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1,054 results on '"Luben, R."'

5. No association of alcohol use and the risk of ulcerative colitis or Crohn's disease: data from a European Prospective cohort study (EPIC)

Author

Bergmann, M M, Hernandez, V, Bernigau, W, Boeing, H, Chan, S S M, Luben, R, Khaw, K-T, Schaik, F van, Oldenburg, B., Bueno-de-Mesquita, B., Overvad, K., Palli, D., Masala, G., Carbonnel, F., Boutron-Ruault, M.C., Olsen, A., and Tjonneland, A.

Subjects
Risk factors, Health aspects, Crohn's disease -- Risk factors, Ulcerative colitis -- Risk factors, Drinking (Alcoholic beverages) -- Health aspects, Drinking of alcoholic beverages -- Health aspects
Abstract

Author(s): M M Bergmann [sup.1] , V Hernandez [sup.1] [sup.2] , W Bernigau [sup.1] , H Boeing [sup.1] , S S M Chan [sup.3] [sup.4] , R Luben [sup.5] , [...], Background/Objectives: The role of long-term alcohol consumption for the risk of developing ulcerative colitis (UC) and Crohn's disease (CD) is unclear. For the first time, to prospectively assess the role of pre-disease alcohol consumption on the risk of developing UC or CD. Subjects/Methods: Nested within the European Prospective Investigation into Cancer and Nutrition (EPIC-IBD), incident UC and CD cases and matched controls where included. At recruitment, participants completed validated food frequency and lifestyle questionnaires. Alcohol consumption was classified as either: non-use, former, light ([[less-than or slanted equal to]0.5 and 1 drink per week), below the recommended limits (BRL) ([[less-than or slanted equal to]1 and 2 drinks per day), moderate ([[less-than or slanted equal to]2.5 and 5 drinks per day), or heavy use (>2.5 and >5 drinks per day) for women and men, respectively; and was expressed as consumption at enrolment and during lifetime. Conditional logistic regression was applied adjusting for smoking and education, taking light users as the reference. Results: Out of 262 451 participants in six countries, 198 UC incident cases/792 controls and 84 CD cases/336 controls were included. At enrolment, 8%/27%/32%/23%/11% UC cases and 7%/29%/40%/19%/5% CD cases were: non-users, light, BRL, moderate and heavy users, respectively. The corresponding figures for lifetime non-use, former, light, BRL, moderate and heavy use were: 3%/5%/23%/44%/19%/6% and 5%/2%/25%/44%/23%/1% for UC and CD cases, respectively. There were no associations between any categories of alcohol consumption and risk of UC or CD in the unadjusted and adjusted odds ratios. Conclusion: There was no evidence of associations between alcohol use and the odds of developing either UC or CD.

Published
2017
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7. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

