We propose to discover novel markers of genetic susceptibility for breast cancer using the combined resources of four large on-going epidemiologic studies of African American women. Our collaboration includes the Carolina Breast Cancer Study, Women's Circle of Health Study, Black Women's Health Study, and the Multiethnic Cohort. DNA samples from a total of 5534 African American cases and 5534 controls will be available for analysis, along with in-person interview data and tumor blocks from cases. Three avenues of investigation are proposed: (1) Dense genotyping and fine-mapping of loci identified in previous genome-wide association studies (GWAS) of breast cancer and related candidate genes, with a particular focus on fine-mapping of loci relevant to African American women. Included in the fine-mapping is a unique locus on chromosome 5q31 we recently identified in a GWAS of African American women;(2) Discovery of potential functional alleles using targeted DNA resequencing and gene expression-based approaches;(3) Statistical analyses aimed at identifying genetic risk factors for subgroups of breast cancer cases defined by early age at onset and tumor biology (ER status and intrinsic subtypes: basal-like, luminal A, luminal B, HER2+/ER-). The combined resources of four epidemiologic studies will facilitate identification of at-risk alleles and haplotypes, permit rapid replication of findings, and produce more precise estimates of effect for breast cancer subgroups. Genotyping and other laboratory studies will be conducted in cooperation with the Biospecimen Core, recruitment and enrollment of additional study participants will be undertaken by the Data Collection Core, and statistical analyses will be conducted in cooperation with the Biostatistics and Data Management Core. Genotype data from Project 1 will be used in conjunction with Projects 2, 3 and 4 to develop complex models for breast cancer susceptibility that incorporate genetic markers, modifiable environmental risk factors, and breast cancer tumor subtypes as distinct disease outcomes.
The lack of major findings regarding genetic variants that may increase risk of breast cancer, particularly in AA women, is likely due to lack of consideration for different types of breast cancer. By identifying breast cancer subtypes, this Project will be able to determine genes that increase risk of aggressive, early onset breast cancer in AA women. Results will help to understand the causes of aggressive breast cancer in AA women, and women with combinations of high-risk genotypes can be targeted for prevention.
|Chandran, Urmila; McCann, Susan E; Zirpoli, Gary et al. (2014) Intake of energy-dense foods, fast foods, sugary drinks, and breast cancer risk in African American and European American women. Nutr Cancer 66:1187-99|
|Robinson, Whitney R; Tse, Chiu Kit; Olshan, Andrew F et al. (2014) Body size across the life course and risk of premenopausal and postmenopausal breast cancer in Black women, the Carolina Breast Cancer Study, 1993-2001. Cancer Causes Control 25:1101-17|
|Chandwani, Sheenu; George, Prethibha A; Azu, Michelle et al. (2014) Role of preoperative magnetic resonance imaging in the surgical management of early-stage breast cancer. Ann Surg Oncol 21:3473-80|
|Quan, Lei; Gong, Zhihong; Yao, Song et al. (2014) Cytokine and cytokine receptor genes of the adaptive immune response are differentially associated with breast cancer risk in American women of African and European ancestry. Int J Cancer 134:1408-21|
|Ambrosone, Christine B; Zirpoli, Gary R; Bovbjerg, Dana Howard et al. (2014) Associations between estrogen receptor-negative breast cancer and timing of reproductive events differ between African American and European American women. Cancer Epidemiol Biomarkers Prev 23:1115-20|
|Ambrosone, Christine B; Zirpoli, Gary; Ruszczyk, Melanie et al. (2014) Parity and breastfeeding among African-American women: differential effects on breast cancer risk by estrogen receptor status in the Women's Circle of Health Study. Cancer Causes Control 25:259-65|
|Palmer, Julie R; Ambrosone, Christine B; Olshan, Andrew F (2014) A collaborative study of the etiology of breast cancer subtypes in African American women: the AMBER consortium. Cancer Causes Control 25:309-19|
|Quan, Lei; Hong, Chi-Chen; Zirpoli, Gary et al. (2014) Variants of estrogen-related genes and breast cancer risk in European and African American women. Endocr Relat Cancer 21:853-64|
|Gong, Zhihong; Ambrosone, Christine B; McCann, Susan E et al. (2014) Associations of dietary folate, Vitamins B6 and B12 and methionine intake with risk of breast cancer among African American and European American women. Int J Cancer 134:1422-35|
|Palmer, Julie R; Viscidi, Emma; Troester, Melissa A et al. (2014) Parity, lactation, and breast cancer subtypes in African American women: results from the AMBER Consortium. J Natl Cancer Inst 106:|
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