Search

Your search keyword '"Rabstein S"' showing total 119 results
Start Over Author "Rabstein S"
119 results on '"Rabstein S"'

2. Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer

Author

Wichert, K, Hoppe, R, Ickstadt, K, Behrens, T, Winter, S, Herold, R, Terschueren, C, Lo, W-Y, Guenel, P, Truong, T, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Lush, M, Andrulis, IL, Brenner, H, Chang-Claude, J, Cox, A, Cross, SS, Czene, K, Eriksson, M, Figueroa, JD, Garcia-Closas, M, Goldberg, MS, Hamann, U, He, W, Holleczek, B, Hopper, JL, Jakubowska, A, Ko, Y-D, Lubinski, J, Mulligan, AM, Obi, N, Rhenius, V, Shah, M, Shu, X-O, Simard, J, Southey, MC, Zheng, W, Dunning, AM, Pharoah, PDP, Hall, P, Easton, DF, Bruening, T, Brauch, H, Harth, V, Rabstein, S, Wichert, K, Hoppe, R, Ickstadt, K, Behrens, T, Winter, S, Herold, R, Terschueren, C, Lo, W-Y, Guenel, P, Truong, T, Bolla, MK, Wang, Q, Dennis, J, Michailidou, K, Lush, M, Andrulis, IL, Brenner, H, Chang-Claude, J, Cox, A, Cross, SS, Czene, K, Eriksson, M, Figueroa, JD, Garcia-Closas, M, Goldberg, MS, Hamann, U, He, W, Holleczek, B, Hopper, JL, Jakubowska, A, Ko, Y-D, Lubinski, J, Mulligan, AM, Obi, N, Rhenius, V, Shah, M, Shu, X-O, Simard, J, Southey, MC, Zheng, W, Dunning, AM, Pharoah, PDP, Hall, P, Easton, DF, Bruening, T, Brauch, H, Harth, V, and Rabstein, S

Abstract

Light-at-night triggers the decline of pineal gland melatonin biosynthesis and secretion and is an IARC-classified probable breast-cancer risk factor. We applied a large-scale molecular epidemiology approach to shed light on the putative role of melatonin in breast cancer. We investigated associations between breast-cancer risk and polymorphisms at genes of melatonin biosynthesis/signaling using a study population of 44,405 women from the Breast Cancer Association Consortium (22,992 cases, 21,413 population-based controls). Genotype data of 97 candidate single nucleotide polymorphisms (SNPs) at 18 defined gene regions were investigated for breast-cancer risk effects. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CI) by logistic regression for the main-effect analysis as well as stratified analyses by estrogen- and progesterone-receptor (ER, PR) status. SNP-SNP interactions were analyzed via a two-step procedure based on logic regression. The Bayesian false-discovery probability (BFDP) was used for all analyses to account for multiple testing. Noteworthy associations (BFDP < 0.8) included 10 linked SNPs in tryptophan hydroxylase 2 (TPH2) (e.g. rs1386492: OR = 1.07, 95% CI 1.02-1.12), and a SNP in the mitogen-activated protein kinase 8 (MAPK8) (rs10857561: OR = 1.11, 95% CI 1.04-1.18). The SNP-SNP interaction analysis revealed noteworthy interaction terms with TPH2- and MAPK-related SNPs (e.g. rs1386483R ∧ rs1473473D ∧ rs3729931D: OR = 1.20, 95% CI 1.09-1.32). In line with the light-at-night hypothesis that links shift work with elevated breast-cancer risks our results point to SNPs in TPH2 and MAPK-genes that may impact the intricate network of circadian regulation.

Published
2023

11. Night shift work and breast cancer: a pooled analysis of population-based case–control studies with complete work history

Author

Cordina-Duverger, E., Menegaux, F., Popa, A., Rabstein, S., Harth, V., Pesch, B., Brüning, T., Fritschi, Lin, Glass, D., Heyworth, J., Erren, T., Castaño-Vinyals, G., Papantoniou, K., Espinosa, A., Kogevinas, M., Grundy, A., Spinelli, J., Aronson, K., Guénel, P., Cordina-Duverger, E., Menegaux, F., Popa, A., Rabstein, S., Harth, V., Pesch, B., Brüning, T., Fritschi, Lin, Glass, D., Heyworth, J., Erren, T., Castaño-Vinyals, G., Papantoniou, K., Espinosa, A., Kogevinas, M., Grundy, A., Spinelli, J., Aronson, K., and Guénel, P.

Abstract

© 2018 Springer Science+Business Media B.V., part of Springer Nature Night shift work has been suspected to increase breast cancer risk but epidemiological studies have been inconsistent due to heterogeneous assessment of exposure to night work. To overcome this limitation, we pooled data of five population-based case–control studies from Australia, Canada, France, Germany, and Spain into a single harmonized dataset using a common definition of night work including 6093 breast cancer cases and 6933 population controls. The odds ratio for breast cancer in women who ever worked at night for at least 3 h between midnight and 5 a.m. as compared to never night workers was 1.12 (95% CI 1.00–1.25). Among pre-menopausal women, this odds ratio was 1.26 [1.06–1.51], increasing to 1.36 [1.07–1.74] for night shifts = 10 h, 1.80 [1.20–2.71] for work = 3 nights/week, and 2.55 [1.03–6.30] for both duration of night work = 10 years and exposure intensity = 3 nights/week. Breast cancer risk in pre-menopausal women was higher in current or recent night workers (OR = 1.41 [1.06–1.88]) than in those who had stopped night work more than 2 years ago. Breast cancer in post-menopausal women was not associated with night work whatever the exposure metric. The increase in risk was restricted to ER+ tumors, particularly those who were both ER+ and HER2+ . These results support the hypothesis that night shift work increases the risk of breast cancer in pre-menopausal women, particularly those with high intensity and long duration of exposure. Risk difference between pre- and post-menopausal women deserves further scrutiny.

Published
2018

12. S3-Leitlinie Nicht erholsamer Schlaf/Schlafstörungen

Author

Riemann, D., Baum, E., Cohrs, S., Crönlein, T., Hajak, G., Hertenstein, E., Klose, P., Langhorst, J., Mayer, G., Nissen, C., Pollmächer, T., Rabstein, S., Schlarb, Angelika, Sitter, H., Weeß, H.-G., Wetter, T., and Spiegelhalder, K.

Published
2017

14. Schichtarbeit und Prostatakrebs

Author

Behrens, T, additional, Rabstein, S, additional, Wichert, K, additional, Dragano, N, additional, Arendt, M, additional, Brüning, T, additional, and Jöckel, KH, additional

Published
2017
Full Text
View/download PDF

15. Typische Bakterien auf einer Schwerbrandverletztenintensivstation und ihre Bedeutung für die Mortalität - Retrospektive Studie 1995 - 2004

Author

Thies Ah, Steinau Hu, Rabstein S, and Steinsträsser L

Subjects
Body surface area, medicine.medical_specialty, biology, business.industry, Retrospective cohort study, Odds ratio, biology.organism_classification, Intensive care unit, Enterococcus faecalis, Surgery, law.invention, Staphylococcus epidermidis, law, Intensive care, Internal medicine, medicine, Population study, Orthopedics and Sports Medicine, business
Abstract

The purpose of this study was to identify risk profiles for wound infection of severely burned patients in a retrospective analysis of patients of an intensive care burn unit during 1995 - 2004. The goal of this study was to identify risk factors on wound infection in severely burned patients. Possible influences on mortality were to be discussed. Inclusion criteria of the study population was a minimum age of 18 years and a body surface area burned of at least 40 % during the time period 1995 - 2004. 912 patients were screened and 96 patients were enrolled. Logistic regression was performed to investigate factors influencing wound infection and mortality in the study population. The initially detectable bacteria in the burn wounds were Staphylococcus aureus (21.1 %), Staphylococcus epidermidis (16.2 %) and Enterococcus faecalis (16.2 %). Of all swabs taken the most frequent initial discovered bacteria were Staphylococcus aureus (18.2 %), Staphylococcus epidermidis (12.7 %), Enterococcus faecalis (12.7 %) and Escherichia coli (13.3 %). The majority of positive swabs were the burn wound followed by nose and tracheal secretion. The risk of a wound infection was more likely in the period 2000 - 2004 in comparison to 1995 - 1999 with an Odds Ratio of 0.17 (95 % KI [0.05 - 0.63], p = 0.008). Wound infection was promoted by longer hospitalization on the burn intensive care unit with an Odds Ratio of 2.62 (95 % KI [1.34 - 5.11], p = 0.005) and by bacterial detection in the unburned parts of the body with an Odds Ratio of 5.36 (95 % KI [1.30 - 22.24], p = 0.02). Death was significantly promoted by age (over 50 years) with an Odds Ratio of 11.62 (95 % KI [2.76 - 48.92], p = 0.0008), wound infection with an Odds Ratio of 0.12 (95 % KI [0.03 - 0.52], p = 0.004) and inhalation injury with an Odds Ratio of 5.95 (95 % KI [1.72 - 20.55], p = 0.005). During the study period a rise of wound infections could be notified. Promoting factors were longer hospitalization on the burn intensive care unit and bacterial detection in the unburned parts of the body. Regarding mortality, higher age, wound infection and inhalation injury were prognostic factors.

Published
2007
Full Text
View/download PDF

16. Poster

Author

Fiebig, H., Weber, B., Cromwell, O., Jutel, M., Fiedler, G., Hanschmann, H., Hansen, I., Stuck, B. A., Hörmann, K., Klimek, L., Jappe, U., Hoffmann, M., Burow, G., Mühlmeier, G., Maier, H., Mušič, E., Košnik, M., Piller, M., Drachenberg, K. J., Urban, E., Schenn, A., Ruëff, F., Weimer, G., Przybilla, B., Sieber, W., Schoppelrey, V., Pfeifer, M., Steiß, J. O., Lindemann, H., Wolf, H., Schnitker, J., Petermann, F., Bergmann, K. C., Zwacka, G., Steinert, B., Markert, U. R., Bijlsma, P. B., Backhaus, B., Weidenhiller, M., Donhauser, N., Hahn, E. G., Raithel, M., Erkelens, W., Hommes, D., Bruno, M., Akkerdaas, J., van Ree, R., Groot, J. A., Taminiau, J. A. J. M., Meinardi, M. M. H. M., Borowski, C., Schäfer, T., Eberhardt, F., Lepp, U., Becker, W.-M., Zabel, P., Hipler, U.-C., Spoo, J., Bauer, A., Elsner, P., Kuefner, M. A., Schwelberger, H. G., Lange, L., Rietschel, E., Riffelmann, F., Lauter, H., Müller, K.-M., Tränkner, A., Mach, K., Reulbach, U., Geyer, D., Leis, B., Ziegert, M., Ahlert, I., Deichmann, K. A., Heinzmann, A., Allmers, H., Beezhold, D., Hamilton, R. G., Sutherland, E. R., Schwanitz, H. J., Scherer, K., Bircher, A. J., Dymek, S., Lex, C., Balzer, S., Schuster, A., Hülsmeier, L., Barker, M., Müller-Lux, A., Göen, T., Koll, W., Koschel, D., Müller-Wening, D., Kütting, B., Janicke, N., Schippke, D., Langer, C., Schulz, T. G., Turowski, S., Drexler, H., Hallier, E., Bickeböller, H., Heutelbeck, A. R. R., Lässig, W., Nordwig, A., Dellweg, D., Schwarz, H., Goldmann, R., Lorenz, C., Achtzehn, U., Stehle, R., Keiper, B., Jilge, B., Beier, L., Schmidt, E. W., van Kampen, V., Haamann, F., Merget, R., Sander, I., Raulf-Heimsoth, M., Rabstein, S., Brüning, T., Ahrens, T., Muesken, H., Bergmann, K.-Ch., Vetter, M., Heitmann, M., Hunzelmann, N., Schuster, J., Kadar, J., Kespohl, S., Petersen, A., Meyer, H. E., Sickmann, A., Kleber, N., Hinrichs, J., Schocker, F., Becker, W. M., Rozynek, P., Dresselhaus, T., Reuter, B., Henzgen, M., Fahlbusch, B., Rudeschko, O., Schlenvoigt, G., Kroegel, C., Rihs, H.-P., Gaspar, Â., Pires, G., Hohenstein, E., Fiedler, E.-M., v. Pelchrzim, R., Focke, M., Zuberbier, T., Worm, M., Janowska, E., Grycmacher-Łapko, V., Kurek, M., Lippert, U., Niedenführ, S., Fuchs, T., Ludwig, A., Koch, A., Balda, B.-R., Oestmann, E., Philipp, S., Spornraft-Ragaller, P., Hammermann, J., Meurer, M., Ott, H., Wurpts, G., Krieg, R., Al Masaoudi, T., Joussen, S., Kiehl, K., Neis, M., Merk, H. F., Baron, J. M., Schmengler, J., John, S. M., Blaschke, V., Bonnekoh, B., Holzamer, N., Schmidt, U., Ambach, A., Oppermann, H., Thriene, B., Gollnick, H., Kraus, T., Häberle, M., Hoopmann, M., Hehl, O., Werfel, T., Heidrich, S., Kelber, J., Hünecke, P., Kasche, A., Klaus, S., Thiel, M., Buters, J., Weichenmeier, I., Ring, J., Traidl-Hoffmann, C., Behrendt, H., Krämer, U., Lau, S., Kim, S., Mahling, H., Schulz, G., Keil, T., Wahn, U., Mock, B., Kugler, J., Cremer, R., Sandner, B., Kaiser, F., Herbst, R. A., Wahl, R., Suck, R., Kügler, K., Frosch, P. J., Nabe, A., Konturek, P., Simon, K., Kressel, J., Nägel, A., Wilken, V., Strehfeld, T., Neubert, K., Pieper, B., Kuhn, M., Winterkamp, S., Pacurar, A., Senger, D., Beskitas, E., Dorrmann, H., Mueller, M. W., Harwanegg, C., Hiller, R., Kinne, R. W., Schröder, C. M., Mahler, V., Schröder, A., Erdmann, S., Schultis, H. W., Buchwald, F., Hampel, W., Maiss, J., Naegel, A., Zahradnik, E., Doekes, G., Runge, D. M., Schwertner, H., Grize, L., Schindler, C., Surber, Ch., Böckelmann, R., Horn, T., Breithaupt, S., Thiele, J. J., Gutermuth, J., Jakob, T., Heinzelmann, J., Varosi, F., Debevc, F., Pöhlmann, T. G., Seyfarth, L., Kindt, F., Löser, C., Niemeier, V., Gieler, U., Kummer, W., Haberberger, R. V., Klockenbring, T., Stöcker, M., Huhn, M., Bauer, R., Goerlich, R., Fischer, R., Barth, S., Suchodolska, A., Soost, S., Bayerl, C., Ludwig, B., Gancs, P., Häusermann, P., Harr, T., Müller, M., Sachs, B., Riegel, S., Schichler, D., Schrooten, J., Heussen, N., Hilgers, R.-D., Seo, J. W., Franke, I., and Strauss, R.

