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103 results on '"Tilanus Linthorst, M"'

1. Tumor characteristics and detection method in the MRISC screening program for the early detection of hereditary breast cancer

Author

Kriege, M., Brekelmans, C. T. M., Peterse, H., Obdeijn, I. M., Boetes, C., Zonderland, H. M., Muller, S. H., Kok, T., Manoliu, R. A., Besnard, A. P. E., Tilanus-Linthorst, M. M. A., Seynaeve, C., Bartels, C. C. M., Meijer, S., Oosterwijk, J. C., Hoogerbrugge, N., Tollenaar, R. A. E. M., de Koning, H. J., Rutgers, E. J. T., and Klijn, J. G. M.

Published
2007
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3. Cost-effective strategies according to the first randomized trial comparing MRI breast cancer screening with mammography in women with a familial risk: FaMRIsc

Author

Tilanus-Linthorst, M., primary, Geuzinge, A., additional, Obdeijn, A.I.M., additional, Rutgers, E., additional, Mann, R., additional, Saadatmand, S., additional, de Roy van Zuidewijn, D., additional, Tollenaar, R., additional, Lobbes, M., additional, Ausems, M., additional, van ’t Riet, M., additional, Hooning, M., additional, Luiten, E., additional, Loo, C., additional, Wesseling, J., additional, Verhoef, C., additional, Oosterwijk, J.G., additional, Heijnsdijk, E., additional, and de Koning, H., additional

Published
2020
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11. Breast cancer-related deaths according to grade in ductal carcinoma in situ: A Dutch population-based study on patients diagnosed between 1999 and 2012

Author

MS Radiologie, Cancer, van Maaren, M C, Lagendijk, M, Tilanus-Linthorst, M M A, de Munck, L, Pijnappel, R M, Schmidt, M K, Wesseling, J, Koppert, L B, Siesling, S, MS Radiologie, Cancer, van Maaren, M C, Lagendijk, M, Tilanus-Linthorst, M M A, de Munck, L, Pijnappel, R M, Schmidt, M K, Wesseling, J, Koppert, L B, and Siesling, S

Published
2018

12. 4LBA - Cost-effective strategies according to the first randomized trial comparing MRI breast cancer screening with mammography in women with a familial risk: FaMRIsc

Author

Tilanus-Linthorst, M., Geuzinge, A., Obdeijn, A.I.M., Rutgers, E., Mann, R., Saadatmand, S., de Roy van Zuidewijn, D., Tollenaar, R., Lobbes, M., Ausems, M., van ’t Riet, M., Hooning, M., Luiten, E., Loo, C., Wesseling, J., Verhoef, C., Oosterwijk, J.G., Heijnsdijk, E., and de Koning, H.

Published
2020
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13. PALB2, CHEK2 and ATM rare variants and cancer risk:data from COGS

Author

Southey, M. C. (Melissa C.), Goldgar, D. E. (David E.), Winqvist, R. (Robert), Pylkäs, K. (Katri), Couch, F. (Fergus), Tischkowitz, M. (Marc), Foulkes, W. D. (William D.), Dennis, J. (Joe), Michailidou, K. (Kyriaki), van Rensburg, E. J. (Elizabeth J.), Heikkinen, T. (Tuomas), Nevanlinna, H. (Heli), Hopper, J. L. (John L.), Doerk, T. (Thilo), Claes, K. B. (Kathleen B. M.), Reis-Filho, J. (Jorge), Teo, Z. L. (Zhi Ling), Radice, P. (Paolo), Catucci, I. (Irene), Peterlongo, P. (Paolo), Tsimiklis, H. (Helen), Odefrey, F. A. (Fabrice A.), Dowty, J. G. (James G.), Schmidt, M. K. (Marjanka K.), Broeks, A. (Annegien), Hogervorst, F. B. (Frans B.), Verhoef, S. (Senno), Carpenter, J. (Jane), Clarke, C. (Christine), Scott, R. J. (Rodney J.), Fasching, P. A. (Peter A.), Haeberle, L. (Lothar), Ekici, A. B. (Arif B.), Beckmann, M. W. (Matthias W.), Peto, J. (Julian), dos-Santos-Silva, I. (Isabel), Fletcher, O. (Olivia), Johnson, N. (Nichola), Bolla, M. K. (Manjeet K.), Sawyer, E. J. (Elinor J.), Tomlinson, I. (Ian), Kerin, M. J. (Michael J.), Miller, N. (Nicola), Marme, F. (Federik), Burwinkel, B. (Barbara), Yang, R. (Rongxi), Guenel, P. (Pascal), Menegaux, F. (Florence), Sanchez, M. (Marie), Bojesen, S. (Stig), Nielsen, S. F. (Sune F.), Flyger, H. (Henrik), Benitez, J. (Javier), Pilar Zamora, M. (M.), Arias Perez, J. I. (Jose Ignacio), Menendez, P. (Primitiva), Anton-Culver, H. (Hoda), Neuhausen, S. (Susan), Ziogas, A. (Argyrios), Clarke, C. A. (Christina A.), Brenner, H. (Hermann), Arndt, V. (Volker), Stegmaier, C. (Christa), Brauch, H. (Hiltrud), Bruening, T. (Thomas), Ko, Y.-D. (Yon-Dschun), Muranen, T. A. (Taru A.), Aittomaki, K. (Kristiina), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia V.), Antonenkova, N. N. (Natalia N.), Lindblom, A. (Annika), Margolin, S. (Sara), Mannermaa, A. (Arto), Kataja, V. (Vesa), Kosma, V.-M. (Veli-Matti), Hartikainen, J. M. (Jaana M.), Spurdle, A. B. (Amanda B.), Wauters, E. (Els), Smeets, D. (Dominiek), Beuselinck, B. (Benoit), Floris, G. (Giuseppe), Chang-Claude, J. (Jenny), Rudolph, A. (Anja), Seibold, P. (Petra), Flesch-Janys, D. (Dieter), Olson, J. E. (Janet E.), Vachon, C. (Celine), Pankratz, V. S. (Vernon S.), McLean, C. (Catriona), Haiman, C. A. (Christopher A.), Henderson, B. E. (Brian E.), Schumacher, F. (Fredrick), Le Marchand, L. (Loic), Kristensen, V. (Vessela), Alnaes, G. G. (Grethe Grenaker), Zheng, W. (Wei), Hunter, D. J. (David J.), Lindstrom, S. (Sara), Hankinson, S. E. (Susan E.), Kraft, P. (Peter), Andrulis, I. (Irene), Knight, J. A. (Julia A.), Glendon, G. (Gord), Mulligan, A. M. (Anna Marie), Jukkola-Vuorinen, A. (Arja), Grip, M. (Mervi), Kauppila, S. (Saila), Devilee, P. (Peter), Tollenaar, R. A. (Robert A. E. M.), Seynaeve, C. (Caroline), Hollestelle, A. (Antoinette), Garcia-Closas, M. (Montserrat), Figueroa, J. (Jonine), Chanock, S. J. (Stephen J.), Lissowska, J. (Jolanta), Czene, K. (Kamila), Darabi, H. (Hatef), Eriksson, M. (Mikael), Eccles, D. M. (Diana M.), Rafiq, S. (Sajjad), Tapper, W. J. (William J.), Gerty, S. M. (Sue M.), Hooning, M. J. (Maartje J.), Martens, J. W. (John W. M.), Collee, J. M. (J. Margriet), Tilanus-Linthorst, M. (Madeleine), Hall, P. (Per), Li, J. (Jingmei), Brand, J. S. (Judith S.), Humphreys, K. (Keith), Cox, A. (Angela), Reed, M. W. (Malcolm W. R.), Luccarini, C. (Craig), Baynes, C. (Caroline), Dunning, A. M. (Alison M.), Hamann, U. (Ute), Torres, D. (Diana), Ulmer, H. U. (Hans Ulrich), Ruediger, T. (Thomas), Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska, K. (Katarzyna), Durda, K. (Katarzyna), Slager, S. (Susan), Toland, A. E. (Amanda E.), Ambrosone, C. B. (Christine B.), Yannoukakos, D. (Drakoulis), Swerdlow, A. (Anthony), Ashworth, A. (Alan), Orr, N. (Nick), Jones, M. (Michael), Gonzalez-Neira, A. (Anna), Pita, G. (Guillermo), Rosario Alonso, M. (M.), Alvarez, N. (Nuria), Herrero, D. (Daniel), Tessier, D. C. (Daniel C.), Vincent, D. (Daniel), Bacot, F. (Francois), Simard, J. (Jacques), Dumont, M. (Martine), Soucy, P. (Penny), Eeles, R. (Rosalind), Muir, K. (Kenneth), Wiklund, F. (Fredrik), Gronberg, H. (Henrik), Schleutker, J. (Johanna), Nordestgaard, B. G. (Borge G.), Weischer, M. (Maren), Travis, R. C. (Ruth C.), Neal, D. (David), Donovan, J. L. (Jenny L.), Hamdy, F. C. (Freddie C.), Khaw, K.-T. (Kay-Tee), Stanford, J. L. (Janet L.), Blot, W. J. (William J.), Thibodeau, S. (Stephen), Schaid, D. J. (Daniel J.), Kelley, J. L. (Joseph L.), Maier, C. (Christiane), Kibel, A. S. (Adam S.), Cybulski, C. (Cezary), Cannon-Albright, L. (Lisa), Butterbach, K. (Katja), Park, J. (Jong), Kaneva, R. (Radka), Batra, J. (Jyotsna), Teixeira, M. R. (Manuel R.), Kote-Jarai, Z. (Zsofia), Al Olama, A. A. (Ali Amin), Benlloch, S. (Sara), Renner, S. P. (Stefan P.), Hartmann, A. (Arndt), Hein, A. (Alexander), Ruebner, M. (Matthias), Lambrechts, D. (Diether), Van Nieuwenhuysen, E. (Els), Vergote, I. (Ignace), Lambretchs, S. (Sandrina), Doherty, J. A. (Jennifer A.), Rossing, M. A. (Mary Anne), Nickels, S. (Stefan), Eilber, U. (Ursula), Wang-Gohrke, S. (Shan), Odunsi, K. (Kunle), Sucheston-Campbell, L. E. (Lara E.), Friel, G. (Grace), Lurie, G. (Galina), Killeen, J. L. (Jeffrey L.), Wilkens, L. R. (Lynne R.), Goodman, M. T. (Marc T.), Runnebaum, I. (Ingo), Hillemanns, P. A. (Peter A.), Pelttari, L. M. (Liisa M.), Butzow, R. (Ralf), Modugno, F. (Francesmary), Edwards, R. P. (Robert P.), Ness, R. B. (Roberta B.), Moysich, K. B. (Kirsten B.), du Bois, A. (Andreas), Heitz, F. (Florian), Harter, P. (Philipp), Kommoss, S. (Stefan), Karlan, B. Y. (Beth Y.), Walsh, C. (Christine), Lester, J. (Jenny), Jensen, A. (Allan), Kjaer, S. K. (Susanne Kruger), Hogdall, E. (Estrid), Peissel, B. (Bernard), Bonanni, B. (Bernardo), Bernard, L. (Loris), Goode, E. L. (Ellen L.), Fridley, B. L. (Brooke L.), Vierkant, R. A. (Robert A.), Cunningham, J. M. (Julie M.), Larson, M. C. (Melissa C.), Fogarty, Z. C. (Zachary C.), Kalli, K. R. (Kimberly R.), Liang, D. (Dong), Lu, K. H. (Karen H.), Hildebrandt, M. A. (Michelle A. T.), Wu, X. (Xifeng), Levine, D. A. (Douglas A.), Dao, F. (Fanny), Bisogna, M. (Maria), Berchuck, A. (Andrew), Iversen, E. S. (Edwin S.), Marks, J. R. (Jeffrey R.), Akushevich, L. (Lucy), Cramer, D. W. (Daniel W.), Schildkraut, J. (Joellen), Terry, K. L. (Kathryn L.), Poole, E. M. (Elizabeth M.), Stampfer, M. (Meir), Tworoger, S. S. (Shelley S.), Bandera, E. V. (Elisa V.), Orlow, I. (Irene), Olson, S. H. (Sara H.), Bjorge, L. (Line), Salvesen, H. B. (Helga B.), van Altena, A. M. (Anne M.), Aben, K. K. (Katja K. H.), Kiemeney, L. A. (Lambertus A.), Massuger, L. F. (Leon F. A. G.), Pejovic, T. (Tanja), Bean, Y. (Yukie), Brooks-Wilson, A. (Angela), Kelemen, L. E. (Linda E.), Cook, L. S. (Linda S.), Le, N. D. (Nhu D.), Grski, B. (Bohdan), Gronwald, J. (Jacek), Menkiszak, J. (Janusz), Hogdall, C. K. (Claus K.), Lundvall, L. (Lene), Nedergaard, L. (Lotte), Engelholm, S. A. (Svend Aage), Dicks, E. (Ed), Tyrer, J. (Jonathan), Campbell, I. (Ian), McNeish, I. (Iain), Paul, J. (James), Siddiqui, N. (Nadeem), Glasspool, R. (Rosalind), Whittemore, A. S. (Alice S.), Rothstein, J. H. (Joseph H.), McGuire, V. (Valerie), Sieh, W. (Weiva), Cai, H. (Hui), Shu, X.-O. (Xiao-Ou), Teten, R. T. (Rachel T.), Sutphen, R. (Rebecca), McLaughlin, J. R. (John R.), Narod, S. A. (Steven A.), Phelan, C. M. (Catherine M.), Monteiro, A. N. (Alvaro N.), Fenstermacher, D. (David), Lin, H.-Y. (Hui-Yi), Permuth, J. B. (Jennifer B.), Sellers, T. A. (Thomas A.), Chen, Y. A. (Y. Ann), Tsai, Y.-Y. (Ya-Yu), Chen, Z. (Zhihua), Gentry-Maharaj, A. (Aleksandra), Gayther, S. A. (Simon A.), Ramus, S. J. (Susan J.), Menon, U. (Usha), Wu, A. H. (Anna H.), Pearce, C. L. (Celeste L.), Van den Berg, D. (David), Pike, M. C. (Malcolm C.), Dansonka-Mieszkowska, A. (Agnieszka), Plisiecka-Halasa, J. (Joanna), Moes-Sosnowska, J. (Joanna), Kupryjanczyk, J. (Jolanta), Pharoah, P. D. (Paul D. P.), Song, H. (Honglin), Winship, I. (Ingrid), Chenevix-Trench, G. (Georgia), Giles, G. G. (Graham G.), Tavtigian, S. V. (Sean V.), Easton, D. F. (Doug F.), and Milne, R. L. (Roger L.)

Subjects
skin and connective tissue diseases
Abstract

Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p = 7.1 × 10⁻⁵), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p = 6.9 × 10⁻⁸) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p = 0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p ≤ 0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p = 0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p = 0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.

Published
2016

14. Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study

Author

Johnson, N., Dudbridge, F., Orr, N., Gibson, L., Jones, M.E., Schoemaker, M.J., Folkerd, E.J., Haynes, B.P., Hopper, J.L., Southey, M.C., Dite, G.S., Apicella, C., Schmidt, M.K., Broeks, A., Van't Veer, L.J., Atsma, F., Muir, K., Lophatananon, A., Fasching, P.A., Beckmann, M.W., Ekici, A.B., Renner, S.P., Sawyer, E., Tomlinson, I., Kerin, M., Miller, N., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Guenel, P., Truong, T., Cordina, E., Menegaux, F., Bojesen, S.E., Nordestgaard, B.G., Flyger, H., Milne, R., Zamora, M.P., Arias Perez, J.I., Benitez, J., Bernstein, L., Anton-Culver, H., Ziogas, A., Dur, C.C., Brenner, H., Mueller, H., Arndt, V., Dieffenbach, A.K., Meindl, A., Heil, J., Bartram, C.R., Schmutzler, R.K., Brauch, H., Justenhoven, C., Ko, Y-D., Nevanlinna, H., Muranen, T.A., Aittomaeki, K., Blomqvist, C., Matsuo, K., Doerk, T., Bogdanova, NV., Antonenkova, N.N., Lindblom, A., Mannermaa, A., Kataja, V., Kosma, V-M., Hartikainen, J.M., Chenevix-Trench, G., Beesley, J., Wu, A.H., Van den Berg, D., Tseng, C-C., Lambrechts, D., Smeets, D., Neven, P., Wildiers, H., Chang-Claude, J., Rudolph, A., Nickels, S., Flesch-Janys, D., Radice, P., Peterlongo, P., Bonanni, B., Pensotti, V., Couch, F.J., Olson, J.E., Wang, X., Fredericksen, Z., Pankratz, V.S., Giles, G.G., Severi, G., Baglietto, L., Haiman, C., Simard, J., Goldberg, M.S., Labreche, F., Dumont, M., Soucy, P., Teo, S., Yip, C.H., Phuah, S.Y., Cornes, B.K., Kristensen, V.N., Alnaes, G.G., Borresen-Dale, A-L., Zheng, W., Winqvist, R., Pylkaes, K., Jukkola-Vuorinen, A., Grip, M., Andrulis, I.L, Knight, J.A., Glendon, G., Mulligan, A.M., Devillee, P., Figueroa, J., Chanock, S.J., Lissowska, J., Sherman, M.E., Hall, P., Schoof, N., Hooning, M., Hollestelle, A., Oldenburg, R.A., Tilanus-Linthorst, M., Liu, J., Cox, A., Brock, I.W., Reed, M.W.R., Cross, S.S., Blot, W., Signorello, L.B., Pharoah, P.D.P., Dunning, A.M., Shah, M., Kang, D., Noh, D-Y., Park, S.K., Choi, J-Y., Hartman, M., Miao, H., Lim, W.Y., Tang, A., Hamann, U., Foersti, A., Ruediger, T., Ulmer, H.U., Jakubowska, A., Lubinski, J., Jaworska-Bieniek, K., Durda, K., Sangrajrang, S., Gaborieau, V., Brennan, P., Mckay, J., Slager, S., Toland, A.E., Vachon, C., Yannoukakos, D., Shen, C-Y., Yu, J-C., Huang, C-S., Hou, M-F., Gonzalez-Neira, A., Tessier, D.C., Vincent, D., Bacot, F., Luccarini, C., Dennis, J., Michailidou, K., Bolla, M.K., Wang, J., Easton, D.F., Garcia-Closas, M., Dowsett, M., Ashworth, A., Swerdlow, A.J., Peto, J., Silva, I.D.S., Fletcher, O., Breast, G.E.I., Investigators, K., Grp, AOCS, Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Dennis, Joe [0000-0003-4591-1214], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository

Subjects
Adult, Menarche, Genotype, Age Factors, Breast Neoplasms, Middle Aged, Polymorphism, Single Nucleotide, White People, Premenopause, Risk Factors, Cytochrome P-450 CYP3A, Humans, Female, Genetic Predisposition to Disease, Age of Onset, Reproductive History, Genetic Association Studies, Aged
Abstract

