, V. (Vittorio), Kraft, P. (Peter), Kooperberg, C. (Charles), Kolonel, L.N. (Laurence N.), Koh, W.P. (Woon-Puay), Klein, R. (Robert), Klein, A.P. (Alison P.), Kim, Y.T. (Young Tae), Kim, Y.H. (Yeul Hong), Kim, H.N. (Hee Nam), Khaw, K.T. (Kay-Tee), Johansen, C. (Christoffer), Jenab, M. (Mazda), Hutchinson, A. (Amy), Hunter, D.J. (David J.), Hu, W. (Wei), Hu, N. (Nan), Hsiung, C.A. (Chao A.), Hoover, R.N. (Robert N.), Hong, Y.C. (Yun-Chul), Holly, E.A. (Elizabeth A.), Henriksson, R. (Roger), Harris, C.C. (Curtis C.), Hankinson, S.E. (Susan E.), Hallmans, G. (Goran), Haiman, C.A. (Christopher A.), Goldstein, A.M. (Alisa M.), Goldin, L. (Lynn), Giovannucci, E.L. (Edward L.), Gillanders, E.M. (Elizabeth M.), Giles, G.G. (Graham G.), Gaziano, J.M. (J. Michael), Gaudet, M.M. (Mia M.), Garcia-Closas, M. (Montserrat), Gapstur, S.M. (Susan M.), Gao, Y.T. (Yu-Tang), Gallinger, S. (Steven), Fuchs, C.S. (Charles S.), Friedenreich, C.M. (Christine M.), Fraumeni, J.F. (Joseph F.), Figueroa, J.D. (Jonine D.), Fan, J.H. (Jin-Hu), Epstein, C.G. (Caroline G.), Duell, E.J. (Eric J.), Doherty, J. (Jennifer), Ding, T. (Ti), De Vivo, I. (Immaculata), Davis, F.G. (Faith G.), Cullen, M. (Michael), Crous Bou, M. (Marta), Cook, L.S. (Linda S.), Chung, C.C. (Charles C.), Chen, K. (Kexin), Chen, C. (Constance), Chen, C. (Chu), Chatterjee, N. (Nilanjan), Chang, I.S. ( I-Shou), Chaffee, K.G. (Kari G.), Carreon, T. (Tania), Canzian, F. (Federico), Butler, M.A. (Mary A.), Buring, J.E. (Julie E.), Burdett, L. (Laurie), Bueno-de-Mesquita, H.B. (H. Bas), Brinton, L.A. (Louise A.), Bracci, P.M. (Paige M.), Bock, C.H. (Cathryn H.), Blot, W.J. (William J.), Black, A. (Amanda), Berndt, S.I. (Sonja I.), Chanock, S.J. (Stephen J.), Yeager, M. (Meredith), Dean, M.C. (Michael C.), Tucker, M. (Margaret), Rothman, N. (Nathaniel), Caporaso, N.E. (Neil E.), Perez-Jurado, L.A. (Luis A.), Beane-Freeman, L.E. (Laura E.), Ziegler, R.G. (Regina G.), Zhou, B. (Baosen), Zheng, W. (Wei), Zeleniuch-Jacquotte, A. (Anne), Zanetti, K.A. (Krista A.), Yu, K. (Kai), Yang, P.C. (Pan-Chyr), Yang, H.P. (Hannah P.), Xia, L. (Lucy), Wunder, J.S. (Jay S.), Arslan, A.A. (Alan A.), Wu, Y.L. (Yi-Long), Wu, Y.Q. (Yan Q.), Wu, T. (Tangchun), Wu, C. (Chen), Wong, M.P. (Maria Pik), Wolpin, B.M. (Brian M.), Wiencke, J.K. (John K.), White, E. (Emily), Wheeler, W. (William), Wentzensen, N. (Nicolas), Amundadottir, L. (Laufey), Wang, Z. (Zhaoming), Wang, J.C. (Jiu-Cun), Wacholder, S. (Sholom), Visvanathan, K. (Kala), Van Den Berg, D. (David), Tobias, G.S. (Geoffrey S.), Teras, L.R. (Lauren R.), Taylor, P.R. (Philip R.), Tang, Z.Z. (Ze-Zhong), Stram, D. (Daniel), Amos, C. (Christopher), Stolzenberg-Solomon, R.Z. (Rachael Z.), Stevens, V.L. (Victoria L.), Spitz, M.R. (Margaret R.), Silverman, D.T. (Debra T.), Shu, X.O. (Xiao-Ou), Shin, M.H. (Min-Ho), Sheng, X. (Xin), Shen, H. (Hongbing), Severi, G. (Gianluca), Setiawan, V.W. (Veronica Wendy), Aldrich, M.C. (Melinda C.), Seow, A. (Adeline), Schwartz, K.L. (Kendra L.), Schwartz, A.G. (Ann G.), Schumacher, F. (Fredrick), Savage, S.A. (Sharon A.), Ruder, A.M. (Avima M.), Rodriguez-Santiago, B. (Benjamin), Risch, H.A. (Harvey A.), Riboli, E. (Elio), Real, F.X. (Francisco X.), Abnet, C.C. (Christian C.), Rajaraman, P. (Preetha), Qiao, Y.L. (You-Lin), Purdue, M. (Mark), Prokunina-Olsson, L. (Ludmila), Prescott, J. (Jennifer), Pooler, L. (Loreall), Petersen, G. (Gloria), Peters, U. (Ulrike), Peplonska, B. (Beata), Park, J.Y. (Jae Yong), Jacobs, K. (Kevin), Orlow, I. (Irene), Olson, S.H. (Sara H.), Moore, L.E. (Lee E.), Mirabello, L. (Lisa), Melin, B.S. (Beatrice S.), McWilliams, R.R. (Robert R.), McNeill, L.H. (Lorna H.), Matsuo, K. (Keitaro), Malats, N. (Nuria), Magliocco, A.M. (Anthony M.), Hautman, C. (Christopher), Dagnall, C. (Casey), Hicks, B. (Belynda), Yang, Q. (Qi), Freedman, N.D. (Neal D.), Sampson, J. (Joshua), Karlins, E. (Eric), Zhou, W. (Weiyin), Mitchell, J.M. (J. Machiela), Machiela, M.J. (Mitchell J.), and Patiño-García, A. (Ana)
Subjects: Chromosome X, Age-related
Abstract: To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
Published: 2016