Author

Cornelis, M C, Byrne, E M, Esko, T, Nalls, M A, Ganna, A, Paynter, N, Monda, K L, Amin, N, Fischer, K, Renstrom, F, Ngwa, J S, Huikari, V, Cavadino, A, Nolte, I M, Teumer, A, Yu, K, Marques-Vidal, P, Rawal, R, Manichaikul, A, Wojczynski, M K, Vink, J M, Zhao, J H, Burlutsky, G, Lahti, J, Mikkilä, V, Lemaitre, R N, Eriksson, J, Musani, S K, Tanaka, T, Geller, F, Luan, J, Hui, J, Mägi, R, Dimitriou, M, Garcia, M E, Ho, W-K, Wright, M J, Rose, L M, Magnusson, P K E, Pedersen, N L, Couper, D, Oostra, B A, Hofman, A, Ikram, M A, Tiemeier, H W, Uitterlinden, A G, van Rooij, F J A, Barroso, I, Johansson, I, Xue, L, Kaakinen, M, Milani, L, Power, C, Snieder, H, Stolk, R P, Baumeister, S E, Biffar, R, Gu, F, Bastardot, F, Kutalik, Z, Jacobs, Jr, D R, Forouhi, N G, Mihailov, E, Lind, L, Lindgren, C, Michaëlsson, K, Morris, A, Jensen, M, Khaw, K-T, Luben, R N, Wang, J J, Männistö, S, Perälä, M-M, Kähönen, M, Lehtimäki, T, Viikari, J, Mozaffarian, D, Mukamal, K, Psaty, B M, Döring, A, Heath, A C, Montgomery, G W, Dahmen, N, Carithers, T, Tucker, K L, Ferrucci, L, Boyd, H A, Melbye, M, Treur, J L, Mellström, D, Hottenga, J J, Prokopenko, I, Tönjes, A, Deloukas, P, Kanoni, S, Lorentzon, M, Houston, D K, Liu, Y, Danesh, J, Rasheed, A, Mason, M A, Zonderman, A B, Franke, L, Kristal, B S, Karjalainen, J, Reed, D R, Westra, H-J, Evans, M K, Saleheen, D, Harris, T B, Dedoussis, G, Curhan, G, Stumvoll, M, Beilby, J, Pasquale, L R, Feenstra, B, Bandinelli, S, Ordovas, J M, Chan, A T, Peters, U, Ohlsson, C, Gieger, C, Martin, N G, Waldenberger, M, Siscovick, D S, Raitakari, O, Eriksson, J G, Mitchell, P, Hunter, D J, Kraft, P, Rimm, E B, Boomsma, D I, Borecki, I B, Loos, R J F, Wareham, N J, Vollenweider, P, Caporaso, N, Grabe, H J, Neuhouser, M L, Wolffenbuttel, B H R, Hu, F B, Hyppönen, E, Järvelin, M-R, Cupples, L A, Franks, P W, Ridker, P M, van Duijn, C M, Heiss, G, Metspalu, A, North, K E, Ingelsson, E, Nettleton, J A, van Dam, R M, and Chasman, D I

Published
2015
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13. P722 Prediagnostic serum vitamin D levels and risk of inflammatory bowel disease: a pan-European, nested case-control study

Author

Opstelten, J., Chan, S., Hart, A., van Schaik, F., Siersema, P., Lentjes, E., Khaw, K.-T., Luben, R., Key, T., Boeing, H., Bergmann, M., Overvad, K., Palli, D., Masala, G., Racine, A., Carbonnel, F., Boutron-Ruault, M.-C., Tjønneland, A., Olsen, A., Andersen, V., Kaaks, R., Kühn, T., Tumino, R., Trichopoulou, A., Verschuren, M., Witteman, B., and Oldenburg, B.

Published
2017
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15. Visual impairment and risk of dementia in two population-based prospective cohorts: UK Biobank and EPIC-Norfolk

Author

Littlejohns, T, Hayat, S, Luben, R, Brayne, C, Conroy, M, Foster, PJ, Khawaja, AP, and Kuźma, E

Abstract

Visual impairment has emerged as a potential modifiable risk factor for dementia. However, there are a lack of large studies with objective measures of vison and with more than ten years of follow-up. We investigated whether visual impairment is associated with an increased risk of incident dementia in UK Biobank and EPIC-Norfolk. In both cohorts, visual acuity was measured using a “logarithm of the minimum angle of resolution” (LogMAR) chart and categorised as no (≤0.30 LogMAR), mild (>0.3 - ≤0.50 LogMAR), and moderate to severe (>0.50 LogMAR) impairment. Dementia was ascertained through linkage to electronic medical records. After restricting to those aged ≥60 years, without prevalent dementia and with eye measures available, the analytic samples consisted of 62,206 UK Biobank and 7,337 EPIC-Norfolk participants, respectively. In UK Biobank and EPIC-Norfolk. respectively, 1,113 and 517 participants developed dementia over 11 and 15 years of follow-up. Using multivariable cox proportional-hazards models, the hazard ratios for mild and moderate to severe visual impairment were 1.26 (95% Confidence Interval [CI] 0.92-1.72) and 2.16 (95% CI 1.37-3.40), in UK Biobank, and 1.05 (95% CI 0.72-1.53) and 1.93 (95% CI 1.05-3.56) in EPIC-Norfolk, compared to no visual impairment. When excluding participants censored within 5 years of follow-up or with prevalent poor or fair self-reported health, the direction of the associations remained similar for moderate impairment but were not statistically significant. Our findings suggest visual impairment might be a promising target for dementia prevention, however the possibility of reverse causation cannot be excluded.