Introduction: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to\ud the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and\ud a modest reduction in risk of breast cancer in women age ≤50 years.\ud Methods: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of\ud 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping\ud of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine\ud whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.\ud Results: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found\ud no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were\ud OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (Ptrend = 0.02). There was\ud no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche\ud in controls (Ptrend = 0.005) but not cases (Ptrend = 0.97). Consequently the association between rs10235235 and breast\ud cancer risk differed according to age at menarche (Phet = 0.02); the rare allele of rs10235235 was associated with a\ud reduction in breast cancer risk for women who had their menarche age ≥15 years (ORhet = 0.84, 95% CI 0.75, 0.94;\ud ORhom = 0.81, 95% CI 0.51, 1.30; Ptrend = 0.002) but not for those who had their menarche age ≤11 years (ORhet = 1.06,\ud 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; Ptrend = 0.29).\ud Conclusions: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both\ud breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche\ud and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

Published
2014

16. PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

Author

Southey, MC, Goldgar, DE, Winqvist, R, Pylkas, K, Couch, F, Tischkowitz, M, Foulkes, WD, Dennis, J, Michailidou, K, van Rensburg, EJ, Heikkinen, T, Nevanlinna, H, Hopper, JL, Doerk, T, Claes, KBM, Reis-Filho, J, Teo, ZL, Radice, P, Catucci, I, Peterlongo, P, Tsimiklis, H, Odefrey, FA, Dowty, JG, Schmidt, MK, Broeks, A, Hogervorst, FB, Verhoef, S, Carpenter, J, Clarke, C, Scott, RJ, Fasching, PA, Haeberle, L, Ekici, AB, Beckmann, MW, Peto, J, dos-Santos-Silva, I, Fletcher, O, Johnson, N, Bolla, MK, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Marme, F, Burwinkel, B, Yang, R, Guenel, P, Therese, T, Menegaux, F, Sanchez, M, Bojesen, S, Nielsen, SF, Flyger, H, Benitez, J, Pilar Zamora, M, Arias Perez, JI, Menendez, P, Anton-Culver, H, Neuhausen, S, Ziogas, A, Clarke, CA, Brenner, H, Arndt, V, Stegmaier, C, Brauch, H, Bruening, T, Ko, Y-D, Muranen, TA, Aittomaki, K, Blomqvist, C, Bogdanova, NV, Antonenkova, NN, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Spurdle, AB, Wauters, E, Smeets, D, Beuselinck, B, Floris, G, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Olson, JE, Vachon, C, Pankratz, VS, McLean, C, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Kristensen, V, Alnaes, GG, Zheng, W, Hunter, DJ, Lindstrom, S, Hankinson, SE, Kraft, P, Andrulis, I, Knight, JA, Glendon, G, Mulligan, AM, Jukkola-Vuorinen, A, Grip, M, Kauppila, S, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Hollestelle, A, Garcia-Closas, M, Figueroa, J, Chanock, SJ, Lissowska, J, Czene, K, Darabi, H, Eriksson, M, Eccles, DM, Rafiq, S, Tapper, WJ, Gerty, SM, Hooning, MJ, Martens, JWM, Collee, JM, Tilanus-Linthorst, M, Hall, P, Li, J, Brand, JS, Humphreys, K, Cox, A, Reed, MWR, Luccarini, C, Baynes, C, Dunning, AM, Hamann, U, Torres, D, Ulmer, HU, Ruediger, T, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Slager, S, Toland, AE, Ambrosone, CB, Yannoukakos, D, Swerdlow, A, Ashworth, A, Orr, N, Jones, M, Gonzalez-Neira, A, Pita, G, Rosario Alonso, M, Alvarez, N, Herrero, D, Tessier, DC, Vincent, D, Bacot, F, Simard, J, Dumont, M, Soucy, P, Eeles, R, Muir, K, Wiklund, F, Gronberg, H, Schleutker, J, Nordestgaard, BG, Weischer, M, Travis, RC, Neal, D, Donovan, JL, Hamdy, FC, Khaw, K-T, Stanford, JL, Blot, WJ, Thibodeau, S, Schaid, DJ, Kelley, JL, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Butterbach, K, Park, J, Kaneva, R, Batra, J, Teixeira, MR, Kote-Jarai, Z, Al Olama, AA, Benlloch, S, Renner, SP, Hartmann, A, Hein, A, Ruebner, M, Lambrechts, D, Van Nieuwenhuysen, E, Vergote, I, Lambretchs, S, Doherty, JA, Rossing, MA, Nickels, S, Eilber, U, Wang-Gohrke, S, Odunsi, K, Sucheston-Campbell, LE, Friel, G, Lurie, G, Killeen, JL, Wilkens, LR, Goodman, MT, Runnebaum, I, Hillemanns, PA, Pelttari, LM, Butzow, R, Modugno, F, Edwards, RP, Ness, RB, Moysich, KB, du Bois, A, Heitz, F, Harter, P, Kommoss, S, Karlan, BY, Walsh, C, Lester, J, Jensen, A, Kjaer, SK, Hogdall, E, Peissel, B, Bonanni, B, Bernard, L, Goode, EL, Fridley, BL, Vierkant, RA, Cunningham, JM, Larson, MC, Fogarty, ZC, Kalli, KR, Liang, D, Lu, KH, Hildebrandt, MAT, Wu, X, Levine, DA, Dao, F, Bisogna, M, Berchuck, A, Iversen, ES, Marks, JR, Akushevich, L, Cramer, DW, Schildkraut, J, Terry, KL, Poole, EM, Stampfer, M, Tworoger, SS, Bandera, EV, Orlow, I, Olson, SH, Bjorge, L, Salvesen, HB, van Altena, AM, Aben, KKH, Kiemeney, LA, Massuger, LFAG, Pejovic, T, Bean, Y, Brooks-Wilson, A, Kelemen, LE, Cook, LS, Le, ND, Grski, B, Gronwald, J, Menkiszak, J, Hogdall, CK, Lundvall, L, Nedergaard, L, Engelholm, SA, Dicks, E, Tyrer, J, Campbell, I, McNeish, I, Paul, J, Siddiqui, N, Glasspool, R, Whittemore, AS, Rothstein, JH, McGuire, V, Sieh, W, Cai, H, Shu, X-O, Teten, RT, Sutphen, R, McLaughlin, JR, Narod, SA, Phelan, CM, Monteiro, AN, Fenstermacher, D, Lin, H-Y, Permuth, JB, Sellers, TA, Chen, YA, Tsai, Y-Y, Chen, Z, Gentry-Maharaj, A, Gayther, SA, Ramus, SJ, Menon, U, Wu, AH, Pearce, CL, Van den Berg, D, Pike, MC, Dansonka-Mieszkowska, A, Plisiecka-Halasa, J, Moes-Sosnowska, J, Kupryjanczyk, J, Pharoah, PDP, Song, H, Winship, I, Chenevix-Trench, G, Giles, GG, Tavtigian, SV, Easton, DF, Milne, RL, Southey, MC, Goldgar, DE, Winqvist, R, Pylkas, K, Couch, F, Tischkowitz, M, Foulkes, WD, Dennis, J, Michailidou, K, van Rensburg, EJ, Heikkinen, T, Nevanlinna, H, Hopper, JL, Doerk, T, Claes, KBM, Reis-Filho, J, Teo, ZL, Radice, P, Catucci, I, Peterlongo, P, Tsimiklis, H, Odefrey, FA, Dowty, JG, Schmidt, MK, Broeks, A, Hogervorst, FB, Verhoef, S, Carpenter, J, Clarke, C, Scott, RJ, Fasching, PA, Haeberle, L, Ekici, AB, Beckmann, MW, Peto, J, dos-Santos-Silva, I, Fletcher, O, Johnson, N, Bolla, MK, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Marme, F, Burwinkel, B, Yang, R, Guenel, P, Therese, T, Menegaux, F, Sanchez, M, Bojesen, S, Nielsen, SF, Flyger, H, Benitez, J, Pilar Zamora, M, Arias Perez, JI, Menendez, P, Anton-Culver, H, Neuhausen, S, Ziogas, A, Clarke, CA, Brenner, H, Arndt, V, Stegmaier, C, Brauch, H, Bruening, T, Ko, Y-D, Muranen, TA, Aittomaki, K, Blomqvist, C, Bogdanova, NV, Antonenkova, NN, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Spurdle, AB, Wauters, E, Smeets, D, Beuselinck, B, Floris, G, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Olson, JE, Vachon, C, Pankratz, VS, McLean, C, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Kristensen, V, Alnaes, GG, Zheng, W, Hunter, DJ, Lindstrom, S, Hankinson, SE, Kraft, P, Andrulis, I, Knight, JA, Glendon, G, Mulligan, AM, Jukkola-Vuorinen, A, Grip, M, Kauppila, S, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Hollestelle, A, Garcia-Closas, M, Figueroa, J, Chanock, SJ, Lissowska, J, Czene, K, Darabi, H, Eriksson, M, Eccles, DM, Rafiq, S, Tapper, WJ, Gerty, SM, Hooning, MJ, Martens, JWM, Collee, JM, Tilanus-Linthorst, M, Hall, P, Li, J, Brand, JS, Humphreys, K, Cox, A, Reed, MWR, Luccarini, C, Baynes, C, Dunning, AM, Hamann, U, Torres, D, Ulmer, HU, Ruediger, T, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Slager, S, Toland, AE, Ambrosone, CB, Yannoukakos, D, Swerdlow, A, Ashworth, A, Orr, N, Jones, M, Gonzalez-Neira, A, Pita, G, Rosario Alonso, M, Alvarez, N, Herrero, D, Tessier, DC, Vincent, D, Bacot, F, Simard, J, Dumont, M, Soucy, P, Eeles, R, Muir, K, Wiklund, F, Gronberg, H, Schleutker, J, Nordestgaard, BG, Weischer, M, Travis, RC, Neal, D, Donovan, JL, Hamdy, FC, Khaw, K-T, Stanford, JL, Blot, WJ, Thibodeau, S, Schaid, DJ, Kelley, JL, Maier, C, Kibel, AS, Cybulski, C, Cannon-Albright, L, Butterbach, K, Park, J, Kaneva, R, Batra, J, Teixeira, MR, Kote-Jarai, Z, Al Olama, AA, Benlloch, S, Renner, SP, Hartmann, A, Hein, A, Ruebner, M, Lambrechts, D, Van Nieuwenhuysen, E, Vergote, I, Lambretchs, S, Doherty, JA, Rossing, MA, Nickels, S, Eilber, U, Wang-Gohrke, S, Odunsi, K, Sucheston-Campbell, LE, Friel, G, Lurie, G, Killeen, JL, Wilkens, LR, Goodman, MT, Runnebaum, I, Hillemanns, PA, Pelttari, LM, Butzow, R, Modugno, F, Edwards, RP, Ness, RB, Moysich, KB, du Bois, A, Heitz, F, Harter, P, Kommoss, S, Karlan, BY, Walsh, C, Lester, J, Jensen, A, Kjaer, SK, Hogdall, E, Peissel, B, Bonanni, B, Bernard, L, Goode, EL, Fridley, BL, Vierkant, RA, Cunningham, JM, Larson, MC, Fogarty, ZC, Kalli, KR, Liang, D, Lu, KH, Hildebrandt, MAT, Wu, X, Levine, DA, Dao, F, Bisogna, M, Berchuck, A, Iversen, ES, Marks, JR, Akushevich, L, Cramer, DW, Schildkraut, J, Terry, KL, Poole, EM, Stampfer, M, Tworoger, SS, Bandera, EV, Orlow, I, Olson, SH, Bjorge, L, Salvesen, HB, van Altena, AM, Aben, KKH, Kiemeney, LA, Massuger, LFAG, Pejovic, T, Bean, Y, Brooks-Wilson, A, Kelemen, LE, Cook, LS, Le, ND, Grski, B, Gronwald, J, Menkiszak, J, Hogdall, CK, Lundvall, L, Nedergaard, L, Engelholm, SA, Dicks, E, Tyrer, J, Campbell, I, McNeish, I, Paul, J, Siddiqui, N, Glasspool, R, Whittemore, AS, Rothstein, JH, McGuire, V, Sieh, W, Cai, H, Shu, X-O, Teten, RT, Sutphen, R, McLaughlin, JR, Narod, SA, Phelan, CM, Monteiro, AN, Fenstermacher, D, Lin, H-Y, Permuth, JB, Sellers, TA, Chen, YA, Tsai, Y-Y, Chen, Z, Gentry-Maharaj, A, Gayther, SA, Ramus, SJ, Menon, U, Wu, AH, Pearce, CL, Van den Berg, D, Pike, MC, Dansonka-Mieszkowska, A, Plisiecka-Halasa, J, Moes-Sosnowska, J, Kupryjanczyk, J, Pharoah, PDP, Song, H, Winship, I, Chenevix-Trench, G, Giles, GG, Tavtigian, SV, Easton, DF, and Milne, RL

Abstract

BACKGROUND: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. METHODS: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. RESULTS: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10-5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10-8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. CONCLUSIONS: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.

Published
2016

17. Long-term psychological distress in women at risk for hereditary breast cancer adhering to regular surveillance: a risk profile

Author

Heijer, M. den, Seynaeve, C., Vanheusden, K., Timman, R., Duivenvoorden, H.J., Tilanus-Linthorst, M., Menke-Pluijmers, M.B.E., Tibben, A., Clinical Genetics, Medical Oncology, Psychiatry, and Surgery

Subjects
SDG 3 - Good Health and Well-being
Abstract

Background: Some women at risk for hereditary breast cancer are at increased risk of psychological distress. In order to tailor support for individual women, the availability of a tool enabling the identification of psychologically vulnerable women at an early stage is warranted. The objectives of this study were (1) to explore long-term psychological distress in women at risk for hereditary breast cancer adhering to regular surveillance, and (2) to identify women being vulnerable for long-term psychological distress, defined in terms of a multifactorial risk profile. Methods: General distress and cancer-related distress were assessed at baseline (T0) and after 5-8 years (T1) in 197 high-risk women adhering to breast cancer surveillance. Coping styles, occurrence of breast cancer in the family of origin, breast cancer risk perception, and frequency of breast self-examination, as assessed at T0, were examined as predictor variables for long-term distress (T1). Results: Across time, women reported a significant reduction in intrusion and avoidance. Intrusion levels were increased among women who had lost a first-degree relative to breast cancer. Predictors of increased long-term distress were passive and palliative coping styles, excessive breast self-examination, and overestimation of breast cancer risk. On the other hand, coping through fostering reassuring thoughts was predictive for decreased long-term distress. Conclusion: On the basis of the identified risk profile, it is possible to identify vulnerable women at an early stage, who then may be offered additional and individually tailored support. Copyright © 2012 John Wiley & Sons, Ltd.

Published
2012

18. The impact of social and personal resources on psychological distress in women at risk for hereditary breast cancer

Author

Heijer, M. den, Vos, J., Seynaeve, C., Vanheusden, K., Duivenvoorden, H.J., Tilanus-Linthorst, M., Menke-Pluymers, M.B.E., Tibben, A., Psychiatry, Erasmus MC other, Medical Oncology, Clinical Genetics, Surgery, Internal medicine, and EMGO - Musculoskeletal health

Subjects
Molecular epidemiology [NCEBP 1], SDG 3 - Good Health and Well-being, Health aging / healthy living Cardiovascular diseases [IGMD 5]
Abstract

Objective: The objectives of the present study were to (1) evaluate whether social and personal resources were independently related to psychological distress and (2) examine the interrelationships of social and personal resources in women at risk for hereditary breast cancer.Methods: General and breast cancer specific distress, family communication regarding hereditary breast cancer, perceived social support, self-esteem, self-concept, and demographics were assessed in 222 high-risk women, having opted either for regular surveillance or prophylactic surgery.Results: Structural equation modeling showed that (1) both personal and social resources were independently associated with psychological distress and (2) the associations between social resources and psychological distress were partially mediated by personal resources. Support from family and friends was associated with a higher level of self-esteem, which in turn was associated with less general distress. Furthermore, communication regarding cancer within the nuclear family was associated with decreased feelings of stigmatization, which in turn was associated with less general and breast cancer specific distress. Moreover, open communication within the family was associated with a reduced sense of vulnerability.Conclusion: Health workers involved in the care of high-risk women should carefully monitor women's personal and social resources, and if compromised refer them for appropriate support. Copyright © 2010 John Wiley & Sons, Ltd. PMID: 21132677 [PubMed - as supplied by publisher]

Published
2012
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19. Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers

Author

Cox, D. G., Simard, J., Sinnett, D., Hamdi, Y., Soucy, P., Ouimet, M., Barjhoux, L., Verny-Pierre, C., McGuffog, L., Healey, S., Szabo, C., Greene, M. H., Mai, P. L., Andrulis, I. L., Thomassen, M., Gerdes, A.-M., Caligo, M. A., Friedman, E., Laitman, Y., Kaufman, B., Paluch, S. S., Borg, A., Karlsson, P., Stenmark Askmalm, M., Barbany Bustinza, G., Nathanson, K. L., Domchek, S. M., Rebbeck, T. R., Benitez, J., Hamann, U., Rookus, M. A., van den Ouweland, A. M. W., Ausems, M. G. E. M., Aalfs, C. M., van Asperen, C. J., Devilee, P., Gille, H. J. J. P., Peock, S., Frost, D., Evans, D. G., Eeles, R., Izatt, L., Adlard, J., Paterson, J., Eason, J., Godwin, A. K., Remon, M.-A., Moncoutier, V., Gauthier-Villars, M., Lasset, C., Giraud, S., Hardouin, A., Berthet, P., Sobol, H., Eisinger, F., Bressac de Paillerets, B., Caron, O., Delnatte, C., Goldgar, D., Miron, A., Ozcelik, H., Buys, S., Southey, M. C., Terry, M. B., Singer, C. F., Dressler, A.-C., Tea, M.-K., Hansen, T. V. O., Johannsson, O., Piedmonte, M., Rodriguez, G. C., Basil, J. B., Blank, S., Toland, A. E., Montagna, M., Isaacs, C., Blanco, I., Gayther, S. A., Moysich, K. B., Schmutzler, R. K., Wappenschmidt, B., Engel, C., Meindl, A., Ditsch, N., Arnold, N., Niederacher, D., Sutter, C., Gadzicki, D., Fiebig, B., Caldes, T., Laframboise, R., Nevanlinna, H., Chen, X., Beesley, J., Spurdle, A. B., Neuhausen, S. L., Ding, Y. C., Couch, F. J., Wang, X., Peterlongo, P., Manoukian, S., Bernard, L., Radice, P., Easton, D. F., Chenevix-Trench, G., Antoniou, A. C., Stoppa-Lyonnet, D., Mazoyer, S., Sinilnikova, O. M., Dumont, M., Greene, M., Glendon, G., Selander, T., Weerasooriya, N., Nordling, M., Bergman, A., Einbeigi, Z., Stenmark-Askmalm, M., Liedgren, S., Loman, N., Olsson, H., Kristoffersson, U., Soller, M., Jernstrom, H., Harbst, K., Henriksson, K., Lindblom, A., Arver, B., von Wachenfeldt, A., Liljegren, A., Barbany-Bustinza, G., Rantala, J., Melin, B., Gronberg, H., Stattin, E.-L., Emanuelsson, M., Ehrencrona, H., Torres, D., Rashid, M. U., Seidel-Renkert, A., Hogervorst, F. B. L., Verhoef, S., Verheus, M., van't Veer, L. J., van Leeuwen, F. E., Collee, M., Jager, A., Hooning, M. J., Tilanus-Linthorst, M. M. A., Seynaeve, C., Wijnen, J. T., Vreeswijk, M. P., Tollenaar, R. A., Ligtenberg, M. J., Hoogerbrugge, N., Ausems, M. G., van der Luijt, R. B., van Os, T. A., Gille, J. J. P., Waisfisz, Q., Meijers-Heijboer, H. E. J., Gomez-Garcia, E. B., van Roozendaal, C. E., Blok, M. J., Caanen, B., Oosterwijk, J. C., van der Hout, A. H., Mourits, M. J., Vasen, H. F., Cook, M., Platte, R., Miedzybrodzka, Z., Gregory, H., Morrison, P., Jeffers, L., Cole, T., Ong, K.-r., Hoffman, J., Donaldson, A., James, M., Downing, S., Taylor, A., Murray, A., Rogers, M. T., McCann, E., Kennedy, M. J., Barton, D., Porteous, M., Drummond, S., Brewer, C., Kivuva, E., Searle, A., Goodman, S., Hill, K., Davidson, R., Murday, V., Bradshaw, N., Snadden, L., Longmuir, M., Watt, C., Gibson, S., Haque, E., Tobias, E., Duncan, A., Jacobs, C., Langman, C., Whaite, A., Dorkins, H., Barwell, J., Chu, C., Miller, J., Ellis, I., Houghton, C., Lalloo, F., Taylor, J., Side, L., Male, A., Berlin, C., Collier, R., Douglas, F., Claber, O., Jobson, I., Walker, L., McLeod, D., Halliday, D., Durell, S., Stayner, B., Shanley, S., Rahman, N., Houlston, R., Bancroft, E., D'Mello, L., Page, E., Ardern-Jones, A., Kohut, K., Wiggins, J., Castro, E., Mitra, A., Robertson, L., Cook, J., Quarrell, O., Bardsley, C., Hodgson, S., Goff, S., Brice, G., Winchester, L., Eddy, C., Tripathi, V., Attard, V., Eccles, D., Lucassen, A., Crawford, G., McBride, D., Smalley, S., Sinilnikova, O., Leone, M., Buecher, B., Houdayer, C., Belotti, M., Tirapo, C., de Pauw, A., Bressac-de-Paillerets, B., Remenieras, A., Byrde, V., Lenoir, G., Bignon, Y.-J., Uhrhammer, N., Bonadona, V., Bourdon, V., Noguchi, T., Coulet, F., Colas, C., Soubrier, F., Coupier, I., Pujol, P., Peyrat, J.-P., Fournier, J., Revillion, F., Vennin, P., Adenis, C., Rouleau, E., Lidereau, R., Demange, L., Nogues, C., Muller, D., Fricker, J.-P., Longy, M., Sevenet, N., Toulas, C., Guimbaud, R., Gladieff, L., Feillel, V., Leroux, D., Dreyfus, H., Rebischung, C., Coron, F., Faivre, L., Prieur, F., Lebrun, M., Ferrer, S. F., Frenay, M., Venat-Bouvet, L., Mortemousque, I., Lynch, H. T., Snyder, C. L., Ejlertsen, B., Andersen, M. K., Kjaergaard, S., Senter, L., Sweet, K., O'Connor, M., Craven, C., Pharoah, P., Ramus, S., Pye, C., Harrington, P., Wozniak, E., Varon-Mateeva, R., Kast, K., Preisler-Adams, S., Deissler, H., Schonbuchner, I., Heinritz, W., Schafer, D., Aittomaki, K., Blomqvist, C., Heikkinen, T., Erkkila, R. N. I., Thorne, H., Niedermayr, E., de la Hoya, M., Perez-Segura, P., Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Centre de recherche du CHU Sainte-Justine [Montreal], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Department of Pediatrics, CHU Sainte Justine [Montréal], Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Queensland Institute of Medical Research, University of Delaware [Newark], Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Clinical Genetics, Odense University Hospital, Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, Department of Oncology, Sahlgrenska University Hospital [Gothenburg], Depts of Medicine and Biostatistics and Epidemology, Abramson Family Cancer Research Institute-Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Human Genetics Group, Spanish National Cancer Research Centre, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Molecular Genetics of Breast Cancer, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Genetic Epidemiology, Leiden University Medical Center (LUMC), Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Yorkshire Regional Genetics Service, Addenbrookes Hospital, Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, génétique, Institut Curie [Paris], Service de Génétique Oncologique, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Consultation d'Oncogénétique, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service d'Oncologie Génétique, de Prévention et Dépistage, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique oncologique (GO - UMR 8125), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Centre René Gauducheau, CRLCC René Gauducheau, Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), Department of Internal Medicine, Huntsman Cancer Institute, Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Dept of OB/GYN and Comprehensive Cancer Center, Medizinische Universität Wien = Medical University of Vienna, Faculty of Medicine, University of Iceland [Reykjavik], Statistical and Data Center, Roswell Park Cancer Institute [Buffalo], Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Lombardi Comprehensive Cancer Center, Georgetown University, Genetic Counselling Unit, IDIBELL-Catalan Institute of Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Ludwig-Maximilians-Universität München (LMU), University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Heidelberg University Hospital [Heidelberg], Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] (MHH), Universität Regensburg (UR), Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Laboratory Medicine and Pathology, Mayo Clinic, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Department of Experimental Oncology, Istituto Europeo di Oncologia-Consortium for Genomics Technology (Cogentech), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Genetic Epidemiology Unit, Department of Public Health and Primary Care, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 6, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Research Centre, CHU Ste Justine, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Génétique moléculaire, signalisation et cancer (GMSC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Human Genetics, Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Tel Aviv University (TAU), University of Pennsylvania-University of Pennsylvania, Universiteit Leiden-Universiteit Leiden, Nottingham University Hospitals NHS Trust (NUH), Roswell Park Cancer Institute [Buffalo] (RPCI), Georgetown University [Washington] (GU), Universität Leipzig, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Génétique moléculaire, signalisation et cancer ( GMSC ), Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University of Cambridge [UK] ( CAM ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Rigshospitalet [Copenhagen]-University of Copenhagen ( KU ), Sahlgrenska University Hospital, Abramson Family Cancer Research Institute-University of Pennsylvania School of Medicine, Deutsches Krebsforschungszentrum ( DKFZ ), INSTITUT CURIE, Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), Centre François Baclesse, Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - AMU - IRD ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ), Génétique oncologique ( GO - UMR 8125 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), Mount Sinai Hospital ( MSH ), Medical University of Vienna-Department of OB/GYN, Medical University of Vienna, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] ( IMISE ), University of Leipzig, Technical University of Munich ( TUM ), Ludwig-Maximilians-Universität München, University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel ( CAU ), University Hospital Düsseldorf-Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Hannover Medical School [Hannover] ( MHH ), University Regensburg, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Human genetics, and CCA - Oncogenesis

Subjects
endocrine system diseases, Electrophoretic Mobility Shift Assay, MESH : Breast Neoplasms, medicine.disease_cause, Linkage Disequilibrium, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Genes, Reporter, Risk Factors, MESH: Risk Factors, Genotype, MESH : Female, Luciferases, skin and connective tissue diseases, Genetics (clinical), MESH: Genetic Association Studies, MESH: Heterozygote, Genetics, 0303 health sciences, MESH : Linkage Disequilibrium, BRCA1 Protein, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Association Studies Articles, MESH: Genetic Predisposition to Disease, General Medicine, MESH : Genes, Reporter, MESH : Risk Factors, 3. Good health, MESH: Linkage Disequilibrium, 030220 oncology & carcinogenesis, MESH : Electrophoretic Mobility Shift Assay, Female, Breast disease, MESH : Mutation, MESH : Heterozygote, Heterozygote, MESH: Mutation, Single-nucleotide polymorphism, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, medicine, Humans, MESH : BRCA1 Protein, MESH : HeLa Cells, Genetic Predisposition to Disease, ddc:610, Allele, Molecular Biology, MESH : Haplotypes, Alleles, Genetic Association Studies, 030304 developmental biology, MESH: BRCA1 Protein, MESH : Luciferases, MESH: Humans, Hereditary cancer and cancer-related syndromes [ONCOL 1], MESH: Alleles, Haplotype, MESH : Humans, MESH: Genes, Reporter, Cancer, MESH : Genetic Association Studies, MESH: Haplotypes, medicine.disease, Haplotypes, Mutation, MESH: Electrophoretic Mobility Shift Assay, MESH: HeLa Cells, Cancer research, MESH : Genetic Predisposition to Disease, MESH: Luciferases, Carcinogenesis, MESH : Alleles, MESH: Female, MESH: Breast Neoplasms, HeLa Cells
Abstract

Item does not contain fulltext Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA1 gene would modify the risk of breast cancer in carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of breast cancer (hazard ratio 0.86, 95% confidence interval 0.77-0.95, P = 0.003). Promoter in vitro assays of the major BRCA1 haplotypes showed that common polymorphisms in the regulatory region alter its activity and that this effect may be attributed to the differential binding affinity of nuclear proteins. In conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1 transcription.

Published
2011
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20. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

Author

Antoniou, A. C., Kartsonaki, C., Sinilnikova, O. M., Soucy, P., Mcguffog, L., Healey, S., Lee, A., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Cattaneo, E., Barile, M., Pensotti, V., Pasini, B., Dolcetti, R., Giannini, Giuseppe, Laura Putignano, A., Varesco, L., Radice, P., Mai, P. L., Greene, M. H., Andrulis, I. L., Glendon, G., Ozcelik, H., Thomassen, M., Gerdes, A. M., Kruse, T. A., Jensen, U. B., Cruger, D. G., Caligo, M. A., Laitman, Y., Milgrom, R., Kaufman, B., Paluch Shimon, S., Friedman, E., Loman, N., Harbst, K., Lindblom, A., Arver, B., Ehrencrona, H., Melin, B., Nathanson, K. L., Domchek, S. M., Rebbeck, T., Jakubowska, A., Lubinski, J., Gronwald, J., Huzarski, T., Byrski, T., Cybulski, C., Gorski, B., Osorio, A., Cajal, T. R., Fostira, F., Andres, R., Benitez, J., Hamann, U., Hogervorst, F. B., Rookus, M. A., Hooning, M. J., Nelen, M. R., Van Der Luijt, R. B., Van Os, T. A. M., Van Asperen, C. J., Devilee, P., Meijers Heijboer, H. E. J., Garcia, E. B. G., Peock, S., Cook, M., Frost, D., Platte, R., Leyland, J., Evans, D. G., Lalloo, F., Eeles, R., Izatt, L., Adlard, J., Davidson, R., Eccles, D., Ong, K. R., Cook, J., Douglas, F., Paterson, J., John Kennedy, M., Miedzybrodzka, Z., Godwin, A., Stoppa Lyonnet, D., Buecher, B., Belotti, M., Tirapo, C., Mazoyer, S., Barjhoux, L., Lasset, C., Leroux, D., Faivre, L., Bronner, M., Prieur, F., Nogues, C., Rouleau, E., Pujol, P., Coupier, I., Frenay, M., Hopper, J. L., Daly, M. B., Terry, M. B., John, E. M., Buys, S. S., Yassin, Y., Miron, A., Goldgar, D., Singer, C. F., Tea, M. K., Pfeiler, G., Catharina Dressler, A., Hansen, T. V. O., Jonson, L., Ejlertsen, B., Barkardottir, R. B., Kirchhoff, T., Offit, K., Piedmonte, M., Rodriguez, G., Small, L., Boggess, J., Blank, S., Basil, J., Azodi, M., Toland, A. E., Montagna, M., Tognazzo, S., Agata, S., Imyanitov, E., Janavicius, R., Lazaro, C., Blanco, I., Pharoah, P. D. P., Sucheston, L., Karlan, B. Y., Walsh, C. S., Olah, E., Bozsik, A., Teo, S. H., Seldon, J. L., Beattie, M. S., Van Rensburg, E. J., Sluiter, M. D., Diez, O., Schmutzler, R. K., Wappenschmidt, B., Engel, C., Meindl, A., Ruehl, I., Varon Mateeva, R., Kast, K., Deissler, H., Niederacher, D., Arnold, N., Gadzicki, D., Schonbuchner, I., Caldes, T., De La Hoya, M., Nevanlinna, H., Aittomaki, K., Dumont, M., Chiquette, J., Tischkowitz, M., Chen, X. Q., Beesley, J., Spurdle, A. B., Neuhausen, S. L., Ding, Y. C., Fredericksen, Z., Wang, X., Pankratz, V. S., Couch, F., Simard, J., Easton, D. F., Chenevix Trench, G., Karlsson, P., Nordling, M., Bergman, A., Einbeigi, Z., Stenmark Askmalm, M., Liedgren, S., Borg, A., Olsson, H., Kristoffersson, U., Jernstrom, H., Henriksson, K., Von Wachenfeldt, A., Liljegren, A., Barbany Bustinza, G., Rantala, J., Gronberg, H., Stattin, E. L., Emanuelsson, M., Brandell, R. R., Dahl, N., Hogervorst, F. B. L., Verhoef, S., Verheus, M., Veer, L. V., Van Leeuwen, F. E., Collee, M., Van Den Ouweland, A. M. W., Jager, A., Tilanus Linthorst, M. M. A., Seynaeve, C., Wijnen, J. T., Vreeswijk, M. P., Tollenaar, R. A., Ligtenberg, M. J., Hoogerbrugge, N., Ausems, M. G., Aalfs, C. M., Van Os, T. A., Gille, J. J. P., Waisfisz, Q., Gomez Garcia, E. B., Van Roozendaal, C. E., Blok, M. J., Caanen, B., Oosterwijk, J. C., Van Der Hout, A. H., Mourits, M. J., Vasen, H. F., Gregory, H., Morrison, P., Jeffers, L., Cole, T., Mckeown, C., Hoffman, J., Donaldson, A., Downing, S., Taylor, A., Murray, A., Rogers, M. T., Mccann, E., Kennedy, M. J., Barton, D., Porteous, M., Drummond, S., Brewer, C., Kivuva, E., Searle, A., Goodman, S., Hill, K., Murday, V., Bradshaw, N., Snadden, L., Longmuir, M., Watt, C., Gibson, S., Haque, E., Tobias, E., Duncan, A., Jacobs, C., Langman, C., Whaite, A., Dorkins, H., Barwell, J., Chu, C., Miller, J., Ellis, I., Houghton, C., Taylor, J., Side, L., Male, A., Berlin, C., Eason, J., Collier, R., Claber, O., Jobson, I., Walker, L., Mcleod, D., Halliday, D., Durell, S., Stayner, B., Shanley, S., Rahman, N., Houlston, R., Bancroft, E., D'Mello, L., Page, E., Ardern Jones, A., Kohut, K., Wiggins, J., Castro, E., Mitra, A., Robertson, L., Quarrell, O., Bardsley, C., Hodgson, S., Goff, S., Brice, G., Winchester, L., Eddy, C., Tripathi, V., Attard, V., Lucassen, A., Crawford, G., Mcbride, D., Smalley, S., University of Groningen, Clinical Genetics, Medical Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] ( CAM ), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Queensland Institute of Medical Research, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Consortium for Genomics Technology (Cogentech), Department of Genetics, Biology and Biochemistry, University of Turin, Cancer Bioimmunotherapy Unit, IRCCS-Centro di Riferimento Oncologico, Department of Experimental Medicine, Università degli Studi di Roma 'La Sapienza' [Rome], Medical Genetics Unit, Department of Clinical Physiopathology, University of Florence, Unit of Hereditary Cancers, Istituto Nazionale per la Ricerca sul Cancro, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Ontario Cancer Genetics Network, Cancer Care Ontario, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Samuel Lunenfeld Research Institute, Mount Sinai Hospital ( MSH ), Department of Clinical Genetics, Odense University Hospital, Rigshospitalet [Copenhagen]-University of Copenhagen ( KU ), The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Department of Oncology, Lund University Hospital, Karolinska University Hospital [Stockholm], Departament of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Department of Radiation Sciences and Oncology, Umeå University, Depts of Medicine and Biostatistics and Epidemology, Abramson Family Cancer Research Institute-University of Pennsylvania School of Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine-Abramson Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University-International Hereditary Cancer Centre, Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, International Hereditary Cancer Center, Pomeranian Medical University, Human Genetics Group, Spanish National Cancer Research Centre, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Department of Medical Oncology, Hospital Sant Pau, Medical Oncology Division, Hospital Clínico de Zaragoza, Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum ( DKFZ ), Department of Genetic Epidemiology, Leiden University Medical Center (LUMC), Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Guy's and St. Thomas' NHS Foundation Trust, Yorkshire Regional Genetics Service, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Wessex Clinical Genetics Service, Princess Anne Hospital, West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Newcastle Upon Tyne Hospitals NHS Trust, Addenbrookes Hospital, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Service de Génétique Oncologique, INSTITUT CURIE, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), génétique, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], Service d'onco-hématologie et génétique, CHU Grenoble, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, Santé Publique, Hôpital René HUGUENIN (Saint-Cloud)-INSTITUT CURIE, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Institut de recherche en cancérologie de Montpellier ( IRCM - U896 Inserm - UM1 ), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ), Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Unité d'Oncogénétique, CRLCC Val d'Aurelle - Paul Lamarque, Consultation d'oncogénétique, CRLCC Antoine Lacassagne, Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Department of Surgery, Harvard Medical School [Boston] ( HMS ), Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Division of Special Gynecology, Medical University of Vienna-Department of OB/GYN, Department of Clinical Biochemistry, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Rigshospitalet [Copenhagen], Department of Pathology, Landspitali-University Hospital, Department of Environmental Medicine, New York University School of Medicine-NYU Cancer Institute, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Statistical and Data Center, Roswell Park Cancer Institute [Buffalo], Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Clinics, State Research Institute Innovative Medicine Center, Molecular Diagnostic Unit, IDIBELL-Catalan Institute of Oncology, Genetic Counselling Unit, Department of Molecular Genetics, National Institute of Oncology, Cancer Research Initiatives Foundation, Sime Darby Medical Centre-Malaysia and University Malaya Cancer Research Institute-University Malaya Medical Centre, Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] ( IMISE ), University of Leipzig, Technical University of Munich ( TUM ), Ludwig-Maximillians University, Charite berlin, University Hospital Carl Gustav Carus, University Hospital Ulm, University Hospital Düsseldorf-Heinrich-Heine-Universität Düsseldorf [Düsseldorf], University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel ( CAU ), Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] ( MHH ), University of Würzburg, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Genetics, Portuguese Oncology Institute, Department of Medical Genetics, Mayo Clinic, Department of Laboratory Medicine and Pathology, Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Università degli studi di Torino = University of Turin (UNITO), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Firenze = University of Florence (UniFI), National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Mount Sinai Hospital [Toronto, Canada] (MSH), Department of Clinical Genetics [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Tel Aviv University (TAU), Uppsala University, Abramson Family Cancer Research Institute-Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Abramson Cancer Center-Perelman School of Medicine, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Pomeranian Medical University [Szczecin] (PUM), Hospital de la Santa Creu i Sant Pau, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Universiteit Leiden-Universiteit Leiden, Birmingham Women's and Children's NHS Foundation Trust, Sheffield Children's NHS Foundation Trust, Newcastle Upon Tyne Hospitals NHS Foundation Trust, University of Kansas Medical Center [Kansas City, KS, USA], Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut Curie [Paris]-Hôpital René HUGUENIN (Saint-Cloud), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Harvard Medical School [Boston] (HMS), Medizinische Universität Wien = Medical University of Vienna, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Department of Clinical Biochemistry [Rigshospitalet], Copenhagen University Hospital, New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-NYU Cancer Institute, Roswell Park Cancer Institute [Buffalo] (RPCI), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Universitätsklinikum Ulm - University Hospital of Ulm, University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), Hannover Medical School [Hannover] (MHH), Julius-Maximilians-Universität Würzburg (JMU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], University of Kansas Medical Center [Lawrence], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital René HUGUENIN (Saint-Cloud)-Institut Curie [Paris], CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Universität Leipzig [Leipzig], Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), University of Florence (UNIFI), Mount Sinai Hospital (MSH), Institut Curie, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie-Hôpital René HUGUENIN (Saint-Cloud), Technical University of Munich (TUM), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Human genetics, CCA - Oncogenesis, Human Genetics, Klinische Genetica, and RS: GROW - School for Oncology and Reproduction

