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  • 701. Wu, Chen
    et al.
    Kraft, Peter
    Stolzenberg-Solomon, Rachael
    Steplowski, Emily
    Brotzman, Michelle
    Xu, Mousheng
    Mudgal, Poorva
    Amundadottir, Laufey
    Arslan, Alan A
    Bueno-de-Mesquita, H Bas
    Gross, Myron
    Helzlsouer, Kathy
    Jacobs, Eric J
    Kooperberg, Charles
    Petersen, Gloria M
    Zheng, Wei
    Albanes, Demetrius
    Boutron-Ruault, Marie-Christine
    Buring, Julie E
    Canzian, Federico
    Cao, Guangwen
    Duell, Eric J
    Elena, Joanne W
    Gaziano, J Michael
    Giovannucci, Edward L
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hutchinson, Amy
    Hunter, David J
    Jenab, Mazda
    Jiang, Guoliang
    Khaw, Kay-Tee
    Lacroix, Andrea
    Li, Zhaoshen
    Mendelsohn, Julie B
    Panico, Salvatore
    Patel, Alpa V
    Qian, Zhi Rong
    Riboli, Elio
    Sesso, Howard
    Shen, Hongbing
    Shu, Xiao-Ou
    Tjonneland, Anne
    Tobias, Geoffrey S
    Trichopoulos, Dimitrios
    Virtamo, Jarmo
    Visvanathan, Kala
    Wactawski-Wende, Jean
    Wang, Chengfeng
    Yu, Kai
    Zeleniuch-Jacquotte, Anne
    Chanock, Stephen
    Hoover, Robert
    Hartge, Patricia
    Fuchs, Charles S
    Lin, Dongxin
    Wolpin, Brian M
    Genome-wide association study of survival in patients with pancreatic adenocarcinoma2014In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, no 1, p. 152-160Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVE: Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. METHODS: We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p≤10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). RESULTS: In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63×10(-7)), rs981621 (p=1.65×10(-7)) and rs16861827 (p=3.75×10(-7)), respectively. 131 SNPs with p≤10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72×10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. CONCLUSIONS: Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.

  • 702. Xun, Wei Wei
    et al.
    Brennan, Paul
    Tjonneland, Anne
    Vogel, Ulla
    Overvad, Kim
    Kaaks, Rudolf
    Canzian, Federico
    Boeing, Heiner
    Trichopoulou, Antonia
    Oustoglou, Erifili
    Giotaki, Zoi
    Johansson, Mattias
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, H Bas
    Peeters, Petra H M
    Lund, Eiliv
    Kumle, Merethe
    Rodríguez, Laudina
    Agudo, Antonio
    Sánchez, Maria-José
    Arriola, Larraitz
    Chirlaque, María-Dolores
    Barricarte, Aurelio
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Key, Tim
    Riboli, Elio
    Vineis, Paolo
    Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC).2011In: Mutagenesis, ISSN 0267-8357, E-ISSN 1464-3804, Vol. 26, no 5, p. 657-666Article in journal (Refereed)
    Abstract [en]

    The single-nucleotide polymorphisms (SNPs) rs402710 (5p15.33), rs16969968 and rs8034191 (15q25.1) have been consistently identified by genome-wide association studies (GWAS) as significant predictors of lung cancer risk, while rs4324798 (6p22.1) was previously found to influence survival time in small-cell lung cancer (SCLC) patients. Using the same population of one of the original GWAS, we investigated whether the selected SNPs and 31 others (also identified in GWAS) influence survival time, assuming an additive model. The effect of each polymorphism on all cause survival was estimated in 1094 lung cancer patients, and lung cancer-specific survival in 763 patients, using Cox regression adjusted for a priori confounders and competing causes of death where appropriate. Overall, after 1558 person-years of post-diagnostic follow-up, 874 deaths occurred from all causes, including 690 from lung cancer. In the lung cancer-specific survival analysis (1102 person-years), only rs7452888 (6q27) and rs2710994 (7p15.3) modified survival, with adjusted hazard ratios of 1.19 (P = 0.009) and 1.32 (P = 0.011) respectively, taking competing risks into account. Some weak associations were identified in subgroup analysis for rs16969968 and rs8034191 (15q25.1) and rs4324798 (6p22.1) and survival in never-smokers, as well as for rs402710 in current smokers and SCLC patients. In conclusion, rs402710 (5p15.33), rs16969968 and rs8034191 (both 15q25.1) and rs4324798 (6p22.1) were found to be unrelated to survival times in this large cohort of lung cancer patients, regardless of whether the cause of death was from lung cancer or not. However, rs7452888 (6q27) was identified as a possible candidate SNP to influence lung cancer survival, while stratified analysis hinted at a possible role for rs8034191, rs16969968 (15q25.1) and rs4324798 (6p22.1) in influencing survival time in lung cancer patients who were never-smokers, based on a small sample.