37. Dairy products, dietary calcium, and risk of inflammatory bowel disease: Results from a European prospective cohort investigation

Author: Opstelten, J.L. Leenders, M. Dik, V.K. Chan, S.S.M. Van Schaik, F.D.M. Khaw, K.-T. Luben, R. Hallmans, G. Karling, P. Lindgren, S. Grip, O. Key, T.J. Crowe, F.L. Boeing, H. Bergmann, M.M. Overvad, K. Palli, D. Masala, G. Racine, A. Carbonnel, F. Boutron-Ruault, M.-C. Tjønneland, A. Olsen, A. Andersen, V. Kaaks, R. Katzke, V.A. Tumino, R. Trichopoulou, A. Siersema, P.D. Bueno-De-Mesquita, H.B. Hart, A.R. Oldenburg, B.
Abstract: Background: Dairy products may be involved in the etiology of inflammatory bowel disease by modulating gut microbiota and immune responses, but data from epidemiological studies examining this relationship are limited. We investigated the association between prediagnostic intake of these foods and dietary calcium, and the subsequent development of Crohn's disease (CD) and ulcerative colitis (UC). Methods: In total, 401,326 participants were enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. At recruitment, consumption of total and specific dairy products (milk, yogurt, and cheese) and dietary calcium was measured using validated food frequency questionnaires. Cases developing incident CD (n 110) or UC (n 244) during follow-up were matched with 4 controls. Conditional logistic regression analyses were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for total energy intake and smoking. Results: Compared with the lowest quartile, the ORs for the highest quartile of total dairy products and dietary calcium intake were 0.61 (95% CI, 0.32-1.19, p trend 0.19) and 0.63 (95% CI, 0.28-1.42, p trend 0.23) for CD, and 0.80 (95% CI, 0.50-1.30, p trend 0.40) and 0.81 (95% CI, 0.49-1.34, p trend 0.60) for UC, respectively. Compared with nonconsumers, individuals consuming milk had significantly reduced odds of CD (OR 0.30, 95% CI, 0.13-0.65) and nonsignificantly reduced odds of UC (OR 0.85, 95% CI, 0.49-1.47). Conclusions: Milk consumption may be associated with a decreased risk of developing CD, although a clear dose-response relationship was not established. Further studies are warranted to confirm this possible protective effect. © 2016 Crohn's & Colitis Foundation of America, Inc.
Published: 2016

