Vitamin D Receptor Gene Polymorphisms and Prognosis of Breast Cancer among African-American and Hispanic Women
PLoS ONE 8(3): e57967. doi:10.1371/journal.pone.0057967
Dhruva K. Mishra, Yanyuan Wu, Marianna Sarkissyan, Suren Sarkissyan, Zujian Chen, Xiying Shang, May Ong, David Heber, H. Phillip Koeffler, Jaydutt V. Vadgama
Background: Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). Although African-Americans have the lowest levels of serum vitamin D, there is a dearth of information on VDR gene polymorphisms and breast cancer among African-Americans and Hispanics. This study examines whether VDR gene polymorphisms are associated with breast cancer in these cohorts.
Methods: Blood was collected from 232 breast cancer patients (Cases) and 349 non-cancer subjects (Controls).
Genotyping for four polymorphic variants of VDR (FokI, BsmI, TaqI and ApaI) was performed using the PCR-RFLP method.
Results: An increased association of the VDR-Fok1 f allele with breast cancer was observed in African-Americans (OR = 1.9, p = 0.07). Furthermore, the FbTA, FbtA and fbtA haplotypes were associated with breast cancer among African-Americans (p<0.05). Latinas were more likely to have the VDR-ApaI alleles (Aa or aa) (p = 0.008). The VDR-ApaI aa genotype was significantly associated with poorly-differentiated breast tumors (p = 0.04) in combined Cases. Kaplan-Meier survival analysis showed decreased 5-year disease-free-survival (DFS) in breast cancer patients who had the VDR-Fok1 FF genotype (p<0.05). The Cox regression with multivariate analysis revealed the independent predictor value of the VDR-FokI polymorphism for DFS. The other three variants of VDR (BsmI, TaqI and ApaI) were not associated with disease outcome.
Conclusions: VDR haplotypes are associated with breast cancer in African-Americans, but not in Hispanic/Latinas.
The VDR-FokI FF genotype is linked with poor prognosis in African-American women with breast cancer.
Received: November 5, 2012; Accepted: January 29, 2013; Published: March 12, 2013
Funding: This work was supported by National Institutes of Health(NIH)/NCI (Grant numbers U56CA101599-01; CA15083-25S3; U54CA14393); NIH/NIDDK (Grant number R25DK067015-01); Department of Defense (BCRP) (Grant number BC043180) – to JVV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Note: more graphs in the PDF
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Suspect that Caucasian women with these VDR genes would need more vitamin D in blood stream to prevent breast cancer.
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