title: Post-GWAS gene-environment interplay in breast cancer: results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79,000 women.
abstract: We studied the interplay between 39 breast cancer (BC) risk SNPs and established BC risk (body mass index, height, age at menarche, parity, age at menopause, smoking, alcohol and family history of BC) and prognostic factors (TNM stage, tumor grade, tumor size, age at diagnosis, estrogen receptor status and progesterone receptor status) as joint determinants of BC risk. We used a nested case-control design within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), with 16 285 BC cases and 19 376 controls. We performed stratified analyses for both the risk and prognostic factors, testing for heterogeneity for the risk factors, and case-case comparisons for differential associations of polymorphisms by subgroups of the prognostic factors. We analyzed multiplicative interactions between the SNPs and the risk factors. Finally, we also performed a meta-analysis of the interaction ORs from BPC3 and the Breast Cancer Association Consortium. After correction for multiple testing, no significant interaction between the SNPs and the established risk factors in the BPC3 study was found. The meta-analysis showed a suggestive interaction between smoking status and SLC4A7-rs4973768 (Pinteraction = 8.84 × 10(-4)) which, although not significant after considering multiple comparison, has a plausible biological explanation. In conclusion, in this study of up to almost 79 000 women we can conclusively exclude any novel major interactions between genome-wide association studies hits and the epidemiologic risk factors taken into consideration, but we propose a suggestive interaction between smoking status and SLC4A7-rs4973768 that if further replicated could help our understanding in the etiology of BC.
authors.affiliation: Division of Cancer Epidemiology and.
authors.forename: Myrto
authors.initials: M
authors.lastname: Barrdahl
authors.affiliation: Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg D-69120, Germany.
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Amit D
authors.initials: AD
authors.lastname: Joshi
authors.affiliation: Cancer Epidemiology Unit, University of Oxford, Oxford OX3 7LF, UK.
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.affiliation: Division of Cancer Epidemiology and.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA School of Public Health, University of Wisconsin, Milwaukee, WI 1240, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Auer
authors.affiliation: Department of Epidemiology, American Cancer Society, Atlanta, GA 30303, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gapstur
authors.affiliation: Department of Epidemiology, American Cancer Society, Atlanta, GA 30303, USA.
authors.forename: Mia
authors.initials: M
authors.lastname: Gaudet
authors.affiliation: Department of Epidemiology, American Cancer Society, Atlanta, GA 30303, USA.
authors.forename: W Ryan
authors.initials: WR
authors.lastname: Diver
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.affiliation: Cancer Center, University of Hawaii, Honolulu, HI 96813, USA.
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Christine D
authors.initials: CD
authors.lastname: Berg
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.affiliation: Division of Cancer Epidemiology and.
authors.forename: Anja
authors.initials: A
authors.lastname: Rudolph
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.affiliation: Cancer Epidemiology Centre Melbourne, Cancer Council Victoria, Carlton South, VIC 3004, Australia Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, VIC 3010, Australia Faculty of Medicine, Monash University, Melbourne, VIC 3800, Australia.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.affiliation: Cancer Epidemiology Centre Melbourne, Cancer Council Victoria, Carlton South, VIC 3004, Australia Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: Laura
authors.initials: L
authors.lastname: Baglietto
authors.affiliation: Cancer Epidemiology Centre Melbourne, Cancer Council Victoria, Carlton South, VIC 3004, Australia Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, MA 01003-9304, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Lindström
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Walter
authors.initials: W
authors.lastname: Willet
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: I-Min
authors.initials: IM
authors.lastname: Lee
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Shumin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: INSERM, Centre for Research in Epidemiology and Population Health, Institut Gustave Roussy, Villejuif F-94805, France Paris South University, Villejuif F-94807, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.affiliation: School of Public Health, Imperial College London, London SW7 2AZ, UK Université de Lyon, Université Lyon 1, ISPB, Lyon F-69007, France INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon F-69008, France Centre Léon Bérard, Lyon F-69008, France.
authors.forename: David G
authors.initials: DG
authors.lastname: Cox
authors.affiliation: Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SP, UK.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: Institute of Community Medicine, University of Tromsø, Tromsø N-9037, Norway.
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.affiliation: Molecular and Genetic Epidemiology Unit, Human Genetics Foundation Torino, Torino I-10126, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.affiliation: School of Public Health, Imperial College London, London SW7 2AZ, UK Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht 3584 CS, The Netherlands.
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peeters
authors.affiliation: Public Health Directorate, Asturias ES-CP33006, Spain.
authors.forename: J Ramón
authors.initials: JR
authors.lastname: Quirós
authors.affiliation: School of Public Health, Imperial College London, London SW7 2AZ, UK.
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.affiliation: Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå S-90185, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Sund
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA Bureau of Epidemiologic Research, Academy of Athens, Athens 10679, Greece Hellenic Health Foundation, Athens 11527, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Ross L
authors.initials: RL
authors.lastname: Prentice
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Division of Cancer Epidemiology and.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.affiliation: Division of Cancer Epidemiology and d.campa@dkfz.de.
authors.forename: Daniele
authors.initials: D
authors.lastname: Campa
mesh_terms: D000483:Alleles; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D014408:Biomarkers, Tumor