38. Menstrual and Reproductive Factors, Hormone Use, and Risk of Pancreatic Cancer: Analysis from the International Pancreatic Cancer Case-Control Consortium (PanC4)

Author: Lujan-Barroso, L. Zhang, W. Olson, S.H. Gao, Y.-T. Yu, H. Baghurst, P.A. Bracci, P.M. Bueno-De-Mesquita, H.B. Foretová, L. Gallinger, S. Holcatova, I. Janout, V. Ji, B.-T. Kurtz, R.C. La Vecchia, C. Lagiou, P. Li, D. Miller, A.B. Serraino, D. Zatonski, W. Risch, H.A. Duell, E.J.
Abstract: Objectives: We aimed to evaluate the relation between menstrual and reproductive factors, exogenous hormones, and risk of pancreatic cancer (PC). Methods: Eleven case-control studies within the International Pancreatic Cancer Case-control Consortium took part in the present study, including in total 2838 case and 4748 controlwomen. Pooled estimates of odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using a 2-step logistic regression model and adjusting for relevant covariates. Results: An inverse ORwas observed inwomenwho reported having had hysterectomy (ORyesvs.no, 0.78; 95% CI, 0.67-0.91), remaining significant in postmenopausalwomen and never-smoking women, adjusted for potential PC confounders. A mutually adjusted model with the joint effect for hormone replacement therapy (HRT) and hysterectomy showed significant inverse associations with PC in women who reported having had hysterectomy with HRT use (OR, 0.64; 95% CI, 0.48-0.84). Conclusions: Our large pooled analysis suggests that women who have had a hysterectomy may have reduced risk of PC. However, we cannot rule out that the reduced risk could be due to factors or indications for having had a hysterectomy. Further investigation of risk according to HRT use and reason for hysterectomy may be necessary. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Published: 2016

39. Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

Author: Duarte-Salles, T. Misra, S. Stepien, M. Plymoth, A. Muller, D. Overvad, K. Olsen, A. Tjønneland, A. Baglietto, L. Severi, G. Boutron-Ruault, M.-C. Turzanski-Fortner, R. Kaaks, R. Boeing, H. Aleksandrova, K. Trichopoulou, A. Lagiou, P. Bamia, C. Pala, V. Palli, D. Mattiello, A. Tumino, R. Naccarati, A. Bueno-De-Mesquita, H.B. Peeters, P.H. Weiderpass, E. Quiros, J.R. Agudo, A. Sanchez-Cantalejo, E. Ardanaz, E. Gavrila, D. Dorronsoro, M. Werner, M. Hemmingsson, O. Ohlsson, B. Sjöberg, K. Wareham, N.J. Khaw, K.-T. Bradbury, K.E. Gunter, M.J. Cross, A.J. Riboli, E. Jenab, M. Hainaut, P. Beretta, L.
Subjects: stomatognathic system, neoplasms, digestive system diseases
Abstract: We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between prediagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function, and a-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95% CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable = 1.30; 95% CI, 1.14-1.48). The association was stronger among cases diagnosed within 2 years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC = 0.86). For cases diagnosed within 2 years, the combination of OPN and AFP was best able to predict HCC risk (AUC = 0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within 2 years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis. © 2016 American Association for Cancer Research.
Published: 2016