  • 703. Zamaratskaia, Galia
    et al.
    Mhd Omar, Nor Adila
    Brunius, Carl
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Jan-Erik
    Andersson, Sven-Olof
    Larsson, Anders
    Åman, Per
    Landberg, Rikard
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden; Department of Biology and Biological Engineering, Division of Food and Nutrition Science, Chalmers University of Technology, Gothenburg, Sweden.
    Consumption of whole grain/bran rye instead of refined wheat decrease concentrations of TNF-R2, e-selectin, and endostatin in an exploratory study in men with prostate cancer2020In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 39, no 1, p. 159-165Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Rye consumption has shown beneficial effects on prostate cancer tumors, as indicated by slower initial tumor growth in animal models and lowering of prostate-specific antigen (PSA) in humans. This study evaluated the effects of whole grain/bran rye consumption on low-grade inflammation and endothelial function biomarkers in men with prostate cancer.

    METHODS: Seventeen men with untreated, low-grade prostate cancer consumed 485 g rye whole grain and bran products (RP) per day or refined wheat products with added cellulose (WP) in a randomized crossover design. Fasting blood samples were taken before and after 2, 4, and 6 weeks of treatment.

    RESULTS: Concentrations of tumor nuclear factor-receptor 2 (TNF-R2), e-selectin, and endostatin were significantly lower after consumption of the RP diet compared with WP (p < 0.05). Cathepsin S concentration was positively correlated to TNF-R2 and endostatin concentrations across all occasions. Strong correlations were consistently found between intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and between interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA). No effect of intervention was found in 92 inflammation-related protein biomarkers measured in a proximity extension assay.

    CONCLUSIONS: RP diet lowered TNF-R2, e-selectin, and endostatin, compared with WP in men with prostate cancer. These effects were accompanied by a reduction in PSA.

  • 704. Zamora-Ros, R.
    et al.
    Knaze, V.
    Lujan-Barroso, L.
    Kuhnle, G. G. C.
    Mulligan, A. A.
    Touillaud, M.
    Slimani, N.
    Romieu, I.
    Powell, N.
    Tumino, R.
    Peeters, P. H. M.
    de Magistris, M. S.
    Ricceri, F.
    Sonestedt, E.
    Drake, I.
    Hjartaker, A.
    Skie, G.
    Mouw, T.
    Wark, P. A.
    Romaguera, D.
    Bueno-de-Mesquita, H. B.
    Ros, M.
    Molina, E.
    Sieri, S.
    Quiros, J. R.
    Huerta, J. M.
    Tjonneland, A.
    Halkjaer, J.
    Masala, G.
    Teucher, B.
    Kaas, R.
    Travis, R. C.
    Dilis, V.
    Benetou, V.
    Trichopoulou, A.
    Amiano, P.
    Ardanaz, E.
    Boeing, H.
    Foerster, J.
    Clavel-Chapelon, F.
    Fagherazzi, G.
    Perquier, F.
    Johansson, Gerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Cassidy, A.
    Overvad, K.
    Gonzalez, C. A.
    Dietary intakes and food sources of phytoestrogens in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24-hour dietary recall cohort2012In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 66, no 8, p. 932-941Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Phytoestrogens are estradiol-like natural compounds found in plants that have been associated with protective effects against chronic diseases, including some cancers, cardiovascular diseases and osteoporosis. The purpose of this study was to estimate the dietary intake of phytoestrogens, identify their food sources and their association with lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. SUBJECTS/METHODS: Single 24-hour dietary recalls were collected from 36 037 individuals from 10 European countries, aged 35-74 years using a standardized computerized interview programe (EPIC-Soft). An ad hoc food composition database on phytoestrogens (isoflavones, lignans, coumestans, enterolignans and equol) was compiled using data from available databases, in order to obtain and describe phytoestrogen intakes and their food sources across 27 redefined EPIC centres. RESULTS: Mean total phytoestrogen intake was the highest in the UK health-conscious group (24.9 mg/day in men and 21.1 mg/day in women) whereas lowest in Greece (1.3 mg/day) in men and Spain-Granada (1.0 mg/day) in women. Northern European countries had higher intakes than southern countries. The main phytoestrogen contributors were isoflavones in both UK centres and lignans in the other EPIC cohorts. Age, body mass index, educational level, smoking status and physical activity were related to increased intakes of lignans, enterolignans and equol, but not to total phytoestrogen, isoflavone or coumestan intakes. In the UK cohorts, the major food sources of phytoestrogens were soy products. In the other EPIC cohorts the dietary sources were more distributed, among fruits, vegetables, soy products, cereal products, non-alcoholic and alcoholic beverages. CONCLUSIONS: There was a high variability in the dietary intake of total and phytoestrogen subclasses and their food sources across European regions.