Subjects
SIT und Insektengiftallergie, Immunology and Allergy
Published
2004
Full Text
View/download PDF

17. Fine-scale mapping of the 4q24 locus identifies & pr two Independent loci associated with breast cancer risk

Author

Guo, X. (Xingyi), Long, J. (Jirong), Zeng, C. (Chenjie), Michailidou, K. (Kyriaki), Ghoussaini, M. (Maya), Bolla, M.K. (Manjeet), Wang, Q. (Qing), Milne, R.L. (Roger L.), Shu, X.-O. (Xiao-Ou), Cai, Q. (Qiuyin), Beesley, J. (Jonathan), Kar, S. (Siddhartha), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Beckmann, M.W. (Matthias), Beeghly-Fadiel, A. (Alicia), Benítez, J. (Javier), Blot, W.J. (William), Bogdanova, N.V. (Natalia), Bojesen, S.E. (Stig), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brinton, L.A. (Louise), Broekss, A. (Annegien), Brüning, T. (Thomas), Burwinkel, B. (Barbara), Cai, H. (Hui), Canisius, S. (Sander), Chang-Claude, J. (Jenny), Choi, J.-Y. (J.), Couch, F.J. (Fergus), Cox, A. (Angela), Cross, S.S. (Simon), Czene, K. (Kamila), Darabi, H. (Hatef), Devilee, P. (Peter), Droit, A. (Arnaud), Dörk, T. (Thilo), Fasching, P.A. (Peter), Fletcher, O. (Olivia), Flyger, H. (Henrik), Fostira, F. (Florentia), Gaborieau, V. (Valerie), García-Closas, M. (Montserrat), Giles, G.G. (Graham G.), Grip, M. (Mervi), Guénel, P. (Pascal), Haiman, C.A. (Christopher A.), Hamann, U. (Ute), Hartman, J.M. (Joost), Hollestelle, A. (Antoinette), Hopper, J.L. (John L.), Hsiung, C.-N. (Chia-Ni), Ito, H. (Hidemi), Jakubowska, A. (Anna), Johnson, N. (Nichola), Kabisch, M. (Maria), Kang, D. (Daehee), Khan, S. (Sofia), Knight, J.A. (Julia), Kosma, V-M. (Veli-Matti), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Li, J. (Jingmei), Lindblom, A. (Annika), Lophatananon, A. (Artitaya), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Marme, F. (Federick), Matsuo, K. (Keitaro), McLean, C.A. (Catriona Ann), Meindl, A. (Alfons), Muir, K. (Kenneth), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nord, S. (Silje), Olson, J.E. (Janet), Orr, N. (Nick), Peterlongo, P. (Paolo), Putti, T.C. (Thomas Choudary), Rudolph, A. (Anja), Sangrajrang, S. (Suleeporn), Sawyer, E.J. (Elinor), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Shen, C-Y. (Chen-Yang), Shi, J. (Jiajun), Shrubsole, M. (Martha), Southey, M.C. (Melissa), Swerdlow, A.J. (Anthony ), Teo, S.H. (Soo Hwang), Thienpont, B. (Bernard), Toland, A.E. (Amanda), Tollenaar, R.A.E.M. (Rob), Tomlinson, I. (Ian), Truong, T. (Thérèse), Tseng, C.-C. (Chiu-chen), Ouweland, A.M.W. (Ans) van den, Wen, W. (Wanqing), Winqvist, R. (Robert), Wu, A. (Anna), Yip, C.H. (Cheng Har), Zamora, M.P. (Pilar), Zheng, Y. (Ying), Hall, P. (Per), Pharoah, P.D.P. (Paul), Simard, J. (Jacques), Chenevix-Trench, G. (Georgia), Dunning, A.M. (Alison), Easton, D.F. (Douglas F.), Zheng, W. (Wei), Eeles, R. (Rosalind), Al Olama, A.A. (Ali Amin), Kote-Jarai, Z., Benlloch, S. (Sara), Antoniou, A.C. (Antonis), McGuffog, L. (Lesley), Offit, K. (Kenneth), Lee, A. (Andrew), Dicks, E. (Ed), Luccarini, C. (Craig), Tessier, D.C. (Daniel C.), Bacot, F. (Francois), Vincent, D. (Daniel), La Boissière, S. (Sylvie), Robidoux, F. (Frederic), Nielsen, S.F. (Sune), Cunningham, J.M. (Julie), Windebank, S.A. (Sharon A.), Hilker, C.A. (Christopher A.), Meyer, J. (Jeffrey), Angelakos, M. (Maggie), Maskiell, J. (Judi), Rutgers, E.J. (Emiel J.), Verhoef, S., Hogervorst, F.B.L. (Frans), Boonyawongviroj, P. (Prat), Siriwanarungsan, P. (Pornthep), Schrauder, A. (André), Rübner, M. (Matthias), Oeser, S. (Sonja), Landrith, S. (Silke), Williams, E. (Eileen), Ryder-Mills, E. (Elaine), Sargus, K. (Kara), McInerney, N. (Niall), Colleran, G. (Gabrielle), Rowan, A. (Andrew), Jones, A. (Angela), Sohn, C. (Christof), Schneeweiß, A. (Andeas), Bugert, P. (Peter), Álvarez, N. (Nuria), Bernstein, L. (Leslie), Lacey, J. (James), Wang, S. (Sophia), Ma, H. (Huiyan), Lu, Y. (Yani), Clague De Hart, J. (Jessica), Deapen, D. (Dennis), Pinder, R. (Rich), Lee, E. (Eunjung), Schumacher, F.R. (Fredrick), Horn-Ross, P. (Pam), Reynolds, P. (Peggy), Nelson, D. (David), Park, H. (Hannah), Ziegler, H. (Hartwig), Wolf, S. (Sonja), Hermann, V. (Volker), Lo, W.-Y. (Wing-Yee), Justenhoven, C. (Christina), Ko, Y.-D. (Yon-Dschun), Baisch, C. (Christian), Fischer, H.-P. (Hans-Peter), Pesch, B. (Beate), Rabstein, S. (Sylvia), Lotz, A. (Anne), Harth, V. (Volker), Heikkinen, T. (Tuomas), Erkkilä, I. (Irja), Aaltonen, K. (Kirsimari), Smitten, K. (Karl) von, Antonenkova, N.N. (Natalia), Hillemanns, P. (Peter), Christiansen, H. (Hans), Myöhänen, E. (Eija), Kemiläinen, H. (Helena), Thorne, H. (Heather), Niedermayr, E. (Eveline), Bowtell, D., De Fazio, A. (Anna), Gertig, D., Green, A., Webb, P. (Penny), Parsons, P., Hayward, N., Webb, P.M. (P.), Whiteman, D., Fung, A. (Annie), Yashiki, J. (June), Peuteman, G. (Gilian), Smeets, D. (Dominiek), Van Brussel, T. (Thomas), Corthouts, K. (Kathleen), Obi, N. (Nadia), Heinz, J. (Judith), Behrens, T.W. (Timothy), Eilber, U. (Ursula), Celik, M. (Muhabbet), Olchers, T. (Til), Peissel, B. (Bernard), Scuvera, G. (Giulietta), Zaffaroni, D. (Daniela), Bonnani, B. (Bernardo), Feroce, I. (Irene), Maniscalco, A. (Angela), Rossi, A. (Alessandra), Bernard, L. (Loris), Tranchant, M. (Martine), Valois, M.-F. (Marie-France), Turgeon, A. (Annie), Heguy, L. (Lea), Yee, P.S. (Phuah Sze), Kang, P. (Peter), Nee, K.I. (Kang In), Mariapun, S. (Shivaani), Sook-Yee, Y. (Yoon), Lee, D.S.C. (Daphne S.C.), Ching, T.Y. (Teh Yew), Taib, N.A.M. (Nur Aishah Mohd), Otsukka, M. (Meeri), Mononen, K. (Kari), Selander, T. (Teresa), Weerasooriya, N. (Nayana), Krol-Warmerdam, E.M.M. (Elly), Molenaar, J., Blom, J., Szeszenia-Dabrowska, N. (Neonilia), Peplonska, B. (Beata), Zatonski, W. (Witold), Chao, P. (Pei), Stagner, M. (Michael), Bos, P. (Petra), Blom, J. (Jannet), Crepin, E. (Ellen), Nieuwlaat, A. (Anja), Heemskerk, A. (Annette), Higham, S. (Sue), Cramp, H.E. (Helen), Connley, D. (Daniel), Balasubramanian, S. (Sabapathy), Brock, I.W. (Ian), Kerin, M. (Michael), Miller, N. (Nicola), Kerbrat, P. (Pierre), Arveux, P. (Patrick), Le Scodan, R. (Romuald), Raoul, Y. (Yves), Laurent-Puig, P. (Pierre), Mulot, C. (Claire), Stegmaier, C. (Christa), Butterbach, K. (Katja), Karstens, J.H. (Johann), Flesch-Janys, D. (Dieter), Seibold, P. (Petra), Vrieling, A. (Alina), Nickels, S. (Stefan), Radice, P. (Paolo), Pykäs, K. (Katri), Jukkola-Vuorinen, A. (Arja), Kauppila, S. (Saila), Conroy, D. (Don), Baynes, C. (Caroline), Chua, K. (Kimberley), Pilarski, R. (Robert), Guo, X. (Xingyi), Long, J. (Jirong), Zeng, C. (Chenjie), Michailidou, K. (Kyriaki), Ghoussaini, M. (Maya), Bolla, M.K. (Manjeet), Wang, Q. (Qing), Milne, R.L. (Roger L.), Shu, X.-O. (Xiao-Ou), Cai, Q. (Qiuyin), Beesley, J. (Jonathan), Kar, S. (Siddhartha), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Beckmann, M.W. (Matthias), Beeghly-Fadiel, A. (Alicia), Benítez, J. (Javier), Blot, W.J. (William), Bogdanova, N.V. (Natalia), Bojesen, S.E. (Stig), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brinton, L.A. (Louise), Broekss, A. (Annegien), Brüning, T. (Thomas), Burwinkel, B. (Barbara), Cai, H. (Hui), Canisius, S. (Sander), Chang-Claude, J. (Jenny), Choi, J.-Y. (J.), Couch, F.J. (Fergus), Cox, A. (Angela), Cross, S.S. (Simon), Czene, K. (Kamila), Darabi, H. (Hatef), Devilee, P. (Peter), Droit, A. (Arnaud), Dörk, T. (Thilo), Fasching, P.A. (Peter), Fletcher, O. (Olivia), Flyger, H. (Henrik), Fostira, F. (Florentia), Gaborieau, V. (Valerie), García-Closas, M. (Montserrat), Giles, G.G. (Graham G.), Grip, M. (Mervi), Guénel, P. (Pascal), Haiman, C.A. (Christopher A.), Hamann, U. (Ute), Hartman, J.M. (Joost), Hollestelle, A. (Antoinette), Hopper, J.L. (John L.), Hsiung, C.-N. (Chia-Ni), Ito, H. (Hidemi), Jakubowska, A. (Anna), Johnson, N. (Nichola), Kabisch, M. (Maria), Kang, D. (Daehee), Khan, S. (Sofia), Knight, J.A. (Julia), Kosma, V-M. (Veli-Matti), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Li, J. (Jingmei), Lindblom, A. (Annika), Lophatananon, A. (Artitaya), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Marme, F. (Federick), Matsuo, K. (Keitaro), McLean, C.A. (Catriona Ann), Meindl, A. (Alfons), Muir, K. (Kenneth), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nord, S. (Silje), Olson, J.E. (Janet), Orr, N. (Nick), Peterlongo, P. (Paolo), Putti, T.C. (Thomas Choudary), Rudolph, A. (Anja), Sangrajrang, S. (Suleeporn), Sawyer, E.J. (Elinor), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Shen, C-Y. (Chen-Yang), Shi, J. (Jiajun), Shrubsole, M. (Martha), Southey, M.C. (Melissa), Swerdlow, A.J. (Anthony ), Teo, S.H. (Soo Hwang), Thienpont, B. (Bernard), Toland, A.E. (Amanda), Tollenaar, R.A.E.M. (Rob), Tomlinson, I. (Ian), Truong, T. (Thérèse), Tseng, C.-C. (Chiu-chen), Ouweland, A.M.W. (Ans) van den, Wen, W. (Wanqing), Winqvist, R. (Robert), Wu, A. (Anna), Yip, C.H. (Cheng Har), Zamora, M.P. (Pilar), Zheng, Y. (Ying), Hall, P. (Per), Pharoah, P.D.P. (Paul), Simard, J. (Jacques), Chenevix-Trench, G. (Georgia), Dunning, A.M. (Alison), Easton, D.F. (Douglas F.), Zheng, W. (Wei), Eeles, R. (Rosalind), Al Olama, A.A. (Ali Amin), Kote-Jarai, Z., Benlloch, S. (Sara), Antoniou, A.C. (Antonis), McGuffog, L. (Lesley), Offit, K. (Kenneth), Lee, A. (Andrew), Dicks, E. (Ed), Luccarini, C. (Craig), Tessier, D.C. (Daniel C.), Bacot, F. (Francois), Vincent, D. (Daniel), La Boissière, S. (Sylvie), Robidoux, F. (Frederic), Nielsen, S.F. (Sune), Cunningham, J.M. (Julie), Windebank, S.A. (Sharon A.), Hilker, C.A. (Christopher A.), Meyer, J. (Jeffrey), Angelakos, M. (Maggie), Maskiell, J. (Judi), Rutgers, E.J. (Emiel J.), Verhoef, S., Hogervorst, F.B.L. (Frans), Boonyawongviroj, P. (Prat), Siriwanarungsan, P. (Pornthep), Schrauder, A. (André), Rübner, M. (Matthias), Oeser, S. (Sonja), Landrith, S. (Silke), Williams, E. (Eileen), Ryder-Mills, E. (Elaine), Sargus, K. (Kara), McInerney, N. (Niall), Colleran, G. (Gabrielle), Rowan, A. (Andrew), Jones, A. (Angela), Sohn, C. (Christof), Schneeweiß, A. (Andeas), Bugert, P. (Peter), Álvarez, N. (Nuria), Bernstein, L. (Leslie), Lacey, J. (James), Wang, S. (Sophia), Ma, H. (Huiyan), Lu, Y. (Yani), Clague De Hart, J. (Jessica), Deapen, D. (Dennis), Pinder, R. (Rich), Lee, E. (Eunjung), Schumacher, F.R. (Fredrick), Horn-Ross, P. (Pam), Reynolds, P. (Peggy), Nelson, D. (David), Park, H. (Hannah), Ziegler, H. (Hartwig), Wolf, S. (Sonja), Hermann, V. (Volker), Lo, W.-Y. (Wing-Yee), Justenhoven, C. (Christina), Ko, Y.-D. (Yon-Dschun), Baisch, C. (Christian), Fischer, H.-P. (Hans-Peter), Pesch, B. (Beate), Rabstein, S. (Sylvia), Lotz, A. (Anne), Harth, V. (Volker), Heikkinen, T. (Tuomas), Erkkilä, I. (Irja), Aaltonen, K. (Kirsimari), Smitten, K. (Karl) von, Antonenkova, N.N. (Natalia), Hillemanns, P. (Peter), Christiansen, H. (Hans), Myöhänen, E. (Eija), Kemiläinen, H. (Helena), Thorne, H. (Heather), Niedermayr, E. (Eveline), Bowtell, D., De Fazio, A. (Anna), Gertig, D., Green, A., Webb, P. (Penny), Parsons, P., Hayward, N., Webb, P.M. (P.), Whiteman, D., Fung, A. (Annie), Yashiki, J. (June), Peuteman, G. (Gilian), Smeets, D. (Dominiek), Van Brussel, T. (Thomas), Corthouts, K. (Kathleen), Obi, N. (Nadia), Heinz, J. (Judith), Behrens, T.W. (Timothy), Eilber, U. (Ursula), Celik, M. (Muhabbet), Olchers, T. (Til), Peissel, B. (Bernard), Scuvera, G. (Giulietta), Zaffaroni, D. (Daniela), Bonnani, B. (Bernardo), Feroce, I. (Irene), Maniscalco, A. (Angela), Rossi, A. (Alessandra), Bernard, L. (Loris), Tranchant, M. (Martine), Valois, M.-F. (Marie-France), Turgeon, A. (Annie), Heguy, L. (Lea), Yee, P.S. (Phuah Sze), Kang, P. (Peter), Nee, K.I. (Kang In), Mariapun, S. (Shivaani), Sook-Yee, Y. (Yoon), Lee, D.S.C. (Daphne S.C.), Ching, T.Y. (Teh Yew), Taib, N.A.M. (Nur Aishah Mohd), Otsukka, M. (Meeri), Mononen, K. (Kari), Selander, T. (Teresa), Weerasooriya, N. (Nayana), Krol-Warmerdam, E.M.M. (Elly), Molenaar, J., Blom, J., Szeszenia-Dabrowska, N. (Neonilia), Peplonska, B. (Beata), Zatonski, W. (Witold), Chao, P. (Pei), Stagner, M. (Michael), Bos, P. (Petra), Blom, J. (Jannet), Crepin, E. (Ellen), Nieuwlaat, A. (Anja), Heemskerk, A. (Annette), Higham, S. (Sue), Cramp, H.E. (Helen), Connley, D. (Daniel), Balasubramanian, S. (Sabapathy), Brock, I.W. (Ian), Kerin, M. (Michael), Miller, N. (Nicola), Kerbrat, P. (Pierre), Arveux, P. (Patrick), Le Scodan, R. (Romuald), Raoul, Y. (Yves), Laurent-Puig, P. (Pierre), Mulot, C. (Claire), Stegmaier, C. (Christa), Butterbach, K. (Katja), Karstens, J.H. (Johann), Flesch-Janys, D. (Dieter), Seibold, P. (Petra), Vrieling, A. (Alina), Nickels, S. (Stefan), Radice, P. (Paolo), Pykäs, K. (Katri), Jukkola-Vuorinen, A. (Arja), Kauppila, S. (Saila), Conroy, D. (Don), Baynes, C. (Caroline), Chua, K. (Kimberley), and Pilarski, R. (Robert)

