The incidence rates of breast cancer vary more than two-fold between Hispanic and non-Hispanic white (NHW) women;Hispanic women have worse survival after diagnosis than NHW women. We propose to evaluate these health disparities in breast cancer development and surival along the continuation of American Indian to NHW women utilizing existing resources from the 4 Corner's States, California, and Mexico City. Existing resources utilized will be behorial and social lifestyle exposure data along with DNA obtained at the time of interview. Survival data has been ongoing and will continue to be monitored via local SEER and CDC tumor registries. Genetic and lifestyle data are available from approximately 8039 Hispanic and NHW cases of breast cancer and population-based controls. By pooling resources from three studies, we will efficiently examine a biological pathway that we believe is important to breast cancer development and survival and that influences differences in breast cancer rates among Hispanic and NHW women. Evaluation of genetic factors will focus on a pathway that appears to work in conjunction with insulin-, estrogen-, and inflammation-related pathways and represents a point of convergence. This pathway, which we call the Convergence of Hormones, Inflammation, and Energy Functioning (CHIEF) Signaling Pathway has not been studied comprehensively in either Hispanic or non-Hispanic white women and will include enes to be studied include SOC1, SOC2, AKT, FRAP1(alias mTOR), P13K, STK11, AMP, PTEN, VEGF, &S6K1,S6K2, CRP, NFKB, IKB, IL10, IL8, IL6, TNFalpha using an Illumina platform. Breast cancer associations will be tested between genetic polymorphisms and haplotypes of these genes in Hispanic and NHW women and by proportion of American Indian ancestry. Interaction of signaling pathway genes with each other and with NSAIDs, aspirin, BMI, estrogen, and physical activity will be examined. These genetic factors will be evaluated with survival to determine their contribution to survival differences observed for Hispanic and NHW women.

Public Health Relevance

Slattery, Martha L Relevance: This study will advance our understanding of breast cancer etiology in Hispanic and American Indian women as well as women overall. The contrast between high and low risk populations will enhance this effort in a cost-efficient manner. Results could identify potential targets for drug therapy. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA140002-06
Application #
8540349
Study Section
Special Emphasis Panel (ZRG1-RPHB-K (50))
Program Officer
Zanetti, Krista A
Project Start
2009-09-25
Project End
2015-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
6
Fiscal Year
2013
Total Cost
$559,897
Indirect Cost
$158,291
Name
University of Utah
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Connor, Avonne E; Baumgartner, Richard N; Baumgartner, Kathy B et al. (2015) Associations between ALOX, COX, and CRP polymorphisms and breast cancer among Hispanic and non-Hispanic white women: The breast cancer health disparities study. Mol Carcinog 54:1541-53
John, Esther M; Sangaramoorthy, Meera; Hines, Lisa M et al. (2015) Overall and abdominal adiposity and premenopausal breast cancer risk among hispanic women: the breast cancer health disparities study. Cancer Epidemiol Biomarkers Prev 24:138-47
Slattery, Martha L; John, Esther M; Torres-Mejia, Gabriela et al. (2014) Angiogenesis genes, dietary oxidative balance and breast cancer risk and progression: the Breast Cancer Health Disparities Study. Int J Cancer 134:629-44
Wang, Wei; Ingles, Sue Ann; Torres-Mejía, Gabriela et al. (2014) Genetic variants and non-genetic factors predict circulating vitamin D levels in Hispanic and non-Hispanic White women: the Breast Cancer Health Disparities Study. Int J Mol Epidemiol Genet 5:31-46
Slattery, Martha L; Lundgreen, Abbie; Stern, Marianna C et al. (2014) The influence of genetic ancestry and ethnicity on breast cancer survival associated with genetic variation in the TGF-*-signaling pathway: The Breast Cancer Health Disparities Study. Cancer Causes Control 25:293-307
Slattery, Martha L; Hines, Lisa H; Lundgreen, Abbie et al. (2014) Diet and lifestyle factors interact with MAPK genes to influence survival: the Breast Cancer Health Disparities Study. Cancer Causes Control 25:1211-25
Slattery, Martha L; Lundgreen, Abbie; Torres-Mejia, Gabriela et al. (2014) Diet and lifestyle factors modify immune/inflammation response genes to alter breast cancer risk and prognosis: the Breast Cancer Health Disparities Study. Mutat Res 770:19-28
Slattery, Martha L; Herrick, Jennifer S; Torres-Mejia, Gabriella et al. (2014) Genetic variants in interleukin genes are associated with breast cancer risk and survival in a genetically admixed population: the Breast Cancer Health Disparities Study. Carcinogenesis 35:1750-9
Slattery, Martha L; Lundgreen, Abbie; Hines, Lisa M et al. (2014) Genetic variation in the JAK/STAT/SOCS signaling pathway influences breast cancer-specific mortality through interaction with cigarette smoking and use of aspirin/NSAIDs: the Breast Cancer Health Disparities Study. Breast Cancer Res Treat 147:145-58
Slattery, Martha L; John, Esther M; Stern, Mariana C et al. (2013) Associations with growth factor genes (FGF1, FGF2, PDGFB, FGFR2, NRG2, EGF, ERBB2) with breast cancer risk and survival: the Breast Cancer Health Disparities Study. Breast Cancer Res Treat 140:587-601

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