Division of Cancer Research and Training, Center to Eliminate Cancer Health Disparities, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA.
PLoS One. 2013;8(3):e57967. doi: 10.1371/journal.pone.0057967. Epub 2013 Mar 12.
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.
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.
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.
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.
维生素 D 在癌症发展中发挥作用，并通过维生素 D 受体 (VDR) 发挥作用。尽管非裔美国人的血清维生素 D 水平最低，但关于非裔美国人和西班牙裔人群中 VDR 基因多态性与乳腺癌的信息却很少。本研究探讨了 VDR 基因多态性是否与这些人群中的乳腺癌相关。
从 232 名乳腺癌患者（病例）和 349 名非癌症患者（对照）中采集血液。使用 PCR-RFLP 方法对 VDR 的四个多态性变体（FokI、BsmI、TaqI 和 ApaI）进行基因分型。
在非裔美国人中，VDR-Fok1 f 等位基因与乳腺癌的相关性增加（OR=1.9，p=0.07）。此外，FbTA、FbtA 和 fbtA 单倍型与非裔美国人的乳腺癌相关（p<0.05）。拉丁裔更有可能具有 VDR-ApaI 等位基因（Aa 或 aa）（p=0.008）。VDR-ApaI aa 基因型与非裔美国人中分化不良的乳腺癌肿瘤显著相关（p=0.04）。联合病例的 Kaplan-Meier 生存分析显示，VDR-Fok1 FF 基因型的乳腺癌患者 5 年无病生存率（DFS）降低（p<0.05）。Cox 回归多因素分析显示，VDR-FokI 多态性对 DFS 有独立的预测价值。VDR 的其他三个变体（BsmI、TaqI 和 ApaI）与疾病结局无关。
VDR 单倍型与非裔美国人的乳腺癌相关，但与西班牙裔/拉丁裔无关。VDR-FokI FF 基因型与非裔美国乳腺癌女性的预后不良相关。