Subjects
MESH : BRCA2 Protein, MESH : Aged, Estrogen receptor, Genome-wide association study, MESH : Breast Neoplasms, VARIANTS, MESH : Chromosomes, Human, Pair 1, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH : Chromosomes, Human, Pair 6, MESH: BRCA2 Protein, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Genotype, CONFER SUSCEPTIBILITY, Chromosomes, Human, MESH : Female, skin and connective tissue diseases, Genetics (clinical), POPULATION, MESH: Heterozygote, MESH: Aged, 0303 health sciences, education.field_of_study, MESH: Middle Aged, BRCA1 Protein, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Association Studies Articles, MESH: Genetic Predisposition to Disease, General Medicine, MESH : Adult, Middle Aged, MESH : Risk Factors, 3. Good health, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 6, Female, MESH : Mutation, Adult, MESH : Heterozygote, Heterozygote, MESH: Mutation, MESH: Chromosomes, Human, Pair 6, MESH: Chromosomes, Human, Pair 1, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Single-nucleotide polymorphism, Breast Neoplasms, Biology, MESH: Chromosomes, Human, Polymorphism, Single Nucleotide, Genomic disorders and inherited multi-system disorders [IGMD 3], 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Genetics, medicine, LOCUS, SNP, Humans, MESH : Middle Aged, MESH : BRCA1 Protein, Genetic Predisposition to Disease, Allele, GENOME-WIDE ASSOCIATION, education, Molecular Biology, Alleles, MESH: BRCA1 Protein, 030304 developmental biology, Aged, BRCA2 Protein, MESH: Humans, 2Q35, MESH: Alleles, MESH : Humans, MESH: Adult, medicine.disease, MESH : Chromosomes, Human, ESTROGEN-RECEPTOR, Mutation, Cancer research, MESH : Genetic Predisposition to Disease, GENETIC MODIFIERS, MESH : Alleles, MESH: Female, MESH: Breast Neoplasms
Abstract

Item does not contain fulltext Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.

Published
2011
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21. FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Author

Evans, Jeff, Agarwal, Devika, Pineda Sanjuan, Silvia, Michailidou, Kyriaki, Herranz, J, Pita, Guillermo, Moreno, T, Alonso, M R, Dennis, Joe, Wang, Qin, Bolla, Manjeet, Meyer, B, Menéndez-Rodríguez, Primitiva, Hardisson, David, Mendiola, Marta, González-Neira, Anna, Lindblom, Annika, Margolin, Sara, Swerdlow, Anthony, Ashworth, Alan, Orr, Nick, Jones, Michael, Matsuo, Keitaro, Ito, Hidemi, Iwata, Hiroji, Kondo, Naoto, Hartman, Mikael, Hui, Miao, Lim, Wei Yee, Iau, P T -C, Sawyer, Elinor, Tomlinson, Ian, Kerin, Michael, Miller, Nicola, Kang, Daehee, Choi, Ji Yeob, Park, Sue, Noh, Dong Young, Hopper, John, Schmidt, Daniel, Makalic, Enes, Southey, Melissa, Teo, Soo, Yip, Cheng Har, Sivanandan, K, Tay, Tin, Brauch, Hiltrud, Brüning, Thomas, Hamann, Ute, Dunning, Alison, Shah, Mitul, Andrulis, Irene, Knight, Julia, Glendon, Gord, Tchatchou, S, Schmidt, Marjanka, Broeks, Annegien, Rosenberg, E H, van't Veer, L J, Fasching, Peter, Renner, S P, Ekici, Arif, Beckmann, Matthias, Shen, Chen Yang, Hsiung, Chia-Ni, Yu, Jy-Cherng, Blot, William, Cai, Qiuyin, Wu, Anna, Tseng, Chiu-Chen, Van Den Berg, David, Stram, Daniel, Cox, Angela, Brock, Ian, Reed, Malcom, Muir, Kenneth, Lophatananon, Artitaya, Stewart-Brown, Sarah, Siriwanarangsan, P, Zheng, Wei, Deming-Halverson, Sandra, Shrubsole, Martha, Long, Jirong, Shu, Xiao-Ou, Lu, W, Gao, Yu-Tang, Zhang, B, Radice, Paolo, Peterlongo, Paolo, Manoukian, Siranoush, Mariette, F, Sangrajrang, Suleeporn, McKay, James, Couch, Fergus, Toland, A E, Yannoukakos, D, Fletcher, Olivia, Johnson, Nicola, dos Santos Silva, I, Peto, Julian, Marme, F, Burwinkel, Barbara, Guénel, Pascal, Truong, Thérèse, Sanchez, M, Mulot, Claire, Bojesen, Stig, Nordestgaard, Borge, Flyer, H, Brenner, Hermann, Dieffenbach, A K, Arndt, Volker, Stegmaier, Christa, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana, Lambrechts, Diether, Yesilyurt, B T, Floris, G, Leunen, K, Chang-Claude, Jenny, Rudolph, Anja, Seibold, P, Flesch-Janys, Dieter, Wang, X, Olson, Janet, Vachon, Celine, Purrington, K, Giles, Graham, Severi, G, Baglietto, L, Haiman, Christopher, Henderson, B E, Schumacher, Fredrick, Marchand, Loïc Le, Simard, Jacques, Dumont, Martine, Goldberg, Mark, Labréche, F, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Devilee, Peter, Tollenaar, Rob, Seynaeve, Caroline, García-Closas, Montserrat, Chanock, Stephen, Lissowska, Jolanta, Figueroa, Jonine, Czene, Kamila, Eriksson, Mikael, Humphreys, Keith, Darabi, H, Hooning, Maartje, Kriege, Margriet, Collée, Margriet, Tilanus-Linthorst, M, Li, Jingmei, Jakubowska, Anna, Lubinski, Jan, Jaworska-Bieniek, K, Durda, K, Nevanlinna, Heli, Muranen, T A, Aittomäki, Kristiina, Blomqvist, Carl, Bogdanova, Natalia, Dörk, Thilo, Hall, Per, Chenevix-Trench, Georgia, Easton, Douglas, Pharroah, Paul, Arias-Perez, José Ignacio, Zamora, P, Benítez, Javier, Milne, Roger, Evans, Jeff, Agarwal, Devika, Pineda Sanjuan, Silvia, Michailidou, Kyriaki, Herranz, J, Pita, Guillermo, Moreno, T, Alonso, M R, Dennis, Joe, Wang, Qin, Bolla, Manjeet, Meyer, B, Menéndez-Rodríguez, Primitiva, Hardisson, David, Mendiola, Marta, González-Neira, Anna, Lindblom, Annika, Margolin, Sara, Swerdlow, Anthony, Ashworth, Alan, Orr, Nick, Jones, Michael, Matsuo, Keitaro, Ito, Hidemi, Iwata, Hiroji, Kondo, Naoto, Hartman, Mikael, Hui, Miao, Lim, Wei Yee, Iau, P T -C, Sawyer, Elinor, Tomlinson, Ian, Kerin, Michael, Miller, Nicola, Kang, Daehee, Choi, Ji Yeob, Park, Sue, Noh, Dong Young, Hopper, John, Schmidt, Daniel, Makalic, Enes, Southey, Melissa, Teo, Soo, Yip, Cheng Har, Sivanandan, K, Tay, Tin, Brauch, Hiltrud, Brüning, Thomas, Hamann, Ute, Dunning, Alison, Shah, Mitul, Andrulis, Irene, Knight, Julia, Glendon, Gord, Tchatchou, S, Schmidt, Marjanka, Broeks, Annegien, Rosenberg, E H, van't Veer, L J, Fasching, Peter, Renner, S P, Ekici, Arif, Beckmann, Matthias, Shen, Chen Yang, Hsiung, Chia-Ni, Yu, Jy-Cherng, Blot, William, Cai, Qiuyin, Wu, Anna, Tseng, Chiu-Chen, Van Den Berg, David, Stram, Daniel, Cox, Angela, Brock, Ian, Reed, Malcom, Muir, Kenneth, Lophatananon, Artitaya, Stewart-Brown, Sarah, Siriwanarangsan, P, Zheng, Wei, Deming-Halverson, Sandra, Shrubsole, Martha, Long, Jirong, Shu, Xiao-Ou, Lu, W, Gao, Yu-Tang, Zhang, B, Radice, Paolo, Peterlongo, Paolo, Manoukian, Siranoush, Mariette, F, Sangrajrang, Suleeporn, McKay, James, Couch, Fergus, Toland, A E, Yannoukakos, D, Fletcher, Olivia, Johnson, Nicola, dos Santos Silva, I, Peto, Julian, Marme, F, Burwinkel, Barbara, Guénel, Pascal, Truong, Thérèse, Sanchez, M, Mulot, Claire, Bojesen, Stig, Nordestgaard, Borge, Flyer, H, Brenner, Hermann, Dieffenbach, A K, Arndt, Volker, Stegmaier, Christa, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana, Lambrechts, Diether, Yesilyurt, B T, Floris, G, Leunen, K, Chang-Claude, Jenny, Rudolph, Anja, Seibold, P, Flesch-Janys, Dieter, Wang, X, Olson, Janet, Vachon, Celine, Purrington, K, Giles, Graham, Severi, G, Baglietto, L, Haiman, Christopher, Henderson, B E, Schumacher, Fredrick, Marchand, Loïc Le, Simard, Jacques, Dumont, Martine, Goldberg, Mark, Labréche, F, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Devilee, Peter, Tollenaar, Rob, Seynaeve, Caroline, García-Closas, Montserrat, Chanock, Stephen, Lissowska, Jolanta, Figueroa, Jonine, Czene, Kamila, Eriksson, Mikael, Humphreys, Keith, Darabi, H, Hooning, Maartje, Kriege, Margriet, Collée, Margriet, Tilanus-Linthorst, M, Li, Jingmei, Jakubowska, Anna, Lubinski, Jan, Jaworska-Bieniek, K, Durda, K, Nevanlinna, Heli, Muranen, T A, Aittomäki, Kristiina, Blomqvist, Carl, Bogdanova, Natalia, Dörk, Thilo, Hall, Per, Chenevix-Trench, Georgia, Easton, Douglas, Pharroah, Paul, Arias-Perez, José Ignacio, Zamora, P, Benítez, Javier, and Milne, Roger

Abstract

Background: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02–1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2., Depto. de Estadística y Ciencia de los Datos, Fac. de Estudios Estadísticos, TRUE, pub

Published
2014

22. Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study

Author

Johnson, N, Dudbridge, F, Orr, N, Gibson, L, Jones, ME, Schoemaker, MJ, Folkerd, EJ, Haynes, BP, Hopper, JL, Southey, MC, Dite, GS, Apicella, C, Schmidt, MK, Broeks, A, Van't Veer, LJ, Atsma, F, Muir, K, Lophatananon, A, Fasching, PA, Beckmann, MW, Ekici, AB, Renner, SP, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Guenel, P, Truong, T, Cordina, E, Menegaux, F, Bojesen, SE, Nordestgaard, BG, Flyger, H, Milne, R, Zamora, MP, Arias Perez, JI, Benitez, J, Bernstein, L, Anton-Culver, H, Ziogas, A, Dur, CC, Brenner, H, Mueller, H, Arndt, V, Dieffenbach, AK, Meindl, A, Heil, J, Bartram, CR, Schmutzler, RK, Brauch, H, Justenhoven, C, Ko, Y-D, Nevanlinna, H, Muranen, TA, Aittomaeki, K, Blomqvist, C, Matsuo, K, Doerk, T, Bogdanova, NV, Antonenkova, NN, Lindblom, A, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Chenevix-Trench, G, Beesley, J, Wu, AH, Van den Berg, D, Tseng, C-C, Lambrechts, D, Smeets, D, Neven, P, Wildiers, H, Chang-Claude, J, Rudolph, A, Nickels, S, Flesch-Janys, D, Radice, P, Peterlongo, P, Bonanni, B, Pensotti, V, Couch, FJ, Olson, JE, Wang, X, Fredericksen, Z, Pankratz, VS, Giles, GG, Severi, G, Baglietto, L, Haiman, C, Simard, J, Goldberg, MS, Labreche, F, Dumont, M, Soucy, P, Teo, S, Yip, CH, Phuah, SY, Cornes, BK, Kristensen, VN, Alnaes, GG, Borresen-Dale, A-L, Zheng, W, Winqvist, R, Pylkaes, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Devillee, P, Figueroa, J, Chanock, SJ, Lissowska, J, Sherman, ME, Hall, P, Schoof, N, Hooning, M, Hollestelle, A, Oldenburg, RA, Tilanus-Linthorst, M, Liu, J, Cox, A, Brock, IW, Reed, MWR, Cross, SS, Blot, W, Signorello, LB, Pharoah, PDP, Dunning, AM, Shah, M, Kang, D, Noh, D-Y, Park, SK, Choi, J-Y, Hartman, M, Miao, H, Lim, WY, Tang, A, Hamann, U, Foersti, A, Ruediger, T, Ulmer, HU, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Sangrajrang, S, Gaborieau, V, Brennan, P, Mckay, J, Slager, S, Toland, AE, Vachon, C, Yannoukakos, D, Shen, C-Y, Yu, J-C, Huang, C-S, Hou, M-F, Gonzalez-Neira, A, Tessier, DC, Vincent, D, Bacot, F, Luccarini, C, Dennis, J, Michailidou, K, Bolla, MK, Wang, J, Easton, DF, Garcia-Closas, M, Dowsett, M, Ashworth, A, Swerdlow, AJ, Peto, J, Silva, IDS, Fletcher, O, Johnson, N, Dudbridge, F, Orr, N, Gibson, L, Jones, ME, Schoemaker, MJ, Folkerd, EJ, Haynes, BP, Hopper, JL, Southey, MC, Dite, GS, Apicella, C, Schmidt, MK, Broeks, A, Van't Veer, LJ, Atsma, F, Muir, K, Lophatananon, A, Fasching, PA, Beckmann, MW, Ekici, AB, Renner, SP, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Guenel, P, Truong, T, Cordina, E, Menegaux, F, Bojesen, SE, Nordestgaard, BG, Flyger, H, Milne, R, Zamora, MP, Arias Perez, JI, Benitez, J, Bernstein, L, Anton-Culver, H, Ziogas, A, Dur, CC, Brenner, H, Mueller, H, Arndt, V, Dieffenbach, AK, Meindl, A, Heil, J, Bartram, CR, Schmutzler, RK, Brauch, H, Justenhoven, C, Ko, Y-D, Nevanlinna, H, Muranen, TA, Aittomaeki, K, Blomqvist, C, Matsuo, K, Doerk, T, Bogdanova, NV, Antonenkova, NN, Lindblom, A, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Chenevix-Trench, G, Beesley, J, Wu, AH, Van den Berg, D, Tseng, C-C, Lambrechts, D, Smeets, D, Neven, P, Wildiers, H, Chang-Claude, J, Rudolph, A, Nickels, S, Flesch-Janys, D, Radice, P, Peterlongo, P, Bonanni, B, Pensotti, V, Couch, FJ, Olson, JE, Wang, X, Fredericksen, Z, Pankratz, VS, Giles, GG, Severi, G, Baglietto, L, Haiman, C, Simard, J, Goldberg, MS, Labreche, F, Dumont, M, Soucy, P, Teo, S, Yip, CH, Phuah, SY, Cornes, BK, Kristensen, VN, Alnaes, GG, Borresen-Dale, A-L, Zheng, W, Winqvist, R, Pylkaes, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Devillee, P, Figueroa, J, Chanock, SJ, Lissowska, J, Sherman, ME, Hall, P, Schoof, N, Hooning, M, Hollestelle, A, Oldenburg, RA, Tilanus-Linthorst, M, Liu, J, Cox, A, Brock, IW, Reed, MWR, Cross, SS, Blot, W, Signorello, LB, Pharoah, PDP, Dunning, AM, Shah, M, Kang, D, Noh, D-Y, Park, SK, Choi, J-Y, Hartman, M, Miao, H, Lim, WY, Tang, A, Hamann, U, Foersti, A, Ruediger, T, Ulmer, HU, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Sangrajrang, S, Gaborieau, V, Brennan, P, Mckay, J, Slager, S, Toland, AE, Vachon, C, Yannoukakos, D, Shen, C-Y, Yu, J-C, Huang, C-S, Hou, M-F, Gonzalez-Neira, A, Tessier, DC, Vincent, D, Bacot, F, Luccarini, C, Dennis, J, Michailidou, K, Bolla, MK, Wang, J, Easton, DF, Garcia-Closas, M, Dowsett, M, Ashworth, A, Swerdlow, AJ, Peto, J, Silva, IDS, and Fletcher, O

Abstract

INTRODUCTION: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. METHODS: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. RESULTS: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 0.29). CONCLUSIONS: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between la

