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

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    Authors
    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 P
    Arias Perez, Jose I
    Benitez, Javier
    Bernstein, Leslie
    Anton-Culver, Hoda
    Ziogas, Argyrios
    Clarke Dur, Christina
    Brenner, Hermann
    Müller, Heiko
    Arndt, Volker
    Dieffenbach, Aida K
    Meindl, Alfons
    Heil, Joerg
    Bartram, Claus R
    Schmutzler, Rita K
    Brauch, Hiltrud
    Justenhoven, Christina
    Ko, Yon-Dschun
    The GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network
    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
    kConFab Investigators
    Australian Ovarian Cancer Study Group
    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 H
    Phuah, Sze Y
    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 M
    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 Y
    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
    Show allShow less
    Issue Date
    2014-05-26
    Keywords
    BREAST CANCER
    GENETICS
    
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    Citation
    Breast Cancer Research. 2014 May 26;16(3):R51
    URI
    http://dx.doi.org/10.1186/bcr3662
    http://hdl.handle.net/10147/560427
    Abstract
    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.
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