40. Particulate matter air pollution components and risk for lung cancer

Author: Raaschou-Nielsen, O. Beelen, R. Wang, M. Hoek, G. Andersen, Z.J. Hoffmann, B. Stafoggia, M. Samoli, E. Weinmayr, G. Dimakopoulou, K. Nieuwenhuijsen, M. Xun, W.W. Fischer, P. Eriksen, K.T. Sørensen, M. Tjønneland, A. Ricceri, F. de Hoogh, K. Key, T. Eeftens, M. Peeters, P.H. Bueno-de-Mesquita, H.B. Meliefste, K. Oftedal, B. Schwarze, P.E. Nafstad, P. Galassi, C. Migliore, E. Ranzi, A. Cesaroni, G. Badaloni, C. Forastiere, F. Penell, J. De Faire, U. Korek, M. Pedersen, N. Östenson, C.-G. Pershagen, G. Fratiglioni, L. Concin, H. Nagel, G. Jaensch, A. Ineichen, A. Naccarati, A. Katsoulis, M. Trichpoulou, A. Keuken, M. Jedynska, A. Kooter, I.M. Kukkonen, J. Brunekreef, B. Sokhi, R.S. Katsouyanni, K. Vineis, P.
Subjects: complex mixtures
Abstract: Background: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. Methods: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis. Results: The 245,782 cohort members contributed 3,229,220person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant. In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 1.25; 95% CI, 1.01-1.53 per 5 ng/m3), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m3), PM10 S (1.58; 1.03-2.44 per 200 ng/m3), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m3) and PM10 K (1.17; 1.02-1.33 per 100 ng/m3). In two-pollutant models, associations between PM10 and PM2.5 and lung cancer were largely explained by PM2.5 S. Conclusions: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important. © 2015 Elsevier Ltd.
Published: 2016

41. Circulating Folate and Vitamin B12 and Risk of Prostate Cancer: A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls

Author: Price, A.J. Travis, R.C. Appleby, P.N. Albanes, D. Barricarte Gurrea, A. Bjørge, T. Bueno-de-Mesquita, H.B. Chen, C. Donovan, J. Gislefoss, R. Goodman, G. Gunter, M. Hamdy, F.C. Johansson, M. King, I.B. Kühn, T. Männistö, S. Martin, R.M. Meyer, K. Neal, D.E. Neuhouser, M.L. Nygård, O. Stattin, P. Tell, G.S. Trichopoulou, A. Tumino, R. Ueland, P.M. Ulvik, A. de Vogel, S. Vollset, S.E. Weinstein, S.J. Key, T.J. Allen, N.E. on behalf of the Endogenous Hormones, Nutritional Biomarkers, Prostate Cancer Collaborative Group
Abstract: Background Folate and vitamin B12 are essential for maintaining DNA integrity and may influence prostate cancer (PCa) risk, but the association with clinically relevant, advanced stage, and high-grade disease is unclear. Objective To investigate the associations between circulating folate and vitamin B12 concentrations and risk of PCa overall and by disease stage and grade. Design, setting, and participants A study was performed with a nested case–control design based on individual participant data from six cohort studies including 6875 cases and 8104 controls; blood collection from 1981 to 2008, and an average follow-up of 8.9 yr (standard deviation 7.3). Odds ratios (ORs) of incident PCa by study-specific fifths of circulating folate and vitamin B12 were calculated using multivariable adjusted conditional logistic regression. Outcome measurements and statistical analysis Incident PCa and subtype by stage and grade. Results and limitations Higher folate and vitamin B12 concentrations were associated with a small increase in risk of PCa (ORs for the top vs bottom fifths were 1.13 [95% confidence interval (CI), 1.02–1.26], ptrend = 0.018, for folate and 1.12 [95% CI, 1.01–1.25], ptrend = 0.017, for vitamin B12), with no evidence of heterogeneity between studies. The association with folate varied by tumour grade (pheterogeneity 0.05). Use of single blood-sample measurements of folate and B12 concentrations is a limitation. Conclusions The association between higher folate concentration and risk of high-grade disease, not evident for low-grade disease, suggests a possible role for folate in the progression of clinically relevant PCa and warrants further investigation. Patient summary Folate, a vitamin obtained from foods and supplements, is important for maintaining cell health. In this study, however, men with higher blood folate levels were at greater risk of high-grade (more aggressive) prostate cancer compared with men with lower folate levels. Further research is needed to investigate the possible role of folate in the progression of this disease. © 2016 European Association of Urology
Published: 2016

42. Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Author: Hughes, D.J. Duarte-Salles, T. Hybsier, S. Trichopoulou, A. Stepien, M. Aleksandrova, K. Overvad, K. Tjønneland, A. Olsen, A. Affret, A. Fagherazzi, G. Boutron-Ruault, M.-C. Katzke, V. Kaaks, R. Boeing, H. Bamia, C. Lagiou, P. Peppa, E. Palli, D. Krogh, V. Panico, S. Tumino, R. Sacerdote, C. Bueno-De-Mesquita, H.B. Peeters, P.H. Engeset, D. Weiderpass, E. Lasheras, C. Agudo, A. Sánchez, M.J. Navarro, C. Ardanaz, E. Dorronsoro, M. Hemmingsson, O. Wareham, N.J. Khaw, K.-T. Bradbury, K.E. Cross, A.J. Gunter, M. Riboli, E. Romieu, I. Schomburg, L. Jenab, M.
Abstract: Selenium status is suboptimal in many Europeans and may be a risk factor for the development of various cancers, including those of the liver and biliary tract. Objective: We wished to examine whether selenium status in advance of cancer onset is associated with hepatobiliary cancers in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Design: We assessed prediagnostic selenium status by measuring serum concentrations of selenium and selenoprotein P (SePP; the major circulating selenium transfer protein) and examined the association with hepatocellular carcinoma (HCC; n = 121), gallbladder and biliary tract cancers (GBTCs; n = 100), and intrahepatic bile duct cancer (IHBC; n = 40) risk in a nested case-control design within the EPIC study. Selenium was measured by total reflection X-ray fluorescence, and SePP was determined by a colorimetric sandwich ELISA. Multivariable ORs and 95% CIs were calculated by using conditional logistic regression. Results: HCC and GBTC cases, but not IHBC cases, showed significantly lower circulating selenium and SePP concentrations than their matched controls. Higher circulating selenium was associated with a significantly lower HCC risk (OR per 20-mg/L increase: 0.41; 95% CI: 0.23, 0.72) but not with the risk of GBTC or IHBC. Similarly, higher SePP concentrations were associated with lowered HCC risk only in both the categorical and continuous analyses (HCC: P-trend ≤ 0.0001; OR per 1.5-mg/L increase: 0.37; 95% CI: 0.21, 0.63). Conclusion: These findings from a large prospective cohort provide evidence that suboptimal selenium status in Europeans may be associated with an appreciably increased risk of HCC development. © 2016 American Society for Nutrition.
Published: 2016

43. Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

Author: Lesseur, C. Diergaarde, B. Olshan, A.F. Wünsch-Filho, V. Ness, A.R. Liu, G. Lacko, M. Eluf-Neto, J. Franceschi, S. Lagiou, P. Macfarlane, G.J. Richiardi, L. Boccia, S. Polesel, J. Kjaerheim, K. Zaridze, D. Johansson, M. Menezes, A.M. Curado, M.P. Robinson, M. Ahrens, W. Canova, C. Znaor, A. Castellsagué, X. Conway, D.I. Holcátová, I. Mates, D. Vilensky, M. Healy, C.M. Szeszenia-Dabrowska, N. Fabiánová, E. Lissowska, J. Grandis, J.R. Weissler, M.C. Tajara, E.H. Nunes, F.D. De Carvalho, M.B. Thomas, S. Hung, R.J. Peters, W.H.M. Herrero, R. Cadoni, G. Bueno-De-Mesquita, H.B. Steffen, A. Agudo, A. Shangina, O. Xiao, X. Gaborieau, V. Chabrier, A. Anantharaman, D. Boffetta, P. Amos, C.I. McKay, J.D. Brennan, P.
Abstract: We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10 â'8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci - 9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1∗1301-HLA-DQA1∗0103-HLA-DQB1∗0603 (odds ratio (OR) = 0.59, P = 2.7 × 10-9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers. © 2016 Nature America, Inc. part of Springer Nature, All Rights reserved.
Published: 2016