Published
2021

32. Comparing Hypertension Guidelines [with Reply]

Author

Scanlon, T. J., Luben, R., Lyle, P., Burr, Andrew J., Lindholm, Lars H., Werkö, Lars, Barton, Stuart, Cranney, Mike, Walley, Tom, Fahey, T. P., and Peters, T. J.

Published
1996

33. Refractive error, axial length and anterior chamber depth of the eye in British adults: the EPIC-Norfolk Eye Study

Author

Foster, P.J., Broadway, D.C., Hayat, S., Luben, R., Dalzell, N., Bingham, S., Wareham, N.J., and Khaw, K.-T.

Subjects
Anterior chamber (Eye) -- Demographic aspects, Anterior chamber (Eye) -- Physiological aspects, Anterior chamber (Eye) -- Research, Eye -- Refractive errors, Eye -- Distribution, Eye -- Demographic aspects, Eye -- Research, Company distribution practices, Health
Published
2010

39. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

Author

Gharahkhani, P., Jorgenson, E., Hysi, P., Khawaja, A.P., Pendergrass, S., Han, X., Ong, J.S., Hewitt, A.W., Segrè, A.V., Rouhana, J.M., Hamel, A.R., Igo, R.P., Jr., Choquet, H., Qassim, A., Josyula, N.S., Bailey, J.N., Bonnemaijer, P.W.M., Iglesias, A., Siggs, O.M., Young, T.L., Vitart, V., Thiadens, A., Karjalainen, J., Uebe, S., Melles, R.B., Nair, K.S., Luben, R., Simcoe, M., Amersinghe, N., Cree, A.J., Hohn, R., Poplawski, A., Chen, L.J., Rong, S.S., Aung, T., Vithana, E.N., Tamiya, G., Shiga, Y., Yamamoto, M., Nakazawa, T., Currant, H., Birney, E., Wang, X, Auton, A., Lupton, M.K., Martin, N.G., Ashaye, A., Olawoye, O., Williams, S.E., Akafo, S., Ramsay, M., Hashimoto, K., Kamatani, Y., Akiyama, M., Momozawa, Y., Foster, P.J., Khaw, P.T., Morgan, J.E., Strouthidis, N.G., Kraft, P., Kang, J.H., Pang, C.P., Pasutto, F., Mitchell, P., Lotery, A.J., Palotie, A., Duijn, C. van, Haines, J.L., Hammond, C., Pasquale, L.R., Klaver, C.C.W., Hauser, M., Khor, C.C., Mackey, D.A., Kubo, M., Cheng, C.Y., Craig, J.E., MacGregor, S., Wiggs, J.L., Gharahkhani, P., Jorgenson, E., Hysi, P., Khawaja, A.P., Pendergrass, S., Han, X., Ong, J.S., Hewitt, A.W., Segrè, A.V., Rouhana, J.M., Hamel, A.R., Igo, R.P., Jr., Choquet, H., Qassim, A., Josyula, N.S., Bailey, J.N., Bonnemaijer, P.W.M., Iglesias, A., Siggs, O.M., Young, T.L., Vitart, V., Thiadens, A., Karjalainen, J., Uebe, S., Melles, R.B., Nair, K.S., Luben, R., Simcoe, M., Amersinghe, N., Cree, A.J., Hohn, R., Poplawski, A., Chen, L.J., Rong, S.S., Aung, T., Vithana, E.N., Tamiya, G., Shiga, Y., Yamamoto, M., Nakazawa, T., Currant, H., Birney, E., Wang, X, Auton, A., Lupton, M.K., Martin, N.G., Ashaye, A., Olawoye, O., Williams, S.E., Akafo, S., Ramsay, M., Hashimoto, K., Kamatani, Y., Akiyama, M., Momozawa, Y., Foster, P.J., Khaw, P.T., Morgan, J.E., Strouthidis, N.G., Kraft, P., Kang, J.H., Pang, C.P., Pasutto, F., Mitchell, P., Lotery, A.J., Palotie, A., Duijn, C. van, Haines, J.L., Hammond, C., Pasquale, L.R., Klaver, C.C.W., Hauser, M., Khor, C.C., Mackey, D.A., Kubo, M., Cheng, C.Y., Craig, J.E., MacGregor, S., and Wiggs, J.L.