Published
2014

23. FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Author

Agarwal, D, Pineda, S, Michailidou, K, Herranz, J, Pita, G, Moreno, LT, Alonso, MR, Dennis, J, Wang, Q, Bolla, MK, Meyer, KB, Menendez-Rodriguez, P, Hardisson, D, Mendiola, M, Gonzalez-Neira, A, Lindblom, A, Margolin, S, Swerdlow, A, Ashworth, A, Orr, N, Jones, M, Matsuo, K, Ito, H, Iwata, H, Kondo, N, Hartman, M, Hui, M, Lim, WY, Iau, PT-C, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Kang, D, Choi, J-Y, Park, SK, Noh, D-Y, Hopper, JL, Schmidt, DF, Makalic, E, Southey, MC, Teo, SH, Yip, CH, Sivanandan, K, Tay, W-T, Brauch, H, Bruening, T, Hamann, U, Dunning, AM, Shah, M, Andrulis, IL, Knight, JA, Glendon, G, Tchatchou, S, Schmidt, MK, Broeks, A, Rosenberg, EH, van't Veer, LJ, Fasching, PA, Renner, SP, Ekici, AB, Beckmann, MW, Shen, C-Y, Hsiung, C-N, Yu, J-C, Hou, M-F, Blot, W, Cai, Q, Wu, AH, Tseng, C-C, Van Den Berg, D, Stram, DO, Cox, A, Brock, IW, Reed, MWR, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Zheng, W, Deming-Halverson, S, Shrubsole, MJ, Long, J, Shu, X-O, Lu, W, Gao, Y-T, Zhang, B, Radice, P, Peterlongo, P, Manoukian, S, Mariette, F, Sangrajrang, S, Mckay, J, Couch, FJ, Toland, AE, Yannoukakos, D, Fletcher, O, Johnson, N, dos Santos Silva, I, Peto, J, Marme, F, Burwinkel, B, Guenel, P, Truong, T, Sanchez, M, Mulot, C, Bojesen, SE, Nordestgaard, BG, Flyer, H, Brenner, H, Dieffenbach, AK, Arndt, V, Stegmaier, C, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Lambrechts, D, Yesilyurt, BT, Floris, G, Leunen, K, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Wang, X, Olson, JE, Vachon, C, Purrington, K, Giles, GG, Severi, G, Baglietto, L, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Simard, J, Dumont, M, Goldberg, MS, Labreche, F, Winqvist, R, Pylkaes, K, Jukkola-Vuorinen, A, Grip, M, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Garcia-Closas, M, Chanock, SJ, Lissowska, J, Figueroa, JD, Czene, K, Eriksson, M, Humphreys, K, Darabi, H, Hooning, MJ, Kriege, M, Collee, JM, Tilanus-Linthorst, M, Li, J, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Nevanlinna, H, Muranen, TA, Aittomaeki, K, Blomqvist, C, Bogdanova, N, Doerk, T, Hall, P, Chenevix-Trench, G, Easton, DF, Pharoah, PDP, Arias-Perez, JI, Zamora, P, Benitez, J, Milne, RL, Agarwal, D, Pineda, S, Michailidou, K, Herranz, J, Pita, G, Moreno, LT, Alonso, MR, Dennis, J, Wang, Q, Bolla, MK, Meyer, KB, Menendez-Rodriguez, P, Hardisson, D, Mendiola, M, Gonzalez-Neira, A, Lindblom, A, Margolin, S, Swerdlow, A, Ashworth, A, Orr, N, Jones, M, Matsuo, K, Ito, H, Iwata, H, Kondo, N, Hartman, M, Hui, M, Lim, WY, Iau, PT-C, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Kang, D, Choi, J-Y, Park, SK, Noh, D-Y, Hopper, JL, Schmidt, DF, Makalic, E, Southey, MC, Teo, SH, Yip, CH, Sivanandan, K, Tay, W-T, Brauch, H, Bruening, T, Hamann, U, Dunning, AM, Shah, M, Andrulis, IL, Knight, JA, Glendon, G, Tchatchou, S, Schmidt, MK, Broeks, A, Rosenberg, EH, van't Veer, LJ, Fasching, PA, Renner, SP, Ekici, AB, Beckmann, MW, Shen, C-Y, Hsiung, C-N, Yu, J-C, Hou, M-F, Blot, W, Cai, Q, Wu, AH, Tseng, C-C, Van Den Berg, D, Stram, DO, Cox, A, Brock, IW, Reed, MWR, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Zheng, W, Deming-Halverson, S, Shrubsole, MJ, Long, J, Shu, X-O, Lu, W, Gao, Y-T, Zhang, B, Radice, P, Peterlongo, P, Manoukian, S, Mariette, F, Sangrajrang, S, Mckay, J, Couch, FJ, Toland, AE, Yannoukakos, D, Fletcher, O, Johnson, N, dos Santos Silva, I, Peto, J, Marme, F, Burwinkel, B, Guenel, P, Truong, T, Sanchez, M, Mulot, C, Bojesen, SE, Nordestgaard, BG, Flyer, H, Brenner, H, Dieffenbach, AK, Arndt, V, Stegmaier, C, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Lambrechts, D, Yesilyurt, BT, Floris, G, Leunen, K, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Wang, X, Olson, JE, Vachon, C, Purrington, K, Giles, GG, Severi, G, Baglietto, L, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Simard, J, Dumont, M, Goldberg, MS, Labreche, F, Winqvist, R, Pylkaes, K, Jukkola-Vuorinen, A, Grip, M, Devilee, P, Tollenaar, RAEM, Seynaeve, C, Garcia-Closas, M, Chanock, SJ, Lissowska, J, Figueroa, JD, Czene, K, Eriksson, M, Humphreys, K, Darabi, H, Hooning, MJ, Kriege, M, Collee, JM, Tilanus-Linthorst, M, Li, J, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Nevanlinna, H, Muranen, TA, Aittomaeki, K, Blomqvist, C, Bogdanova, N, Doerk, T, Hall, P, Chenevix-Trench, G, Easton, DF, Pharoah, PDP, Arias-Perez, JI, Zamora, P, Benitez, J, and Milne, RL

Abstract

BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.

Published
2014

25. Body image and psychological distress after prophylactic mastectomy and breast reconstruction in genetically predisposed women: a prospective long-term follow-up study.

Author

Heijer, M. den, Seynaeve, C., Timman, R., Duivenvoorden, H.J., Vanheusden, K., Tilanus-Linthorst, M., Menke-Pluijmers, M.B., Tibben, A., Heijer, M. den, Seynaeve, C., Timman, R., Duivenvoorden, H.J., Vanheusden, K., Tilanus-Linthorst, M., Menke-Pluijmers, M.B., and Tibben, A.

Abstract

1 juni 2012, Item does not contain fulltext, PURPOSE: To explore the course of psychological distress and body image at long-term follow-up (6-9 years) after prophylactic mastectomy and breast reconstruction (PM/BR) in women at risk for hereditary breast cancer, and to identify pre-PM risk factors for poor body image on the long-term. METHODS: Psychological distress (general and breast cancer specific) and body image (general and breast specific) were assessed in 36 high-risk women before PM (T0), at 6 months (T1) and 6-9 years (T2) after PM/BR. Investigated predictive variables (assessed at T0) for long-term body image (assessed at T2) included psychological distress, body image and coping styles. RESULTS: Breast cancer specific and general distress significantly decreased from T0 to T1 as well as from T1 to T2. Problems regarding breast related and general body image were significantly higher at T1 than at T0. Subsequently, breast related body image scores significantly decreased from T1 to T2, while the decrease in general body image scores were not significant. Active coping and seeking social support were predictive of lower scores (i.e. less problems) on breast related and general body image at long-term follow-up. Furthermore, higher scores on general body image before PM/BR were predictive for increased general body image scores at long-term follow-up. CONCLUSION: Our findings indicate that psychological distress is decreased after PM/BR, at the cost of persistent problems regarding body image. Exploration of coping styles and body image perception before PM/BR may help to identify vulnerable women who may benefit from additional support.

Published
2012

27. Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers

Author

Ramus, S, Kartsonaki, C, Gayther, S, Pharoah, P, Sinilnikova, O, Beesley, J, Chen, X, Mcguffog, L, Healey, S, Couch, F, Wang, X, Fredericksen, Z, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Roversi, G, Barile, M, Viel, A, Allavena, A, Ottini, L, Papi, L, Gismondi, V, Capra, F, Radice, P, Greene, M, Mai, P, Andrulis, I, Glendon, G, Ozcelik, H, Thomassen, M, Gerdes, A, Kruse, T, Cruger, D, Jensen, U, Caligo, M, Olsson, H, Kristoffersson, U, Lindblom, A, Arver, B, Karlsson, P, Stenmark Askmalm, M, Borg, A, Neuhausen, S, Ding, Y, Nathanson, K, Domchek, S, Jakubowska, A, Lubiński, J, Huzarski, T, Byrski, T, Gronwald, J, Górski, B, Cybulski, C, Dębniak, T, Osorio, A, Durán, M, Tejada, M, Benítez, J, Hamann, U, Rookus, M, Verhoef, S, Tilanus Linthorst, M, Vreeswijk, M, Bodmer, D, Ausems, M, van Os, T, Asperen, C, Blok, M, Meijers Heijboer, H, Peock, S, Cook, M, Oliver, C, Frost, D, Dunning, A, Evans, D, Eeles, R, Pichert, G, Cole, T, Hodgson, S, Brewer, C, Morrison, P, Porteous, M, Kennedy, M, Rogers, M, Side, L, Donaldson, A, Gregory, H, Godwin, A, Stoppa Lyonnet, D, Moncoutier, V, Castera, L, Mazoyer, S, Barjhoux, L, Bonadona, V, Leroux, D, Faivre, L, Lidereau, R, Nogues, C, Bignon, Y, Prieur, F, Collonge Rame, M, Venat Bouvet, L, Fert Ferrer, S, Miron, A, Buys, S, Hopper, J, Daly, M, John, E, Terry, M, Goldgar, D, Hansen, T, Jønson, L, Ejlertsen, B, Agnarsson, B, Offit, K, Kirchhoff, T, Vijai, J, Dutra Clarke, A, Przybylo, J, Montagna, M, Casella, C, Imyanitov, E, Janavicius, R, Blanco, I, Lázaro, C, Moysich, K, Karlan, B, Gross, J, Beattie, M, Schmutzler, R, Wappenschmidt, B, Meindl, A, Ruehl, I, Fiebig, B, Sutter, C, Arnold, N, Deissler, H, Varon Mateeva, R, Kast, K, Niederacher, D, Gadzicki, D, Caldes, T, de la Hoya, M, Nevanlinna, H, Aittomäki, K, Simard, J, Soucy, P, Spurdle, A, Holland, H, Chenevix Trench, G, Easton, D, Antoniou, A, Ramus, SJ, Gayther, SA, Pharoah, PDP, Sinilnikova, OM, McGuffog, L, Couch, FJ, Greene, MH, Mai, PL, Andrulis, IL, Kruse, TA, Jensen, UB, Caligo, MA, Neuhausen, SL, Ding, YC, Nathanson, KL, Domchek, SM, Rookus, MA, Tilanus Linthorst, MA, Vreeswijk, MP, Ausems, MGEM, van Os, TA, Asperen, CJ, Blok, MJ, Meijers Heijboer, HEJ, Dunning, AM, Evans, DG, Morrison, PJ, Kennedy, MJ, Rogers, MT, Side, LE, Buys, SS, Hopper, JL, Daly, MB, John, EM, Terry, MB, Hansen, TvO, Agnarsson, BA, Dutra Clarke, AVC, Przybylo, JA, Imyanitov, EN, Moysich, KB, Karlan, BY, Beattie, MS, Spurdle, AB, Easton, DF, Antoniou, AC, ROVERSI, GAIA, Ramus, S, Kartsonaki, C, Gayther, S, Pharoah, P, Sinilnikova, O, Beesley, J, Chen, X, Mcguffog, L, Healey, S, Couch, F, Wang, X, Fredericksen, Z, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Roversi, G, Barile, M, Viel, A, Allavena, A, Ottini, L, Papi, L, Gismondi, V, Capra, F, Radice, P, Greene, M, Mai, P, Andrulis, I, Glendon, G, Ozcelik, H, Thomassen, M, Gerdes, A, Kruse, T, Cruger, D, Jensen, U, Caligo, M, Olsson, H, Kristoffersson, U, Lindblom, A, Arver, B, Karlsson, P, Stenmark Askmalm, M, Borg, A, Neuhausen, S, Ding, Y, Nathanson, K, Domchek, S, Jakubowska, A, Lubiński, J, Huzarski, T, Byrski, T, Gronwald, J, Górski, B, Cybulski, C, Dębniak, T, Osorio, A, Durán, M, Tejada, M, Benítez, J, Hamann, U, Rookus, M, Verhoef, S, Tilanus Linthorst, M, Vreeswijk, M, Bodmer, D, Ausems, M, van Os, T, Asperen, C, Blok, M, Meijers Heijboer, H, Peock, S, Cook, M, Oliver, C, Frost, D, Dunning, A, Evans, D, Eeles, R, Pichert, G, Cole, T, Hodgson, S, Brewer, C, Morrison, P, Porteous, M, Kennedy, M, Rogers, M, Side, L, Donaldson, A, Gregory, H, Godwin, A, Stoppa Lyonnet, D, Moncoutier, V, Castera, L, Mazoyer, S, Barjhoux, L, Bonadona, V, Leroux, D, Faivre, L, Lidereau, R, Nogues, C, Bignon, Y, Prieur, F, Collonge Rame, M, Venat Bouvet, L, Fert Ferrer, S, Miron, A, Buys, S, Hopper, J, Daly, M, John, E, Terry, M, Goldgar, D, Hansen, T, Jønson, L, Ejlertsen, B, Agnarsson, B, Offit, K, Kirchhoff, T, Vijai, J, Dutra Clarke, A, Przybylo, J, Montagna, M, Casella, C, Imyanitov, E, Janavicius, R, Blanco, I, Lázaro, C, Moysich, K, Karlan, B, Gross, J, Beattie, M, Schmutzler, R, Wappenschmidt, B, Meindl, A, Ruehl, I, Fiebig, B, Sutter, C, Arnold, N, Deissler, H, Varon Mateeva, R, Kast, K, Niederacher, D, Gadzicki, D, Caldes, T, de la Hoya, M, Nevanlinna, H, Aittomäki, K, Simard, J, Soucy, P, Spurdle, A, Holland, H, Chenevix Trench, G, Easton, D, Antoniou, A, Ramus, SJ, Gayther, SA, Pharoah, PDP, Sinilnikova, OM, McGuffog, L, Couch, FJ, Greene, MH, Mai, PL, Andrulis, IL, Kruse, TA, Jensen, UB, Caligo, MA, Neuhausen, SL, Ding, YC, Nathanson, KL, Domchek, SM, Rookus, MA, Tilanus Linthorst, MA, Vreeswijk, MP, Ausems, MGEM, van Os, TA, Asperen, CJ, Blok, MJ, Meijers Heijboer, HEJ, Dunning, AM, Evans, DG, Morrison, PJ, Kennedy, MJ, Rogers, MT, Side, LE, Buys, SS, Hopper, JL, Daly, MB, John, EM, Terry, MB, Hansen, TvO, Agnarsson, BA, Dutra Clarke, AVC, Przybylo, JA, Imyanitov, EN, Moysich, KB, Karlan, BY, Beattie, MS, Spurdle, AB, Easton, DF, Antoniou, AC, and ROVERSI, GAIA

Abstract

Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2 and decreased risk of ovarian cancer for women in the general population. We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2.

Published
2011

28. Exploring the link between MORF4L1 and risk of breast cancer

Author

Martrat, G, Maxwell, C, Tominaga, E, Porta de la Riva, M, Bonifaci, N, Gómez Baldó, L, Bogliolo, M, Lázaro, C, Blanco, I, Brunet, J, Aguilar, H, Fernández Rodríguez, J, Seal, S, Renwick, A, Rahman, N, Kühl, J, Neveling, K, Schindler, D, Ramírez, M, Castellà, M, Hernández, G, Embrace, Easton, D, Peock, S, Cook, M, Oliver, C, Frost, D, Platte, R, Evans, D, Lalloo, F, Eeles, R, Izatt, L, Chu, C, Davidson, R, Ong, K, Cook, J, Douglas, F, Hodgson, S, Brewer, C, Morrison, P, Porteous, M, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Roversi, G, Barile, M, Viel, A, Pasini, B, Ottini, L, Putignano, A, Savarese, A, Bernard, L, Radice, P, Healey, S, Spurdle, A, Chen, X, Beesley, J, Rookus, M, Verhoef, S, Tilanus Linthorst, M, Vreeswijk, M, Asperen, C, Bodmer, D, Ausems, M, van Os, T, Blok, M, Meijers Heijboer, H, Hogervorst, F, Goldgar, D, Buys, S, John, E, Miron, A, Southey, M, Daly, M, Harbst, K, Borg, A, Rantala, J, Barbany Bustinza, G, Ehrencrona, H, Stenmark Askmalm, M, Kaufman, B, Laitman, Y, Milgrom, R, Friedman, E, Domchek, S, Nathanson, K, Rebbeck, T, Johannsson, O, Couch, F, Wang, X, Fredericksen, Z, Cuadras, D, Moreno, V, Pientka, F, Depping, R, Caldés, T, Osorio, A, Benítez, J, Bueren, J, Heikkinen, T, Nevanlinna, H, Hamann, U, Torres, D, Caligo, M, Godwin, A, Imyanitov, E, Janavicius, R, Sinilnikova, O, Stoppa Lyonnet, D, Mazoyer, S, Verny Pierre, C, Castera, L, de Pauw, A, Bignon, Y, Uhrhammer, N, Peyrat, J, Vennin, P, Ferrer, S, Collonge Rame, M, Mortemousque, I, Mcguffog, L, Chenevix Trench, G, Pereira Smith, O, Antoniou, A, Cerón, J, Tominaga, K, Surrallés, J, Pujana, M, Maxwell, CM, Ramírez, MJ, Easton, DF, Oliver, CT, Evans, DG, Chu ,C, Ong, KR, Morrison, PJ, Putignano, AL, Rookus, MA, Tilanus Linthorst, MA, Vreeswijk, MP, Asperen, CJ, Ausems, MG, van Os, TA, Blok, MJ, Meijers Heijboer, HE, Hogervorst, FB, Goldgar, DE, John, EM, Daly, MB, Domchek, SM, Nathanson, KL, Rebbeck, TR, Johannsson, OT, Couch, FJ, Pientka, FK, Caligo, MA, Godwin, AK, Imyanitov, EN, Sinilnikova, OM, Bignon, YJ, Peyrat, JP, Ferrer, SF, Collonge Rame, MA, McGuffog, L, Pereira Smith, OM, Antoniou, AC, Pujana, MA, ROVERSI, GAIA, Martrat, G, Maxwell, C, Tominaga, E, Porta de la Riva, M, Bonifaci, N, Gómez Baldó, L, Bogliolo, M, Lázaro, C, Blanco, I, Brunet, J, Aguilar, H, Fernández Rodríguez, J, Seal, S, Renwick, A, Rahman, N, Kühl, J, Neveling, K, Schindler, D, Ramírez, M, Castellà, M, Hernández, G, Embrace, Easton, D, Peock, S, Cook, M, Oliver, C, Frost, D, Platte, R, Evans, D, Lalloo, F, Eeles, R, Izatt, L, Chu, C, Davidson, R, Ong, K, Cook, J, Douglas, F, Hodgson, S, Brewer, C, Morrison, P, Porteous, M, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Roversi, G, Barile, M, Viel, A, Pasini, B, Ottini, L, Putignano, A, Savarese, A, Bernard, L, Radice, P, Healey, S, Spurdle, A, Chen, X, Beesley, J, Rookus, M, Verhoef, S, Tilanus Linthorst, M, Vreeswijk, M, Asperen, C, Bodmer, D, Ausems, M, van Os, T, Blok, M, Meijers Heijboer, H, Hogervorst, F, Goldgar, D, Buys, S, John, E, Miron, A, Southey, M, Daly, M, Harbst, K, Borg, A, Rantala, J, Barbany Bustinza, G, Ehrencrona, H, Stenmark Askmalm, M, Kaufman, B, Laitman, Y, Milgrom, R, Friedman, E, Domchek, S, Nathanson, K, Rebbeck, T, Johannsson, O, Couch, F, Wang, X, Fredericksen, Z, Cuadras, D, Moreno, V, Pientka, F, Depping, R, Caldés, T, Osorio, A, Benítez, J, Bueren, J, Heikkinen, T, Nevanlinna, H, Hamann, U, Torres, D, Caligo, M, Godwin, A, Imyanitov, E, Janavicius, R, Sinilnikova, O, Stoppa Lyonnet, D, Mazoyer, S, Verny Pierre, C, Castera, L, de Pauw, A, Bignon, Y, Uhrhammer, N, Peyrat, J, Vennin, P, Ferrer, S, Collonge Rame, M, Mortemousque, I, Mcguffog, L, Chenevix Trench, G, Pereira Smith, O, Antoniou, A, Cerón, J, Tominaga, K, Surrallés, J, Pujana, M, Maxwell, CM, Ramírez, MJ, Easton, DF, Oliver, CT, Evans, DG, Chu ,C, Ong, KR, Morrison, PJ, Putignano, AL, Rookus, MA, Tilanus Linthorst, MA, Vreeswijk, MP, Asperen, CJ, Ausems, MG, van Os, TA, Blok, MJ, Meijers Heijboer, HE, Hogervorst, FB, Goldgar, DE, John, EM, Daly, MB, Domchek, SM, Nathanson, KL, Rebbeck, TR, Johannsson, OT, Couch, FJ, Pientka, FK, Caligo, MA, Godwin, AK, Imyanitov, EN, Sinilnikova, OM, Bignon, YJ, Peyrat, JP, Ferrer, SF, Collonge Rame, MA, McGuffog, L, Pereira Smith, OM, Antoniou, AC, Pujana, MA, and ROVERSI, GAIA