44. Physical activity and risk of Amyotrophic Lateral Sclerosis in a prospective cohort study

Author: Gallo, V. Vanacore, N. Bueno-de-Mesquita, H.B. Vermeulen, R. Brayne, C. Pearce, N. Wark, P.A. Ward, H.A. Ferrari, P. Jenab, M. Andersen, P.M. Wennberg, P. Wareham, N. Katzke, V. Kaaks, R. Weiderpass, E. Peeters, P.H. Mattiello, A. Pala, V. Barricante, A. Chirlaque, M.-D. Travier, N. Travis, R.C. Sanchez, M.-J. Pessah-Rasmussen, H. Petersson, J. Tjønneland, A. Tumino, R. Quiros, J.R. Trichopoulou, A. Kyrozis, A. Oikonomidou, D. Masala, G. Sacerdote, C. Arriola, L. Boeing, H. Vigl, M. Claver-Chapelon, F. Middleton, L. Riboli, E. Vineis, P.
Abstract: Previous case–control studies have suggested a possible increased risk of Amyotrophic Lateral Sclerosis (ALS) with physical activity (PA), but this association has never been studied in prospective cohort studies. We therefore assessed the association between PA and risk of death from ALS in the European Prospective Investigation into Cancer and Nutrition. A total of 472,100 individuals were included in the analysis, yielding 219 ALS deaths. At recruitment, information on PA was collected thorough standardised questionnaires. Total PA was expressed by the Cambridge Physical Activity Index (CPAI) and analysed in relation to ALS mortality, using Cox hazard models. Interactions with age, sex, and anthropometric measures were assessed. Total PA was weakly inversely associated with ALS mortality with a borderline statistically significant trend across categories (p = 0.042), with those physically active being 33 % less likely to die from ALS compared to those inactive: HR = 0.67 (95 % CI 0.42–1.06). Anthropometric measures, sex, and age did not modify the association with CPAI. The present study shows a slightly decreased—not increased like in case–control studies—risk of dying from ALS in those with high levels of total PA at enrolment. This association does not appear confounded by age, gender, anthropometry, smoking, and education. Ours was the first prospective cohort study on ALS and physical activity. © 2016, The Author(s).
Published: 2016

45. Pre-diagnostic vitamin D concentrations and cancer risks in older individuals: an analysis of cohorts participating in the CHANCES consortium

Author: Ordóñez-Mena, J.M. Schöttker, B. Fedirko, V. Jenab, M. Olsen, A. Halkjær, J. Kampman, E. de Groot, L. Jansen, E. Bueno-de-Mesquita, H.B. Peeters, P.H. Siganos, G. Wilsgaard, T. Perna, L. Holleczek, B. Pettersson-Kymmer, U. Orfanos, P. Trichopoulou, A. Boffetta, P. Brenner, H.
Abstract: The associations of circulating 25-hydroxyvitamin D [25(OH)D] concentrations with total and site-specific cancer incidence have been examined in several epidemiological studies with overall inconclusive findings. Very little is known about the association of vitamin D with cancer incidence in older populations. We assessed the association of pre-diagnostic serum 25(OH)D levels with incidence of all cancers combined and incidence of lung, colorectal, breast, prostate and lymphoid malignancies among older adults. Pre-diagnostic 25(OH)D concentrations and cancer incidence were available in total for 15,486 older adults (mean age 63, range 50–84 years) participating in two cohort studies: ESTHER (Germany) and TROMSØ (Norway); and a subset of previously published nested-case control data from a another cohort study: EPIC-Elderly (Greece, Denmark, Netherlands, Spain and Sweden) from the CHANCES consortium on health and aging. Cox proportional hazards or logistic regression were used to derive multivariable adjusted hazard and odds ratios, respectively, and their 95 % confidence intervals across 25(OH)D categories. Meta-analyses with random effects models were used to pool study-specific risk estimates. Overall, lower 25(OH)D concentrations were not significantly associated with increased incidence of most of the cancers assessed. However, there was some evidence of increased breast cancer and decreased lymphoma risk with higher 25(OH)D concentrations. Our meta-analyses with individual participant data from three large European population-based cohort studies provide at best limited support for the hypothesis that vitamin D may have a major role in cancer development and prevention among European older adults. © 2015, Springer Science+Business Media Dordrecht.
Published: 2016

46. WHO guidelines for a healty diet and mortality from cardiovascular disease in European and American elderly: the CHANCES project