Abstract

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P=2.51 × 10-4; OR, 1.04; 95% confidence interval (CI), 1.02-1.07] and rs77928427 (P=1.86 × 10-4; OR, 1.04; 95% CI, 1.02-1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor-binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.

Published
2015
Full Text
View/download PDF

19. Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk

Author

Gaudet, M.M. (Mia), Kuchenbaecker, K.B. (Karoline), Vijai, J. (Joseph), Klein, R.J. (Robert), Kircchoff, T. (Tomas), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Dunning, A.M. (Alison), Lee, A. (Andrew), Dennis, J. (Joe), Healey, S. (Sue), Dicks, E. (Ed), Soucy, P. (Penny), Sinilnikova, O. (Olga), Pankratz, V.S. (Shane), Wang, X. (Xing), Eldridge, S. (Steve), Tessier, Y. (Yann), Vincent, D. (Daniel), Bacot, F. (Francois), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Peterlongo, P. (Paolo), Schmutzler, R.K. (Rita), Nathanson, K.L. (Katherine), Piedmonte, M. (Marion), Singer, C.F. (Christian), Thomassen, M. (Mads), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Blanco, I. (Ignacio), Greene, M.H. (Mark), Garber, J., Weitzel, J.N. (Jeffrey), Andrulis, I.L. (Irene), Goldgar, D. (David), D'Andrea, E. (Emma), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Rensburg, E.J. (Elizabeth) van, Arason, A. (Adalgeir), Rennert, G. (Gad), Ouweland, A.M.W. (Ans) van den, Hout, A.H. (Annemarie) van der, Kets, C.M. (Marleen), Aalfs, C.M. (Cora), Wijnen, J.T. (Juul), Ausems, M.G.E.M. (Margreet), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Jacobs, C. (Chris), Adlard, J.W. (Julian), Tischkowitz, M. (Marc), Porteous, M.E. (Mary), Damiola, F. (Francesca), Golmard, L. (Lisa), Barjhoux, L. (Laure), Longy, M. (Michel), Belotti, M. (Muriel), Ferrer, S.F., Mazoyer, S. (Sylvie), Spurdle, A.B. (Amanda), Manoukian, S. (Siranoush), Barile, M. (Monica), Genuardi, M. (Maurizio), Arnold, N. (Norbert), Meindl, A. (Alfons), Sutter, C. (Christian), Wapenschmidt, B. (Barbara), Domchek, S.M. (Susan), Pfeiler, G. (Georg), Friedman, E. (Eitan), Jensen, U.B., Robson, M. (Mark), Shah, S. (Sonia), Lázaro, C. (Conxi), Mai, P.L. (Phuong), Benítez, J. (Javier), Southey, M.C. (Melissa), Schmidt, M.K. (Marjanka), Fasching, P.A. (Peter), Peto, J. (Julian), Humphreys, M.K. (Manjeet), Wang, Q. (Qing), Michailidou, K. (Kyriaki), Sawyer, E.J. (Elinor), Burwinkel, B. (Barbara), Guénel, P. (Pascal), Bojesen, S.E. (Stig), Milne, R.L. (Roger), Brenner, H. (Hermann), Lochmann, M. (Magdalena), Brauch, H. (Hiltrud), Ko, Y-D. (Yon-Dschun), Baisch, C. (Christian), Fischer, H.-P., Bruening, T. (Thomas), Pesch, B. (Beate), Rabstein, S. (Sylvia), Spickenheuer, A. (Anne), Aittomäki, K. (Kristiina), Dörk, T. (Thilo), Margolin, S. (Sara), Mannermaa, A. (Arto), Lambrechts, D. (Diether), Chang-Claude, J. (Jenny), Radice, P. (Paolo), Giles, G.G. (Graham), Haiman, C.A. (Christopher), Winqvist, R. (Robert), Devillee, P. (Peter), García-Closas, M. (Montserrat), Schoof, N. (Nils), Hooning, M.J. (Maartje), Cox, A. (Angela), Pharoah, P.D.P. (Paul), Jakubowska, A. (Anna), Orr, N. (Nick), González-Neira, A. (Anna), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Hall, A.S. (Alistair), Couch, F.J. (Fergus), Simard, J. (Jacques), Altshuler, D. (David), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Offit, K. (Kenneth), Rookus, M.A. (Matti), Leeuwen, F.E. (Flora) van, Verhoef, S., Lange, J.L. (J.) de, Collée, J.M. (Margriet), Seynaeve, C.M. (Caroline), Deurzen, C.H.M. (Carolien) van, Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Devilee, P. (Peter), Cronenburg, T.C.T.E.F. van, Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Os, T.A.M. (Theo) van, Gille, J.J. (Johan), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gómez García, E.B. (Encarna), Blok, M.J. (Marinus), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Vasen, H. (Hans), Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Gregory, H. (Helen), Morrison, P.J. (Patrick), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), Donaldson, A. (Alan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Alexandra), Rogers, M.T. (Mark), McCann, E. (Emma), Kennedy, M.J. (John), Barton, D.E. (David), Drummond, S. (Sarah), Brewer, C. (C.), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Izatt, L. (Louise), Langman, C. (Caroline), Brady, A.F. (Angela), Dorkins, H. (Huw), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Houghton, C. (Catherine), Lalloo, F. (Fiona), Taylor, J. (James), Side, L. (Lucy), Male, A. (Alison), Berlin, C. (Cheryl), Eason, J. (Jacqueline), Collier, R. (Rebecca), Douglas, F. (Fiona), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Eeles, R. (Rosalind), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Cook, J. (Jackie), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Hodgson, S.V. (Shirley), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Eccles, D. (Diana), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Léone, M. (Mélanie), Gauthier-Villars, M. (Marion), Buecher, B. (Bruno), Houdayer, C. (Claude), Moncoutier, V. (Virginie), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Handallou, S. (Sandrine), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Sobol, H. (Hagay), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Coupier, I. (Isabelle), Pujol, P. (Pascal), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Rouleau, E. (Etienne), Lidereau, R. (Rosette), Demange, L. (Liliane), Nogues, C. (Catherine), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Frenay, M. (Marc), Vénat-Bouvet, L. (Laurence), Delnatte, C.D. (Capucine), Mortemousque, I. (Isabelle), Lynch, H. (Henry), Snyder, C.L. (Carrie), Gaudet, M.M. (Mia), Kuchenbaecker, K.B. (Karoline), Vijai, J. (Joseph), Klein, R.J. (Robert), Kircchoff, T. (Tomas), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Dunning, A.M. (Alison), Lee, A. (Andrew), Dennis, J. (Joe), Healey, S. (Sue), Dicks, E. (Ed), Soucy, P. (Penny), Sinilnikova, O. (Olga), Pankratz, V.S. (Shane), Wang, X. (Xing), Eldridge, S. (Steve), Tessier, Y. (Yann), Vincent, D. (Daniel), Bacot, F. (Francois), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Peterlongo, P. (Paolo), Schmutzler, R.K. (Rita), Nathanson, K.L. (Katherine), Piedmonte, M. (Marion), Singer, C.F. (Christian), Thomassen, M. (Mads), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Blanco, I. (Ignacio), Greene, M.H. (Mark), Garber, J., Weitzel, J.N. (Jeffrey), Andrulis, I.L. (Irene), Goldgar, D. (David), D'Andrea, E. (Emma), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Rensburg, E.J. (Elizabeth) van, Arason, A. (Adalgeir), Rennert, G. (Gad), Ouweland, A.M.W. (Ans) van den, Hout, A.H. (Annemarie) van der, Kets, C.M. (Marleen), Aalfs, C.M. (Cora), Wijnen, J.T. (Juul), Ausems, M.G.E.M. (Margreet), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Jacobs, C. (Chris), Adlard, J.W. (Julian), Tischkowitz, M. (Marc), Porteous, M.E. (Mary), Damiola, F. (Francesca), Golmard, L. (Lisa), Barjhoux, L. (Laure), Longy, M. (Michel), Belotti, M. (Muriel), Ferrer, S.F., Mazoyer, S. (Sylvie), Spurdle, A.B. (Amanda), Manoukian, S. (Siranoush), Barile, M. (Monica), Genuardi, M. (Maurizio), Arnold, N. (Norbert), Meindl, A. (Alfons), Sutter, C. (Christian), Wapenschmidt, B. (Barbara), Domchek, S.M. (Susan), Pfeiler, G. (Georg), Friedman, E. (Eitan), Jensen, U.B., Robson, M. (Mark), Shah, S. (Sonia), Lázaro, C. (Conxi), Mai, P.L. (Phuong), Benítez, J. (Javier), Southey, M.C. (Melissa), Schmidt, M.K. (Marjanka), Fasching, P.A. (Peter), Peto, J. (Julian), Humphreys, M.K. (Manjeet), Wang, Q. (Qing), Michailidou, K. (Kyriaki), Sawyer, E.J. (Elinor), Burwinkel, B. (Barbara), Guénel, P. (Pascal), Bojesen, S.E. (Stig), Milne, R.L. (Roger), Brenner, H. (Hermann), Lochmann, M. (Magdalena), Brauch, H. (Hiltrud), Ko, Y-D. (Yon-Dschun), Baisch, C. (Christian), Fischer, H.-P., Bruening, T. (Thomas), Pesch, B. (Beate), Rabstein, S. (Sylvia), Spickenheuer, A. (Anne), Aittomäki, K. (Kristiina), Dörk, T. (Thilo), Margolin, S. (Sara), Mannermaa, A. (Arto), Lambrechts, D. (Diether), Chang-Claude, J. (Jenny), Radice, P. (Paolo), Giles, G.G. (Graham), Haiman, C.A. (Christopher), Winqvist, R. (Robert), Devillee, P. (Peter), García-Closas, M. (Montserrat), Schoof, N. (Nils), Hooning, M.J. (Maartje), Cox, A. (Angela), Pharoah, P.D.P. (Paul), Jakubowska, A. (Anna), Orr, N. (Nick), González-Neira, A. (Anna), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Hall, A.S. (Alistair), Couch, F.J. (Fergus), Simard, J. (Jacques), Altshuler, D. (David), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Offit, K. (Kenneth), Rookus, M.A. (Matti), Leeuwen, F.E. (Flora) van, Verhoef, S., Lange, J.L. (J.) de, Collée, J.M. (Margriet), Seynaeve, C.M. (Caroline), Deurzen, C.H.M. (Carolien) van, Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Devilee, P. (Peter), Cronenburg, T.C.T.E.F. van, Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Os, T.A.M. (Theo) van, Gille, J.J. (Johan), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gómez García, E.B. (Encarna), Blok, M.J. (Marinus), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Vasen, H. (Hans), Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Gregory, H. (Helen), Morrison, P.J. (Patrick), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), Donaldson, A. (Alan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Alexandra), Rogers, M.T. (Mark), McCann, E. (Emma), Kennedy, M.J. (John), Barton, D.E. (David), Drummond, S. (Sarah), Brewer, C. (C.), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Izatt, L. (Louise), Langman, C. (Caroline), Brady, A.F. (Angela), Dorkins, H. (Huw), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Houghton, C. (Catherine), Lalloo, F. (Fiona), Taylor, J. (James), Side, L. (Lucy), Male, A. (Alison), Berlin, C. (Cheryl), Eason, J. (Jacqueline), Collier, R. (Rebecca), Douglas, F. (Fiona), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Eeles, R. (Rosalind), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Cook, J. (Jackie), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Hodgson, S.V. (Shirley), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Eccles, D. (Diana), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Léone, M. (Mélanie), Gauthier-Villars, M. (Marion), Buecher, B. (Bruno), Houdayer, C. (Claude), Moncoutier, V. (Virginie), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Handallou, S. (Sandrine), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Sobol, H. (Hagay), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Coupier, I. (Isabelle), Pujol, P. (Pascal), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Rouleau, E. (Etienne), Lidereau, R. (Rosette), Demange, L. (Liliane), Nogues, C. (Catherine), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Frenay, M. (Marc), Vénat-Bouvet, L. (Laurence), Delnatte, C.D. (Capucine), Mortemousque, I. (Isabelle), Lynch, H. (Henry), and Snyder, C.L. (Carrie)