Abstract

Contains fulltext : 235429.pdf (Publisher’s version ) (Open Access), Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.

Published
2021

40. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

Author

Gharahkhani, P, Jorgenson, E, Hysi, P, Khawaja, AP, Pendergrass, S, Han, X, Ong, JS, Hewitt, AW, Segre, A, Rouhana, JM, Hamel, AR, Igo, RP, Choquet, H, Qassim, A, Josyula, NS, Bailey, JNC, Bonnemaijer, PWM, Iglesias, A, Siggs, OM, Young, TL, Vitart, V, Thiadens, AAHJ, Karjalainen, J, Uebe, S, Melles, RB, Nair, KS, Luben, R, Simcoe, M, Amersinghe, N, Cree, AJ, Hohn, R, Poplawski, A, Chen, LJ, Rong, S-S, Aung, T, Vithana, EN, Tamiya, G, Shiga, Y, Yamamoto, M, Nakazawa, T, Currant, H, Birney, E, Wang, X, Auton, A, Lupton, MK, Martin, NG, Ashaye, A, Olawoye, O, Williams, SE, Akafo, S, Ramsay, M, Hashimoto, K, Kamatani, Y, Akiyama, M, Momozawa, Y, Foster, PJ, Khaw, PT, Morgan, JE, Strouthidis, NG, Kraft, P, Kang, JH, Pang, CP, Pasutto, F, Mitchell, P, Lotery, AJ, Palotie, A, van Duijn, C, Haines, JL, Hammond, C, Pasquale, LR, Klaver, CCW, Hauser, M, Khor, CC, Mackey, DA, Kubo, M, Cheng, C-Y, Craig, JE, MacGregor, S, Wiggs, JL, Gharahkhani, P, Jorgenson, E, Hysi, P, Khawaja, AP, Pendergrass, S, Han, X, Ong, JS, Hewitt, AW, Segre, A, Rouhana, JM, Hamel, AR, Igo, RP, Choquet, H, Qassim, A, Josyula, NS, Bailey, JNC, Bonnemaijer, PWM, Iglesias, A, Siggs, OM, Young, TL, Vitart, V, Thiadens, AAHJ, Karjalainen, J, Uebe, S, Melles, RB, Nair, KS, Luben, R, Simcoe, M, Amersinghe, N, Cree, AJ, Hohn, R, Poplawski, A, Chen, LJ, Rong, S-S, Aung, T, Vithana, EN, Tamiya, G, Shiga, Y, Yamamoto, M, Nakazawa, T, Currant, H, Birney, E, Wang, X, Auton, A, Lupton, MK, Martin, NG, Ashaye, A, Olawoye, O, Williams, SE, Akafo, S, Ramsay, M, Hashimoto, K, Kamatani, Y, Akiyama, M, Momozawa, Y, Foster, PJ, Khaw, PT, Morgan, JE, Strouthidis, NG, Kraft, P, Kang, JH, Pang, CP, Pasutto, F, Mitchell, P, Lotery, AJ, Palotie, A, van Duijn, C, Haines, JL, Hammond, C, Pasquale, LR, Klaver, CCW, Hauser, M, Khor, CC, Mackey, DA, Kubo, M, Cheng, C-Y, Craig, JE, MacGregor, S, and Wiggs, JL

Abstract

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.

