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Int J Cancer. 2016 May 1;138(9):2118-26. doi: 10.1002/ijc.29954. Epub 2015 Dec 28.

Genetic variations in vitamin D-related pathways and breast cancer risk in African American women in the AMBER consortium.

Author information

1
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY.
2
Slone Epidemiology Center at Boston University, Boston, MA.
3
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY.
4
Department of Biostatistics, Boston University School of Public Health, Boston, MA.
5
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
6
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY.
7
Inova Schar Cancer Institute, Falls Church, VA.
8
Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA.

Abstract

Studies of genetic variations in vitamin D-related pathways and breast cancer risk have been conducted mostly in populations of European ancestry, and only sparsely in African Americans (AA), who are known for a high prevalence of vitamin D deficiency. We analyzed 24,445 germline variants in 63 genes from vitamin D-related pathways in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium, including 3,663 breast cancer cases and 4,687 controls. Odds ratios (OR) were derived from logistic regression models for overall breast cancer, by estrogen receptor (ER) status (1,983 ER positive and 1,098 ER negative), and for case-only analyses of ER status. None of the three vitamin D-related pathways were associated with breast cancer risk overall or by ER status. Gene-level analyses identified associations with risk for several genes at a nominal p ≤ 0.05, particularly for ER- breast cancer, including rs4647707 in DDB2. In case-only analyses, vitamin D metabolism and signaling pathways were associated with ER- cancer (pathway-level p = 0.02), driven by a single gene CASR (gene-level p = 0.001). The top SNP in CASR was rs112594756 (p = 7 × 10(-5), gene-wide corrected p = 0.01), followed by a second signal from a nearby SNP rs6799828 (p = 1 × 10(-4), corrected p = 0.03). In summary, several variants in vitamin D pathways were associated with breast cancer risk in AA women. In addition, CASR may be related to tumor ER status, supporting a role of vitamin D or calcium in modifying breast cancer phenotypes.

KEYWORDS:

African American; breast cancer; estrogen receptor; genetic variation; vitamin D

PMID:
26650177
PMCID:
PMC5087916
DOI:
10.1002/ijc.29954
[Indexed for MEDLINE]
Free PMC Article

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