Author: Jankovic, N., Geelen, A., Streppel, M.T., de Groot, C.P.G.M., Kiefte-de Jong, J.C., Bueno-de Mesquita, H.B., Kampman, E., and Feskens, E.J.M.
Subjects: Global Nutrition, Aging, Meta-analysis, Wereldvoeding, Nutrition and Disease, Voeding en Ziekte, Cohort, Cardiovascular disease, CHANCES, VLAG
Abstract: Background: Cardiovascular disease (CVD) represents a leading cause of mortality worldwide, especially in the elderly. Lowering the number of CVD deaths requires preventive strategies targeted on the elderly. Objective: The objective was to generate evidence on the association between WHO dietary recommendations and mortality from CVD, coronary artery disease (CAD), and stroke in the elderly aged =60 y. Design: We analyzed data from 10 prospective cohort studies from Europe and the United States comprising a total sample of 281,874 men and women free from chronic diseases at baseline. Components of the Healthy Diet Indicator (HDI) included saturated fatty acids, polyunsaturated fatty acids, mono- and disaccharides, protein, cholesterol, dietary fiber, and fruit and vegetables. Cohort-specific HRs adjusted for sex, education, smoking, physical activity, and energy and alcohol intakes were pooled by using a random-effects model. Results: During 3,322,768 person-years of follow-up, 12,492 people died of CVD. An increase of 10 HDI points (complete adherence to an additional WHO guideline) was, on average, not associated with CVD mortality (HR: 0.94; 95% CI: 0.86, 1.03), CAD mortality (HR: 0.99; 95% CI: 0.85, 1.14), or stroke mortality (HR: 0.95; 95% CI: 0.88, 1.03). However, after stratification of the data by geographic region, adherence to the HDI was associated with reduced CVD mortality in the southern European cohorts (HR: 0.87; 95% CI: 0.79, 0.96; I2 = 0%) and in the US cohort (HR: 0.85; 95% CI: 0.83, 0.87; I2 = not applicable). Conclusion: Overall, greater adherence to the WHO dietary guidelines was not significantly associated with CVD mortality, but the results varied across regions. Clear inverse associations were observed in elderly populations in southern Europe and the United States.
Published: 2015

47. Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort

Author: Engeset, D. Braaten, T. Teucher, B. Kühn, T. Bueno-de-Mesquita, H.B. Leenders, M. Agudo, A. Bergmann, M.M. Valanou, E. Naska, A. Trichopoulou, A. Key, T.J. Crowe, F.L. Overvad, K. Sonestedt, E. Mattiello, A. Peeters, P.H. Wennberg, M. Jansson, J.H. Boutron-Ruault, M.-C. Dossus, L. Dartois, L. Li, K. Barricarte, A. Ward, H. Riboli, E. Agnoli, C. Huerta, J.M. Sánchez, M.-J. Tumino, R. Altzibar, J.M. Vineis, P. Masala, G. Ferrari, P. Muller, D.C. Johansson, M. Luisa Redondo, M. Tjønneland, A. Olsen, A. Olsen, K.S. Brustad, M. Skeie, G. Lund, E.
Abstract: Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992–1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99 % confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p
Published: 2015

48. Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: The European prospective investigation into cancer and nutrition study (EPIC)

Author: Ekelund, U. Ward, H.A. Norat, T. Luan, J. May, A.M. Weiderpass, E. Sharp, S.J. Overvad, K. Østergaard, J.N. Tjønneland, A. Johnsen, N.F. Mesrine, S. Fournier, A. Fagherazzi, G. Trichopoulou, A. Lagiou, P. Trichopoulos, D. Li, K. Kaaks, R. Ferrari, P. Licaj, I. Jenab, M. Bergmann, M. Boeing, H. Palli, D. Sieri, S. Panico, S. Tumino, R. Vineis, P. Peeters, P.H. Monnikhof, E. Bueno-De-Mesquita, H.B. Quirós, J.R. Agudo, A. Sánchez, M.-J. Huerta, J.M. Ardanaz, E. Arriola, L. Hedblad, B. Wirfält, E. Sund, M. Johansson, M. Key, T.J. Travis, R.C. Khaw, K.-T. Brage, S. Wareham, N.J. Riboli, E.
Abstract: Background: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear. Objective: We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures. Design: This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Centerspecific PAF associated with inactivity, body mass index (BMI; in kg/m2) (>30), and WC (≥102 cm for men, ≥88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures. Results: Significant interactions (PA × BMI and PA × WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16-30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity. Conclusion: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health. © 2015 American Society for Nutrition.
Published: 2015

