Major shifts in three cancer risk factors over the past decade are changing the profile of women's cancer risks. The California Teachers Study (CTS), a prospective cohort study that has actively followed 133,479 female California public school professionals for incidence of cancer and other outcomes since 1995, is ideally poised to evaluate how the societal transitions of decreasing physical activity, increasing obesity, and increasing aspirin use affect risk of breast and other cancers. The CTS is a unique repository of exposure data over the life course on these important, modifiable cancer risk factors. Our three aims address associations between these shifting exposures and risk for breast cancer overall;breast cancer subtypes defined by hormone receptor status, HER-2 status, histology and stage;and other cancers, with subtypes defined by tumor location or histology. For breast cancer, gene-environment interactions will be assessed by genotyping single nucleotide polymorphisms (SNPs) in genes in key mechanistic pathways (particularly in inflammation, immune function, and insulin resistance pathways), as well as highly significant, replicated SNPs from genome-wide association studies.
In Aim 1, we seek to understand better how physical activity reduces breast cancer risk, investigating whether variation in genes involved in fitness or athletic ability interacts with physical activity patterns defined by age and recency, and whether any associations with physical activity are modified by other environmental or genetic risk factors. We also examine how lifelong and changing patterns of body fat and obesity (Aim 2) and aspirin use (Aim 3), over a woman's lifespan influence women's breast, endometrial, ovarian or colon cancer risk overall and by subtype, investigating effect modification, and, for breast cancer, gene-environment interactions. To accomplish these aims, we will continue our current follow-up for cancer and other outcomes, which link to databases that capture 100% of these endpoints among California residents. We will collect and update time-dependent exposure data to broaden our existing information on key exposures from teenage years to old age. We will expand blood collection among breast cancer cases and controls, employing new collection approaches to ensure high participation and forging new scientific collaborations to fully utilize this biospecimen resource. We will continue analyzing key etiologic predictors of cancer using statistical approaches that account for missing data and secular changes in exposures and incorporate high-dimensional genetic data into existing models. Public Health Relevance: Successful completion of these aims, following a decade of profound transition in physical activity, obesity, and aspirin use, will permit evaluation of the population impact of these changes on women's cancer incidence, and provide insight into the interplay of genes and exposures for breast cancer. This application focuses on the etiology of major women's cancers and emphasizes common, modifiable, behavioral risk factors in ways that can facilitate future population-wide cancer prevention efforts.

Public Health Relevance

The California Teachers Study spans more than a decade of profound transitions in women's health behaviors, including increasing physical inactivity, obesity, and aspirin use. By examining how these common, modifiable risk factors interact with other environmental and genetic risk factors to influence development of breast and other cancers in women, this study will provide critical new knowledge that can serve as the basis for behavioral public health interventions that benefit women on a population-wide scale.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-PSE-D (03))
Program Officer
Su, Joseph
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
City of Hope/Beckman Research Institute
United States
Zip Code
Vigen, Cheryl; Kwan, Marilyn L; John, Esther M et al. (2016) Validation of self-reported comorbidity status of breast cancer patients with medical records: the California Breast Cancer Survivorship Consortium (CBCSC). Cancer Causes Control 27:391-401
(2016) No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. Gynecol Oncol 141:386-401
Sposto, Richard; Keegan, Theresa H M; Vigen, Cheryl et al. (2016) The Effect of Patient and Contextual Characteristics on Racial/Ethnic Disparity in Breast Cancer Mortality. Cancer Epidemiol Biomarkers Prev 25:1064-72
(2016) Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus. Breast Cancer Res 18:64
(2016) Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170. Nat Genet 48:374-86
Wang, Sophia S; Deapen, Dennis; Voutsinas, Jenna et al. (2016) Breast implants and anaplastic large cell lymphomas among females in the California Teachers Study cohort. Br J Haematol 174:480-3
Costas, Laura; Lambert, Brice H; Birmann, Brenda M et al. (2016) A Pooled Analysis of Reproductive Factors, Exogenous Hormone Use, and Risk of Multiple Myeloma among Women in the International Multiple Myeloma Consortium. Cancer Epidemiol Biomarkers Prev 25:217-21
Zhao, Zhiguo; Wen, Wanqing; Michailidou, Kyriaki et al. (2016) Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry. Cancer Causes Control 27:679-93
Liu, Ruiling; Nelson, David O; Hurley, Susan et al. (2016) Association between Serum Polybrominated Diphenyl Ether Levels and Residential Proximity to Solid-Waste Facilities. Environ Sci Technol 50:3945-53
McGuire, Valerie; Hartge, Patricia; Liao, Linda M et al. (2016) Parity and Oral Contraceptive Use in Relation to Ovarian Cancer Risk in Older Women. Cancer Epidemiol Biomarkers Prev 25:1059-63

Showing the most recent 10 out of 198 publications