American women of African ancestry are more likely than European Americans to have estrogen-receptor-negative (ER-negative) breast cancer. There continues to be discussion about the role of low levels of vitamin D in the development of breast cancer for these women. New research by a team from Roswell Park Cancer Institute (RPCI) and four other institutions has shown that specific genetic variations in the vitamin D receptor (VDR) and in CYP24A1 (responsible for deactivating vitamin D) are associated with an increase in breast cancer risk — particularly for ER-negative breast cancer — for African-American women.
When a team of researchers led by RPCI's Song Yao, PhD, Research Assistant Professor of Oncology, and Christine Ambrosone, PhD, Professor of Oncology and Chair of the Department of Cancer Prevention and Control, compared levels of vitamin D in the blood of women without breast cancer, they found that severe vitamin D deficiency in African-American women was almost six times more common than in European-American women. However, because low levels of vitamin D can also be caused by disease, or by treatment, the researchers decided to focus their studies on genetic variations in VDR and the enzymes responsible for breaking down vitamin D in the body.
The results, published in BioMed Central's open-access journal Breast Cancer Research, showed that African-American women with the highest levels of vitamin D also had a specific variation in VDR. Although this variation was present in European Americans, it was not associated with alteration in their levels of vitamin D. African-American women with the specific variation associated with the higher levels of vitamin D had half the risk of breast cancer compared to women without it.
When the researchers looked in detail at the patterns of genetic variation for women with ER-negative breast cancer, they found that seven SNPs in the gene coding for CYP24A1 were associated with ER-negative breast cancer risk, and that two of these seemed to account for the higher risk of ER-negative breast cancer in African-American women.
"While it is difficult to determine the exact effect of low levels of vitamin D on the risk of developing breast cancer," said Dr. Yao, "our results show that these genetic variations, which contribute to the function of vitamin D, are strongly associated with ER-negative breast cancer and may contribute to the more aggressive breast cancer features seen in African-American women."
Co-authors included researchers from the University of Pittsburgh Cancer Institute, Mount Sinai School of Medicine, New Jersey State Cancer Registry, and The Cancer Institute of New Jersey at the Robert Wood Johnson Medical School.
Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: a case-control study. Song Yao, Gary Zirpoli, Dana H Bovbjerg, Lina Jandorf, Chi-Chen Hong, Hua Zhao, Lara E Sucheston, Li Tang, Michelle Roberts, Gregory Ciupak, Warren Davis, Helena Hwang, Candace S Johnson, Donald L Trump, Susan E McCann, Foluso Ademuyiwa, Karen S Pawlish, Elisa V Bandera and Christine B Ambrosone. Breast Cancer Research 2012, 14:R58 doi:10.1186/bcr3162
Roswell Park Cancer Institute