Abbas Sascha, Nieters Alexandra, Linseisen Jakob, Slanger Tracy, Kropp Silke, Mutschelknauss Elke Jonny, Flesch-Janys Dieter, Chang-Claude Jenny
Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld, 69120 Heidelberg, Germany.
Breast Cancer Res. 2008;10(2):R31. doi: 10.1186/bcr1994. Epub 2008 Apr 17.
Vitamin D receptor (VDR) genotypes may influence breast cancer risk by altering potential anticarcinogenic effects of vitamin D, but epidemiological studies have been inconsistent. Effect modification by serum 25-hydroxyvitamin D (25 [OH]D), the biomarker for vitamin D status in humans, has rarely been examined.
We assessed the effects of two frequently analyzed polymorphisms (FokI and TaqI) and two potentially functional variants (VDR-5132 and Cdx2) in the VDR gene, which thus far have not been analyzed with respect to breast cancer risk, on postmenopausal breast cancer risk in a population-based, case-control study including 1,408 patients (cases) and 2,612 control individuals (controls) matched for year of birth. Odds ratios (ORs) for breast cancer adjusted for potential confounders were calculated for genotypes and estimated haplotypes.
No differences in serum 25(OD)D concentrations by VDR genotype were observed. None of the analyzed polymorphisms was associated with overall risk for postmenopausal breast cancer. However, the TaqI polymorphism was associated with a significantly increased risk for oestrogen receptor positive tumours (OR = 1.18, 95% confidence interval [CI] = 1.00 to 1.38, comparing t allele carriers with noncarriers) but not for oestrogen receptor negative tumours (OR = 0.88, 95% CI = 0.69 to 1.13; P for interaction = 0.04). Haplotype analysis revealed the haplotype FtCA (FokI F, TaqI t, VDR-5132 C, Cdx2 A), which contains the TaqI t allele, to be associated with a significantly greater breast cancer risk as compared with the most frequent haplotype FTCG (OR = 1.43, 95% CI = 1.00 to 2.05). No significant interaction between VDR genotypes or haplotypes and 25(OH)D was observed.
Our results support potential effects of VDR polymorphisms on postmenopausal breast cancer risk and possible differential effects of receptor status of the tumour. However, further studies focusing on the influence of polymorphisms and haplotypes on VDR functionality, activity and concentration are needed.
维生素D受体（VDR）基因型可能通过改变维生素D潜在的抗癌作用来影响乳腺癌风险，但流行病学研究结果并不一致。作为人体维生素D状态生物标志物的血清25-羟基维生素D（25[OH]D）的效应修饰作用很少被研究。
在一项基于人群的病例对照研究中，我们评估了VDR基因中两个经常分析的多态性（FokI和TaqI）以及两个潜在的功能性变体（VDR-5132和Cdx2）对绝经后乳腺癌风险的影响，这些多态性和变体到目前为止尚未针对乳腺癌风险进行分析。该研究纳入了1408例患者（病例组）和2612名对照个体（对照组），两组按出生年份进行匹配。计算了根据潜在混杂因素调整后的乳腺癌优势比（OR），用于分析基因型和估计单倍型。
未观察到VDR基因型与血清25(OD)D浓度之间存在差异。所分析的多态性均与绝经后乳腺癌的总体风险无关。然而，TaqI多态性与雌激素受体阳性肿瘤的风险显著增加相关（OR = 1.18，95%置信区间[CI] = 1.00至1.38，t等位基因携带者与非携带者相比），但与雌激素受体阴性肿瘤无关（OR = 0.88，95%CI = 0.69至1.13；交互作用P值 = 0.04）。单倍型分析显示，包含TaqI t等位基因的单倍型FtCA（FokI F、TaqI t、VDR-5132 C、Cdx2 A）与最常见的单倍型FTCG相比，乳腺癌风险显著更高（OR = 1.43，95%CI = 1.00至2.05）。未观察到VDR基因型或单倍型与25(OH)D之间存在显著交互作用。
我们的结果支持VDR多态性对绝经后乳腺癌风险的潜在影响以及肿瘤受体状态可能存在的差异效应。然而，需要进一步研究多态性和单倍型对VDR功能、活性和浓度的影响。