Published
2013
Full Text
View/download PDF

20. Breast cancer risk and 6q22.33: Combined results from breast cancer association consortium and consortium of investigators on modifiers of brca1/2

Author

Kircchoff, T. (Tomas), Offit, K. (Kenneth), Gaudet, M.M. (Mia), Pharoah, P.D.P. (Paul), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), McGuffog, L. (Lesley), Humphreys, M.K. (Manjeet), Dunning, A.M. (Alison), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Flyger, H. (Henrik), Kang, D. (Daehee), Yoo, K-Y. (Keun-Young), Noh, D-Y. (Dong-Young), Ahn, S.-H. (Sei-Hyun), Dörk, T. (Thilo), Schürmann, P. (Peter), Karstens, J.H. (Johann), Hillemanns, P. (Peter), Couch, F.J. (Fergus), Olson, J.E. (Janet), Vachon, C. (Celine), Cox, A. (Angela), Brock, I.W. (Ian), Elliott, G. (Graeme), Reed, M.W.R. (Malcolm), Burwinkel, B. (Barbara), Meindl, A. (Alfons), Brauch, H. (Hiltrud), Justenhoven, C. (Christina), Hamann, U. (Ute), Ko, Y-D. (Yon-Dschun), Fischer, H.-P., Brüning, T. (Thomas), Pesch, B. (Beate), Harth, V. (Volker), Rabstein, S. (Sylvia), Broeks, A. (Annegien), Schmidt, M.K. (Marjanka), Veer, L.J. (Laura) van 't, Braaf, L.M. (Linde), Johnson, N. (Nichola), Fletcher, O. (Olivia), Gibson, L.J. (Lorna), Peto, J. (Julian), Turnbull, C. (Clare), Seal, S. (Sheila), Renwick, A. (Anthony), Rahman, N. (Nazneen), Wu, P.-E. (Pei-Ei), Yu, J-C. (Jyh-Cherng), Hsiung, C.-N. (Chia-Ni), Shen, C-Y. (Chen-Yang), Southey, M.C. (Melissa), Hopper, J.L. (John), Hammet, F. (Fleur), Dorpe, T. (Thijs) van, Dieudonné, A.-S. (Anne-Sophie), Hatse, S. (Sigrid), Lambrechts, D. (Diether), Andrulis, I.L. (Irene), Bogdanova, N.V. (Natalia), Antonenkova, N.N. (Natalia), Rogov, J.I. (Juri), Prokofieva, D. (Daria), Bermisheva, M. (Marina), Khusnutdinova, E.K. (Elza), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Hooning, M.J. (Maartje), Devilee, P. (Peter), Margolin, S. (Sara), Lindblom, A. (Annika), Milne, R.L. (Roger), Arias Pérez, J.I. (José Ignacio), Zamora, M.P. (Pilar), Benítez, J. (Javier), Severi, G. (Gianluca), Baglietto, L. (Laura), Giles, G.G. (Graham), Chenevix-Trench, G. (Georgia), Spurdle, A.B. (Amanda), Beesley, J. (Jonathan), Chen, X. (Xiaoqing), Holland, H. (Helene), Healey, S. (Sue), Wang-Gohrke, S. (Shan), Chang-Claude, J. (Jenny), Mannermaa, A. (Arto), Kosma, V-M. (Veli-Matti), Kauppinen, J. (Jaana), Kataja, V. (Vesa), Agnarsson, B.A. (Bjarni), Caligo, M.A. (Maria), Godwin, A.K. (Andrew), Nevanlinna, H. (Heli), Heikinen, T. (Tuomas), Fredericksen, Z. (Zachary), Lindor, N.M. (Noralane), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Loman, N. (Niklas), Karlsson, P. (Per), Askmalm, M.S. (Marie), Melin, B. (Beatrice), Wachenfeldt, A. (Anna) von, Hogervorst, F.B.L. (Frans), Verheus, M. (Martijn), Rookus, M.A. (Matti), Seynaeve, C.M. (Caroline), Oldenburg, R.A. (Rogier), Ligtenberg, M.J. (Marjolijn), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Gille, H.J.P. (Hans), Wijnen, J.T. (Juul), Gómez García, E.B. (Encarna), Peock, S. (Susan), Cook, M. (Margaret), Oliver, C.T. (Clare), Frost, D. (Debra), Luccarini, C. (Craig), Pichert, G. (Gabriella), Davidson, R. (Rosemarie), Eccles, D. (Diana), Ong, K.-R. (Kai-Ren), Cook, J. (Jackie), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Evans, D.G. (Gareth), Eeles, R. (Rosalind), Gold, B. (Bert), Wang, X. (Xianshu), Chu, C. (Carol), Kircchoff, T. (Tomas), Offit, K. (Kenneth), Gaudet, M.M. (Mia), Pharoah, P.D.P. (Paul), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), McGuffog, L. (Lesley), Humphreys, M.K. (Manjeet), Dunning, A.M. (Alison), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Flyger, H. (Henrik), Kang, D. (Daehee), Yoo, K-Y. (Keun-Young), Noh, D-Y. (Dong-Young), Ahn, S.-H. (Sei-Hyun), Dörk, T. (Thilo), Schürmann, P. (Peter), Karstens, J.H. (Johann), Hillemanns, P. (Peter), Couch, F.J. (Fergus), Olson, J.E. (Janet), Vachon, C. (Celine), Cox, A. (Angela), Brock, I.W. (Ian), Elliott, G. (Graeme), Reed, M.W.R. (Malcolm), Burwinkel, B. (Barbara), Meindl, A. (Alfons), Brauch, H. (Hiltrud), Justenhoven, C. (Christina), Hamann, U. (Ute), Ko, Y-D. (Yon-Dschun), Fischer, H.-P., Brüning, T. (Thomas), Pesch, B. (Beate), Harth, V. (Volker), Rabstein, S. (Sylvia), Broeks, A. (Annegien), Schmidt, M.K. (Marjanka), Veer, L.J. (Laura) van 't, Braaf, L.M. (Linde), Johnson, N. (Nichola), Fletcher, O. (Olivia), Gibson, L.J. (Lorna), Peto, J. (Julian), Turnbull, C. (Clare), Seal, S. (Sheila), Renwick, A. (Anthony), Rahman, N. (Nazneen), Wu, P.-E. (Pei-Ei), Yu, J-C. (Jyh-Cherng), Hsiung, C.-N. (Chia-Ni), Shen, C-Y. (Chen-Yang), Southey, M.C. (Melissa), Hopper, J.L. (John), Hammet, F. (Fleur), Dorpe, T. (Thijs) van, Dieudonné, A.-S. (Anne-Sophie), Hatse, S. (Sigrid), Lambrechts, D. (Diether), Andrulis, I.L. (Irene), Bogdanova, N.V. (Natalia), Antonenkova, N.N. (Natalia), Rogov, J.I. (Juri), Prokofieva, D. (Daria), Bermisheva, M. (Marina), Khusnutdinova, E.K. (Elza), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Hooning, M.J. (Maartje), Devilee, P. (Peter), Margolin, S. (Sara), Lindblom, A. (Annika), Milne, R.L. (Roger), Arias Pérez, J.I. (José Ignacio), Zamora, M.P. (Pilar), Benítez, J. (Javier), Severi, G. (Gianluca), Baglietto, L. (Laura), Giles, G.G. (Graham), Chenevix-Trench, G. (Georgia), Spurdle, A.B. (Amanda), Beesley, J. (Jonathan), Chen, X. (Xiaoqing), Holland, H. (Helene), Healey, S. (Sue), Wang-Gohrke, S. (Shan), Chang-Claude, J. (Jenny), Mannermaa, A. (Arto), Kosma, V-M. (Veli-Matti), Kauppinen, J. (Jaana), Kataja, V. (Vesa), Agnarsson, B.A. (Bjarni), Caligo, M.A. (Maria), Godwin, A.K. (Andrew), Nevanlinna, H. (Heli), Heikinen, T. (Tuomas), Fredericksen, Z. (Zachary), Lindor, N.M. (Noralane), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Loman, N. (Niklas), Karlsson, P. (Per), Askmalm, M.S. (Marie), Melin, B. (Beatrice), Wachenfeldt, A. (Anna) von, Hogervorst, F.B.L. (Frans), Verheus, M. (Martijn), Rookus, M.A. (Matti), Seynaeve, C.M. (Caroline), Oldenburg, R.A. (Rogier), Ligtenberg, M.J. (Marjolijn), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Gille, H.J.P. (Hans), Wijnen, J.T. (Juul), Gómez García, E.B. (Encarna), Peock, S. (Susan), Cook, M. (Margaret), Oliver, C.T. (Clare), Frost, D. (Debra), Luccarini, C. (Craig), Pichert, G. (Gabriella), Davidson, R. (Rosemarie), Eccles, D. (Diana), Ong, K.-R. (Kai-Ren), Cook, J. (Jackie), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Evans, D.G. (Gareth), Eeles, R. (Rosalind), Gold, B. (Bert), Wang, X. (Xianshu), and Chu, C. (Carol)

Abstract

Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I2 = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.

Published
2012
Full Text
View/download PDF

22. Untersuchung des Einflusses einer differenzierten Klassifizierung des NAT2-Acetyliererstatus als potenzieller Suszeptibilitätsfaktor für Brustkrebs

Author

Rabstein, S, primary, Brüning, T, additional, Harth, V, additional, Fischer, H, additional, Haas, S, additional, Christina, J, additional, Illig, T, additional, Vollmert, C, additional, Christian, B, additional, Spickenheuer, A, additional, Hamann, U, additional, Brauch, H, additional, and Pesch, B, additional

Published
2010
Full Text
View/download PDF

24. Beruf — Umwelt — Prävention

Author

Pfefferle, P. I., primary, Kaminski, A., additional, Benz, D., additional, Renz, H., additional, Soost, S., additional, Graupner, I., additional, Morch-Röder, A., additional, Pohrt, U., additional, Worm, M., additional, Bünger, J., additional, Raulf-Heimsoth, M., additional, Sander, I., additional, Brüning, T., additional, Merget, R., additional, Schröder, C. M., additional, Lange, K., additional, Breuer, K., additional, Skudlik, C., additional, John, S., additional, van Kampen, V., additional, Liebers, V., additional, Rabstein, S., additional, Broding, H., additional, Keller, C., additional, Müsken, H., additional, Overlack, A., additional, Schultze-Werninghaus, G., additional, Walusiak, J., additional, Muche-Borowski, C., additional, Schäfer, T., additional, Zahradnik, E., additional, Tolba, R., additional, Renström, A., additional, Doekes, G., additional, Heutelbeck, A., additional, Robert, M., additional, and Hallier, E., additional

Published
2007
Full Text
View/download PDF

28. Menopausal status and factors affecting cessation of menses in the region of Bonn, Germany.

Author

Pierl, C., Rabstein, S., Harth, V., Brüning, T., Brauch, H., Fischer, H., Hamann, U., Justenhoven, C., Ko, Y., and Pesch, B.

Abstract

Because of the high prevalence of hormone use and reproductive surgeries in Western women natural menopause is a less frequent condition. Our aim was to examine the influences of hormonal and other factors on timing of cessation of menses. We analysed population controls of a German case-control study on breast cancer risks. The sample comprised N=829 women without hysterectomy or bilateral oophorectomy. We estimated the risk for the occurrence of last menses by Cox proportional hazard modelling. For calculating hazard rate ratios (HRR) and 95% confidence intervals (CI) women with menstrual cycles up to one year before interview were censored at that age. Median age at cessation of menses was 50 years (inter-quartile range 47–53 years). A significant later cessation of menses resulted from oral contraceptive use (HRR 0.74, 95% CI 0.59–0.93 for up to 10 years), and hormone therapy use until last menses (HRR 0.57, 95% CI 0.47–0.70). Also, thyroidal medications were associated with a delayed cessation of menses (HRR 0.64, 95% CI 0.42–0.96 for more than 10 years of use). Smoking until at least two years before last menses and allergies revealed an earlier cessation of bleedings (HRR 1.50, 95% CI 1.22–1.83 and HRR 1.28, 95% CI 1.07–1.53 respectively). Natural menopause is difficult to determine. Factors affecting the ovaries or the endocrine system can modulate timing of menopause. Endocrine biomarkers should be additionally taken into account when defining menopausal status. [ABSTRACT FROM AUTHOR]

Published
2007
Full Text
View/download PDF

29. Determination of sequence variants of metabolizing enzymes after occupational exposure to fumes of bitumen under high processing temperatures.

Author

Rihs H, Raulf-Heimsoth M, Spickenheuer A, Rabstein S, Pesch B, Schott K, Bramer R, Angerer J, Hahn J, and Brüning T

Abstract

Data concerning the influence of sequence variants of metabolizing enzymes on the effect modulation of current exposure to fumes of bitumen in humans are limited. To assess effect modulation of genetic variants of metabolizing enzymes, 18 single nucleotide polymorphisms (SNPs) in metabolic enzymes were analyzed regarding their impact on the urinary levels of metabolites of polycyclic aromatic hydrocarbons. Based on personal ambient monitoring data for bitumen emissions a group of 180 workers exposed to fumes of bitumen under high processing temperatures during a shift were divided into two exposure groups: 24 with high exposure (> 10 mg/m(3)) and 156 with low ( G, which showed increased levels of 1-OHP (p = 0.013) and OHPhe (p = 0.001). The GG variant of EPHX1 15543A > G showed a significant effect (p = 0.006) only on OHPhe. Selected variants of metabolic enzymes can modulate the metabolite levels under exposure to bitumen. The SNP-related modulation of these biomarkers did not exceed a factor of two and is more pronounced for OHPhe than for 1-OHP. [ABSTRACT FROM AUTHOR]

Published
2007

30. ERCC2 genotypes and a corresponding haplotype are linked with breast cancer risk in a German population

Author

Justenhoven C, Hamann U, Pesch B, Harth V, Rabstein S, Baisch C, Vollmert C, Illig T, Yd, Ko, Brüning T, and Hiltrud Brauch

Abstract

The polygenic concept of breast cancer susceptibility calls for the identification of genetic variants that contribute to breast cancer risk. Reduced DNA repair proficiencies in women with breast cancer pointed to a possible role of DNA repair enzymes in the risk to develop the disease. The nucleotide excision repair enzyme encoded by the excision repair cross-complementing group 2 gene ERCC2 (formerly XPD) known to cause skin cancer by germ line mutations has multiple regulatory cellular functions, including nucleotide excision repair, basal transcription, cell cycle control, and apoptosis. ERCC2 polymorphisms ERCC2_6540_G>A (Asp312Asn) and ERCC2_18880_A>C (Lys751Gln) within the coding region of this evolutionarily highly conserved gene have been of functional relevance and therefore are potential candidates to confer breast cancer susceptibility. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we analyzed genotype frequencies in constitutional DNA of study participants of a German case-control study that included 688 cases of incident breast cancer and 724 population-based, age-matched controls. We identified ERCC2_6540_GG (Asp312Asp) as an at-risk genotype [odds ratio (OR), 2.06; 95% confidence interval (95% CI), 1.39-3.07]. The ERCC2_6540_GG-associated breast cancer risk was even higher in women who were also carriers of the ERCC2_18880_CC (Gln751Gln) genotype (OR, 3.69; 95% CI, 1.76-7.74). We identified ERCC2_6540_G/ERCC2_18880_C (Asp312/Gln751) as the most potent risk-conferring haplotype (OR, 3.49; 95% CI, 2.30-5.28). To our knowledge, this is the first study assigning breast cancer risk to both the ERCC2 genotype encoding Asp312Asp and the haplotype encoding Asp312/Gln751.