Published
2021

41. Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis

Author

Escala-Garcia, M. (Maria), Canisius, S. (Sander), Keeman, R. (Renske), Beesley, J. (Jonathan), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Augustinsson, A. (Annelie), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Bermisheva, M. (Marina), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brenner, H. (Hermann), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Couch, F. J. (Fergus J.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Dennis, J. (Joe), Devilee, P. (Peter), Dork, T. (Thilo), Dunning, A. M. (Alison M.), Easton, D. F. (Douglas F.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Fasching, P. A. (Peter A.), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Geisler, J. (Juergen), Giles, G. G. (Graham G.), Grip, M. (Mervi), Guendert, M. (Melanie), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hartikainen, J. M. (Jaana M.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Hunter, D. J. (David J.), Jacot, W. (William), Jakubowska, A. (Anna), John, E. M. (Esther M.), Jung, A. Y. (Audrey Y.), Kaaks, R. (Rudolf), Khusnutdinova, E. (Elza), Koppert, L. B. (Linetta B.), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lindblom, A. (Annika), Luben, R. N. (Robert N.), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Muranen, T. A. (Taru A.), Nevanlinna, H. (Heli), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa V.), Peterlongo, P. (Paolo), Pharoah, P. D. (Paul D. P.), Punie, K. (Kevin), Radice, P. (Paolo), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Romero, A. (Atocha), Roylance, R. (Rebecca), Ruediger, T. (Thomas), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schoemaker, M. J. (Minouk J.), Scott, C. (Christopher), Southey, M. C. (Melissa C.), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Teras, L. R. (Lauren R.), Thomas, E. (Emilie), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Vachon, C. M. (Celine M.), Wang, Q. (Qin), Winqvist, R. (Robert), Wolk, A. (Alicja), Ziogas, A. (Argyrios), Michailidou, K. (Kyriaki), Chenevix-Trench, G. (Georgia), Bachelot, T. (Thomas), Schmidt, M. K. (Marjanka K.), Escala-Garcia, M. (Maria), Canisius, S. (Sander), Keeman, R. (Renske), Beesley, J. (Jonathan), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Augustinsson, A. (Annelie), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Bermisheva, M. (Marina), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brenner, H. (Hermann), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Couch, F. J. (Fergus J.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Dennis, J. (Joe), Devilee, P. (Peter), Dork, T. (Thilo), Dunning, A. M. (Alison M.), Easton, D. F. (Douglas F.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Fasching, P. A. (Peter A.), Flyger, H. (Henrik), Gago-Dominguez, M. (Manuela), Garcia-Closas, M. (Montserrat), Garcia-Saenz, J. A. (Jose A.), Geisler, J. (Juergen), Giles, G. G. (Graham G.), Grip, M. (Mervi), Guendert, M. (Melanie), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hartikainen, J. M. (Jaana M.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Hollestelle, A. (Antoinette), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Hunter, D. J. (David J.), Jacot, W. (William), Jakubowska, A. (Anna), John, E. M. (Esther M.), Jung, A. Y. (Audrey Y.), Kaaks, R. (Rudolf), Khusnutdinova, E. (Elza), Koppert, L. B. (Linetta B.), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lindblom, A. (Annika), Luben, R. N. (Robert N.), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Muranen, T. A. (Taru A.), Nevanlinna, H. (Heli), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa V.), Peterlongo, P. (Paolo), Pharoah, P. D. (Paul D. P.), Punie, K. (Kevin), Radice, P. (Paolo), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Romero, A. (Atocha), Roylance, R. (Rebecca), Ruediger, T. (Thomas), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schoemaker, M. J. (Minouk J.), Scott, C. (Christopher), Southey, M. C. (Melissa C.), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Teras, L. R. (Lauren R.), Thomas, E. (Emilie), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Vachon, C. M. (Celine M.), Wang, Q. (Qin), Winqvist, R. (Robert), Wolk, A. (Alicja), Ziogas, A. (Argyrios), Michailidou, K. (Kyriaki), Chenevix-Trench, G. (Georgia), Bachelot, T. (Thomas), and Schmidt, M. K. (Marjanka K.)

