title: Polymorphisms of Insulin-Like Growth Factor 1 Pathway Genes and Breast Cancer Risk.
abstract: Genetic variants of insulin-like growth factor 1 (IGF1) pathway genes have been shown to be associated with breast density and IGF1 levels and, therefore, may also influence breast cancer risk via pro-survival signaling cascades. The aim of this study was to investigate associations between IGF1 pathway single nucleotide polymorphisms (SNPs) and breast cancer risk among European and East Asian women, and potential interactions with menopausal status and breast tumor subtype. Stratified analyses of 1,037 cases and 1,050 controls from a population-based case-control study were conducted to assess associations with breast cancer for 22 SNPs across 5 IGF1 pathway genes in European and East Asian women. Odds ratios were calculated using logistic regression in additive genetic models. Polytomous logistic regression was used to assess heterogeneity by breast tumor subtype. Two SNPs of the IGF1 gene (rs1019731 and rs12821878) were associated with breast cancer risk among European women. Four highly linked IGF1 SNPs (rs2288378, rs17727841, rs7136446, and rs7956547) were modified by menopausal status among East Asian women only and associated with postmenopausal breast cancers. The association between rs2288378 and breast cancer risk was also modified by breast tumor subtype among East Asian women. Several IGF1 polymorphisms were found to be associated with breast cancer risk and some of these associations were modified by menopausal status or breast tumor subtype. Such interactions should be considered when assessing the role of these variants in breast cancer etiology.
authors.affiliation: Department of Public Health Sciences, Cancer Research Institute, Queen's University , Kingston, ON , Canada.
authors.forename: Joy
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Public Health Sciences, Cancer Research Institute, Queen's University , Kingston, ON , Canada.
authors.forename: Kristan J
authors.initials: KJ
authors.lastname: Aronson
authors.affiliation: Individuals and Families, Alberta Cancer Prevention Legacy Fund, Alberta Health Services , Calgary, AB , Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Grundy
authors.affiliation: Department of Epidemiology and Public Health, University College London , London , UK.
authors.forename: Lindsay C
authors.initials: LC
authors.lastname: Kobayashi
authors.affiliation: Department of Environmental and Occupational Health, Drexel University , Philadelphia, PA , USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Burstyn
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency , Vancouver, BC , Canada.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Schuetz
authors.affiliation: Department of Medical Oncology, British Columbia Cancer Agency , Vancouver, BC , Canada.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Lohrisch
authors.affiliation: Department of Pathology and Molecular Medicine, Queen's University , Kingston, ON , Canada.
authors.forename: Sandip K
authors.initials: SK
authors.lastname: SenGupta
authors.affiliation: Department of Cancer Control Research, British Columbia Cancer Agency , Vancouver, BC , Canada.
authors.forename: Agnes S
authors.initials: AS
authors.lastname: Lai
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada; Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Angela
authors.initials: A
authors.lastname: Brooks-Wilson
authors.affiliation: Department of Cancer Control Research, British Columbia Cancer Agency, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
authors.forename: John J
authors.initials: JJ
authors.lastname: Spinelli
authors.affiliation: Department of Public Health Sciences, Cancer Research Institute, Queen's University , Kingston, ON , Canada.
authors.forename: Harriet
authors.initials: H
authors.lastname: Richardson
keywords: IGF; breast cancer; breast cancer subtypes; case–control; interactions; polymorphisms