  • 705. Zamora-Ros, R
    et al.
    Sacerdote, C
    Ricceri, F
    Weiderpass, E
    Roswall, N
    Buckland, G
    St-Jules, D E
    Overvad, K
    Kyrø, C
    Fagherazzi, G
    Kvaskoff, M
    Severi, G
    Chang-Claude, J
    Kaaks, R
    Nöthlings, U
    Trichopoulou, A
    Naska, A
    Trichopoulos, D
    Palli, D
    Grioni, S
    Mattiello, A
    Tumino, R
    Gram, I T
    Engeset, D
    Huerta, J M
    Molina-Montes, E
    Argüelles, M
    Amiano, P
    Ardanaz, E
    Ericson, U
    Lindkvist, B
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Arctic Research Centre at Umeå University.
    Kiemeney, L A
    Ros, M
    Bueno-de-Mesquita, H B
    Peeters, P H M
    Khaw, K-T
    Wareham, N J
    Knaze, V
    Romieu, I
    Scalbert, A
    Brennan, P
    Wark, P
    Vineis, P
    Riboli, E
    González, C A
    Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study2014In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 111, no 9, p. 1870-1880Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases. RESULTS: During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC. CONCLUSIONS: Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.

  • 706. Zamora-Ros, Raul
    et al.
    Barupal, Dinesh K.
    Rothwell, Joseph A.
    Jenab, Mazda
    Fedirko, Veronika
    Romieu, Isabelle
    Aleksandrova, Krasimira
    Overvad, Kim
    Kyro, Cecilie
    Tjonneland, Anne
    Affret, Aurelie
    His, Mathilde
    Boutron-Ruault, Marie-Christine
    Katzke, Verena
    Kuehn, Tilman
    Boeing, Heiner
    Trichopoulou, Antonia
    Naska, Androniki
    Kritikou, Maria
    Saieva, Calogero
    Agnoli, Claudia
    de Magistris, Maria Santucci
    Tumino, Rosario
    Fasanelli, Francesca
    Weiderpass, Elisabete
    Skeie, Guri
    Merino, Susana
    Jakszyn, Paula
    Sanchez, Maria-Jose
    Dorronsoro, Miren
    Navarro, Carmen
    Ardanaz, Eva
    Sonestedt, Emily
    Ericson, Ulrika
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Arctic Research Centre at Umeå University.
    Bodén, Stina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bueno-de-Mesquita, H. B. (as)
    Peeters, Petra H.
    Perez-Cornago, Aurora
    Wareham, Nicholas J.
    Khaw, Kay-Thee
    Freisling, Heinz
    Cross, Amanda J.
    Riboli, Elio
    Scalbert, Augustin
    Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, no 8, p. 1836-1844Article in journal (Refereed)
    Abstract [en]

    Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of development of CRC, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477,312 adult men and women were recruited in 10 European countries. At baseline, dietary intakes of total flavonoids and individual subclasses were estimated using centre-specific validated dietary questionnaires and composition data from the Phenol-Explorer database. During an average of 11 years of follow-up, 4,517 new cases of primary CRC were identified, of which 2,869 were colon (proximal = 1,298 and distal = 1,266) and 1,648 rectal tumours. No association was found between total flavonoid intake and the risk of overall CRC (HR for comparison of extreme quintiles 1.05, 95% CI 0.93-1.18; p-trend = 0.58) or any CRC subtype. No association was also observed with any intake of individual flavonoid subclasses. Similar results were observed for flavonoid intake expressed as glycosides or aglycone equivalents. Intake of total flavonoids and flavonoid subclasses, as estimated from dietary questionnaires, did not show any association with risk of CRC development.

