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dc.contributor.authorChan, Carmen
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date2016-09-06 14:14:09.203en
dc.date.accessioned2016-09-06T19:04:57Z
dc.date.issued2016-09-06
dc.identifier.urihttp://hdl.handle.net/1974/14838
dc.descriptionThesis (Master, Community Health & Epidemiology) -- Queen's University, 2016-09-06 14:14:09.203en
dc.description.abstractBackground: Mechanisms underlying the effect of estrogen exposure on breast cancer risk remain unclear. Insulin-like growth factor-1 (IGF-1) levels have been positively associated with breast cancer and are a potential mechanism. Objectives: The objectives of this thesis are: 1) to explore whether the reproductive risk factors and the lifetime cumulative number of menstrual cycles (LCMC), as measures for long-term estrogen exposure, are associated with IGF-1 levels, and 2) to examine the effect of an aromatase inhibitor (AI) on IGF-1 levels, and the potential interaction with BMI. Methods: A cross sectional study and a randomized controlled trial nested with the MAP.3 chemoprevention trial were used to address objective 1 and 2, respectively. 567 postmenopausal women were selected. Anthropometric measurements, lifestyle factors, reproductive characteristics and serum IGF-1 concentrations were collected at baseline and one year. Objective 1. The LCMC was computed as a composite measure of the reproductive characteristics. Multivariable linear regression models were used to assess the association between IGF-1 levels and LCMC and the hormonal risk factors, while adjusting for potential covariates. Objective 2. Changes in IGF-1 were compared between the exemestane and placebo, and effect modification by BMI was tested with an interaction term. Results: Objective 1. Women aged 55 years or older at menopause had 16.26 ng/mL (95% CI: 1.76, 30.75) higher IGF-1 compared to women aged less than 50 years at menopause. Women in the highest category of menstrual cycles (≥500 cycles) had an average 19.00 ng/mL (95%CI: 5.86, 32.14) higher concentration of IGF-1 compared to women in the lowest category (<350). Exogenous hormones had no effect on postmenopausal IGF-1 levels. Objective 2. Exemestane significantly increased IGF-1 levels by 18% (95% CI: 14%-22%); while, placebo had no effect on IGF-1. The changes in IGF-1 were significantly different between the treatment arms (P<0.0001) and no significant interaction was observed between treatment and BMI on IGF-1 changes (P=0.1327). Conclusion: Objective 1. Larger number of menstrual cycles and a later age at menopause are positively associated with IGF-1. IGF-1 may be one mechanism by which prolonged estrogen exposure increases cancer risk. Objective 2. We conclude that the reduced cancer risk observed with AI therapy likely occurs in an IGF-1 independent mechanism. Further studies exploring the clinical consequences of increased IGF-1 on AI therapy are needed.en_US
dc.languageenen
dc.language.isoenen_US
dc.relation.ispartofseriesCanadian thesesen
dc.rightsQueen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canadaen
dc.rightsProQuest PhD and Master's Theses International Dissemination Agreementen
dc.rightsIntellectual Property Guidelines at Queen's Universityen
dc.rightsCopying and Preserving Your Thesisen
dc.rightsCreative Commons - Attribution - CC BYen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectestrogenen_US
dc.subjectinsulin-like growth factor-1en_US
dc.subjectBreast canceren_US
dc.subjectchemopreventionen_US
dc.subjectexemestaneen_US
dc.subjectreproductive risk factorsen_US
dc.titleHormonal factors and insulin-like growth factor-1 in North American postmenopausal womenen_US
dc.typethesisen_US
dc.description.restricted-thesisManuscripts in preparation for publication in peer-reviewed journalen
dc.description.degreeMasteren
dc.contributor.supervisorKing, Will D.en
dc.contributor.supervisorRichardson, Harrieten
dc.contributor.departmentCommunity Health and Epidemiologyen
dc.embargo.terms1825en
dc.embargo.liftdate2021-09-05


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