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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA077398-13
Application #
8152197
Study Section
Special Emphasis Panel (ZRG1-PSE-D (03))
Program Officer
Su, Joseph
Project Start
1998-09-25
Project End
2015-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
13
Fiscal Year
2011
Total Cost
$2,524,331
Indirect Cost
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
O'Mara, Tracy A; Glubb, Dylan M; Amant, Frederic et al. (2018) Identification of nine new susceptibility loci for endometrial cancer. Nat Commun 9:3166
Lee, Eunjung; Luo, Jianning; Schumacher, Fredrick R et al. (2018) Growth factor genes and change in mammographic density after stopping combined hormone therapy in the California Teachers Study. BMC Cancer 18:1072
Hurley, Susan; Hertz, Andrew; Nelson, David O et al. (2017) Tracing a Path to the Past: Exploring the Use of Commercial Credit Reporting Data to Construct Residential Histories for Epidemiologic Studies of Environmental Exposures. Am J Epidemiol 185:238-246
Powers, Scott; McGuire, Valerie; Bernstein, Leslie et al. (2017) Evaluating disease prediction models using a cohort whose covariate distribution differs from that of the target population. Stat Methods Med Res :962280217723945
Nichols, Hazel B; Schoemaker, Minouk J; Wright, Lauren B et al. (2017) The Premenopausal Breast Cancer Collaboration: A Pooling Project of Studies Participating in the National Cancer Institute Cohort Consortium. Cancer Epidemiol Biomarkers Prev 26:1360-1369
Michailidou, Kyriaki (see original citation for additional authors) (2017) Association analysis identifies 65 new breast cancer risk loci. Nature 551:92-94
Arentsen, Luke; Hansen, Karen E; Yagi, Masashi et al. (2017) Use of dual-energy computed tomography to measure skeletal-wide marrow composition and cancellous bone mineral density. J Bone Miner Metab 35:428-436
Hurley, Susan; Goldberg, Debbie; Nelson, David O et al. (2017) Temporal Evaluation of Polybrominated Diphenyl Ether (PBDE) Serum Levels in Middle-Aged and Older California Women, 2011-2015. Environ Sci Technol 51:4697-4704
Clarke, Christina A; Canchola, Alison J; Moy, Lisa M et al. (2017) Regular and low-dose aspirin, other non-steroidal anti-inflammatory medications and prospective risk of HER2-defined breast cancer: the California Teachers Study. Breast Cancer Res 19:52
Milne, Roger L (see original citation for additional authors) (2017) Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet 49:1767-1778

Showing the most recent 10 out of 214 publications