title: Interactions between breast cancer susceptibility loci and menopausal hormone therapy in relationship to breast cancer in the Breast and Prostate Cancer Cohort Consortium.
abstract: Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal breast cancer risk, and observed associations might be modified by known breast cancer susceptibility loci. To provide the most comprehensive assessment of interactions of prospectively collected data on MHT and 17 confirmed susceptibility loci with invasive breast cancer risk, a nested case-control design among eight cohorts within the NCI Breast and Prostate Cancer Cohort Consortium was used. Based on data from 13,304 cases and 15,622 controls, multivariable-adjusted logistic regression analyses were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Effect modification of current and past use was evaluated on the multiplicative scale. P values <1.5 × 10(-3) were considered statistically significant. The strongest evidence of effect modification was observed for current MHT by 9q31-rs865686. Compared to never users of MHT with the rs865686 GG genotype, the association between current MHT use and breast cancer risk for the TT genotype (OR 1.79, 95 % CI 1.43-2.24; P interaction = 1.2 × 10(-4)) was less than expected on the multiplicative scale. There are no biological implications of the sub-multiplicative interaction between MHT and rs865686. Menopausal hormone therapy is unlikely to have a strong interaction with the common genetic variants associated with invasive breast cancer.
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA. mia.gaudet@cancer.org.
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Myrto
authors.initials: M
authors.lastname: Barrdahl
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Lindström
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, University of Oxford, UK.
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|School of Public Health, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Auer
authors.affiliation: Divisions of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.|Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, MA, 02115, USA.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.|Core Genotyping Facility Frederick National Laboratory for Cancer Research, Gaithersburg, MD, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.|Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
authors.forename: A Heather
authors.initials: AH
authors.lastname: Eliassen
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gapstur
authors.affiliation: Cancer Epidemiology Centre Melbourne, Cancer Council Victoria, Carlton South, Melbourne, 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: Department of Epidemiology Biostatistics, School of Public Health, Imperial College, South Kensington Campus, London, SW7 2AZ, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Gunter
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Haiman
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Amit D
authors.initials: AD
authors.lastname: Joshi
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
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: Divisions of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
authors.forename: I-Min
authors.initials: IM
authors.lastname: Lee
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA.
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Cancer Epidemiology Centre Melbourne, Cancer Council Victoria, Carlton South, Melbourne, 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: Roger L
authors.initials: RL
authors.lastname: Milne
authors.affiliation: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 6 NL-3508, Stratenum, The Netherlands.|MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, South Kensington Campus, London, SW7 2AZ, UK.
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.affiliation: Department of Surgical and Perioperative Sciences, Surgery, Umeå University, 90185, Umeå, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Sund
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.|Department of Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
authors.forename: Rulla
authors.initials: R
authors.lastname: Tamimi
authors.affiliation: Hellenic Health Foundation, 13 Kaisareias and Alexandroupoleos Street, 115 27, Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, 9037, Tromsø, Norway.|Department of Research, Cancer Registry of Norway, Fridtjof Nansens vei 19, 0304, Oslo, Norway.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels Väg 12A, 17177, Stockholm, Sweden.|Samfundet Folkhälsan, Topeliusgatan 20, 00250, Helsinki, Finland.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Xiaohong R
authors.initials: XR
authors.lastname: Yang
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Ross L
authors.initials: RL
authors.lastname: Prentice
authors.affiliation: Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA.
authors.forename: Heather Spencer
authors.initials: HS
authors.lastname: Feigelson
authors.affiliation: Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D004198:Disease Susceptibility; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D020249:Hormone Replacement Therapy; D006801:Humans; D008297:Male; D008593:Menopause / Q000187:drug effects / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
keywords: Breast cancer; Genetic variation; Menopausal hormone therapy