49. Association of CRP genetic variants with blood concentrations of C-reactive protein and colorectal cancer risk

Author: Nimptsch, K. Aleksandrova, K. Boeing, H. Janke, J. Lee, Y.-A. Jenab, M. Bueno-De-Mesquita, H.B. Jansen, E.H.J.M. Tsilidis, K.K. Trichopoulou, A. Weiderpass, E. Wu, C. Overvad, K. Tjønneland, A. Boutron-Ruault, M.-C. Dossus, L. Racine, A. Kaaks, R. Canzian, F. Lagiou, P. Trichopoulos, D. Palli, D. Agnoli, C. Tumino, R. Vineis, P. Panico, S. Johansson, A. Van Guelpen, B. Khaw, K.-T. Wareham, N. Peeters, P.H. Quirós, J.R. García, A.V. Molina-Montes, E. Dorronsoro, M. Chirlaque, M.-D. Gurrea, A.B. Key, T.J. Duarte-Salles, T. Stepien, M. Gunter, M.J. Riboli, E. Pischon, T.
Abstract: High blood concentrations of C-reactive protein (CRP) have been associated with elevated risk of colorectal cancer in several prospective studies including the European Prospective Investigation into Cancer and Nutrition (EPIC), but it is unknown whether these observations reflect a causal relationship. We aimed to investigate whether CRP genetic variants associated with lifelong higher CRP concentrations translate into higher colorectal cancer risk. We conducted a prospective nested case-control study within EPIC including 727 cases diagnosed between 1992 and 2003 and 727 matched controls selected according to an incidence-density sampling protocol. Baseline CRP concentrations were measured in plasma samples by a high sensitivity assay. Tagging single nucleotide polymorphisms (SNPs) in the CRP gene (rs1205, rs1800947, rs1130864, rs2808630, rs3093077) were identified via HapMap. The causal effect of CRP on colorectal cancer risk was examined in a Mendelian Randomization approach utilizing multiple CRP genetic variants as instrumental variables. The SNPs rs1205, rs1800947, rs1130864 and rs3093077 were significantly associated with CRP concentrations and were incorporated in a CRP allele score which was associated with 13% higher CRP concentrations per allele count (95% confidence interval 8-19%). Using the CRPscore as instrumental variable, genetically twofold higher CRP concentrations were associated with higher risk of colorectal cancer (odds ratio 1.74, 95% confidence interval 1.06-2.85). Similar observations were made using alternative definitions of instrumental variables. Our findings give support to the hypothesis that elevated circulating CRP may play a direct role in the etiology of colorectal cancer. © 2014 UICC.
Published: 2015

50. Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer

Author: Childs, E.J. Mocci, E. Campa, D. Bracci, P.M. Gallinger, S. Goggins, M. Li, D. Neale, R.E. Olson, S.H. Scelo, G. Amundadottir, L.T. Bamlet, W.R. Bijlsma, M.F. Blackford, A. Borges, M. Brennan, P. Brenner, H. Bueno-De-Mesquita, H.B. Canzian, F. Capurso, G. Cavestro, G.M. Chaffee, K.G. Chanock, S.J. Cleary, S.P. Cotterchio, M. Foretova, L. Fuchs, C. Funel, N. Gazouli, M. Hassan, M. Herman, J.M. Holcatova, I. Holly, E.A. Hoover, R.N. Hung, R.J. Janout, V. Key, T.J. Kupcinskas, J. Kurtz, R.C. Landi, S. Lu, L. Malecka-Panas, E. Mambrini, A. Mohelnikova-Duchonova, B. Neoptolemos, J.P. Oberg, A.L. Orlow, I. Pasquali, C. Pezzilli, R. Rizzato, C. Saldia, A. Scarpa, A. Stolzenberg-Solomon, R.Z. Strobel, O. Tavano, F. Vashist, Y.K. Vodicka, P. Wolpin, B.M. Yu, H. Petersen, G.M. Risch, H.A. Klein, A.P.
Abstract: Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 × 10-14), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 × 10-8) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 × 10-8). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 × 10-9), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk. © 2015 Nature America, Inc. All rights reserved.
Published: 2015

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