31. N-acetyltransferase 2 phenotype, occupation, and bladder cancer risk: results from the EPIC cohort

Author

Mattias Johansson, Pietro Ferrari, Salvatore Panico, Kim Overvad, Hans-Peter Rihs, Timothy J. Key, Miren Dorronsoro, Domenico Palli, Martine M. Ros, Paolo Vineis, José Ramón Quirós, Jenny Chang-Claude, Roy Ehrnström, H. Bas Bueno-de-Mesquita, Sylvia Rabstein, Anne Tjønneland, Aurelio Barricarte, Carlos González, Elio Riboli, Laure Dossus, Katarzyna Gawrych, Kay-Tee Khaw, Isabelle Romieu, Börje Ljungberg, Marie-Christine Boutron-Ruault, Steffen Weikert, María José Sánchez, Norman Klopp, Françoise Clavel-Chapelon, Rudolph Kaaks, Sabina Sieri, Carmen Navarro, Dimitrios Trichopoulos, Hui Ding, Jürgen Angerer, Nicholas J. Wareham, Swaantje Casjens, Nina Roswall, David Ulmert, Heiner Boeing, Beate Pesch, Thomas Brüning, Rosario Tumino, Tobias Weiss, Thomas Illig, Pesch, B, Gawrych, K, Rabstein, S, Weiss, T, Casjens, S, Rihs, Hp, Ding, H, Angerer, J, Illig, T, Klopp, N, Bueno de Mesquita, B, Ros, Mm, Kaaks, R, Chang Claude, J, Roswall, N, Tj?nneland, A, Overvad, K, Clavel Chapelon, F, Boutron Ruault, Mc, Dossus, L, Boeing, H, Weikert, S, Trichopoulos, D, Palli, D, Sieri, S, Tumino, R, Panico, Salvatore, Quir?s, Jr, Gonz?lez, C, S?nchez, Mj, Dorronsoro, M, Navarro, C, Barricarte, A, Ljungberg, B, Johansson, M, Ulmert, D, Ehrnstr?m, R, Khaw, Kt, Wareham, N, Key, Tj, Ferrari, P, Romieu, I, Riboli, E, Br?ning, T, and Vineis, P.

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Pathology, Genotype, Epidemiology, Arylamine N-Acetyltransferase, Polymorphism, Single Nucleotide, Young Adult, Risk Factors, Internal medicine, Occupational Exposure, medicine, Humans, Amines, Polycyclic Aromatic Hydrocarbons, Genotyping, Genetic testing, Aged, Bladder cancer, medicine.diagnostic_test, business.industry, Acetylation, Middle Aged, medicine.disease, Confidence interval, European Prospective Investigation into Cancer and Nutrition, Phenotype, Urinary Bladder Neoplasms, Case-Control Studies, Cohort, Female, business, Cohort study
Abstract

Background: An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case–control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case–control study nested in the European Prospective Investigation into Cancer and Nutrition. Methods: Exposure to aromatic amines and polycyclic aromatic hydrocarbons (PAH) could be assessed for 754 cases and 833 controls for whom occupational information was documented. A semiquantitative job-exposure matrix was applied to at-risk occupations to estimate the exposure as low, medium, or high based on tertiles of the distribution of the exposure score in controls. Using a comprehensive genotyping, NAT2 acetylation status could be categorized from 6-single-nucleotide polymorphism genotypes as slow or fast in 607 cases and 695 controls with DNA from archived blood samples. Results: Occupational exposure to aromatic amines and PAH was associated with an increased bladder cancer risk [upper tertile of the distribution of the exposure score: OR = 1.37; 95% confidence interval (CI), 1.02–1.84, and OR = 1.50; 95% CI, 1.09–2.05, respectively]. NAT2 slow acetylation did not modify these risk estimates and was not itself associated with bladder cancer risk (OR = 1.02; 95% CI, 0.81–1.29). Conclusions: These findings confirm established or suspected occupational risk factors but not the anticipated role of NAT2 slow acetylation in bladder cancer. No interaction was detected between NAT2 and any exposure of interest, including smoking. Impact: Genetic testing for NAT2 would be inappropriate in occupational settings. Cancer Epidemiol Biomarkers Prev; 22(11); 2055–65. ©2013 AACR.

Published
2013
Full Text
View/download PDF

33. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

Author

Jing Hua Zhao, Vilmundur Gudnason, Robin Haring, Enda M. Byrne, Christian Gieger, Marek Zygmunt, Lude Franke, Peter Kraft, Eric Boerwinkle, Matthias W. Beckmann, Catharina A. Hartman, Thorkild I. A. Sørensen, Aida Karina Dieffenbach, André G. Uitterlinden, Grant W. Montgomery, Graham G. Giles, Felix R. Day, Anja Rudolph, Arto Mannermaa, Sven Bergmann, Nora Franceschini, Julian Peto, Ellen W. Demerath, Diana L. Cousminer, Wei Ang, Gudmar Thorleifsson, Patrick F. McArdle, Dieter Flesch-Janys, Albertine J. Oldehinkel, Irene L. Andrulis, Aarno Palotie, Nicholas J. Timpson, Paolo Peterlongo, Johan G. Eriksson, Bernardo Bonanni, Dorret I. Boomsma, J. Margriet Collée, Immaculata De Vivo, Bjarke Feenstra, Teresa Ferreira, Cornelia M. van Duijn, Nancy L. Pedersen, Deborah J. Thompson, Peter Vollenweider, Douglas F. Easton, Pascal Guénel, Anna Maria Storniolo, Erik Ingelsson, Gisli Masson, Annika Lindblom, Stefania Bandinelli, Elisabeth Widen, Doris Stöckl, Veikko Salomaa, Zoltán Kutalik, Nicholas J. Wareham, Joanne M. Murabito, Eleonora Porcu, Fergus J. Couch, Katri Pylkäs, Luigi Ferrucci, Wendy L. McArdle, Frank Geller, Andrea D. Coviello, Lynda M. Rose, Daniel L. Koller, Ute Hamann, Ulla Sovio, Daniel F. Gudbjartsson, Georgia Chenevix-Trench, Roger L. Milne, Unnur Thorsteinsdottir, Paul M. Ridker, Henry Völzke, John R. B. Perry, Stephen J. Chanock, Tanguy Corre, Mads Melbye, Ben A. Oostra, Albert V. Smith, Tõnu Esko, Melissa E. Garcia, Debbie A Lawlor, Meir J. Stampfer, Per Hall, Patrick Sulem, Massimo Mangino, Nicholas G. Martin, David J. Hunter, Laura Crisponi, Tatiana Foroud, Antonietta Robino, Michael J. Econs, Susan M. Ring, Natalia Tšernikova, Dirkje S. Postma, Lavinia Paternoster, Peter A. Fasching, Tamara B. Harris, Ellen A. Nohr, Javier Benitez, Ruth J. F. Loos, Robert Winqvist, Andres Metspalu, Jenny A. Visser, Heather A. Boyd, Jonathan Tyrer, Alexander Teumer, Tim D. Spector, Sandra Lai, Douglas P. Kiel, Kamila Czene, Hiltrud Brauch, George Davey Smith, Julia A. Knight, Erin K. Wagner, Suiqun Guo, Tune H. Pers, Patrik K. E. Magnusson, Kathryn L. Lunetta, Hoda Anton-Culver, Marjanka K. Schmidt, George McMahon, Ken K. Ong, Adamo Pio D'Adamo, Veli-Matti Kosma, Jinhui Chen, Paul D.P. Pharoah, Diether Lambrechts, Femke Atsma, Serena Sanna, Ilja M. Nolte, Eco de Geus, Daniel I. Chasman, Emmi Tikkanen, John L. Hopper, Anna Murray, Laura M. Yerges-Armstrong, Sanela Kjellqvist, Eva Albrecht, Hermann Brenner, Paolo Gasparini, Bruce H. R. Wolffenbuttel, Alison M. Dunning, John P. Rice, Craig E. Pennell, Mark I. McCarthy, Andrea Ganna, Henri Wallaschofski, Frank B. Hu, Gérard Waeber, Henrik Flyger, Evelin Mihailov, Peter Devilee, Lisette Stolk, Behrooz Z. Alizadeh, Jouke-Jan Hottenga, Najaf Amin, Patrick Neven, Reedik Mägi, Kyriaki Michailidou, Kari Stefansson, Munro Peacock, Julie E. Buring, Laura J. Bierut, Cathy E. Elks, Marjo-Riitta Järvelin, Montserrat Garcia-Closas, Anneli Pouta, David Schlessinger, Harold Snieder, Chunyan He, Joe Dennis, Heli Nevanlinna, Gonneke Willemsen, Andrew C. Heath, Elizabeth A. Streeten, Albert Hofman, Angela Cox, Maartje J. Hooning, Lili Milani, Margaret J. Wright, Fernando Rivadeneira, Gudny Eiriksdottir, Mellissa C. Southey, Qin Wang, Paolo Radice, Manjeet K. Bolla, Kay-Tee Khaw, Carl Blomqvist, Melanie Waldenberger, Sheila Ulivi, David Couper, Jenny Chang-Claude, David Karasik, Stig E. Bojesen, Andrew D. Johnson, David P. Strachan, Perry, John [0000-0001-6483-3771], Day, Felix [0000-0003-3789-7651], Thompson, Deborah [0000-0003-1465-5799], Zhao, Jing Hua [0000-0003-4930-3582], Dennis, Joe [0000-0003-4591-1214], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Sovio, Ulla [0000-0002-0799-1105], Tyrer, Jonathan [0000-0003-3724-4757], Wang, Jean [0000-0002-9139-0627], Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Easton, Douglas [0000-0003-2444-3247], Ong, Kenneth [0000-0003-4689-7530], Apollo - University of Cambridge Repository, Australian Ovarian Cancer Study, GENICA Network, kConFab, LifeLines Cohort Study, InterAct Consortium, Early Growth Genetics (EGG) Consortium, Cousminer, D.L., Stergiakouli, E., Berry, D.J., Ang, W., Groen-Blokhuis, M.M., Körner, A., Siitonen, N., Ntalla, I., Marinelli, M., Perry, J.R., Kettunen, J., Jansen, R., Surakka, I., Timpson, N.J., Ring, S., McMahon, G., Power, C., Wang, C., Kähönen, M., Viikari, J., Lehtimäki, T., Middeldorp, C.M., Hulshoff Pol, H.E., Neef, M., Weise, S., Pahkala, K., Niinikoski, H., Zeggini, E., Panoutsopoulou, K., Bustamante, M., Penninx, B.W., Murabito, J., Torrent, M., Dedoussis, G.V., Kiess, W., Boomsma, D.I., Pennell, C.E., Raitakari, O.T., Hyppönen, E., Davey Smith, G., Ripatti, S., McCarthy, M.I., Widén, E., Alizadeh, B.Z., de Boer, R.A., Boezen, H.M., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, H.L., van der Klauw, M.M., Navis, G., Ormel, J., Postma, D., Rosmalen, J.G., Slaets, J.P., Snieder, H., Stolk, R.P., Wolffenbuttel, B.H., Wijmenga, C., Forouhi, N., Kerrison, N.D., Langenberg, C., Scott, R.A., Sharp, S.J., Sims, M., Barroso, I., Deloukas, P., Arriola, L., Balkau, B., Barricarte, A., Boeing, H., Franks, P.W., Gonzalez, C., Grioni, S., Kaaks, R., Key, T.J., Navarro, C., Nilsson, P.M., Overvad, K., Palli, D., Panico, S., Quirós, J., Rolandsson, O., Sacerdote, C., Sánchez, M.J., Slimani, N., Tjonneland, A., Tumino, R., van der A, D.L., van der Schouw, Y.T., Riboli, E., Wareham, N.J., Bowtell, D.D., Green, A., Chenevix-Trench, G., deFazio, A., Gertig, D., Webb, P.M., Brauch, H., Justenhoven, C., Hamann, U., Ko, Y.D., Baisch, C., Fischer, H.P., Pesch, B., Rabstein, S., Spickenheuer, A., Harth, V., Aghmesheh, M., Amor, D., Andrews, L., Antill, Y., Armitage, S., Arnold, L., Balleine, R., Bankier, A., Bastick, P., Beesley, J., Beilby, J., Bennett, I., Bennett, B., Berry, G., Blackburn, A., Bogwitz, M., Brennan, M., Brown, M., Buckley, M., Burgess, M., Burke, J., Butow, P., Byron, K., Callen, D., Campbell, I., Chauhan, D., Christian, A., Clarke, C., Colley, A., Cotton, D., Crook, A., Cui, J., Culling, B., Cummings, M., Dawson, S.J., Delatycki, M., Dickson, R., Dixon, J., Dobrovic, A., Dudding, T., Edkins, T., Edwards, S., Eisenbruch, M., Farshid, G., Fawcett, S., Fellows, A., Fenton, G., Field, M., Firgaira, F., Flanagan, J., Fleming, J., Fong, P., Forbes, J., Fox, S., French, J., Friedlander, M., Gaff, C., Gardner, M., Gattas, M., George, P., Giles, G., Gill, G., Goldblatt, J., Greening, S., Grist, S., Eric, H., Hardie, K., Harris, M., Hart, S., Hayward, N., Healey, S., Heiniger, L., Hopper, J., Humphrey, E., Hunt, C., James, P., Jenkins, M., Jones, A., Kefford, R., Kidd, A., Kiely, B., Kirk, J., Koehler, J., Kollias, J., Kovalenko, S., Lakhani, S., Leaming, A., Leary, J., Lim, J., Lindeman, G., Lipton, L., Lobb, L., Mann, G., Marsh, D., McLachlan, S.A., Meiser, B., Meldrum, C., Milne, R., Mitchell, G., Newman, B., O'Connell, S., O'Loughlin, I., Osborne, R., Pachter, N., Patterson, B., Peters, L., Phillips, K., Price, M., Purser, L., Reeve, J., Reeve, T., Richards, R., Rickard, E., Robinson, B., Rudzki, B., Saleh, M., Salisbury, E., Sambrook, J., Saunders, C., Saunus, J., Sayer, R., Scott, E., Scott, R., Scott, C., Seshadri, R., Sexton, A., Sharma, R., Shelling, A., Simpson, P., Southey, M., Spurdle, A., Suthers, G., Sykes, P., Taylor, D., Taylor, J., Thierry, B., Thompson, E., Thorne, H., Townshend, S., Trainer, A., Tran, L., Tucker, K., Tyler, J., Visvader, J., Walker, L., Walpole, I., Waring, P., Warner, B., Warren, G., Williams, R., Wilson, J., Winship, I., Wu, K., Young, M.A., Public Health, Internal Medicine, Epidemiology, Clinical Genetics, Medical Oncology, Child and Adolescent Psychiatry / Psychology, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Groningen Research Institute for Asthma and COPD (GRIAC), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Political Science, Perry, John R. B, Day, Felix, Elks, Cathy E, Sulem, Patrick, Thompson, Deborah J, Ferreira, Teresa, He, Chunyan, Chasman, Daniel I, Esko, Tõnu, Thorleifsson, Gudmar, Albrecht, Eva, Ang, Wei Q, Corre, Tanguy, Cousminer, Diana L, Feenstra, Bjarke, Franceschini, Nora, Ganna, Andrea, Johnson, Andrew D, Kjellqvist, Sanela, Lunetta, Kathryn L, Mcmahon, George, Nolte, Ilja M, Paternoster, Lavinia, Porcu, Eleonora, Smith, Albert V, Stolk, Lisette, Teumer, Alexander, Tšernikova, Natalia, Tikkanen, Emmi, Ulivi, Sheila, Wagner, Erin K, Amin, Najaf, Bierut, Laura J, Byrne, Enda M, Hottenga, Jouke Jan, Koller, Daniel L, Mangino, Massimo, Pers, Tune H, Yerges Armstrong, Laura M, Hua Zhao, Jing, Andrulis, Irene L, Anton Culver, Hoda, Atsma, Femke, Bandinelli, Stefania, Beckmann, Matthias W, Benitez, Javier, Blomqvist, Carl, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Buring, Julie E, Chang Claude, Jenny, Chanock, Stephen, Chen, Jinhui, Chenevix Trench, Georgia, Collée, J. Margriet, Couch, Fergus J, Couper, David, Coviello, Andrea D, Cox, Angela, Czene, Kamila, D'Adamo, Adamo Pio, Davey Smith, George, De Vivo, Immaculata, Demerath, Ellen W, Dennis, Joe, Devilee, Peter, Dieffenbach, Aida K, Dunning, Alison M, Eiriksdottir, Gudny, Eriksson, Johan G, Fasching, Peter A, Ferrucci, Luigi, Flesch Janys, Dieter, Flyger, Henrik, Foroud, Tatiana, Franke, Lude, Garcia, Melissa E, García Closas, Montserrat, Geller, Frank, de Geus, Eco E. J, Giles, Graham G, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Guénel, Pascal, Guo, Suiqun, Hall, Per, Hamann, Ute, Haring, Robin, Hartman, Catharina A, Heath, Andrew C, Hofman, Albert, Hooning, Maartje J, Hopper, John L, Hu, Frank B, Hunter, David J, Karasik, David, Kiel, Douglas P, Knight, Julia A, Kosma, Veli Matti, Kutalik, Zoltan, Lai, Sandra, Lambrechts, Diether, Lindblom, Annika, Mägi, Reedik, Magnusson, Patrik K, Mannermaa, Arto, Martin, Nicholas G, Masson, Gisli, Mcardle, Patrick F, Mcardle, Wendy L, Melbye, Mad, Michailidou, Kyriaki, Mihailov, Evelin, Milani, Lili, Milne, Roger L, Nevanlinna, Heli, Neven, Patrick, Nohr, Ellen A, Oldehinkel, Albertine J, Oostra, Ben A, Palotie, Aarno, Peacock, Munro, Pedersen, Nancy L, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P, Postma, Dirkje S, Pouta, Anneli, Pylkäs, Katri, Radice, Paolo, Ring, Susan, Rivadeneira, Fernando, Robino, Antonietta, Rose, Lynda M, Rudolph, Anja, Salomaa, Veikko, Sanna, Serena, Schlessinger, David, Schmidt, Marjanka K, Southey, Mellissa C, Sovio, Ulla, Stampfer, Meir J, Stöckl, Dori, Storniolo, Anna M, Timpson, Nicholas J, Tyrer, Jonathan, Visser, Jenny A, Vollenweider, Peter, Völzke, Henry, Waeber, Gerard, Waldenberger, Melanie, Wallaschofski, Henri, Wang, Qin, Willemsen, Gonneke, Winqvist, Robert, Wolffenbuttel, Bruce H. R, Wright, Margaret J, Boomsma, Dorret I, Econs, Michael J, Khaw, Kay Tee, Loos, Ruth J. F, Mccarthy, Mark I, Montgomery, Grant W, Rice, John P, Streeten, Elizabeth A, Thorsteinsdottir, Unnur, van Duijn, Cornelia M, Alizadeh, Behrooz Z, Bergmann, Sven, Boerwinkle, Eric, Boyd, Heather A, Crisponi, Laura, Gasparini, Paolo, Gieger, Christian, Harris, Tamara B, Ingelsson, Erik, Järvelin, Marjo Riitta, Kraft, Peter, Lawlor, Debbie, Metspalu, Andre, Pennell, Craig E, Ridker, Paul M, Snieder, Harold, Sørensen, Thorkild I. A, Spector, Tim D, Strachan, David P, Uitterlinden, André G, Wareham, Nicholas J, Widen, Elisabeth, Zygmunt, Marek, Murray, Anna, Easton, Douglas F, Stefansson, Kari, Murabito, Joanne M, Ong, Ken K., Panico, Salvatore, Perry, John R. B., Elks, Cathy E., Thompson, Deborah J., Chasman, Daniel I., Ang, Wei Q., Cousminer, Diana L., Johnson, Andrew D., Lunetta, Kathryn L., Nolte, Ilja M., Smith, Albert V., Wagner, Erin K., Bierut, Laura J., Byrne, Enda M., Koller, Daniel L., Pers, Tune H., Yerges Armstrong, Laura M., Zhao, Jing Hua, Andrulis, Irene L., Beckmann, Matthias W., Bojesen, Stig E., Bolla, Manjeet K., Buring, Julie E., Couch, Fergus J., Coviello, Andrea D., D'Adamo, ADAMO PIO, Smith, George Davey, Demerath, Ellen W., Dieffenbach, Aida K., Dunning, Alison M., Eriksson, Johan G., Fasching, Peter A., Garcia, Melissa E., De Geus, Eco E. J., Giles, Graham G., Gudbjartsson, Daniel F., Hartman, Catharina A., Heath, Andrew C., Hooning, Maartje J., Hopper, John L., Hu, Frank B., Hunter, David J., Kiel, Douglas P., Knight, Julia A., Magnusson, Patrik K., Martin, Nicholas G., Mcardle, Patrick F., Mcardle, Wendy L., Milne, Roger L., Nohr, Ellen A., Oldehinkel, Albertine J., Oostra, Ben A., Pedersen, Nancy L., Pharoah, Paul D. P., Postma, Dirkje S., Rose, Lynda M., Schmidt, Marjanka K., Southey, Mellissa C., Stampfer, Meir J., Storniolo, Anna M., Timpson, Nicholas J., Visser, Jenny A., Wolffenbuttel, Bruce H. R., Wright, Margaret J., Boomsma, Dorret I., Econs, Michael J., Loos, Ruth J. F., Mccarthy, Mark I., Montgomery, Grant W., Rice, John P., Streeten, Elizabeth A., Van Duijn, Cornelia M., Alizadeh, Behrooz Z., Boyd, Heather A., Harris, Tamara B., Pennell, Craig E., Ridker, Paul M., Sørensen, Thorkild I. A., Spector, Tim D., Strachan, David P., Uitterlinden, André G., Wareham, Nicholas J., Easton, Douglas F., and Murabito, Joanne M.