  • 707. Zamora-Ros, Raul
    et al.
    Cayssials, Valerie
    Jenab, Mazda
    Rothwell, Joseph A.
    Fedirko, Veronika
    Aleksandrova, Krasimira
    Tjønneland, Anne
    Kyrø, Cecilie
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Carbonnel, Franck
    Mahamat-Saleh, Yahya
    Kaaks, Rudolf
    Kühn, Tilman
    Boeing, Heiner
    Trichopoulou, Antonia
    Valanou, Elissavet
    Vasilopoulou, Effie
    Masala, Giovanna
    Pala, Valeria
    Panico, Salvatore
    Tumino, Rosario
    Ricceri, Fulvio
    Weiderpass, Elisabete
    Lukic, Marko
    Sandanger, Torkjel M.
    Lasheras, Cristina
    Agudo, Antonio
    Sánchez, Maria-Jose
    Amiano, Pilar
    Navarro, Carmen
    Ardanaz, Eva
    Sonestedt, Emily
    Ohlsson, Bodil
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Rutegård, Martin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Bueno-de-Mesquita, Bas
    Peeters, Petra H.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Bradbury, Kathryn
    Freisling, Heinz
    Romieu, Isabelle
    Cross, Amanda J.
    Vineis, Paolo
    Scalbert, Augustin
    Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort2018In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 33, no 11, p. 1063-1075Article in journal (Refereed)
    Abstract [en]

    Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HRlog2 = 1.06, 95% CI 0.99–1.14) or in men (HRlog2 = 0.97, 95% CI 0.90–1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HRlog2 = 0.91, 95% CI 0.85–0.97) and positively associated with rectal cancer in women (HRlog2 = 1.10, 95% CI 1.02–1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.

  • 708. Zamora-Ros, Raul
    et al.
    Knaze, Viktoria
    Lujan-Barroso, Leila
    Slimani, Nadia
    Romieu, Isabelle
    Fedirko, Veronika
    de Magistris, Maria Santucci
    Ericson, Ulrica
    Amiano, Pilar
    Trichopoulou, Antonia
    Dilis, Vardis
    Naska, Androniki
    Engeset, Dagrun
    Skeie, Guri
    Cassidy, Aedin
    Overvad, Kim
    Peeters, Petra H. M.
    Maria Huerta, Jose
    Sanchez, Maria-Jose
    Ramon Quiros, J.
    Sacerdote, Carlotta
    Grioni, Sara
    Tumino, Rosario
    Johansson, Gerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Drake, Isabel
    Crowe, Francesca L.
    Barricarte, Aurelio
    Kaaks, Rudolf
    Teucher, Birgit
    Bueno-de-Mesquita, H. Bas
    van Rossum, Caroline T. M.
    Norat, Teresa
    Romaguera, Dora
    Vergnaud, Anne-Claire
    Tjonneland, Anne
    Halkjaer, Jytte
    Clavel-Chapelon, Francoise
    Boutron-Ruault, Marie-Christine
    Touillaud, Marina
    Salvini, Simonetta
    Khaw, Kay-Thee
    Wareham, Nicholas
    Boeing, Heiner
    Foerster, Jana
    Riboli, Elio
    Gonzalez, Carlos A.
    Estimated dietary intakes of flavonols, flavanones and flavones in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24 hour dietary recall cohort2011In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 106, no 12, p. 1915-1925Article in journal (Refereed)
    Abstract [en]

