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

Johnson, Nichola ; Dudbridge, Frank ; Orr, Nick ; Gibson, Lorna ; Jones, Michael E. ; Schoemaker, Minouk J. ; Folkerd, Elizabeth J. ; Haynes, Ben P. ; Hopper, John L. ; Southey, Melissa C. ; Dite, Gillian S. ; Apicella, Carmel ; Schmidt, Marjanka K. ; Broeks, Annegien ; Van’t Veer, Laura J. ; Atsma, Femke ; Muir, Kenneth ; Lophatananon, Artitaya ; Fasching, Peter A. ; Beckmann, Matthias W. ; Ekici, Arif B. ; Renner, Stefan P. ; Sawyer, Elinor ; Tomlinson, Ian ; Kerin, Michael ; Miller, Nicola ; Burwinkel, Barbara ; Marme, Frederik ; Schneeweiß, Andreas ; Sohn, Christof ; Guénel, Pascal ; Truong, Therese ; Cordina, Emilie ; Menegaux, Florence ; Bojesen, Stig E. ; Nordestgaard, Børge G. ; Flyger, Henrik ; Milne, Roger ; Zamora, M. Pilar ; Perez, Jose Ignacio Arias ; Benitez, Javier ; Bernstein, Leslie ; Anton-Culver, Hoda ; Ziogas, Argyrios ; Clarke Dur, Christina ; Brenner, Hermann ; Müller, Heiko ; Arndt, Volker ; Dieffenbach, Aida Karina ; Meindl, Alfons ; Heil, Jörg ; Bartram, Claus R. ; Schmutzler, Rita K. ; Brauch, Hiltrud ; Justenhoven, Christina ; Ko, Yon-Dschun ; Nevanlinna, Heli ; Muranen, Taru A. ; Aittomäki, Kristiina ; Blomqvist, Carl ; Matsuo, Keitaro ; Dörk, Thilo ; Bogdanova, Natalia V. ; Antonenkova, Natalia N. ; Lindblom, Annika ; Mannermaa, Arto ; Kataja, Vesa ; Kosma, Veli-Matti ; Hartikainen, Jaana M ; Chenevix-Trench, Georgia ; Beesley, Jonathan ; Wu, Anna H. ; Van den Berg, David ; Tseng, Chiu-Chen ; Lambrechts, Diether ; Smeets, Dominiek ; Neven, Patrick ; Wildiers, Hans ; Chang-Claude, Jenny ; Rudolph, Anja ; Nickels, Stefan ; Flesch-Janys, Dieter ; Radice, Paolo ; Peterlongo, Paolo ; Bonanni, Bernardo ; Pensotti, Valeria ; Couch, Fergus J. ; Olson, Janet E. ; Wang, Xianshu ; Fredericksen, Zachary ; Pankratz, Vernon S. ; Giles, Graham G. ; Severi, Gianluca ; Baglietto, Laura ; Haiman, Chris ; Simard, Jacques ; Goldberg, Mark S ; Labrèche, France ; Dumont, Martine ; Soucy, Penny ; Teo, Soo ; Yip, Cheng Har ; Phuah, Sze Yee ; Cornes, Belinda K. ; Kristensen, Vessela N. ; Grenaker Alnæs, Grethe ; Børresen-Dale, Anne-Lise ; Zheng, Wei ; Winqvist, Robert ; Pylkäs, Katri ; Jukkola-Vuorinen, Arja ; Grip, Mervi ; Andrulis, Irene L. ; Knight, Julia A. ; Glendon, Gord ; Mulligan, Anna Marie ; Devillee, Peter ; Figueroa, Jonine ; Chanock, Stephen J. ; Lissowska, Jolanta ; Sherman, Mark E ; Hall, Per ; Schoof, Nils ; Hooning, Maartje ; Hollestelle, Antoinette ; Oldenburg, Rogier A. ; Tilanus-Linthorst, Madeleine ; Liu, Jianjun ; Cox, Angie ; Brock, Ian W. ; Reed, Malcolm WR ; Cross, Simon S. ; Blot, William ; Signorello, Lisa B. ; Pharoah, Paul DP ; Dunning, Alison M. ; Shah, Mitul ; Kang, Daehee ; Noh, Dong-Young ; Park, Sue K. ; Choi, Ji-Yeob ; Hartman, Mikael ; Miao, Hui ; Lim, Wei Yen ; Tang, Anthony ; Hamann, Ute ; Försti, Asta ; Rüdiger, Thomas ; Ulmer, Hans U. ; Jakubowska, Anna ; Lubinski, Jan ; Jaworska-Bieniek, Katarzyna ; Durda, Katarzyna ; Sangrajrang, Suleeporn ; Gaborieau, Valerie ; Brennan, Paul ; McKay, James ; Slager, Susan ; Toland, Amanda E ; Vachon, Celine ; Yannoukakos, Drakoulis ; Shen, Chen-Yang ; Yu, Jyh-Cherng ; Huang, Chiun-Sheng ; Hou, Ming-Feng ; González-Neira, Anna ; Tessier, Daniel C. ; Vincent, Daniel ; Bacot, Francois ; Luccarini, Craig ; Dennis, Joe ; Michailidou, Kyriaki ; Bolla, Manjeet K. ; Wang, Jean ; Easton, Douglas F. ; García-Closas, Montserrat ; Dowsett, Mitch ; Ashworth, Alan ; Swerdlow, Anthony J. ; Peto, Julian ; dos Santos Silva, Isabel ; Fletcher, Olivia