Subjects
Netherlands Twin Register (NTR), Male, Parents, CENTRAL PRECOCIOUS PUBERTY, Genome-wide association study, Disease, VARIANTS, DISEASE, Body Mass Index, 0302 clinical medicine, Adolescent, Age Factors, Alleles, Breast Neoplasms/genetics, Cardiovascular Diseases/genetics, Child, Diabetes Mellitus, Type 2/genetics, Europe/ethnology, Female, Genetic Loci/genetics, Genome-Wide Association Study, Genomic Imprinting/genetics, Humans, Hypothalamo-Hypophyseal System/physiology, Intercellular Signaling Peptides and Proteins/genetics, Membrane Proteins/genetics, Menarche/genetics, Obesity/genetics, Ovary/physiology, Polymorphism, Single Nucleotide/genetics, Potassium Channels, Tandem Pore Domain/genetics, Proteins/genetics, Quantitative Trait Loci/genetics, Receptors, GABA-B/metabolism, Receptors, Retinoic Acid/metabolism, Ribonucleoproteins/genetics, Intercellular Signaling Peptides and Protein, Age Factor, Tandem Pore Domain, GENE-EXPRESSION, 0303 health sciences, BREAST-CANCER RISK, 3. Good health, Ribonucleoproteins, Cardiovascular Diseases, Menarche, Intercellular Signaling Peptides and Proteins, Science & Technology - Other Topics, GENICA Network, Breast Neoplasm, Type 2, Human, Hypothalamo-Hypophyseal System, Quantitative Trait Loci, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, REVEALS, Diabetes Mellitus, Polymorphism, METAANALYSIS, Science & Technology, ta1184, Calcium-Binding Proteins, Proteins, HUMAN PREFRONTAL CORTEX, ta3121, ta3123, Diabetes Mellitus, Type 2, Genetic Loci, CELLS, 030217 neurology & neurosurgery, LifeLines Cohort Study, Potassium Channels, Receptors, Retinoic Acid, Retinoic Acid, Australian Ovarian Cancer Study, Polymorphism (computer science), Cardiovascular Disease, Receptors, WIDE ASSOCIATION, Membrane Protein, Allele, 2. Zero hunger, Genetics, Multidisciplinary, Single Nucleotide, Europe, Multidisciplinary Sciences, kConFab, Breast Neoplasms, Genomic Imprinting, Membrane Proteins, Obesity, Ovary, Polymorphism, Single Nucleotide, Potassium Channels, Tandem Pore Domain, Receptors, GABA-B, General Science & Technology, Ubiquitin-Protein Ligases, Quantitative trait locus, Biology, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Early Growth Genetics (EGG) Consortium, 030304 developmental biology, Protein, GABA-B, Ribonucleoprotein, InterAct Consortium, Genetic architecture, Parent, Genomic imprinting
Abstract

Contains fulltext : 136472.pdf (Publisher’s version ) (Closed access) Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

Full Text
View/download PDF

34. Altered coordination between sleep timing and cortisol profiles in night working female hospital employees.

Author

Burek K, Rabstein S, Kantermann T, Vetter C, Wang-Sattler R, Lehnert M, Pallapies D, Jöckel KH, Brüning T, and Behrens T

Subjects
Humans, Female, Adult, Middle Aged, Cross-Sectional Studies, Personnel, Hospital, Wakefulness physiology, Polysomnography, Hydrocortisone analysis, Hydrocortisone metabolism, Saliva chemistry, Saliva metabolism, Circadian Rhythm physiology, Sleep physiology, Shift Work Schedule, Work Schedule Tolerance physiology
Abstract

Background: Cortisol typically peaks in the morning after waking up and declines throughout the day, reaching its lowest levels during nighttime sleep. Shift work can cause misalignment between cortisol levels and sleep-wake timing. We analyzed this misalignment in female shift workers focusing on the timing and extent of these changes., Methods: We conducted a cross-sectional study involving 68 shift workers (aged 37 ± 10 years) and 21 non-shift workers (aged 45 ± 10 years) from a hospital. Shift workers were monitored through two day shifts and three night shifts, whereas non-shift workers were monitored during two day shifts. Each participant collected six to eight saliva samples (depending on their shift type) and provided sleep timing information, which was recorded via polysomnography and sleep diaries. Generalized additive mixed models were used to estimate shift-specific differences in cortisol smooth curves. Summary measures calculated for the cortisol smooth curves included cortisol awakening response, peak-to-bed slope, and total output., Results: Between shift workers and non-shift workers, we observed similar diurnal cortisol profiles with a steep negative diurnal slope during day shifts. In shift workers on night shifts, a flattened U-shaped cortisol profile after the post-awakening maximum was observed, with a peak-to-bed slope close to zero. When comparing night to day shifts in the group of shift workers, mean cortisol levels were lower between 42 and 56 minutes and 1.8-11.9 hours after waking up, and higher between 14.9 and 22 hours after waking up., Conclusion: Our findings indicate altered cortisol profiles in female hospital employees on night shifts. Specifically, cortisol levels were lower at night when higher levels would typically be necessary for work activities, and higher at bedtime after a night shift, when levels should normally be low., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
Full Text
View/download PDF

35. Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer.

Author

Wichert K, Hoppe R, Ickstadt K, Behrens T, Winter S, Herold R, Terschüren C, Lo WY, Guénel P, Truong T, Bolla MK, Wang Q, Dennis J, Michailidou K, Lush M, Andrulis IL, Brenner H, Chang-Claude J, Cox A, Cross SS, Czene K, Eriksson M, Figueroa JD, García-Closas M, Goldberg MS, Hamann U, He W, Holleczek B, Hopper JL, Jakubowska A, Ko YD, Lubiński J, Mulligan AM, Obi N, Rhenius V, Shah M, Shu XO, Simard J, Southey MC, Zheng W, Dunning AM, Pharoah PDP, Hall P, Easton DF, Brüning T, Brauch H, Harth V, and Rabstein S

Subjects
Humans, Female, Bayes Theorem, Polymorphism, Single Nucleotide, Logistic Models, Case-Control Studies, Genetic Predisposition to Disease, Breast Neoplasms genetics, Breast Neoplasms epidemiology, Melatonin genetics, Melatonin metabolism
Abstract

Light-at-night triggers the decline of pineal gland melatonin biosynthesis and secretion and is an IARC-classified probable breast-cancer risk factor. We applied a large-scale molecular epidemiology approach to shed light on the putative role of melatonin in breast cancer. We investigated associations between breast-cancer risk and polymorphisms at genes of melatonin biosynthesis/signaling using a study population of 44,405 women from the Breast Cancer Association Consortium (22,992 cases, 21,413 population-based controls). Genotype data of 97 candidate single nucleotide polymorphisms (SNPs) at 18 defined gene regions were investigated for breast-cancer risk effects. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CI) by logistic regression for the main-effect analysis as well as stratified analyses by estrogen- and progesterone-receptor (ER, PR) status. SNP-SNP interactions were analyzed via a two-step procedure based on logic regression. The Bayesian false-discovery probability (BFDP) was used for all analyses to account for multiple testing. Noteworthy associations (BFDP < 0.8) included 10 linked SNPs in tryptophan hydroxylase 2 (TPH2) (e.g. rs1386492: OR = 1.07, 95% CI 1.02-1.12), and a SNP in the mitogen-activated protein kinase 8 (MAPK8) (rs10857561: OR = 1.11, 95% CI 1.04-1.18). The SNP-SNP interaction analysis revealed noteworthy interaction terms with TPH2- and MAPK-related SNPs (e.g. rs1386483 R ∧ rs1473473 D ∧ rs3729931 D : OR = 1.20, 95% CI 1.09-1.32). In line with the light-at-night hypothesis that links shift work with elevated breast-cancer risks our results point to SNPs in TPH2 and MAPK-genes that may impact the intricate network of circadian regulation., (© 2023. The Author(s).)