    Flavonols, flavanones and flavones (FLAV) are sub-classes of flavonoids that exert cardioprotective and anti-carcinogenic properties in vitro and in vivo. We aimed to estimate the FLAV dietary intake, their food sources and associated lifestyle factors in ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. FLAV intake and their food sources for 36 037 subjects, aged between 35 and 74 years, in twenty-seven study centres were obtained using standardised 24 h dietary recall software (EPIC-SOFT). An ad hoc food composition database on FLAV was compiled using data from US Department of Agriculture and Phenol-Explorer databases and was expanded using recipes, estimations and flavonoid retention factors in order to increase its correspondence with the 24 h dietary recall. Our results showed that the highest FLAV-consuming centre was the UK health-conscious group, with 130.9 and 97.0 mg/d for men and women, respectively. The lowest FLAV intakes were 36.8 mg/d in men from Umea and 37.2 mg/d in women from Malmo (Sweden). The flavanone sub-class was the main contributor to the total FLAV intake ranging from 46.6 to 52.9% depending on the region. Flavonols ranged from 38.5 to 47.3% and flavones from 5.8 to 8.6%. FLAV intake was higher in women, non-smokers, increased with level of education and physical activity. The major food sources were citrus fruits and citrus-based juices (especially for flavanones), tea, wine, other fruits and some vegetables. We concluded that the present study shows heterogeneity in intake of these three sub-classes of flavonoids across European regions and highlights differences by sex and other sociodemographic and lifestyle factors.

  • 709. Zamora-Ros, Raul
    et al.
    Knaze, Viktoria
    Lujan-Barroso, Leila
    Slimani, Nadia
    Romieu, Isabelle
    Touillaud, Marina
    Kaaks, Rudolf
    Teucher, Birgit
    Mattiello, Amalia
    Grioni, Sara
    Crowe, Francesca
    Boeing, Heiner
    Foerster, Jana
    Ramon Quiros, J.
    Molina, Esther
    Maria Huerta, Jose
    Engeset, Dagrun
    Skeie, Guri
    Trichopoulou, Antonia
    Dilis, Vardis
    Tsiotas, Konstantinos
    Peeters, Petra H. M.
    Khaw, Kay-Thee
    Wareham, Nicholas
    Bueno-de-Mesquita, Bas
    Ocke, Marga C.
    Olsen, Anja
    Tjonneland, Anne
    Tumino, Rosario
    Johansson, Gerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Ardanaz, Eva
    Sacerdote, Carlotta
    Sonestedt, Emily
    Ericson, Ulrika
    Clavel-Chapelon, Francoise
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Salvini, Simonetta
    Amiano, Pilar
    Riboli, Elio
    Gonzalez, Carlos A.
    Estimation of the intake of anthocyanidins and their food sources in the European Prospective Investigation into Cancer and Nutrition (EPIC) study2011In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 106, no 7, p. 1090-1099Article in journal (Refereed)
    Abstract [en]

    Anthocyanidins are bioactive flavonoids with potential health-promoting effects. These may vary among single anthocyanidins considering differences in their bioavailability and some of the mechanisms involved. The aim of the present study was to estimate the dietary intake of anthocyanidins, their food sources and the lifestyle factors (sex, age, BMI, smoking status, educational level and physisical activity) involved among twenty-seven centres in ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthocyanidin intake and their food sources for 36 037 subjects, aged between 35 and 74 years, in twenty-seven redefined centres were obtained using standardised 24 h dietary recall software (EPIC-SOFT). An ad hoc food composition database on anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin) was compiled using data from the US Department of Agriculture and Phenol-Explorer databases and was expanded by adding recipes, estimated values and cooking factors. For men, the total anthocyanidin mean intake ranged from 19.83 (SE 1.53) mg/d (Bilthoven, The Netherlands) to 64.88 (SE 1.86) mg/d (Turin, Italy), whereas for women the range was 18.73 (SE 2.80) mg/d (Granada, Spain) to 44.08 (SE 2.45) mg/d (Turin, Italy). A clear south to north gradient intake was observed. Cyanidins and malvidins were the main anthocynidin contributors depending on the region and sex. Anthocyanidin intake was higher in non-obese older females, non-smokers, and increased with educational level and physical activity. The major food sources were fruits, wine, non-alcoholic beverages and some vegetables. The present study shows differences in both total and individual anthocyanidin intakes and various lifestyle factors throughout Europe, with some geographical variability in their food sources.