In: Breast cancer research, 16 (2014), Nr. R51. pp. 1-13. ISSN 1465-542X

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Download (459kB) | Lizenz: Creative Commons LizenzvertragGenetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study by Johnson, Nichola ; Dudbridge, Frank ; Orr, Nick ; Gibson, Lorna ; Jones, Michael E. ; Schoemaker, Minouk J. ; Folkerd, Elizabeth J. ; Haynes, Ben P. ; Hopper, John L. ; Southey, Melissa C. ; Dite, Gillian S. ; Apicella, Carmel ; Schmidt, Marjanka K. ; Broeks, Annegien ; Van’t Veer, Laura J. ; Atsma, Femke ; Muir, Kenneth ; Lophatananon, Artitaya ; Fasching, Peter A. ; Beckmann, Matthias W. ; Ekici, Arif B. ; Renner, Stefan P. ; Sawyer, Elinor ; Tomlinson, Ian ; Kerin, Michael ; Miller, Nicola ; Burwinkel, Barbara ; Marme, Frederik ; Schneeweiß, Andreas ; Sohn, Christof ; Guénel, Pascal ; Truong, Therese ; Cordina, Emilie ; Menegaux, Florence ; Bojesen, Stig E. ; Nordestgaard, Børge G. ; Flyger, Henrik ; Milne, Roger ; Zamora, M. Pilar ; Perez, Jose Ignacio Arias ; Benitez, Javier ; Bernstein, Leslie ; Anton-Culver, Hoda ; Ziogas, Argyrios ; Clarke Dur, Christina ; Brenner, Hermann ; Müller, Heiko ; Arndt, Volker ; Dieffenbach, Aida Karina ; Meindl, Alfons ; Heil, Jörg ; Bartram, Claus R. ; Schmutzler, Rita K. ; Brauch, Hiltrud ; Justenhoven, Christina ; Ko, Yon-Dschun ; Nevanlinna, Heli ; Muranen, Taru A. ; Aittomäki, Kristiina ; Blomqvist, Carl ; Matsuo, Keitaro ; Dörk, Thilo ; Bogdanova, Natalia V. ; Antonenkova, Natalia N. ; Lindblom, Annika ; Mannermaa, Arto ; Kataja, Vesa ; Kosma, Veli-Matti ; Hartikainen, Jaana M ; Chenevix-Trench, Georgia ; Beesley, Jonathan ; Wu, Anna H. ; Van den Berg, David ; Tseng, Chiu-Chen ; Lambrechts, Diether ; Smeets, Dominiek ; Neven, Patrick ; Wildiers, Hans ; Chang-Claude, Jenny ; Rudolph, Anja ; Nickels, Stefan ; Flesch-Janys, Dieter ; Radice, Paolo ; Peterlongo, Paolo ; Bonanni, Bernardo ; Pensotti, Valeria ; Couch, Fergus J. ; Olson, Janet E. ; Wang, Xianshu ; Fredericksen, Zachary ; Pankratz, Vernon S. ; Giles, Graham G. ; Severi, Gianluca ; Baglietto, Laura ; Haiman, Chris ; Simard, Jacques ; Goldberg, Mark S ; Labrèche, France ; Dumont, Martine ; Soucy, Penny ; Teo, Soo ; Yip, Cheng Har ; Phuah, Sze Yee ; Cornes, Belinda K. ; Kristensen, Vessela N. ; Grenaker Alnæs, Grethe ; Børresen-Dale, Anne-Lise ; Zheng, Wei ; Winqvist, Robert ; Pylkäs, Katri ; Jukkola-Vuorinen, Arja ; Grip, Mervi ; Andrulis, Irene L. ; Knight, Julia A. ; Glendon, Gord ; Mulligan, Anna Marie ; Devillee, Peter ; Figueroa, Jonine ; Chanock, Stephen J. ; Lissowska, Jolanta ; Sherman, Mark E ; Hall, Per ; Schoof, Nils ; Hooning, Maartje ; Hollestelle, Antoinette ; Oldenburg, Rogier A. ; Tilanus-Linthorst, Madeleine ; Liu, Jianjun ; Cox, Angie ; Brock, Ian W. ; Reed, Malcolm WR ; Cross, Simon S. ; Blot, William ; Signorello, Lisa B. ; Pharoah, Paul DP ; Dunning, Alison M. ; Shah, Mitul ; Kang, Daehee ; Noh, Dong-Young ; Park, Sue K. ; Choi, Ji-Yeob ; Hartman, Mikael ; Miao, Hui ; Lim, Wei Yen ; Tang, Anthony ; Hamann, Ute ; Försti, Asta ; Rüdiger, Thomas ; Ulmer, Hans U. ; Jakubowska, Anna ; Lubinski, Jan ; Jaworska-Bieniek, Katarzyna ; Durda, Katarzyna ; Sangrajrang, Suleeporn ; Gaborieau, Valerie ; Brennan, Paul ; McKay, James ; Slager, Susan ; Toland, Amanda E ; Vachon, Celine ; Yannoukakos, Drakoulis ; Shen, Chen-Yang ; Yu, Jyh-Cherng ; Huang, Chiun-Sheng ; Hou, Ming-Feng ; González-Neira, Anna ; Tessier, Daniel C. ; Vincent, Daniel ; Bacot, Francois ; Luccarini, Craig ; Dennis, Joe ; Michailidou, Kyriaki ; Bolla, Manjeet K. ; Wang, Jean ; Easton, Douglas F. ; García-Closas, Montserrat ; Dowsett, Mitch ; Ashworth, Alan ; Swerdlow, Anthony J. ; Peto, Julian ; dos Santos Silva, Isabel ; Fletcher, Olivia underlies the terms of Creative Commons Attribution 3.0 Germany

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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 (ORhet = 0.84, 95% CI 0.75, 0.94; ORhom = 0.81, 95% CI 0.51, 1.30; P trend = 0.002) but not for those who had their menarche age ≤11 years (ORhet = 1.06, 95% CI 0.95, 1.19, ORhom = 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.

Item Type: Article
Journal or Publication Title: Breast cancer research
Volume: 16
Number: R51
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 19 Jan 2016 09:01
Date: 2014
ISSN: 1465-542X
Page Range: pp. 1-13
Faculties / Institutes: Service facilities > German Cancer Research Center (DKFZ)
Service facilities > Netzwerk Alternsforschung
Medizinische Fakultät Heidelberg > Universitäts-Frauenklinik
Medizinische Fakultät Heidelberg > Institut für Humangenetik
Subjects: 610 Medical sciences Medicine
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