Published
2023
Full Text
View/download PDF

36. Investigating the influence of shift work rosters on stress measured as cortisol in hair during the SARS-CoV-2 pandemic.

Author

Casjens S, Tisch A, Brenscheidt F, Beermann B, Brüning T, Behrens T, and Rabstein S

Subjects
Hair, Humans, Hydrocortisone, Pandemics, Retrospective Studies, SARS-CoV-2, COVID-19, Shift Work Schedule
Abstract

The COVID-19 pandemic has increased the workload and has affected physical and mental health of many employees. Hair cortisol concentration (HCC) has proven useful as a marker for retrospective assessment of stress in epidemiological studies and was measured here in non-healthcare night-shift workers with standard shifts (8-h shifts) and extended shifts (12-h shifts) before and during the first wave of the COVID-19 pandemic in Germany. Results showed a twofold increase in HCC among shift workers during the first wave of the COVID-19 pandemic compared with previous measurements. Subjectively reported measures of psychosomatic stress were not found to be reliable predictors of HCC. No statistically significant HCC differences were found between rosters. Working 12-h shifts does not appear to be an additional stressor in the already demanding COVID-19 pandemic., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Published
2022
Full Text
View/download PDF

37. Night work, chronotype and cortisol at awakening in female hospital employees.

Author

Burek K, Rabstein S, Kantermann T, Vetter C, Rotter M, Wang-Sattler R, Lehnert M, Pallapies D, Jöckel KH, Brüning T, and Behrens T

Subjects
Adult, Circadian Rhythm physiology, Female, Hospitals, Humans, Middle Aged, Sleep physiology, Hydrocortisone, Work Schedule Tolerance physiology
Abstract

To examine the effect of night shift on salivary cortisol at awakening (C1), 30 min later (C2), and on the cortisol awakening response (CAR, the difference between C2 and C1). We compared shift and non-shift workers with a focus on the impact of worker chronotype. Our study included 66 shift-working females (mean age = 37.3 years, SD = 10.2) and 21 non-shift working females (mean age = 47.0 years, SD = 8.9). The shift workers collected their saliva samples at C1 and C2 on each two consecutive day shifts and night shifts. Non-shift workers collected their samples on two consecutive day shifts. We applied linear mixed-effects models (LMM) to determine the effect of night shift on CAR and log-transformed C1 and C2 levels. LMMs were stratified by chronotype group. Compared to non-shift workers, shift workers before day shifts (i.e. after night sleep) showed lower cortisol at C1 (exp [Formula: see text]=0.58, 95% CI 0.42, 0.81) but not at C2. In shift workers, the CARs after night shifts (i.e. after day sleep) were lower compared to CARs before day shifts ([Formula: see text]= - 11.07, 95% CI - 15.64, - 6.50). This effect was most pronounced in early chronotypes (early: [Formula: see text]= - 16.61, 95% CI - 27.87, - 5.35; intermediate: [Formula: see text]= - 11.82, 95% CI - 18.35, - 5.29; late: [Formula: see text]= - 6.27, 95% CI - 14.28, 1.74). Chronotype did not modify the association between night shift and CAR. In our population of shift workers, there was a mismatch between time of waking up and their natural cortisol peak at waking up (CAR) both during day and night shift duties., (© 2022. The Author(s).)

Published
2022
Full Text
View/download PDF

38. Social jetlag and sleep debts are altered in different rosters of night shift work.

Author

Casjens S, Brenscheidt F, Tisch A, Beermann B, Brüning T, Behrens T, and Rabstein S

Subjects
Adult, Female, Humans, Male, Middle Aged, Surveys and Questionnaires, Time Factors, Young Adult, Circadian Rhythm, Jet Lag Syndrome epidemiology, Shift Work Schedule statistics & numerical data, Sleep Deprivation epidemiology, Sleep Wake Disorders epidemiology, Work Schedule Tolerance
Abstract

Background: Night and shift work are suspected to cause various adverse effects on health and sleep. Sleep deprivation through shift work is assumed to be compensated on free days. So far it is not clear how different shift systems and shift lengths affect sleep structure on work and free days. Especially working night shifts disrupts the circadian rhythm but also extended working hours (12h) might affect sleep characteristics. Hitherto, the magnitude of sleep debt, social jetlag, and Locomotor Inactivity During Sleep (LIDS) in different shift systems is unknown., Methods: Here, we investigated the impact of five different shift rosters on sleep in 129 industrial workers from Germany. Permanent night work with multiple shift systems with and without night shifts and with different shift lengths were compared. Wrist-activity was monitored over 28 days revealing sleep on- and offsets as well as LIDS as proxy for sleep quality. Overall, 3,865 sleep bouts comprising 22,310 hours of sleep were examined., Results: The mean daily age-adjusted sleep duration (including naps) was 6:43h and did not differ between shift workers of different rosters. However, sleep duration on workdays was particularly low in rotational shift systems with 12h-shifts (5:00h), while overall sleep debt was highest. Shift workers showed a median absolute social jetlag of 3:03h, which differed considerably between shift types and rosters (p<0.0001). Permanent night workers had the highest social jetlag (5:08h) and latest mid-sleeps on workdays and free days. Sleep quality was reduced in permanent night shift workers compared with shift workers in other rosters and differed between daytime and nighttime sleep., Conclusions: Shift work leads to partial sleep deprivation, which particularly affects workers in 12h-shifts and permanent night shifts. Working these shifts resulted in higher sleep debts and larger absolute social jetlag whereas sleep quality was especially reduced in permanent night shift workers compared with shift workers of other rosters., Competing Interests: The authors have declared that no competing interests exist.

Published
2022
Full Text
View/download PDF

39. Impact of shift work on the risk of depression.

Author

Behrens T, Burek K, Rabstein S, Wichert K, Erbel R, Eisele L, Arendt M, Dragano N, Brüning T, and Jöckel KH

Subjects
Circadian Rhythm, Depression epidemiology, Female, Humans, Life Style, Male, Middle Aged, Prospective Studies, Shift Work Schedule adverse effects
Abstract

We studied the association between shift work and depressive symptoms in the prospective Heinz Nixdorf Recall Study, considering various demographic, lifestyle and work-related factors. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression (CES-D)-Scale (≥17 points defined as high symptoms) and the Patient Health Questionnaire (PHQ) with a cutoff ≥9, or prescription of an anti-depressant. The definition of shift work included work hours outside 7:00 to 18:00, whereas night work was defined as a shift including work between 0:00 and 5:00. Poisson regression with robust error variances was calculated to estimate relative risks (RR) and 95% confidence intervals (CI), adjusted for age at follow-up, diurnal preference, monthly household income and education. Analyses were stratified by sex. We performed various sensitivity and stratified analyses to test the robustness of our results. At baseline, 1,500 gainfully employed subjects, 45-73 years of age and without a history of depression, were included. Until the 5-year follow-up, 896 participants were observed, and 486 participants survived through the 10-year follow-up. Although most analyses did not reach the level of formal statistical significance, women working night shifts tended to show increased relative risks for depressive symptoms according to the PHQ (RR = 1.78; 95% CI 0.71-4.45), in particular when working night shifts for ≥20 years (RR = 2.70; 95% CI 0.48-15.4). Stratification by age group revealed no increased risks among women above 60 years of age. Stratified analyses indicated that over-commitment was associated with higher risks for depressive symptoms among women (RR = 4.59; 95% CI 0.95-22.2 in the CES-D and RR = 12.7; 95% CI 2.89-56.1 in the PHQ). Exclusion of subgroups for the purpose of sensitivity analyses generally strengthened associations in women, whereas little evidence for an increased risk of depression remained among male shift workers. In summary, negative effects on depression were suggested among female shift workers, although results were based on small numbers. Among men, we did not identify consistently increased risks for depressive symptoms in relation to shift work.

Published
2021
Full Text
View/download PDF

40. Associations between shift work and risk of colorectal cancer in two German cohort studies.

Author

Wichert K, Rabstein S, Stang A, Erbel R, Eisele L, Arendt M, Keimer A, Dragano N, Hoffmann W, Lerch MM, Roskoden FC, Schmidt CO, Völzke H, Jöckel KH, Brüning T, and Behrens T

Subjects
Circadian Rhythm, Cohort Studies, Humans, Male, Risk Factors, Work Schedule Tolerance, Colorectal Neoplasms epidemiology, Colorectal Neoplasms etiology, Shift Work Schedule adverse effects
Abstract

The association between shift work and the risk of colorectal cancer (CRC) is still unclear. Therefore, we studied the associations between exposure to shift or night work and incident CRC in two German population-based cohort studies, the Heinz Nixdorf Recall Study (HNR) and the Study of Health in Pomerania (SHIP). Including up to 6,903 participants, we analyzed the cohorts pooled and individually. We estimated incidence rate ratios (IRRs) with adjusted log-linear Poisson regression models with the natural logarithm of person-years as offset and performed subgroup analyses by sex and tumor localization in HNR. The pooled analysis revealed no increased risks for men working in night shifts (IRR: 1.03, 95% CI: 0.62; 1.71). In male HNR participants, we found an increased risk estimate for cancer of the distal colon in shift workers (IRR: 1.60, 95% CI: 0.53; 4.87) and in shift workers who did not perform night work (IRR: 3.93, 95% CI: 0.98; 15.70), but not in night workers. In SHIP, we observed elevated CRC risk estimates for rotating shift work including night work (IRR: 1.45, 95% CI: 0.72; 2.92) and for long-term exposure (IRR: 1.79, 95% CI: 0.81; 3.92) for men. In conclusion, night-shift work was not associated with CRC, although an increased risk was suggested for rotating shift work including nights in SHIP. The heterogeneity of shift-work jobs and schedules and associated lifestyle factors should be taken into account to disentangle a possible relationship between shift work and the risk for CRC in future investigations.

Published
2020
Full Text
View/download PDF

41. Linking the non-visual effects of light exposure with occupational health.

Author

Price LLA, Udovičić L, Behrens T, van Drongelen A, Garde AH, Hogenelst K, Jensen MA, Khazova M, Nowak K, Rabstein S, Romanus E, and Wolska A

Subjects
Biomarkers, Chronobiology Disorders physiopathology, Chronobiology Disorders therapy, Cognition, Humans, Hydrocortisone analysis, Neuropsychological Tests, Phototherapy methods, Pigments, Biological physiology, Retinal Ganglion Cells physiology, Sunlight, Circadian Rhythm physiology, Occupational Exposure, Occupational Health, Research Design, Shift Work Schedule
Published
2019
Full Text
View/download PDF

42. Decreased psychomotor vigilance of female shift workers after working night shifts.

Author

Behrens T, Burek K, Pallapies D, Kösters L, Lehnert M, Beine A, Wichert K, Kantermann T, Vetter C, Brüning T, and Rabstein S

Subjects
Adult, Female, Germany, Humans, Linear Models, Middle Aged, Reaction Time, Work Schedule Tolerance, Health Personnel psychology, Psychomotor Performance physiology, Shift Work Schedule adverse effects, Wakefulness physiology
Abstract

Background: We compared psychomotor vigilance in female shift workers of the Bergmannsheil University Hospital in Bochum, Germany (N = 74, 94% nurses) after day and night shifts., Methods: Participants performed a 3-minute Psychomotor Vigilance Task (PVT) test bout at the end of two consecutive day and three consecutive night shifts, respectively. Psychomotor vigilance was analyzed with respect to mean reaction time, percentage of lapses and false starts, and throughput as an overall performance score, combining reaction time and error frequencies. We also determined the reaction time coefficient of variation (RTCV) to assess relative reaction time variability after day and night shifts. Further, we examined the influence of shift type (night vs. day) by mixed linear models with associated 95% confidence intervals (CI), adjusted for age, chronotype, study day, season, and the presence of obstructive sleep apnea (OSA)., Results: At the end of a night shift, reaction times were increased (β = 7.64; 95% CI 0.94; 14.35) and the number of lapses higher compared to day shifts (exp(β) = 1.55; 95% CI 1.16-2.08). By contrast, we did not observe differences in the number of false starts between day and night shifts. Throughput was reduced after night shifts (β = -15.52; 95% CI -27.49; -3.46). Reaction times improved across consecutive day and night shifts, whereas the frequency of lapses decreased after the third night. RTCV remained unaffected by both, night shifts and consecutive shift blocks., Discussion: Our results add to the growing body of literature demonstrating that night-shift work is associated with decreased psychomotor vigilance. As the analysis of RTCV suggests, performance deficits may selectively be driven by few slow reactions at the lower end of the reaction time distribution function. Comparing intra-individual PVT-performances over three consecutive night and two consecutive day shifts, we observed performance improvements after the third night shift. Although a training effect cannot be ruled out, this finding may suggest better adaptation to the night schedule if avoiding fast-changing shift schedules., Competing Interests: TB, KB, KW, DP, AB, ML, TBr, and SR as staff of the Institute for Prevention and Occupational Medicine (IPA), are employed at the “Berufsgenossenschaft Rohstoffe und chemische Industrie” (BG RCI), a public body, which is a member of the study’s main sponsor, the German Social Accident Insurance. IPA is an independent research institute of the Ruhr University Bochum. The authors are independent from the German Social Accident Insurance in study design, access to the collected data, responsibility for data analysis and interpretation, and the right to publish. The views expressed in this paper are those of the authors and not necessarily those of the sponsor.The study was funded by the German Social Accident Insurance (DGUV) (Project No.: FF463 FP0321). As stated above, this does not alter our adherence to PLOS ONE policies on sharing data and materials.

Published
2019
Full Text
View/download PDF

43. Differences in twenty-four-hour profiles of blue-light exposure between day and night shifts in female medical staff.