  • 710. Zamora-Ros, Raul
    et al.
    Knaze, Viktoria
    Rothwell, Joseph A.
    Hémon, Bertrand
    Moskal, Aurelie
    Overvad, Kim
    Tjønneland, Anne
    Kyrø, Cecilie
    Fagherazzi, Guy
    Boutron-Ruault, Marie-Christine
    Touillaud, Marina
    Katzke, Verena
    Kühn, Tilman
    Boeing, Heiner
    Förster, Jana
    Trichopoulou, Antonia
    Valanou, Elissavet
    Peppa, Eleni
    Palli, Domenico
    Agnoli, Claudia
    Ricceri, Fulvio
    Tumino, Rosario
    de Magistris, Maria Santucci
    Peeters, Petra H. M.
    Bueno-de-Mesquita, H Bas
    Engeset, Dagrun
    Skeie, Guri
    Hjartåker, Anette
    Menéndez, Virginia
    Agudo, Antonio
    Molina-Montes, Esther
    Huerta, José María
    Barricarte, Aurelio
    Amiano, Pilar
    Sonestedt, Emily
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Arctic Research Centre at Umeå University.
    Landberg, Rikard
    Key, Timothy J.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Lu, Yunxia
    Slimani, Nadia
    Romieu, Isabelle
    Riboli, Elio
    Scalbert, Augustin
    Dietary polyphenol intake in Europe: the European Prospective Investigation into Cancer and Nutrition (EPIC) study2016In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 55, no 4, p. 1359-1375Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Polyphenols are plant secondary metabolites with a large variability in their chemical structure and dietary occurrence that have been associated with some protective effects against several chronic diseases. To date, limited data exist on intake of polyphenols in populations. The current cross-sectional analysis aimed at estimating dietary intakes of all currently known individual polyphenols and total intake per class and subclass, and to identify their main food sources in the European Prospective Investigation into Cancer and Nutrition cohort.

    METHODS: Dietary data at baseline were collected using a standardized 24-h dietary recall software administered to 36,037 adult subjects. Dietary data were linked with Phenol-Explorer, a database with data on 502 individual polyphenols in 452 foods and data on polyphenol losses due to cooking and food processing.

    RESULTS: Mean total polyphenol intake was the highest in Aarhus-Denmark (1786 mg/day in men and 1626 mg/day in women) and the lowest in Greece (744 mg/day in men and 584 mg/day in women). When dividing the subjects into three regions, the highest intake of total polyphenols was observed in the UK health-conscious group, followed by non-Mediterranean (non-MED) and MED countries. The main polyphenol contributors were phenolic acids (52.5-56.9 %), except in men from MED countries and in the UK health-conscious group where they were flavonoids (49.1-61.7 %). Coffee, tea, and fruits were the most important food sources of total polyphenols. A total of 437 different individual polyphenols were consumed, including 94 consumed at a level >1 mg/day. The most abundant ones were the caffeoylquinic acids and the proanthocyanidin oligomers and polymers.

    CONCLUSION: This study describes the large number of dietary individual polyphenols consumed and the high variability of their intakes between European populations, particularly between MED and non-MED countries.

  • 711. Zamora-Ros, Raul
    et al.
    Luján-Barroso, Leila
    Bueno-de-Mesquita, H Bas
    Dik, Vincent K
    Boeing, Heiner
    Steffen, Annika
    Tjønneland, Anne
    Olsen, Anja
    Bech, Bodil Hammer
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Fagherazzi, Guy
    Kuhn, Tilman
    Katzke, Verena
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Tumino, Rosario
    Panico, Salvatore
    Vineis, Paolo
    Grioni, Sara
    Palli, Domenico
    Weiderpass, Elisabete
    Skeie, Guri
    Huerta, José María
    Sánchez, María-José
    Argüelles, Marcial
    Amiano, Pilar
    Ardanaz, Eva
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Arctic Research Centre at Umeå University.
    Wallner, Bengt
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindkvist, Björn
    Wallström, Peter
    Peeters, Petra H M
    Key, Timothy J
    Khaw, Kay-Thee
    Wareham, Nicholas J
    Freisling, Heinz
    Stepien, Magdalena
    Ferrari, Pietro
    Gunter, Marc J
    Murphy, Neil
    Riboli, Elio
    González, Carlos A
    Tea and coffee consumption and risk of esophageal cancer: the European Prospective Investigation into Cancer and Nutrition (EPIC) study2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 6, p. 1470-1479Article in journal (Refereed)
    Abstract [en]

