The California Teachers Study (CTS) is a prospective cohort of 133,479 women. The cohort was initiated in the fall of 1995 and participants were all current and former public school teachers or administrators that belonged to the California State Teachers Retirement System (STRS). Each member joined the cohort when she completed the study baseline questionnaire assessing information on known breast cancer risk factors in addition to background, dietary, physical, reproductive, personal health, and family health histories. Members meeting residency requirements and giving consent were followed and incident invasive breast cancer diagnoses were identified through annual linkages with the California Cancer Registry (CCR). ❧ This dissertation evaluates the role of postmenopausal hormone therapy as well as genetic variation in hormone-related genes for their respective and combined role in breast cancer risk in the CTS. ❧ Chapter 1, entitled “Menopausal hormone therapy and subsequent risk of specific invasive breast cancer subtypes in the California Teachers Study” is the study of use, recency, duration, and formulation of hormone therapy in its relation to breast cancer risk. An abstract was published in the conference proceedings and a poster was accepted as part of the 2009 American Association for Cancer Research (AACR) Annual Meeting, Denver, Colorado. The complete manuscript is published in Cancer Epidemiology, Biomarkers & Prevention (Cancer Epidemiol Biomarkers Prev. 2010 Sep;19(9):2366-78. Epub 2010 Aug 10.). ❧ Chapter 2, entitled “Hormone-related genes, body mass index, menopausal hormone therapy, and breast cancer risk in the California Teachers Study,” examines the risk of breast cancer associated with common variation in five candidate hormone binding genes. Additionally, it evaluates how variation in these genes interacts with body mass index and menopausal hormone therapy in determining risk of invasive breast cancer. This analysis was completed in a nested case-control study in the CTS. Overall as well as breast cancer subtype specific results are presented for single nucleotide polymorphisms (SNPs) in AR, ESR1, ESR2, PGR, and SHBG. The manuscript is currently under review by the CTS Steering Committee. ❧ Chapter 3, entitled “Genetic Variation in Hormone Metabolism Pathway Genes, Reproductive-Related Factors, and Breast Cancer Risk in the California Teachers Study,” is another analysis in the CTS nested case-control study. It analyses 452 SNPs in 29 candidate genes in the hormone metabolism pathway for an interaction with reproductive breast cancer risk factors. Age at menarche, parity, age at first full-term pregnancy and age at natural menopause are analyzed for interaction with these common SNPs separately for all invasive breast cancer as well as ER+/PR+ invasive breast tumors.
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