Author

Rabstein S, Burek K, Lehnert M, Beine A, Vetter C, Harth V, Putzke S, Kantermann T, Walther J, Wang-Sattler R, Pallapies D, Brüning T, and Behrens T

Subjects
Adult, Circadian Rhythm, Female, Germany, Humans, Linear Models, Middle Aged, Personnel, Hospital, Radiation Exposure analysis, Shift Work Schedule
Abstract

Light is the strongest zeitgeber currently known for the synchronization of the human circadian timing system. Especially shift workers are exposed to altered daily light profiles. Our objective is the characterization of differences in blue-light exposures between day and night shift taking into consideration modifying factors such as chronotype. We describe 24-hour blue-light profiles as measured with ambient light data loggers (LightWatcher) during up to three consecutive days with either day or night shifts in 100 female hospital staff including 511 observations. Linear mixed models were applied to analyze light profiles and to select time-windows for the analysis of associations between shift work, individual factors, and log mean light exposures as well as the duration of darkness per day. Blue-light profiles reflected different daily activities and were mainly influenced by work time. Except for evening (7-9 p.m.), all time windows showed large differences in blue-light exposures between day and night shifts. Night work reduced the duration of darkness per day by almost 4 h (β^ = -3:48 hh:mm, 95% CI (-4:27; -3.09)). Late chronotypes had higher light exposures in the morning and evening compared to women with intermediate chronotype (e.g. morning β^ = 0.50 log(mW/m 2 /nm), 95% CI (0.08; 0.93)). Women with children had slightly higher light exposures in the afternoon than women without children (β^ = 0.48, 95% CI (-0.10; 1,06)). Time windows for the description of light should be chosen carefully with regard to timing of shifts. Our results are helpful for future studies to capture relevant light exposure differences and potential collinearities with individual factors. Improvement of well-being of shift workers with altered light profiles may therefore require consideration of both - light at the workplace and outside working hours., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Published
2019
Full Text
View/download PDF

44. Dilution correction for dynamically influenced urinary analyte data.

Author

Hertel J, Rotter M, Frenzel S, Zacharias HU, Krumsiek J, Rathkolb B, Hrabe de Angelis M, Rabstein S, Pallapies D, Brüning T, Grabe HJ, and Wang-Sattler R

Subjects
Female, Humans, Indicator Dilution Techniques, Kinetics, Urinalysis
Abstract

Urinary analyte data has to be corrected for the sample specific dilution as the dilution varies intra- and interpersonally dramatically, leading to non-comparable concentration measures. Most methods of dilution correction utilized nowadays like probabilistic quotient normalization or total spectra normalization result in a division of the raw data by a dilution correction factor. Here, however, we show that the implicit assumption behind the application of division, log-linearity between the urinary flow rate and the raw urinary concentration, does not hold for analytes which are not in steady state in blood. We explicate the physiological reason for this short-coming in mathematical terms and demonstrate the empirical consequences via simulations and on multiple time-point metabolomic data, showing the insufficiency of division-based normalization procedures to account for the complex non-linear analyte specific dependencies on the urinary flow rate. By reformulating normalization as a regression problem, we propose an analyte specific way to remove the dilution variance via a flexible non-linear regression methodology which then was shown to be more effective in comparison to division-based normalization procedures. In the progress, we developed several, easily applicable methods of normalization diagnostics to decide on the method of dilution correction in a given sample. On the way, we identified furthermore the time-span since last urination as an important variance factor in urinary metabolome data which is until now completely neglected. In conclusion, we present strong theoretical and empirical evidence that normalization has to be analyte specific in dynamically influenced data. Accordingly, we developed a normalization methodology for removing the dilution variance in urinary data respecting the single analyte kinetics., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Published
2018
Full Text
View/download PDF

45. Night Shift Work Affects Urine Metabolite Profiles of Nurses with Early Chronotype.

Author

Rotter M, Brandmaier S, Covic M, Burek K, Hertel J, Troll M, Bader E, Adam J, Prehn C, Rathkolb B, Hrabe de Angelis M, Grabe HJ, Daniel H, Kantermann T, Harth V, Illig T, Pallapies D, Behrens T, Brüning T, Adamski J, Lickert H, Rabstein S, and Wang-Sattler R

Abstract

Night shift work can have a serious impact on health. Here, we assess whether and how night shift work influences the metabolite profiles, specifically with respect to different chronotype classes. We have recruited 100 women including 68 nurses working both, day shift and night shifts for up to 5 consecutive days and collected 3640 spontaneous urine samples. About 424 waking-up urine samples were measured using a targeted metabolomics approach. To account for urine dilution, we applied three methods to normalize the metabolite values: creatinine-, osmolality- and regression-based normalization. Based on linear mixed effect models, we found 31 metabolites significantly (false discovery rate <0.05) affected in nurses working in night shifts. One metabolite, acylcarnitine C10:2, was consistently identified with all three normalization methods. We further observed 11 and 4 metabolites significantly associated with night shift in early and late chronotype classes, respectively. Increased levels of medium- and long chain acylcarnitines indicate a strong impairment of the fatty acid oxidation. Our results show that night shift work influences acylcarnitines and BCAAs, particularly in nurses in the early chronotype class. Women with intermediate and late chronotypes appear to be less affected by night shift work.

Published
2018
Full Text
View/download PDF

46. Vitamin D supply in shift working nurses.

Author

Lehnert M, Beine A, Burek K, Putzke S, Schlösser S, Pallapies D, Brüning T, Behrens T, and Rabstein S

Subjects
Adult, Biomarkers blood, Body Mass Index, Cross-Sectional Studies, Female, Germany epidemiology, Humans, Middle Aged, Obesity blood, Obesity diagnosis, Obesity epidemiology, Prevalence, Seasons, Time Factors, Vitamin D blood, Vitamin D Deficiency diagnosis, Vitamin D Deficiency epidemiology, Nursing Staff, Occupational Health, Shift Work Schedule, Vitamin D analogs & derivatives, Vitamin D Deficiency blood
Abstract

We studied determinants of Vitamin D in serum of 67 female health care workers (aged 25-60 years), including age, body mass index, physical activity, and shift work. Overall, vitamin D levels were low, ranging from 6 to 51 ng/mL (median: 20 ng/mL). Lower serum levels were found in samples drawn in winter and spring and in obese subjects. Shift work had only small effects on vitamin D levels. The high prevalence of vitamin D undersupply is in line with observations from the German general population. Vitamin D supply particularly in winter and spring should be ensured to avoid health problems.

Published
2018
Full Text
View/download PDF

47. Night shift work and breast cancer: a pooled analysis of population-based case-control studies with complete work history.

Author

Cordina-Duverger E, Menegaux F, Popa A, Rabstein S, Harth V, Pesch B, Brüning T, Fritschi L, Glass DC, Heyworth JS, Erren TC, Castaño-Vinyals G, Papantoniou K, Espinosa A, Kogevinas M, Grundy A, Spinelli JJ, Aronson KJ, and Guénel P

Subjects
Female, Humans, Risk Assessment, Breast Neoplasms etiology, Circadian Rhythm, Shift Work Schedule adverse effects, Work Schedule Tolerance
Abstract

Night shift work has been suspected to increase breast cancer risk but epidemiological studies have been inconsistent due to heterogeneous assessment of exposure to night work. To overcome this limitation, we pooled data of five population-based case-control studies from Australia, Canada, France, Germany, and Spain into a single harmonized dataset using a common definition of night work including 6093 breast cancer cases and 6933 population controls. The odds ratio for breast cancer in women who ever worked at night for at least 3 h between midnight and 5 a.m. as compared to never night workers was 1.12 (95% CI 1.00-1.25). Among pre-menopausal women, this odds ratio was 1.26 [1.06-1.51], increasing to 1.36 [1.07-1.74] for night shifts ≥ 10 h, 1.80 [1.20-2.71] for work ≥ 3 nights/week, and 2.55 [1.03-6.30] for both duration of night work ≥ 10 years and exposure intensity ≥ 3 nights/week. Breast cancer risk in pre-menopausal women was higher in current or recent night workers (OR = 1.41 [1.06-1.88]) than in those who had stopped night work more than 2 years ago. Breast cancer in post-menopausal women was not associated with night work whatever the exposure metric. The increase in risk was restricted to ER+ tumors, particularly those who were both ER+ and HER2+ . These results support the hypothesis that night shift work increases the risk of breast cancer in pre-menopausal women, particularly those with high intensity and long duration of exposure. Risk difference between pre- and post-menopausal women deserves further scrutiny.

Published
2018
Full Text
View/download PDF

48. Shift work and the incidence of prostate cancer: a 10-year follow-up of a German population-based cohort study.

Author

Behrens T, Rabstein S, Wichert K, Erbel R, Eisele L, Arendt M, Dragano N, Brüning T, and Jöckel KH

Subjects
Aged, Follow-Up Studies, Germany epidemiology, Humans, Incidence, Male, Middle Aged, Prospective Studies, Risk Factors, Surveys and Questionnaires, Prostatic Neoplasms epidemiology, Shift Work Schedule adverse effects, Work Schedule Tolerance physiology
Abstract

Objectives We investigated the association of shift and night work with the incidence of prostate cancer using data of the population-based prospective Heinz Nixdorf Recall Study from the highly industrialized Ruhr area in Germany. Methods Participants of the baseline survey were recruited between 2000-2003. A follow-up survey including, a detailed interview on shift and night work, was conducted from 2011-2014. We included 1757 men who did not report a history of prostate cancer at baseline. We assessed shift- and night-work exposure up to time of the baseline interview. Incident prostate cancers were recorded from baseline through September 2014. We calculated hazard ratios (HR) of shift- and night-work exposure using Cox proportional hazards regression with age at event as timescale, adjusting for smoking status, family history of prostate cancer, education (≤13, 14-17, ≥18 years), and equivalent income (low, medium, high). Results We observed a twofold increased HR for prostate cancer among shift and night workers. Ever employment in shift work was associated with HR 2.29, 95% confidence interval (CI) 1.43-3.67 and night work with HR 2.27, 95% CI 1.42-3.64. HR increased steadily with duration of employment in shift or night work. Stratifying analyses by preferred midpoint of sleep, yielded strongly elevated HR among subjects with early sleep preference, although these analyses were limited by small number of cases. Conclusions We identified increased risks for prostate cancer among men with employment in shift or night work. HR were strongly elevated among long-term employed shift workers and men with early preferred midpoint of sleep.

Published
2017
Full Text
View/download PDF

49. Stability of targeted metabolite profiles of urine samples under different storage conditions.

Author

Rotter M, Brandmaier S, Prehn C, Adam J, Rabstein S, Gawrych K, Brüning T, Illig T, Lickert H, Adamski J, and Wang-Sattler R

Abstract

Introduction: Few studies have investigated the influence of storage conditions on urine samples and none of them used targeted mass spectrometry (MS)., Objectives: We investigated the stability of metabolite profiles in urine samples under different storage conditions using targeted metabolomics., Methods: Pooled, fasting urine samples were collected and stored at -80 °C (biobank standard), -20 °C (freezer), 4 °C (fridge), ~9 °C (cool pack), and ~20 °C (room temperature) for 0, 2, 8 and 24 h. Metabolite concentrations were quantified with MS using the AbsoluteIDQ™ p150 assay. We used the Welch-Satterthwaite-test to compare the concentrations of each metabolite. Mixed effects linear regression was used to assess the influence of the interaction of storage time and temperature., Results: The concentrations of 63 investigated metabolites were stable at -20 and 4 °C for up to 24 h when compared to samples immediately stored at -80 °C. When stored at ~9 °C for 24 h, few amino acids (Arg, Val and Leu/Ile) significantly decreased by 40% in concentration ( P  < 7.9E-04); for an additional three metabolites (Ser, Met, Hexose H1) when stored at ~20 °C reduced up to 60% in concentrations. The concentrations of four more metabolites (Glu, Phe, Pro, and Thr) were found to be significantly influenced when considering the interaction between exposure time and temperature., Conclusion: Our findings indicate that 78% of quantified metabolites were stable for all examined storage conditions. Particularly, some amino acid concentrations were sensitive to changes after prolonged storage at room temperature. Shipping or storing urine samples on cool packs or at room temperature for more than 8 h and multiple numbers of freeze and thaw cycles should be avoided., Competing Interests: Markus Rotter, Stefan Brandmaier, Cornelia Prehn, Jonathan Adam, Sylvia Rabstein, Katarzyna Gawrych, Thomas Brüning, Thomas Illig, Heiko Lickert, Jerzy Adamski, Rui Wang-Sattler declare that they have no conflict of interest. Ethical approval Since there was no identifying information obtained from our participants who donated urine for our study, the ‘Bayerische Landesärztekammer’ declared that our study was not subject to compliance with ethical standards regarding the use of humans in research.

Published
2017
Full Text
View/download PDF

50. Polymorphisms in circadian genes, night work and breast cancer: results from the GENICA study.

Author

Rabstein S, Harth V, Justenhoven C, Pesch B, Plöttner S, Heinze E, Lotz A, Baisch C, Schiffermann M, Brauch H, Hamann U, Ko Y, and Brüning T

Subjects
ARNTL Transcription Factors genetics, Adult, Aged, Aged, 80 and over, Basic Helix-Loop-Helix Transcription Factors genetics, Breast Neoplasms epidemiology, CLOCK Proteins genetics, Case-Control Studies, Epistasis, Genetic, Female, Germany epidemiology, Humans, Middle Aged, Models, Genetic, Multivariate Analysis, Nerve Tissue Proteins genetics, Receptor, Melatonin, MT2 genetics, Young Adult, Breast Neoplasms etiology, Breast Neoplasms genetics, Circadian Clocks genetics, Polymorphism, Single Nucleotide, Work Schedule Tolerance
Abstract

Objectives: The role of genetic variants and environmental factors in breast cancer etiology has been intensively studied in the last decades. Gene-environment interactions are now increasingly being investigated to gain more insights into the development of breast cancer, specific subtypes, and therapeutics. Recently, night shift work that involves circadian disruption has gained rising interest as a potential non-genetic breast cancer risk factor. Here, we analyzed genetic polymorphisms in genes of cellular clocks, melatonin biosynthesis and signaling and their association with breast cancer as well as gene-gene and gene-night work interactions in a German case-control study on breast cancer., Methods: GENICA is a population-based case-control study on breast cancer conducted in the Greater Region of Bonn. Associations between seven polymorphisms in circadian genes (CLOCK, NPAS2, ARTNL, PER2 and CRY2), genes of melatonin biosynthesis and signaling (AANAT and MTNR1B) and breast cancer were analyzed with conditional logistic regression models, adjusted for potential confounders for 1022 cases and 1014 controls. Detailed shift-work information was documented for 857 breast cancer cases and 892 controls. Gene-gene and gene-shiftwork interactions were analyzed using model-based multifactor dimensionality reduction (mbMDR)., Results: For combined heterozygotes and rare homozygotes a slightly elevated breast cancer risk was found for rs8150 in gene AANAT (OR 1.17; 95% CI 1.01-1.36), and a reduced risk for rs3816358 in gene ARNTL (OR 0.82; 95% CI 0.69-0.97) in the complete study population. In the subgroup of shift workers, rare homozygotes for rs10462028 in the CLOCK gene had an elevated risk of breast cancer (OR for AA vs. GG: 3.53; 95% CI 1.09-11.42). Shift work and CLOCK gene interactions were observed in the two-way interaction analysis. In addition, gene-shiftwork interactions were detected for MTNR1B with NPAS2 and ARNTL., Conclusions: In conclusion, the results of our population-based case-control study support a putative role of the CLOCK gene in the development of breast cancer in shift workers. In addition, higher order interaction analyses suggest a potential relevance of MTNR1B with the key transcriptional factor NPAS2 with ARNTL. Hence, in the context of circadian disruption, multivariable models should be preferred that consider a wide range of polymorphisms, e.g. that may influence chronotype or light sensitivity. The investigation of these interactions in larger studies is needed.

Published
2014
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results