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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. and Southey, Melissa C., et al. (2014) In Breast Cancer Research 16(R51). p.1-13
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... (More)
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. (Less)
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Breast Cancer Research
volume
16
issue
R51
pages
1 - 13
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BioMed Central
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  • wos:000349083900007
  • scopus:84901151196
ISSN
1465-5411
DOI
10.1186/bcr3662
language
English
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yes
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d55e04a1-77c6-471a-b3e4-2200f3214c3c (old id 5200928)
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2015-04-01 07:36:13
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2017-01-01 04:13:22
@article{d55e04a1-77c6-471a-b3e4-2200f3214c3c,
  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 &lt;= 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 &gt;= 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 &lt;= 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.},
  author       = {Johnson, Nichola and Dudbridge, Frank and Orr, Nick and Gibson, Lorna and Jones, Michael E. and Schoemaker, Minouk J. and Folkerd, Elizabeth J. and Haynes, Ben P. and Hopper, John L. and Southey, Melissa C. and Dite, Gillian S. and Apicella, Carmel and Schmidt, Marjanka K. and Broeks, Annegien and Van't Veer, Laura J. and Atsma, Femke and Muir, Kenneth and Lophatananon, Artitaya and Fasching, Peter A. and Beckmann, Matthias W. and Ekici, Arif B. and Renner, Stefan P. and Sawyer, Elinor and Tomlinson, Ian and Kerin, Michael and Miller, Nicola and Burwinkel, Barbara and Marme, Frederik and Schneeweiss, Andreas and Sohn, Christof and Guenel, Pascal and Truong, Therese and Cordina, Emilie and Menegaux, Florence and Bojesen, Stig E. and Nordestgaard, Borge G. and Flyger, Henrik and Milne, Roger and Zamora, M. Pilar and Arias Perez, Jose Ignacio and Benitez, Javier and Bernstein, Leslie and Anton-Culver, Hoda and Ziogas, Argyrios and Dur, Christina Clarke and Brenner, Hermann and Mueller, Heiko and Arndt, Volker and Dieffenbach, Aida Karina and Meindl, Alfons and Heil, Joerg and Bartram, Claus R. and Schmutzler, Rita K. and Brauch, Hiltrud and Justenhoven, Christina and Ko, Yon-Dschun and Nevanlinna, Heli and Muranen, Taru A. and Aittomaeki, Kristiina and Blomqvist, Carl and Matsuo, Keitaro and Doerk, Thilo and Bogdanova, Natalia V. and Antonenkova, Natalia N. and Lindblom, Annika and Mannermaa, Arto and Kataja, Vesa and Kosma, Veli-Matti and Hartikainen, Jaana M. and Chenevix-Trench, Georgia and Beesley, Jonathan and Wu, Anna H. and Van den Berg, David and Tseng, Chiu-Chen and Lambrechts, Diether and Smeets, Dominiek and Neven, Patrick and Wildiers, Hans and Chang-Claude, Jenny and Rudolph, Anja and Nickels, Stefan and Flesch-Janys, Dieter and Radice, Paolo and Peterlongo, Paolo and Bonanni, Bernardo and Pensotti, Valeria and Couch, Fergus J. and Olson, Janet E. and Wang, Xianshu and Fredericksen, Zachary and Pankratz, Vernon S. and Giles, Graham G. and Severi, Gianluca and Baglietto, Laura and Haiman, Chris and Simard, Jacques and Goldberg, Mark S. and Labreche, France and Dumont, Martine and Soucy, Penny and Teo, Soo and Yip, Cheng Har and Phuah, Sze Yee and Cornes, Belinda K. and Kristensen, Vessela N. and Alnaes, Grethe Grenaker and Borresen-Dale, Anne-Lise and Zheng, Wei and Winqvist, Robert and Pylkaes, Katri and Jukkola-Vuorinen, Arja and Grip, Mervi and Andrulis, Irene L. and Knight, Julia A. and Glendon, Gord and Mulligan, Anna Marie and Devillee, Peter and Figueroa, Jonine and Chanock, Stephen J. and Lissowska, Jolanta and Sherman, Mark E. and Hall, Per and Schoof, Nils and Hooning, Maartje and Hollestelle, Antoinette and Oldenburg, Rogier A. and Tilanus-Linthorst, Madeleine and Liu, Jianjun and Cox, Angie and Brock, Ian W. and Reed, Malcolm W. R. and Cross, Simon S. and Blot, William and Signorello, Lisa B. and Pharoah, Paul D. P. and Dunning, Alison M. and Shah, Mitul and Kang, Daehee and Noh, Dong-Young and Park, Sue K. and Choi, Ji-Yeob and Hartman, Mikael and Miao, Hui and Lim, Wei Yen and Tang, Anthony and Hamann, Ute and Försti, Asta and Ruediger, Thomas and Ulmer, Hans Ulrich and Jakubowska, Anna and Lubinski, Jan and Jaworska-Bieniek, Katarzyna and Durda, Katarzyna and Sangrajrang, Suleeporn and Gaborieau, Valerie and Brennan, Paul and Mckay, James and Slager, Susan and Toland, Amanda E. and Vachon, Celine and Yannoukakos, Drakoulis and Shen, Chen-Yang and Yu, Jyh-Cherng and Huang, Chiun-Sheng and Hou, Ming-Feng and Gonzalez-Neira, Anna and Tessier, Daniel C. and Vincent, Daniel and Bacot, Francois and Luccarini, Craig and Dennis, Joe and Michailidou, Kyriaki and Bolla, Manjeet K. and Wang, Jean and Easton, Douglas F. and Garcia-Closas, Montserrat and Dowsett, Mitch and Ashworth, Alan and Swerdlow, Anthony J. and Peto, Julian and Silva, Isabel dos Santos and Fletcher, Olivia},
  issn         = {1465-5411},
  language     = {eng},
  number       = {R51},
  pages        = {1--13},
  publisher    = {BioMed Central},
  series       = {Breast Cancer Research},
  title        = {Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study},
  url          = {http://dx.doi.org/10.1186/bcr3662},
  volume       = {16},
  year         = {2014},
}