Abstract

Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.

Published
2021

42. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

Author

Morra, A. (Anna), Escala-Garcia, M. (Maria), Beesley, J. (Jonathan), Keeman, R. (Renske), Canisius, S. (Sander), Ahearn, T. U. (Thomas U.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Auer, P. L. (Paul L.), Augustinsson, A. (Annelie), Freeman, L. E. (Laura E. Beane), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brenner, H. (Hermann), Bruening, T. (Thomas), Buys, S. S. (Saundra S.), Caan, B. (Bette), Campa, D. (Daniele), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Cheng, T. D. (Ting-Yuan David), Clarke, C. L. (Christine L.), Colonna, S. V. (Sarah, V), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Dennis, J. (Joe), Dork, T. (Thilo), Dossus, L. (Laure), Dunning, A. M. (Alison M.), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Flyger, H. (Henrik), Fritschi, L. (Lin), Gago-Dominguez, M. (Manuela), Garcia-Saenz, J. A. (Jose A.), Giles, G. G. (Graham G.), Grip, M. (Mervi), Guenel, P. (Pascal), Guendert, M. (Melanie), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hart, S. N. (Steven N.), Hartikainen, J. M. (Jaana M.), Hartmann, A. (Arndt), He, W. (Wei), Hooning, M. J. (Maartje J.), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Howell, A. (Anthony), Hunter, D. J. (David J.), Jager, A. (Agnes), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Jung, A. Y. (Audrey Y.), Kaaks, R. (Rudolf), Keupers, M. (Machteld), Kitahara, C. M. (Cari M.), Koutros, S. (Stella), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lacey, J. V. (James, V), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lindblom, A. (Annika), Linet, M. (Martha), Luben, R. N. (Robert N.), Lush, M. (Michael), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Martens, J. W. (John W. M.), Martinez, M. E. (Maria Elena), Mavroudis, D. (Dimitrios), Michailidou, K. (Kyriaki), Milne, R. L. (Roger L.), Mulligan, A. M. (Anna Marie), Muranen, T. A. (Taru A.), Nevanlinna, H. (Heli), Newman, W. G. (William G.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Orr, N. (Nick), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa, V), Peissel, B. (Bernard), Peterlongo, P. (Paolo), Plaseska-Karanfilska, D. (Dijana), Prajzendanc, K. (Karolina), Prentice, R. (Ross), Presneau, N. (Nadege), Rack, B. (Brigitte), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Romero, A. (Atocha), Roylance, R. (Rebecca), Lubinski, J. (Jan), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Scott, C. (Christopher), Shah, M. (Mitul), Smichkoska, S. (Snezhana), Southey, M. C. (Melissa C.), Stone, J. (Jennifer), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Vachon, C. M. (Celine M.), Wang, Q. (Qin), Hurson, A. N. (Amber N.), Winqvist, R. (Robert), Wolk, A. (Alicja), Ziogas, A. (Argyrios), Brauch, H. (Hiltrud), Garcia-Closas, M. (Montserrat), Pharoah, P. D. (Paul D. P.), Easton, D. F. (Douglas F.), Chenevix-Trench, G. (Georgia), Schmidt, M. K. (Marjanka K.), Morra, A. (Anna), Escala-Garcia, M. (Maria), Beesley, J. (Jonathan), Keeman, R. (Renske), Canisius, S. (Sander), Ahearn, T. U. (Thomas U.