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

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

Breast Cancer Res 2014 May 26;16(3):R51. Epub 2014 May 26.

Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK.

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.

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http://dx.doi.org/10.1186/bcr3662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522594PMC

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May 2014
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