Abstract

Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P(trend) = 0.45 and 0.05, P(2df) = 0.51 and 0.14, respectively; and rs10519219, P(trend) =

Published
2011

31. Eerste Nederlandse ervaringen met een presymptomatische DNA-test bij familiair mamma-/ovariumcarcinoom. Rotterdamse Werkgroep voor Erfelijke Tumoren

Author

Klijn, J. G., Devilee, P., van Geel, A. N., Tilanus-Linthorst, M. M., Dudok-de Wit, C., Meijers-Heijboer, E. J., and Other departments

Subjects
skin and connective tissue diseases
Abstract

Recent discoveries in the field of molecular-genetic research make it possible to detect an increased genetic risk of tumours, because several genes are linked to hereditary forms of breast cancer. The breast cancer gene BRCA1, located on chromosome 17q, is quantitatively the most important gene so far. A BRCA1 gene mutation is estimated to occur in 1-3 per 1000 women in the general population, i.e. in about 10,000 women among the 4 million Dutch women aged 25-55 years. In this study experiences are described concerning oncologic, clinical-genetic and psychologic aspects in the first Dutch family in which a BRCA1-gene defect was detected with the corresponding hereditary breast/ovarian cancer syndrome. Of the relatives 88% participated in the genetic family study and 76% wished to be informed on the individual DNA-test results. From the first-degree relatives of the breast cancer patients 54% appeared to be gene mutation carrier. The detection of a gene mutation in a woman could make her decide to undergo preventive mastectomy and (or) ovariectomy, besides regular breast examination and mammography. Surgeons and radiotherapists, the group of doctors who treat primary breast cancer, have to anticipate more radical operations with regard to breasts in this selected group of (future) patients. Detection of the gene may also have consequences for family planning. Identification of carriers of the gene mutation can lead to a selection of women with increased risk of breast cancer. Primary or secondary preventive measures, early diagnostic management and regular examination may lead to a decrease in death from breast cancer

Published
1995

32. Contralateral Breast Cancer in BRCA1/2 Mutation Carriers: Risk Assessment by Age at Diagnosis of the First Primary Breast Cancer.

Author

Hooning, M., primary, Heemskerk-Gerritsen, B., additional, Jager, A., additional, Collee, M., additional, van den Ouweland, A., additional, Menke - Pluymers, M., additional, van Geel, B., additional, van Doorn, L., additional, Tilanus - Linthorst, M., additional, Bartels, C., additional, and Seynaeve, C., additional

Published
2009
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34. Tumor characteristics and detection method in the MRISC screening program for the early detection of hereditary breast cancer

Author

Kriege, M., primary, Brekelmans, C. T. M., additional, Peterse, H., additional, Obdeijn, I. M., additional, Boetes, C., additional, Zonderland, H. M., additional, Muller, S. H., additional, Kok, T., additional, Manoliu, R. A., additional, Besnard, A. P. E., additional, Tilanus-Linthorst, M. M. A., additional, Seynaeve, C., additional, Bartels, C. C. M., additional, Meijer, S., additional, Oosterwijk, J. C., additional, Hoogerbrugge, N., additional, Tollenaar, R. A. E. M., additional, de Koning, H. J., additional, Rutgers, E. J. T., additional, and Klijn, J. G. M., additional

Published
2006
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37. Survival and Tumour Characteristics of Breast-Cancer Patients with Germline Mutations of BRCA1

Author

Verhoog, L. C., primary, Brekelmans, C. T. M., additional, Seynaeve, C., additional, van den Bosch, L. M. C., additional, Dahmen, G., additional, van Geel, A. N., additional, Tilanus-Linthorst, M. M. A., additional, Bartels, C. C. M., additional, Wagner, A., additional, van den Ouweland, A., additional, Devilee, P., additional, Meijers-Heijboer, E. J., additional, and Klijn, J. G. M., additional

Published
1998
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41. Optimal age to start preventive measures in women with BRCA1/2 mutations or high familial breast cancer risk.

Author

Tilanus-Linthorst, M. M. A., Lingsma, H., Evans, G. D., Kaas, R., Manders, P., Hooning, M. J., van Asperen, C. J., Thompson, D., Eeles, R., Oosterwijk, J. C., Leach, M. O., and Steyerberg, E. J.

Subjects
*BREAST cancer research, *BREAST cancer diagnosis, *BREAST cancer patients, *REGRESSION analysis, *GENETICS of breast cancer, *BREAST cancer, *CANCER prevention
Abstract

Background: Women from high risk breast cancer families consider preventive measures including screening. Guidelines on screening differ considerably regarding starting age. We investigated whether age at diagnosis in affected family members is predictive for age at diagnosis of a relative. Methods: We analyzed the age of breast cancer detection of 1304 first and second degree relatives of 314 BRCA1, 164 BRCA2 and 244 high-risk participants of the Dutch MRI-SCreening study. The within and between family variance in age at diagnosis was analyzed with a random effect linear regression model. We compared the starting age of screening based on risk-group (25 years for BRCA1, 30 years for BRCA2 and 35 years for familial risk), on family history, and on the model, which combines both. The findings were validated in 63 families from the UK- MARIBS study. Results: Mean age at diagnosis in the family varied between families; 95% range of mean family ages was 35-55 in BRCA1-, 41-57 in BRCA2- and 44-60 in high-risk families. 14% of the variance in age at diagnosis was explained by family history, 7% by risk group. Approaches to determining start of screening based on the model and on risk-group were similar in terms of cancers missed and years of screening. The approach based on familial history only, missed more cancers and required more screening years in both the Dutch and UK datasets. Conclusion: Age at breast cancer diagnosis is in part dependent on family history which may assist planning starting age for preventive measures. [ABSTRACT FROM AUTHOR]

Published
2012
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42. Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers

Author

Thomas v O Hansen, Amanda B. Spurdle, Anne-Marie Gerdes, Sue Healey, Per Karlsson, Tomasz Huzarski, Mary B. Daly, Mary Porteous, T. Caldes, Ulf Kristoffersson, Ignacio Blanco, A. Miron, Laurence Faivre, Barbara Wappenschmidt, Laurence Venat-Bouvet, Marie Stenmark Askmalm, Olga M. Sinilnikova, Susan Peock, Alessandra Viel, Conxi Lázaro, Katherine L. Nathanson, Laurent Castera, Douglas F. Easton, Susan L. Neuhausen, Jan Lubinski, Phuong L. Mai, Virginie Moncoutier, Paolo Radice, Heli Nevanlinna, Christi J Asperen, Xianshu Wang, Brita Arver, Christian Sutter, Senno Verhoef, Rosette Lidereau, Mary S Beattie, Bjarni A Agnarsson, Ina Ruehl, Monica Barile, Bent Ejlertsen, Laura Ottini, Catherine Noguès, Jennifer A. Przybylo, Cinzia Casella, Trevor Cole, Norbert Arnold, Sandra Fert-Ferrer, Hilmi Ozcelik, Irene L. Andrulis, Susan M. Domchek, Valérie Bonadona, Kirsten B. Moysich, David E. Goldgar, Anna Jakubowska, Paul D.P. Pharoah, Beth Y. Karlan, Jenny Gross, Gaia Roversi, Tadeusz Dębniak, Hanne Meijers-Heijboer, Susan J. Ramus, Dorthe G. Crüger, Zachary S. Fredericksen, Siranoush Manoukian, Viviana Gismondi, Maria A. Caligo, Helene Holland, Laure Barjhoux, Gord Glendon, Ana Osorio, Jacques Simard, John L. Hopper, Mercedes Durán, Kristiina Aittomäki, Håkan Olsson, Mads Thomassen, Fabio Capra, Patrick J. Morrison, Britta Fiebig, Mary Beth Terry, Marinus J. Blok, Evgeny N. Imyanitov, Joseph Vijai, Javier Benitez, Mark T. Rogers, D. Gareth Evans, Helmut Deissler, Tomasz Byrski, Sylvie Mazoyer, Laura Papi, Dominique Stoppa-Lyonnet, Marco Montagna, Kenneth Offit, Cezary Cybulski, Dominique Leroux, Georgia Chenevix-Trench, Danielle Bodmer, Lucy Side, Margaret Cook, Ros Eeles, Alan Donaldson, Christiana Kartsonaki, Carole Brewer, Matti A. Rookus, Jacek Gronwald, Dorothea Gadzicki, Shirley Hodgson, Jonathan Beesley, Gabriella Pichert, Andrew K. Godwin, Dieter Niederacher, Yuan Chun Ding, Torben A Kruse, Paolo Peterlongo, Rita K. Schmutzler, Xiaoqing Chen, Annika Lindblom, Fergus J. Couch, Maaike P.G. Vreeswijk, Mark H. Greene, Esther M. John, Raymonda Varon-Mateeva, Simon A. Gayther, Margreet G. E. M. Ausems, Tomas Kirchhoff, Lars Jønson, Madeleine M. A. Tilanus-Linthorst, Ute Hamann, Marie-Agnès Collonge-Rame, Antonis C. Antoniou, M John Kennedy, Karin Kast, Theo A. M. van Os, Penny Soucy, Debra Frost, Alison M. Dunning, Daniela Zaffaroni, Anna Allavena, Maria-Isabel Tejada, Yves-Jean Bignon, Lesley McGuffog, Bohdan Górski, Åke Borg, Fabienne Prieur, Bernard Peissel, Helen Gregory, Clare Oliver, Saundra S. Buys, Ana Dutra-Clarke, Alfons Meindl, Ramunas Janavicius, Uffe Birk Jensen, Miguel de la Hoya, Ramus, S, Kartsonaki, C, Gayther, S, Pharoah, P, Sinilnikova, O, Beesley, J, Chen, X, Mcguffog, L, Healey, S, Couch, F, Wang, X, Fredericksen, Z, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Roversi, G, Barile, M, Viel, A, Allavena, A, Ottini, L, Papi, L, Gismondi, V, Capra, F, Radice, P, Greene, M, Mai, P, Andrulis, I, Glendon, G, Ozcelik, H, Thomassen, M, Gerdes, A, Kruse, T, Cruger, D, Jensen, U, Caligo, M, Olsson, H, Kristoffersson, U, Lindblom, A, Arver, B, Karlsson, P, Stenmark Askmalm, M, Borg, A, Neuhausen, S, Ding, Y, Nathanson, K, Domchek, S, Jakubowska, A, Lubiński, J, Huzarski, T, Byrski, T, Gronwald, J, Górski, B, Cybulski, C, Dębniak, T, Osorio, A, Durán, M, Tejada, M, Benítez, J, Hamann, U, Rookus, M, Verhoef, S, Tilanus Linthorst, M, Vreeswijk, M, Bodmer, D, Ausems, M, van Os, T, Asperen, C, Blok, M, Meijers Heijboer, H, Peock, S, Cook, M, Oliver, C, Frost, D, Dunning, A, Evans, D, Eeles, R, Pichert, G, Cole, T, Hodgson, S, Brewer, C, Morrison, P, Porteous, M, Kennedy, M, Rogers, M, Side, L, Donaldson, A, Gregory, H, Godwin, A, Stoppa Lyonnet, D, Moncoutier, V, Castera, L, Mazoyer, S, Barjhoux, L, Bonadona, V, Leroux, D, Faivre, L, Lidereau, R, Nogues, C, Bignon, Y, Prieur, F, Collonge Rame, M, Venat Bouvet, L, Fert Ferrer, S, Miron, A, Buys, S, Hopper, J, Daly, M, John, E, Terry, M, Goldgar, D, Hansen, T, Jønson, L, Ejlertsen, B, Agnarsson, B, Offit, K, Kirchhoff, T, Vijai, J, Dutra Clarke, A, Przybylo, J, Montagna, M, Casella, C, Imyanitov, E, Janavicius, R, Blanco, I, Lázaro, C, Moysich, K, Karlan, B, Gross, J, Beattie, M, Schmutzler, R, Wappenschmidt, B, Meindl, A, Ruehl, I, Fiebig, B, Sutter, C, Arnold, N, Deissler, H, Varon Mateeva, R, Kast, K, Niederacher, D, Gadzicki, D, Caldes, T, de la Hoya, M, Nevanlinna, H, Aittomäki, K, Simard, J, Soucy, P, Spurdle, A, Holland, H, Chenevix Trench, G, Easton, D, Antoniou, A, Faculteit Medische Wetenschappen/UMCG, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Klinische Genetica, Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Clinical Genetics, Pediatric Surgery, Human genetics, CCA - Oncogenesis, and Human Genetics

Subjects
Oncology, Cancer Research, endocrine system diseases, Genes, BRCA2, Genes, BRCA1, Genome-wide association study, FAMILIES, 0302 clinical medicine, Risk Factors, Retrospective Studie, Genotype, Odds Ratio, skin and connective tissue diseases, POPULATION, Genetics, Ovarian Neoplasms, Aged, 80 and over, Allele, 0303 health sciences, education.field_of_study, Likelihood Functions, Articles, GERMLINE MUTATIONS, Middle Aged, Likelihood Function, female genital diseases and pregnancy complications, 3. Good health, 030220 oncology & carcinogenesis, Female, Chromosomes, Human, Pair 9, Human, Adult, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], medicine.medical_specialty, Heterozygote, SUSCEPTIBILITY LOCI, PROTEINS, Population, Biology, Polymorphism, Single Nucleotide, BASONUCLIN-2, 03 medical and health sciences, Breast cancer, Germline mutation, SDG 3 - Good Health and Well-being, Internal medicine, medicine, BREAST-CANCER, Humans, GENOME-WIDE ASSOCIATION, education, Alleles, Germ-Line Mutation, 030304 developmental biology, Retrospective Studies, Aged, IDENTIFICATION, Risk Factor, Ovarian Neoplasm, Editorials, Cancer, medicine.disease, Minor allele frequency, Ovarian cancer
Abstract

[Background]: Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2 and decreased risk of ovarian cancer for women in the general population. We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2. [Methods]: We genotyped rs3814113 in 10 029 BRCA1 mutation carriers and 5837 BRCA2 mutation carriers. Associations with ovarian and breast cancer were assessed with a retrospective likelihood approach. All statistical tests were two-sided. [Results]: The minor allele of rs3814113 was associated with a reduced risk of ovarian cancer among BRCA1 mutation carriers (per-allele hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.72 to 0.85; P = 4.8 × 10-9) and BRCA2 mutation carriers (hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.67 to 0.90; P = 5.5 × 10-4). This SNP was not associated with breast cancer risk among either BRCA1 or BRCA2 mutation carriers. BRCA1 mutation carriers with the TT genotype at SNP rs3814113 were predicted to have an ovarian cancer risk to age 80 years of 48%, and those with the CC genotype were predicted to have a risk of 33%. [Conclusion]: Common genetic variation at the 9p22.2 locus was associated with decreased risk of ovarian cancer for carriers of a BRCA1 or BRCA2 mutation., Spanish National Cancer Center (CNIO) and the Spanish Consortium: Partially supported by Fundación Mutua Madrileña, Asociación Española Contra el Cáncer, and the Spanish Ministry of Science and Innovation (FIS PI08 1120).

Published
2011
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43. Cost-effectiveness of screening with additional MRI for women with familial risk for breast cancer without a genetic predisposition.

Author

Saadatmand, S., Heijnsdijk, E. A., Rutgers, E. J., Hoogerbrugge, N., Oosterwijk, J. C., Tollenaar, R. A., Hooning, M., Obdeijn, I.-M., de Koning, H. J., and Tilanus-Linthorst, M. M.