    Epidemiological data regarding tea and coffee consumption and risk of esophageal cancer (EC) is still inconclusive. We examined the association of tea and coffee consumption with EC risk among 442,143 men and women without cancer at baseline from 9 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC). Tea and coffee intakes were recorded using country-specific validated dietary questionnaires. Cox regression models were used to analyze the relationships between tea and coffee intake and EC risk. During a mean follow-up of 11.1 years, 339 participants developed EC, of which 142 were esophageal adenocarcinoma (EAC) and 174 were esophageal squamous cell carcinoma (ESCC). In the multivariable models, no significant associations between tea (mostly black tea), and coffee intake and risk of EC, EAC and ESCC were observed. In stratified analyses, among men coffee consumption was inversely related to ESCC (HR for comparison of extreme tertiles 0.42, 95% CI 0.20-0.88; P-trend=0.022), but not among women. In current smokers, a significant and inverse association was observed between ESCC risk and tea (HR 0.46, 95% CI 0.23-0.93; P-trend=0.053) and coffee consumption (HR 0.37, 95% CI 0.19-0.73; P-trend=0.011). However, no statistically significant findings were observed using the continuous variable (per 100mL/d). These data did not show a significant association between tea and coffee consumption and EC, EAC and ESCC, although a decreased risk of ESCC among men and current smokers is suggested, but need to be confirmed in further prospective studies including more cases.

  • 712. Zeleniuch-Jacquotte, A
    et al.
    Shore, R E
    Afanasyeva, Y
    Lukanova, A
    Sieri, S
    Koenig, K L
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Krogh, V
    Liu, M
    Ohlson, Nina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Muti, P
    Arslan, A A
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Berrino, F
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, P
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer2011In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 105, no 9, p. 1458-1464Article in journal (Refereed)
    Abstract [en]

    Background: It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful.

    Methods: We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16α-hydroxyestrone (2-OHE1 : 16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay.

    Results: Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16α-OHE1 ratio.

    Conclusion: Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.

  • 713. Zeleniuch-Jacquotte, Anne
    et al.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Micheli, Andrea
    Koenig, Karen L
    Lenner, Per
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Muti, Paola
    Shore, Roy E
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Odontology, Cariology.
    Krogh, Vittorio
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Afanasyeva, Yelena
    Rinaldi, Sabina
    Arslan, Alan A
    Kaaks, Rudolf
    Berrino, Franco
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, Paolo
    Adlercreutz, Herman
    Circulating enterolactone and risk of endometrial cancer2006In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 119, no 10, p. 2376-2381Article in journal (Refereed)
    Abstract [en]

    It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer.