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Auer, P. L. (Paul L.), Augustinsson, A. (Annelie), Freeman, L. E. (Laura E. Beane), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Bojesen, S. E. (Stig E.), Bolla, M. K. (Manjeet K.), Brenner, H. (Hermann), Bruening, T. (Thomas), Buys, S. S. (Saundra S.), Caan, B. (Bette), Campa, D. (Daniele), Canzian, F. (Federico), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Cheng, T. D. (Ting-Yuan David), Clarke, C. L. (Christine L.), Colonna, S. V. (Sarah, V), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Dennis, J. (Joe), Dork, T. (Thilo), Dossus, L. (Laure), Dunning, A. M. (Alison M.), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Eliassen, A. H. (A. Heather), Eriksson, M. (Mikael), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Flyger, H. (Henrik), Fritschi, L. (Lin), Gago-Dominguez, M. (Manuela), Garcia-Saenz, J. A. (Jose A.), Giles, G. G. (Graham G.), Grip, M. (Mervi), Guenel, P. (Pascal), Guendert, M. (Melanie), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Hart, S. N. (Steven N.), Hartikainen, J. M. (Jaana M.), Hartmann, A. (Arndt), He, W. (Wei), Hooning, M. J. (Maartje J.), Hoppe, R. (Reiner), Hopper, J. L. (John L.), Howell, A. (Anthony), Hunter, D. J. (David J.), Jager, A. (Agnes), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Jung, A. Y. (Audrey Y.), Kaaks, R. (Rudolf), Keupers, M. (Machteld), Kitahara, C. M. (Cari M.), Koutros, S. (Stella), Kraft, P. (Peter), Kristensen, V. N. (Vessela N.), Kurian, A. W. (Allison W.), Lacey, J. V. (James, V), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lindblom, A. (Annika), Linet, M. (Martha), Luben, R. N. (Robert N.), Lush, M. (Michael), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Margolin, S. (Sara), Martens, J. W. (John W. M.), Martinez, M. E. (Maria Elena), Mavroudis, D. (Dimitrios), Michailidou, K. (Kyriaki), Milne, R. L. (Roger L.), Mulligan, A. M. (Anna Marie), Muranen, T. A. (Taru A.), Nevanlinna, H. (Heli), Newman, W. G. (William G.), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Olshan, A. F. (Andrew F.), Olsson, H. (Hakan), Orr, N. (Nick), Park-Simon, T.-W. (Tjoung-Won), Patel, A. V. (Alpa, V), Peissel, B. (Bernard), Peterlongo, P. (Paolo), Plaseska-Karanfilska, D. (Dijana), Prajzendanc, K. (Karolina), Prentice, R. (Ross), Presneau, N. (Nadege), Rack, B. (Brigitte), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Romero, A. (Atocha), Roylance, R. (Rebecca), Lubinski, J. (Jan), Ruebner, M. (Matthias), Saloustros, E. (Emmanouil), Sawyer, E. J. (Elinor J.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Scott, C. (Christopher), Shah, M. (Mitul), Smichkoska, S. (Snezhana), Southey, M. C. (Melissa C.), Stone, J. (Jennifer), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Teras, L. R. (Lauren R.), Terry, M. B. (Mary Beth), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Troester, M. A. (Melissa A.), Truong, T. (Therese), Vachon, C. M. (Celine M.), Wang, Q. (Qin), Hurson, A. N. (Amber N.), Winqvist, R. (Robert), Wolk, A. (Alicja), Ziogas, A. (Argyrios), Brauch, H. (Hiltrud), Garcia-Closas, M. (Montserrat), Pharoah, P. D. (Paul D. P.), Easton, D. F. (Douglas F.), Chenevix-Trench, G. (Georgia), and Schmidt, M. K. (Marjanka K.)

Abstract

Background: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP & 0.15). Results: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E−08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E−07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E−08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E−08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic varia

Published
2021

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