Subjects
*BREAST cancer, *CANCER in women, *CANCER-related mortality, *FAMILY history (Medicine), *MAGNETIC resonance imaging, *AGE groups
Abstract

Background: To reduce mortality risk, women with a family history of breast cancer are often screened with mammography before 50 years of age. Additional Magnetic Resonance Imaging (MRI) can improve sensitivity. MRI screening is cost-effective for BRCA1/2 mutation carriers. However, for women with a family history of breast cancer without a proven mutation cost-effectiveness is not clear. We evaluated the cost- effectiveness of additional MRI for women with a familial risk in the largest prospective MRI screening study: the Dutch MRI Screening Study (MRISC). Materials & Methods: Between 1999 and 2007 a total of 1597 women (8370 women years at risk) between 25-70 years, with an estimated cumulative lifetime risk of 15-50% for breast cancer participated in the MRISC. Women were screened with clinical breast examination (CBE) every six months and annual mammography and MRI. We calculated the costs per detected breast cancer. In addition, MRISC data were incorporated into a micro simulation screening analysis model: MISCAN. This model simulates screening programs with different screening modalities and time intervals. Different screening schemes were evaluated and the cost per life-year gained (CLYG) estimated. Results: Forty-seven breast cancers, including 9 Ductal Carcinoma in Situ, were detected. Screening with additional MRI leads to a cost per detected breast cancer treated of 101,962. In increasing age-cohorts the cost decreased, probably due to the higher breast cancer incidence. The cost per detected and treated breast cancer in age group 40-50 years doubled in the age group >60 years. We will demonstrate these results more extensively. With MISCAN modeling we predicted that screening with this scheme from age 35 to 60 years reduces breast cancer mortality by 30% at a CLYG of 119,945 (3.5% discounting), compared to 21% estimated mortality reduction at 45,707 CLYG with mammography and CBE alone. Conclusion: Screening with MRI may improve survival for women with familial risk for breast cancer, but is expensive. However, it may be cost-effective for a select group. We will discuss subgroups that may benefit from MRI screening and in which age category MRI was most effective in our study. [ABSTRACT FROM AUTHOR]

Published
2012
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44. Exploring the link between MORF4L1 and risk of breast cancer

Author

Martrat, G., Maxwell, C.A., Tominaga, E., Porta-de-la-Riva, M., Bonifaci, N., Gomez-Baldo, L., Bogliolo, M., Lazaro, C., Blanco, I., Brunet, J., Aguilar, H., Fernandez-Rodriguez, J., Seal, S., Renwick, A., Rahman, N., Kuhl, J., Neveling, K., Schindler, D., Ramirez, M.J., Castella, M., Hernandez, G., Easton, D.F., Peock, S., Cook, M., Oliver, C.T., Frost, D., Platte, R., Evans, D.G., Lalloo, F., Eeles, R., Izatt, L., Chu, C., Davidson, R., Ong, K.R., Cook, J., Douglas, F., Hodgson, S., Brewer, C., Morrison, P.J., Porteous, M., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Roversi, G., Barile, M., Viel, A., Pasini, B., Ottini, L., Putignano, A.L., Savarese, A., Bernard, L., Radice, P., Healey, S., Spurdle, A., Chen, X.Q., Beesley, J., Rookus, M.A., Verhoef, S., Tilanus-Linthorst, M.A., Vreeswijk, M.P., Asperen, C.J., Bodmer, D., Ausems, M.G.E.M., Os, T.A. van, Blok, M.J., Meijers-Heijboer, H.E.J., Hogervorst, F.B.L., Goldgar, D.E., Buys, S., John, E.M., Miron, A., Southey, M., Daly, M.B., Harbst, K., Borg, A., Rantala, J., Barbany-Bustinza, G., Ehrencrona, H., Stenmark-Askmalm, M., Kaufman, B., Laitman, Y., Milgrom, R., Friedman, E., Domchek, S.M., Nathanson, K.L., Rebbeck, T.R., Oskar, T., Couch, F.J., Wang, X.S., Fredericksen, Z., Cuadras, D., Moreno, V., Pientka, F.K., Depping, R., Caldes, T., Osorio, A., Benitez, J., Bueren, J., Heikkinen, T., Nevanlinna, H., Hamann, U., Torres, D., Caligo, M.A., Godwin, A.K., Imyanitov, E.N., Janavicius, R., Sinilnikova, O.M., Stoppa-Lyonnet, D., Mazoyer, S., Verny-Pierre, C., Castera, L., Pauw, A. de, Bignon, Y.J., Uhrhammer, N., Peyrat, J.P., Vennin, P., Ferrer, S.F., Collonge-Rame, M.A., Mortemousque, I., McGuffog, L., Chenevix-Trench, G., Pereira-Smith, O.M., Antoniou, A.C., Ceron, J., Tominaga, K., Surralles, J., Pujana, M.A., EMBRACE, kConFab, HEBON, BCFR, SWE-BRCA, GEMO Study Collaborators, Human Genetics, BMC, Ed., Translational Research Laboratory, Catalan Institute of Oncology-Bellvitge Institute for Biomedical Research, Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), Catalan Institute of Oncology, Department of Cellular and Structural Biology, The University of Texas Health Science Center at Houston (UTHealth)-Sam and Ann Barshop Institute for Longevity and Aging Studies, Chemoresistance and Predictive Factors of Tumor Response and Stromal Microenvironment, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Biomarkers and Susceptibility Unit, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona (UAB), Biomedical Research Centre Network for Rare Diseases (CIBERER), Genetic Counseling and Hereditary Cancer Programme, Section of Cancer Genetics, Institute of cancer research, Department of Human Genetics, Julius-Maximilians-Universität Würzburg (JMU), Strangeways Research Laboratory, University of Cambridge [UK] (CAM)-Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, Centre for Cancer Genetic Epidemiology [Cambridge], University of Cambridge [UK] (CAM)-Department of Oncology, Genetic Medicine, St Mary's Hospital-NHS Foundation Trust-Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Clinical Genetics Department, Guy's and St Thomas NHS Foundation Trust, Yorkshire Regional Genetics Service, St James's hospital, Ferguson-Smith Centre for Clinical Genetics, West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Institute of Human Genetics, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Queen Mary University of London (QMUL)-St George's Hospital, Department of Clinical Genetics, Royal Devon & Exeter Hospital, Northern Ireland Regional Genetics Centre, Belfast City Hospital, South East of Scotland Regional Genetics Service, Western General Hospital, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine-Fondazione IRCCS Istituto Nazionale Tumori (INT), Department of Preventive and Predictive Medicine, IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Unit of Medical Genetics, Fondazione IRCCS INT, Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Division of Experimental Oncology 1, Centro di Riferimento Oncologico (CRO), Department of Genetics, Biology and Biochemistry, Università degli studi di Torino = University of Turin (UNITO), Department of Molecular Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Firenze = University of Florence (UniFI), Fiorgen Foundation for Pharmacogenomics, Division of Medical Oncology, Regina Elena Cancer Institute, Department of Experimental Oncology, IEO, Division of Genetics and Population Health, Queensland Institute of Medical Research, Department of Epidemiology, The Netherlands Cancer Institute, Family Cancer Clinic, Department of Surgical Oncology, Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), DNA Diagnostics, Radboud University Medical Center [Nijmegen], Department of Medical Genetics, University Medical Center [Utrecht], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), University Hospital Maastricht, VU Medical Center, Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Department of Internal Medicine, Huntsman Cancer Institute, Cancer Prevention Institute of California, Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Department of Surgery, Harvard Medical School [Boston] (HMS), Centre for Molecular, Environmental, Genetic and Analytic Epidemiology (MEGA), University of Melbourne-Melbourne School of Population Health, Division of Population Science, Fox Chase Cancer Center, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, Karolinska University Hospital [Stockholm], Department of Genetics and Pathology, Uppsala University, Department of Oncology, University Hospital-Hälsouniversitetet Universitetssjukhuset, The Institute of Oncology, Chaim Sheba Medical Center, The Susanne Levy Gertner Oncogenetics Unit, Sackler Faculty of Medicine, Tel Aviv University (TAU), Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Department of Medicine, Medical Genetics, Abramson Cancer Center-Perelman School of Medicine, Center for Clinical Epidemiology and Biostatistics, Faculty of Medicine, University of Iceland [Reykjavik], Department of Laboratory Medicine and Pathology, Mayo Clinic, Department of Health Sciences Research, Statistical Assessment Service, Department of Physiology, Universität zu Lübeck = University of Lübeck [Lübeck]-Center for Structural and Cell Biology in Medicine, Medical Oncology Branch, Hospital Clínico San Carlos, Human Cancer Genetics Programme, CIBER de Enfermedades Raras (CIBERER)-Spanish National Cancer Research Centre, Division of Hematopoiesis and Gene Therapy, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas [Madrid] (CIEMAT), Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Molecular Genetics of Breast Cancer, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Instituto de Genética Humana, Pontificia Universidad Javeriana (PUJ), Section of Genetic Oncology, University of Pisa - Università di Pisa, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center [Kansas City, KS, USA], Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion, Vilnius University [Vilnius]-Hospital Santariskiu Clinics, Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Oncologique, Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Oncogénétique, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Laboratoire d'Oncologie Moléculaire Humaine, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Consultation d'Oncogénétique, Laboratoire de Génétique Chromosomique, CH Chambéry, Département de Génétique et Reproduction, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, The CIMBA data management is supported by Cancer Research - UK., kConFab, HEBON, BCFR, SWE-BRCA, GEMO Study Collaborators, Autonomous University of Barcelona, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Department of Oncology-University of Cambridge [UK] (CAM), University of Turin, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Departament of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Tel Aviv University [Tel Aviv], University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Universität zu Lübeck [Lübeck]-Center for Structural and Cell Biology in Medicine, University of Kansas Medical Center [Lawrence], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Universiteit Leiden-Universiteit Leiden, Skåne University Hospital-Lund University [Lund], University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Abramson Cancer Center, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Clinical Genetics, Faculteit der Geneeskunde, Klinische Genetica, RS: GROW - School for Oncology and Reproduction, Genetica & Celbiologie, Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Martrat, G, Maxwell, C, Tominaga, E, Porta de la Riva, M, Bonifaci, N, Gómez Baldó, L, Bogliolo, M, Lázaro, C, Blanco, I, Brunet, J, Aguilar, H, Fernández Rodríguez, J, Seal, S, Renwick, A, Rahman, N, Kühl, J, Neveling, K, Schindler, D, Ramírez, M, Castellà, M, Hernández, G, Embrace, Easton, D, Peock, S, Cook, M, Oliver, C, Frost, D, Platte, R, Evans, D, Lalloo, F, Eeles, R, Izatt, L, Chu, C, Davidson, R, Ong, K, Cook, J, Douglas, F, Hodgson, S, Brewer, C, Morrison, P, Porteous, M, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Roversi, G, Barile, M, Viel, A, Pasini, B, Ottini, L, Putignano, A, Savarese, A, Bernard, L, Radice, P, Healey, S, Spurdle, A, Chen, X, Beesley, J, Rookus, M, Verhoef, S, Tilanus Linthorst, M, Vreeswijk, M, Asperen, C, Bodmer, D, Ausems, M, van Os, T, Blok, M, Meijers Heijboer, H, Hogervorst, F, Goldgar, D, Buys, S, John, E, Miron, A, Southey, M, Daly, M, Harbst, K, Borg, A, Rantala, J, Barbany Bustinza, G, Ehrencrona, H, Stenmark Askmalm, M, Kaufman, B, Laitman, Y, Milgrom, R, Friedman, E, Domchek, S, Nathanson, K, Rebbeck, T, Johannsson, O, Couch, F, Wang, X, Fredericksen, Z, Cuadras, D, Moreno, V, Pientka, F, Depping, R, Caldés, T, Osorio, A, Benítez, J, Bueren, J, Heikkinen, T, Nevanlinna, H, Hamann, U, Torres, D, Caligo, M, Godwin, A, Imyanitov, E, Janavicius, R, Sinilnikova, O, Stoppa Lyonnet, D, Mazoyer, S, Verny Pierre, C, Castera, L, de Pauw, A, Bignon, Y, Uhrhammer, N, Peyrat, J, Vennin, P, Ferrer, S, Collonge Rame, M, Mortemousque, I, Mcguffog, L, Chenevix Trench, G, Pereira Smith, O, Antoniou, A, Cerón, J, Tominaga, K, Surrallés, J, Pujana, M, Human genetics, CCA - Oncogenesis, Biomedical Research Centre Network for Epidemiology and Public Health ( CIBERESP ), The University of Texas Health Science Center at San Antonio-Sam and Ann Barshop Institute for Longevity and Aging Studies, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] ( IDIBELL ), Biomedical Research Centre Network for Rare Diseases ( CIBERER ), University of Würzburg, University of Cambridge [UK] ( CAM ) -Department of Public Health and Primary Care-Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] ( CAM ) -Department of Oncology, Birmingham Women's Hospital Healthcare NHS Trust, Sheffield Children's Hospital, Newcastle Upon Tyne Hospitals NHS Trust, Queen Mary University of London ( QMUL ) -St George's Hospital, IFOM, Istituto FIRC di Oncologia Molecolare ( IFOM ), Università degli Studi di Roma 'La Sapienza' [Rome], University of Florence, Erasmus MC-Daniel den Hoed Cancer Center-Family Cancer Clinic, University Medical Center Utrecht, Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), Harvard Medical School [Boston] ( HMS ), Centre for Molecular, Environmental, Genetic and Analytic Epidemiology ( MEGA ), University of Pennsylvania School of Medicine, University of Pennsylvania School of Medicine-Abramson Cancer Center, Centro de Investigaciones Energéticas, Deutsches Krebsforschungszentrum ( DKFZ ), Pontificia Universidad Javeriana, University of Pisa [Pisa], University of Kansas Medical Center, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), INSTITUT CURIE, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CRLCC Jean Perrin, CRLCC Oscar Lambret, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Hôpital Bretonneau-CHRU Tours, and Universitat de Barcelona

Subjects
DNA Repair, Genes, BRCA2, RAD51, Genes, BRCA1, Germ-Cell, Helicase Brip1, medicine.disease_cause, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Mice, 0302 clinical medicine, Breast cancer, Fanconi anemia, Risk Factors, Replication Protein A, Teknik och teknologier, Homologous Recombination, skin and connective tissue diseases, C-Elegans, Genetics, Medicine(all), ddc:616, 0303 health sciences, Mutation, Fanconi Anemia Complementation Group D2 Protein, Nuclear Proteins, Anèmia aplàstica, 3. Good health, 030220 oncology & carcinogenesis, Chromodomain Protein, Engineering and Technology, Female, RNA Interference, Fanconi Anemia Complementation Group N Protein, Aplastic anemia, Research Article, BRCA2 Mutation Carrier, DNA repair, PALB2, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Cell Line, Càncer de mama, Genomic disorders and inherited multi-system disorders [IGMD 3], 03 medical and health sciences, SDG 3 - Good Health and Well-being, [SDV.CAN] Life Sciences [q-bio]/Cancer, Two-Hybrid System Techniques, medicine, Genetic predisposition, Animals, Humans, Genetic Predisposition to Disease, Caenorhabditis elegans, Gene, 030304 developmental biology, Phenocopy, Caenorhabditis-Elegan, Tumor Suppressor Proteins, medicine.disease, BRCA1, BRCA2, Pancreatic-Cancer, Fanconi Anemia, Genes, Cancer and Oncology, Fanconi-Anemia, Cancer research, Rad51 Recombinase, Susceptibility Gene, DNA Damage, Transcription Factors
Abstract

Introduction Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to γ-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. Conclusions While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.

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45. Breast cancer-related deaths according to grade in ductal carcinoma in situ: A Dutch population-based study on patients diagnosed between 1999 and 2012.

Author

van Maaren MC, Lagendijk M, Tilanus-Linthorst MMA, de Munck L, Pijnappel RM, Schmidt MK, Wesseling J, Koppert LB, and Siesling S

Subjects
Aged, Breast Neoplasms mortality, Carcinoma, Ductal, Breast mortality, Carcinoma, Intraductal, Noninfiltrating mortality, Cohort Studies, Female, Humans, Kaplan-Meier Estimate, Middle Aged, Neoplasm Grading, Netherlands, Population Surveillance methods, Proportional Hazards Models, Registries statistics & numerical data, Survival Rate, Breast pathology, Breast Neoplasms pathology, Carcinoma, Ductal, Breast pathology, Carcinoma, Intraductal, Noninfiltrating pathology
Abstract

Background: The incidence of ductal carcinoma in situ (DCIS) has drastically increased over the past decades. Because DCIS is resected after diagnosis similar to invasive breast cancer, the natural cause and behaviour of DCIS is not well known. We aimed to determine breast cancer-specific survival (BCSS) and overall survival (OS) according to grade in DCIS patients after surgical treatment in the Netherlands., Patients and Methods: All DCIS patients diagnosed between 1999 and 2012 were selected from the Netherlands Cancer Registry. The cause of death was obtained from 'Statistics Netherlands'. BCSS and OS were estimated using multivariable Cox regression in the entire cohort and stratified for grades., Results: In total, 12,256 patients were included, of whom 1509 (12.3%) presented with grade I, 3675 (30.0%) with grade II, 6064 (49.5%) with grade III and 1008 (8.2%) with an unknown grade. During a median follow-up of 7.8 years, 1138 (9.3%) deaths were observed, and 179 (1.5%) were breast cancer-related. Of these, 10 patients had grade I; 46 grade II; 95 grade III and 28 an unknown grade. After adjustment for confounding, grade II and III were related to worse BCSS than grade I with hazard ratios of 1.92 (95% confidence interval [CI]: 0.97-3.81) and 2.14 (95% CI: 1.11-4.12), respectively. No association between grades and OS was observed., Conclusion: BCSS and OS in DCIS patients were excellent. Because superior rates were observed for low-grade DCIS, it seems justified to investigate whether active surveillance may be a balanced alternative for conventional surgical treatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
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46. PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.