  • 714. Zheng, B Y
    et al.
    Li, X D
    Wiklund, F
    Chowdhry, S
    Angstrom, T
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Dillner, J
    Wallin, K L
    Detection of adeno-associated virus type 2 genome in cervical carcinoma.2006In: British Journal of Cancer, ISSN 0007-0920, Vol. 94, no 12, p. 1913-7Article in journal (Refereed)
  • 715. Zheng, Biying
    et al.
    Wiklund, Fredrik
    Gharizadeh, Baback
    Sadat, Mehdi
    Gambelunghe, Giovanni
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Dillner, Joakim
    Wallin, Keng-Ling
    Ghaderi, Mehran
    Genetic polymorphism of chemokine receptors CCR2 and CCR5 in Swedish cervical cancer patients.2006In: Anticancer Res, ISSN 0250-7005, Vol. 26, no 5B, p. 3669-74Article in journal (Refereed)
  • 716. Zheng, Hou-Feng
    et al.
    Forgetta, Vincenzo
    Hsu, Yi-Hsiang
    Estrada, Karol
    Rosello-Diez, Alberto
    Leo, Paul J.
    Dahia, Chitra L.
    Park-Min, Kyung Hyun
    Tobias, Jonathan H.
    Kooperberg, Charles
    Kleinman, Aaron
    Styrkarsdottir, Unnur
    Liu, Ching-Ti
    Uggla, Charlotta
    Evans, Daniel S.
    Nielson, Carrie M.
    Walter, Klaudia
    Pettersson-Kymmer, Ulrika
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    McCarthy, Shane
    Eriksson, Joel
    Kwan, Tony
    Jhamai, Mila
    Trajanoska, Katerina
    Memari, Yasin
    Min, Josine
    Huang, Jie
    Danecek, Petr
    Wilmot, Beth
    Li, Rui
    Chou, Wen-Chi
    Mokry, Lauren E.
    Moayyeri, Alireza
    Claussnitzer, Melina
    Cheng, Chia-Ho
    Cheung, Warren
    Medina-Gomez, Carolina
    Ge, Bing
    Chen, Shu-Huang
    Choi, Kwangbom
    Oei, Ling
    Fraser, James
    Kraaij, Robert
    Hibbs, Matthew A.
    Gregson, Celia L.
    Paquette, Denis
    Hofman, Albert
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Tranah, Gregory J.
    Marshall, Mhairi
    Gardiner, Brooke B.
    Cremin, Katie
    Auer, Paul
    Hsu, Li
    Ring, Sue
    Tung, Joyce Y.
    Thorleifsson, Gudmar
    Enneman, Anke W.
    van Schoor, Natasja M.
    de Groot, Lisette C. P. G. M.
    van der Velde, Nathalie
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Kemp, John P.
    Christiansen, Claus
    Sayers, Adrian
    Zhou, Yanhua
    Calderari, Sophie
    van Rooij, Jeroen
    Carlson, Chris
    Peters, Ulrike
    Berlivet, Soizik
    Dostie, Josee
    Uitterlinden, Andre G.
    Williams, Stephen R.
    Farber, Charles
    Grinberg, Daniel
    LaCroix, Andrea Z.
    Haessler, Jeff
    Chasman, Daniel I.
    Giulianini, Franco
    Rose, Lynda M.
    Ridker, Paul M.
    Eisman, John A.
    Nguyen, Tuan V.
    Center, Jacqueline R.
    Nogues, Xavier
    Garcia-Giralt, Natalia
    Launer, Lenore L.
    Gudnason, Vilmunder
    Mellstrom, Dan
    Vandenput, Liesbeth
    Amin, Najaf
    van Duijn, Cornelia M.
    Karlsson, Magnus K.
    Ljunggren, Osten
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Rousseau, Francois
    Giroux, Sylvie
    Bussiere, Johanne
    Arp, Pascal P.
    Koromani, Fjorda
    Prince, Richard L.
    Lewis, Joshua R.
    Langdahl, Bente L.
    Hermann, A. Pernille
    Jensen, Jens-Erik B.
    Kaptoge, Stephen
    Khaw, Kay-Tee
    Reeve, Jonathan
    Formosa, Melissa M.
    Xuereb-Anastasi, Angela
    Akesson, Kristina
    McGuigan, Fiona E.
    Garg, Gaurav
    Olmos, Jose M.
    Zarrabeitia, Maria T.
    Riancho, Jose A.
    Ralston, Stuart H.
    Alonso, Nerea
    Jiang, Xi
    Goltzman, David
    Pastinen, Tomi
    Grundberg, Elin
    Gauguier, Dominique
    Orwoll, Eric S.
    Karasik, David
    Davey-Smith, George
    Smith, Albert V.
    Siggeirsdottir, Kristin
    Harris, Tamara B.
    Zillikens, M. Carola
    van Meurs, Joyce B. J.
    Thorsteinsdottir, Unnur
    Maurano, Matthew T.
    Timpson, Nicholas J.
    Soranzo, Nicole
    Durbin, Richard
    Wilson, ScottG.
    Ntzani, Evangelia E.
    Brown, Matthew A.
    Stefansson, Kari
    Hinds, David A.
    Spector, Tim
    Cupples, L. Adrienne
    Ohlsson, Claes
    Greenwood, Celia M. T.
    Jackson, Rebecca D.
    Rowe, David W.
    Loomis, Cynthia A.
    Evans, David M.
    Ackert-Bicknell, Cheryl L.
    Joyner, Alexandra L.
    Duncan, Emma L.
    Kiel, Douglas P.
    Rivadeneira, Fernando
    Richards, J. Brent
    Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 526, no 7571, p. 112-+Article in journal (Refereed)
    Abstract [en]

    The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

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