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

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 P, Beckmann M, Ekici AB, Renner S, 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 YD, Nevanlinna H, Muranen TA, Aittomaeki K, Blomqvist C, Matsuo K, Doerk 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, Labreche F, Dumont M, Soucy P, Teo S, Yip CH, Phuah SY, Cornes BK, Kristensen VN, Alnaes GG, Borresen-Dale AL, 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 DY, Park SK, Choi JY, 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 CY, Yu JC, Huang CS, Hou MF, 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 (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Book Volume: 16

Pages Range: R51

Journal Issue: 3

DOI: 10.1186/bcr3662

Abstract

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.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.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).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.

Authors with CRIS profile

Involved external institutions

Klinikum Mittelbaden Baden-Baden Balg Germany (DE) Centre hospitalier universitaire de Québec Canada (CA) Université de Montréal Canada (CA) McGill University Canada (CA) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) The University of Melbourne Australia (AU) Mayo Clinic United States (USA) (US) IFOM - FIRC Institute of Molecular Oncology Italy (IT) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Université Catholique de Louvain (UCL) Belgium (BE) University of Southern California (USC) United States (USA) (US) University of Eastern Finland Finland (FI) Karolinska Institute Sweden (SE) N.N. Alexandrov National Cancer Centre of Belarus for Oncology and Medical Radiology Belarus (BY) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Helsingin yliopisto / University of Helsinki Finland (FI) Robert Bosch Stiftung Germany (DE) Universitätsklinikum Köln Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) National University of Ireland (NUI), Galway Ireland (IE) Technische Universität München (TUM) Germany (DE) Cancer Prevention Institute of California (CPIC) United States (USA) (US) University of California Irvine United States (USA) (US) City of Hope Medical Center United States (USA) (US) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Hospital Monte Naranco Spain (ES) Hospital Universitario La Paz Spain (ES) Copenhagen University Hospital Denmark (DK) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) France (FR) University Hospital Galway Ireland (IE) University of Oxford United Kingdom (GB) University of Warwick United Kingdom (GB) Guy's and St Thomas' (NHS Foundation Trust) United Kingdom (GB) Radboud University Nijmegen Netherlands (NL) Antoni van Leeuwenhoek Netherlands (NL) Royal Marsden Hospital / The Royal Marsden NHS Foundation Trust United Kingdom (GB) Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam Netherlands (NL) National Cancer Institute (NCI) United States (USA) (US) National University Health System (NUHS) Singapore (SG) Harvard University United States (USA) (US) National University of Singapore (NUS) Singapore (SG) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) University of Cambridge United Kingdom (GB) Vanderbilt University United States (USA) (US) University of Sheffield United Kingdom (GB) Genome Institute of Singapore Singapore (SG) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Leiden University Netherlands (NL) University of Toronto Canada (CA) Mount Sinai Hospital (MSH) Canada (CA) Oulun Yliopisto / University of Oulo Finland (FI) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) University of Oslo Norway (NO) University of Malaya (UM) / Universiti Malaya Malaysia (MY) Evangelische Kliniken Bonn gGmbH Germany (DE) Aichi Cancer Center Research Institute Japan (JP) London School of Hygiene and Tropical Medicine United Kingdom (GB) Kaohsiung Medical University (KMU) / 高雄醫學大學 Taiwan (TW) National Taiwan University Hospital (NTUH) / 國立台灣大學醫學院附設醫院 Taiwan (TW) China Medical University (CMU) / 中國醫藥大學 Taiwan (TW) National Centre for Scientific Research (NCSR) "Demokritos" Greece (GR) Ohio State University United States (USA) (US) International Agency for Research on Cancer (IARC) France (FR) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Städtisches Klinikum Karlsruhe Germany (DE) Tri-Service General Hospital (TSGH) / 三軍總醫院 Taiwan (TW)

How to cite

APA:

Johnson, N., Dudbridge, F., Orr, N., Gibson, L., Jones, M.E., Schoemaker, M.J.,... Fletcher, O. (2014). Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study. Breast Cancer Research, 16(3), R51. https://doi.org/10.1186/bcr3662

MLA:

Johnson, Nichola, et al. "Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study." Breast Cancer Research 16.3 (2014): R51.

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