Author

Southey MC, Goldgar DE, Winqvist R, Pylkäs K, Couch F, Tischkowitz M, Foulkes WD, Dennis J, Michailidou K, van Rensburg EJ, Heikkinen T, Nevanlinna H, Hopper JL, Dörk T, Claes KB, Reis-Filho J, Teo ZL, Radice P, Catucci I, Peterlongo P, Tsimiklis H, Odefrey FA, Dowty JG, Schmidt MK, Broeks A, Hogervorst FB, Verhoef S, Carpenter J, Clarke C, Scott RJ, Fasching PA, Haeberle L, Ekici AB, Beckmann MW, Peto J, Dos-Santos-Silva I, Fletcher O, Johnson N, Bolla MK, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Marme F, Burwinkel B, Yang R, Guénel P, Truong T, Menegaux F, Sanchez M, Bojesen S, Nielsen SF, Flyger H, Benitez J, Zamora MP, Perez JI, Menéndez P, Anton-Culver H, Neuhausen S, Ziogas A, Clarke CA, Brenner H, Arndt V, Stegmaier C, Brauch H, Brüning T, Ko YD, Muranen TA, Aittomäki K, Blomqvist C, Bogdanova NV, Antonenkova NN, Lindblom A, Margolin S, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Spurdle AB, Investigators K, Wauters E, Smeets D, Beuselinck B, Floris G, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Olson JE, Vachon C, Pankratz VS, McLean C, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Kristensen V, Alnæs GG, Zheng W, Hunter DJ, Lindstrom S, Hankinson SE, Kraft P, Andrulis I, Knight JA, Glendon G, Mulligan AM, Jukkola-Vuorinen A, Grip M, Kauppila S, Devilee P, Tollenaar RA, Seynaeve C, Hollestelle A, Garcia-Closas M, Figueroa J, Chanock SJ, Lissowska J, Czene K, Darabi H, Eriksson M, Eccles DM, Rafiq S, Tapper WJ, Gerty SM, Hooning MJ, Martens JW, Collée JM, Tilanus-Linthorst M, Hall P, Li J, Brand JS, Humphreys K, Cox A, Reed MW, Luccarini C, Baynes C, Dunning AM, Hamann U, Torres D, Ulmer HU, Rüdiger T, Jakubowska A, Lubinski J, Jaworska K, Durda K, Slager S, Toland AE, Ambrosone CB, Yannoukakos D, Swerdlow A, Ashworth A, Orr N, Jones M, González-Neira A, Pita G, Alonso MR, Álvarez N, Herrero D, Tessier DC, Vincent D, Bacot F, Simard J, Dumont M, Soucy P, Eeles R, Muir K, Wiklund F, Gronberg H, Schleutker J, Nordestgaard BG, Weischer M, Travis RC, Neal D, Donovan JL, Hamdy FC, Khaw KT, Stanford JL, Blot WJ, Thibodeau S, Schaid DJ, Kelley JL, Maier C, Kibel AS, Cybulski C, Cannon-Albright L, Butterbach K, Park J, Kaneva R, Batra J, Teixeira MR, Kote-Jarai Z, Olama AA, Benlloch S, Renner SP, Hartmann A, Hein A, Ruebner M, Lambrechts D, Van Nieuwenhuysen E, Vergote I, Lambretchs S, Doherty JA, Rossing MA, Nickels S, Eilber U, Wang-Gohrke S, Odunsi K, Sucheston-Campbell LE, Friel G, Lurie G, Killeen JL, Wilkens LR, Goodman MT, Runnebaum I, Hillemanns PA, Pelttari LM, Butzow R, Modugno F, Edwards RP, Ness RB, Moysich KB, du Bois A, Heitz F, Harter P, Kommoss S, Karlan BY, Walsh C, Lester J, Jensen A, Kjaer SK, Høgdall E, Peissel B, Bonanni B, Bernard L, Goode EL, Fridley BL, Vierkant RA, Cunningham JM, Larson MC, Fogarty ZC, Kalli KR, Liang D, Lu KH, Hildebrandt MA, Wu X, Levine DA, Dao F, Bisogna M, Berchuck A, Iversen ES, Marks JR, Akushevich L, Cramer DW, Schildkraut J, Terry KL, Poole EM, Stampfer M, Tworoger SS, Bandera EV, Orlow I, Olson SH, Bjorge L, Salvesen HB, van Altena AM, Aben KK, Kiemeney LA, Massuger LF, Pejovic T, Bean Y, Brooks-Wilson A, Kelemen LE, Cook LS, Le ND, Górski B, Gronwald J, Menkiszak J, Høgdall CK, Lundvall L, Nedergaard L, Engelholm SA, Dicks E, Tyrer J, Campbell I, McNeish I, Paul J, Siddiqui N, Glasspool R, Whittemore AS, Rothstein JH, McGuire V, Sieh W, Cai H, Shu XO, Teten RT, Sutphen R, McLaughlin JR, Narod SA, Phelan CM, Monteiro AN, Fenstermacher D, Lin HY, Permuth JB, Sellers TA, Chen YA, Tsai YY, Chen Z, Gentry-Maharaj A, Gayther SA, Ramus SJ, Menon U, Wu AH, Pearce CL, Van Den Berg D, Pike MC, Dansonka-Mieszkowska A, Plisiecka-Halasa J, Moes-Sosnowska J, Kupryjanczyk J, Pharoah PD, Song H, Winship I, Chenevix-Trench G, Giles GG, Tavtigian SV, Easton DF, and Milne RL

Subjects
Breast Neoplasms epidemiology, Breast Neoplasms genetics, Case-Control Studies, Fanconi Anemia Complementation Group N Protein, Female, Genetic Association Studies, Humans, Male, Ovarian Neoplasms epidemiology, Ovarian Neoplasms genetics, Ovarian Neoplasms metabolism, Prostatic Neoplasms epidemiology, Prostatic Neoplasms genetics, Risk, Ataxia Telangiectasia Mutated Proteins genetics, Breast Neoplasms metabolism, Checkpoint Kinase 2 genetics, Genetic Predisposition to Disease, Mutation, Nuclear Proteins genetics, Prostatic Neoplasms metabolism, Tumor Suppressor Proteins genetics
Abstract

Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study., Methods: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant., Results: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10 -5 ), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10 -8 ) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants., Conclusions: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Published
2016
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47. Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression.

Author

Darabi H, McCue K, Beesley J, Michailidou K, Nord S, Kar S, Humphreys K, Thompson D, Ghoussaini M, Bolla MK, Dennis J, Wang Q, Canisius S, Scott CG, Apicella C, Hopper JL, Southey MC, Stone J, Broeks A, Schmidt MK, Scott RJ, Lophatananon A, Muir K, Beckmann MW, Ekici AB, Fasching PA, Heusinger K, Dos-Santos-Silva I, Peto J, Tomlinson I, Sawyer EJ, Burwinkel B, Marme F, Guénel P, Truong T, Bojesen SE, Flyger H, Benitez J, González-Neira A, Anton-Culver H, Neuhausen SL, Arndt V, Brenner H, Engel C, Meindl A, Schmutzler RK, Arnold N, Brauch H, Hamann U, Chang-Claude J, Khan S, Nevanlinna H, Ito H, Matsuo K, Bogdanova NV, Dörk T, Lindblom A, Margolin S, Kosma VM, Mannermaa A, Tseng CC, Wu AH, Floris G, Lambrechts D, Rudolph A, Peterlongo P, Radice P, Couch FJ, Vachon C, Giles GG, McLean C, Milne RL, Dugué PA, Haiman CA, Maskarinec G, Woolcott C, Henderson BE, Goldberg MS, Simard J, Teo SH, Mariapun S, Helland Å, Haakensen V, Zheng W, Beeghly-Fadiel A, Tamimi R, Jukkola-Vuorinen A, Winqvist R, Andrulis IL, Knight JA, Devilee P, Tollenaar RA, Figueroa J, García-Closas M, Czene K, Hooning MJ, Tilanus-Linthorst M, Li J, Gao YT, Shu XO, Cox A, Cross SS, Luben R, Khaw KT, Choi JY, Kang D, Hartman M, Lim WY, Kabisch M, Torres D, Jakubowska A, Lubinski J, McKay J, Sangrajrang S, Toland AE, Yannoukakos D, Shen CY, Yu JC, Ziogas A, Schoemaker MJ, Swerdlow A, Borresen-Dale AL, Kristensen V, French JD, Edwards SL, Dunning AM, Easton DF, Hall P, and Chenevix-Trench G

Subjects
Age Factors, Asian People genetics, Autophagy-Related Proteins, Body Mass Index, Chromosome Mapping, Female, Genome-Wide Association Study, Genotype, Humans, Luciferases, Odds Ratio, Polymorphism, Single Nucleotide genetics, Quantitative Trait Loci genetics, Regression Analysis, Trans-Activators metabolism, White People genetics, Breast Neoplasms genetics, Chromosomes, Human, Pair 10 genetics, DNA-Binding Proteins genetics, Enhancer Elements, Genetic genetics, Gene Expression Regulation genetics, Trans-Activators genetics, Transcription Factors genetics
Abstract

Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely causal SNPs, we fine mapped the association signal by genotyping 428 SNPs across the region in 89,050 European and 12,893 Asian case and control subjects from the Breast Cancer Association Consortium. We identified four independent sets of correlated, highly trait-associated variants (iCHAVs), three of which were located within ZNF365. The most strongly risk-associated SNP, rs10995201 in iCHAV1, showed clear evidence of association with both estrogen receptor (ER)-positive (OR = 0.85 [0.82-0.88]) and ER-negative (OR = 0.87 [0.82-0.91]) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:D) and iCHAV3 (lead SNP, rs7922449) were also associated with ER-positive (OR = 0.93 [0.91-0.95] and OR = 1.06 [1.03-1.09]) and ER-negative (OR = 0.95 [0.91-0.98] and OR = 1.08 [1.04-1.13]) disease. There was weaker evidence for iCHAV4, located 5' of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90-0.96]). We found 12, 17, 18, and 2 candidate causal SNPs for breast cancer in iCHAVs 1-4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365, but identified a protective haplotype in iCHAV2, associated with silencing of the NRBF2 promoter, implicating this gene in the etiology of breast cancer., (Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Published
2015
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48. Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study.

Author

Johnson N, Dudbridge F, Orr N, Gibson L, Jones ME, Schoemaker MJ, Folkerd EJ, Haynes BP, Hopper JL, Southey MC, Dite GS, Apicella C, Schmidt MK, Broeks A, Van't Veer LJ, Atsma F, Muir K, Lophatananon A, Fasching PA, Beckmann MW, Ekici AB, Renner SP, Sawyer E, Tomlinson I, Kerin M, Miller N, Burwinkel B, Marme F, Schneeweiss A, Sohn C, Guénel P, Truong T, Cordina E, Menegaux F, Bojesen SE, Nordestgaard BG, Flyger H, Milne R, Zamora MP, Arias Perez JI, Benitez J, Bernstein L, Anton-Culver H, Ziogas A, Clarke Dur C, Brenner H, Müller H, Arndt V, Dieffenbach AK, Meindl A, Heil J, Bartram CR, Schmutzler RK, Brauch H, Justenhoven C, Ko YD, Nevanlinna H, Muranen TA, Aittomäki K, Blomqvist C, Matsuo K, Dörk T, Bogdanova NV, Antonenkova NN, Lindblom A, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Chenevix-Trench G, Beesley J, Wu AH, Van den Berg D, Tseng CC, Lambrechts D, Smeets D, Neven P, Wildiers H, Chang-Claude J, Rudolph A, Nickels S, Flesch-Janys D, Radice P, Peterlongo P, Bonanni B, Pensotti V, Couch FJ, Olson JE, Wang X, Fredericksen Z, Pankratz VS, Giles GG, Severi G, Baglietto L, Haiman C, Simard J, Goldberg MS, Labrèche F, Dumont M, Soucy P, Teo S, Yip CH, Phuah SY, Cornes BK, Kristensen VN, Grenaker Alnæs G, Børresen-Dale AL, Zheng W, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Andrulis IL, Knight JA, Glendon G, Mulligan AM, Devillee P, Figueroa J, Chanock SJ, Lissowska J, Sherman ME, Hall P, Schoof N, Hooning M, Hollestelle A, Oldenburg RA, Tilanus-Linthorst M, Liu J, Cox A, Brock IW, Reed MW, Cross SS, Blot W, Signorello LB, Pharoah PD, Dunning AM, Shah M, Kang D, Noh DY, Park SK, Choi JY, Hartman M, Miao H, Lim WY, Tang A, Hamann U, Försti A, Rüdiger T, Ulmer HU, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Sangrajrang S, Gaborieau V, Brennan P, McKay J, Slager S, Toland AE, Vachon C, Yannoukakos D, Shen CY, Yu JC, Huang CS, Hou MF, González-Neira A, Tessier DC, Vincent D, Bacot F, Luccarini C, Dennis J, Michailidou K, Bolla MK, Wang J, Easton DF, García-Closas M, Dowsett M, Ashworth A, Swerdlow AJ, Peto J, dos Santos Silva I, and Fletcher O

Subjects
Adult, Age Factors, Age of Onset, Aged, Breast Neoplasms pathology, Female, Genetic Predisposition to Disease, Genotype, Humans, Middle Aged, Polymorphism, Single Nucleotide, Premenopause genetics, Reproductive History, Risk Factors, White People, Breast Neoplasms genetics, Cytochrome P-450 CYP3A genetics, Genetic Association Studies, Menarche genetics
Abstract

Introduction: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years., Methods: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics., Results: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 0.29)., Conclusions: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

Published
2014
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49. FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium.

Author

Agarwal D, Pineda S, Michailidou K, Herranz J, Pita G, Moreno LT, Alonso MR, Dennis J, Wang Q, Bolla MK, Meyer KB, Menéndez-Rodríguez P, Hardisson D, Mendiola M, González-Neira A, Lindblom A, Margolin S, Swerdlow A, Ashworth A, Orr N, Jones M, Matsuo K, Ito H, Iwata H, Kondo N, Hartman M, Hui M, Lim WY, Iau PT, Sawyer E, Tomlinson I, Kerin M, Miller N, Kang D, Choi J-, Park SK, Noh D-, Hopper JL, Schmidt DF, Makalic E, Southey MC, Teo SH, Yip CH, Sivanandan K, Tay W-, Brauch H, Brüning T, Hamann U, Dunning AM, Shah M, Andrulis IL, Knight JA, Glendon G, Tchatchou S, Schmidt MK, Broeks A, Rosenberg EH, van't Veer LJ, Fasching PA, Renner SP, Ekici AB, Beckmann MW, Shen C-, Hsiung C-, Yu J-, Hou M-, Blot W, Cai Q, Wu AH, Tseng C-, Van Den Berg D, Stram DO, Cox A, Brock IW, Reed MW, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Zheng W, Deming-Halverson S, Shrubsole MJ, Long J, Shu X-, Lu W, Gao Y-, Zhang B, Radice P, Peterlongo P, Manoukian S, Mariette F, Sangrajrang S, McKay J, Couch FJ, Toland AE, Yannoukakos D, Fletcher O, Johnson N, dos Santos Silva I, Peto J, Marme F, Burwinkel B, Guénel P, Truong T, Sanchez M, Mulot C, Bojesen SE, Nordestgaard BG, Flyer H, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Mannermaa A, Kataja V, Kosma V-, Hartikainen JM, Lambrechts D, Yesilyurt BT, Floris G, Leunen K, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Wang X, Olson JE, Vachon C, Purrington K, Giles GG, Severi G, Baglietto L, Haiman CA, Henderson BE, Schumacher F, Marchand LL, Simard J, Dumont M, Goldberg MS, Labréche F, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Devilee P, Tollenaar RA, Seynaeve C, García-Closas M, Chanock SJ, Lissowska J, Figueroa JD, Czene K, Eriksson M, Humphreys K, Darabi H, Hooning MJ, Kriege M, Collée JM, Tilanus-Linthorst M, Li J, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Nevanlinna H, Muranen TA, Aittomäki K, Blomqvist C, Bogdanova N, Dörk T, Hall P, Chenevix-Trench G, Easton DF, Pharroah PD, Arias-Perez JI, Zamora P, Benítez J, and Milne RL

Subjects
Case-Control Studies, Female, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide genetics, Receptor, Fibroblast Growth Factor, Type 1 genetics, Receptor, Fibroblast Growth Factor, Type 3 genetics, Receptor, Fibroblast Growth Factor, Type 4 genetics, Receptor, Fibroblast Growth Factor, Type 5 genetics, Breast Neoplasms genetics, Genetic Predisposition to Disease, Receptor, Fibroblast Growth Factor, Type 2 genetics
Abstract

Background: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium., Methods: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression., Results: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2., Conclusion: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.

Published
2014
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50. Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers.

Author

French JD, Ghoussaini M, Edwards SL, Meyer KB, Michailidou K, Ahmed S, Khan S, Maranian MJ, O'Reilly M, Hillman KM, Betts JA, Carroll T, Bailey PJ, Dicks E, Beesley J, Tyrer J, Maia AT, Beck A, Knoblauch NW, Chen C, Kraft P, Barnes D, González-Neira A, Alonso MR, Herrero D, Tessier DC, Vincent D, Bacot F, Luccarini C, Baynes C, Conroy D, Dennis J, Bolla MK, Wang Q, Hopper JL, Southey MC, Schmidt MK, Broeks A, Verhoef S, Cornelissen S, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Fasching PA, Loehberg CR, Ekici AB, Beckmann MW, Peto J, dos Santos Silva I, Johnson N, Aitken Z, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Marme F, Schneeweiss A, Sohn C, Burwinkel B, Guénel P, Truong T, Laurent-Puig P, Menegaux F, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Milne RL, Zamora MP, Arias Perez JI, Benitez J, Anton-Culver H, Brenner H, Müller H, Arndt V, Stegmaier C, Meindl A, Lichtner P, Schmutzler RK, Engel C, Brauch H, Hamann U, Justenhoven C, Aaltonen K, Heikkilä P, Aittomäki K, Blomqvist C, Matsuo K, Ito H, Iwata H, Sueta A, Bogdanova NV, Antonenkova NN, Dörk T, Lindblom A, Margolin S, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Wu AH, Tseng CC, Van Den Berg D, Stram DO, Lambrechts D, Peeters S, Smeets A, Floris G, Chang-Claude J, Rudolph A, Nickels S, Flesch-Janys D, Radice P, Peterlongo P, Bonanni B, Sardella D, Couch FJ, Wang X, Pankratz VS, Lee A, Giles GG, Severi G, Baglietto L, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Simard J, Goldberg MS, Labrèche F, Dumont M, Teo SH, Yip CH, Ng CH, Vithana EN, Kristensen V, Zheng W, Deming-Halverson S, Shrubsole M, Long J, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Andrulis IL, Knight JA, Glendon G, Mulligan AM, Devilee P, Seynaeve C, García-Closas M, Figueroa J, Chanock SJ, Lissowska J, Czene K, Klevebring D, Schoof N, Hooning MJ, Martens JW, Collée JM, Tilanus-Linthorst M, Hall P, Li J, Liu J, Humphreys K, Shu XO, Lu W, Gao YT, Cai H, Cox A, Balasubramanian SP, Blot W, Signorello LB, Cai Q, Pharoah PD, Healey CS, Shah M, Pooley KA, Kang D, Yoo KY, Noh DY, Hartman M, Miao H, Sng JH, Sim X, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Sangrajrang S, Gaborieau V, McKay J, Toland AE, Ambrosone CB, Yannoukakos D, Godwin AK, Shen CY, Hsiung CN, Wu PE, Chen ST, Swerdlow A, Ashworth A, Orr N, Schoemaker MJ, Ponder BA, Nevanlinna H, Brown MA, Chenevix-Trench G, Easton DF, and Dunning AM

Subjects
Binding Sites, Case-Control Studies, Cell Line, Tumor, Chromatin chemistry, Chromatin genetics, Chromatin Immunoprecipitation, Cyclin D1 metabolism, Electrophoretic Mobility Shift Assay, Female, GATA3 Transcription Factor antagonists & inhibitors, GATA3 Transcription Factor genetics, GATA3 Transcription Factor metabolism, Gene Expression Regulation, Neoplastic, Humans, Luciferases metabolism, Promoter Regions, Genetic genetics, RNA, Messenger genetics, RNA, Small Interfering genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Silencer Elements, Transcriptional genetics, ets-Domain Protein Elk-4 antagonists & inhibitors, ets-Domain Protein Elk-4 genetics, ets-Domain Protein Elk-4 metabolism, Breast Neoplasms genetics, Chromosomes, Human, Pair 11 genetics, Cyclin D1 genetics, Enhancer Elements, Genetic genetics, Polymorphism, Single Nucleotide genetics
Abstract

Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1., (Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Published
2013
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