Polymorphisms in the vitamin D receptor and risk of ovarian cancer in four studies.
Polymorphisms in the vitamin D receptor and risk of ovarian cancer in four studies.
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DOI：
10.1158/0008-5472.can-08-3515
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发表时间：
2009-03-01
期刊：
影响因子：
11.2
通讯作者：
Hankinson SE
中科院分区：
文献类型：
--
作者：
Tworoger SS;Gates MA;Lee IM;Buring JE;Titus-Ernstoff L;Cramer D;Hankinson SE
先前的研究表明，维生素D可以降低卵巢癌的风险。因此，我们在回顾性病例对照研究（新英格兰病例对照研究，NECC）和三项前瞻性队列研究（护士健康研究（NHS），NHSII和妇女健康研究（WHS））的嵌套病例对照研究中，研究了维生素D受体（VDR）基因（Fok 1，Bsm 1，Cdx 2）中的三种单核苷酸多态性（SNP）是否与上皮性卵巢癌的风险相关。将队列研究的数据合并，并使用条件logistic回归进行分析，并与NECC的结果合并，使用随机效应模型，使用非条件logistic回归进行分析。我们获得了1,473例病例和2,006例对照的基因型数据。我们在汇总分析中观察到Fok 1 f等位基因数量与卵巢癌风险之间存在显著正相关（p趋势=0.03）。ff与FF基因型的比值比（OR）为1.26（95%置信区间（CI）=1.01-1.57）。Bsm 1（p趋势=0.96）或Cdx 2（p趋势=0.13）SNP与卵巢癌风险均无显著相关性。在前瞻性研究中，血浆维生素D水平对卵巢癌的风险没有明显的基因型差异。例如，在Fok 1 FF基因型女性中，血浆25-羟基维生素D ≥32 ng/mL与<32 ng/mL的OR为0.66（95%CI=0.34-1.28），在Ff或ff基因型女性中，OR为0.71（95%CI=0.43-1.18）。我们与Fok 1 VDR多态性相关的结果进一步支持维生素D通路在卵巢癌发生中的作用。
Prior studies have suggested that vitamin D may reduce ovarian cancer risk. Thus, we examined whether three single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene (Fok1, Bsm1, Cdx2) were associated with risk of epithelial ovarian cancer in a retrospective case-control study (New England Case-Control study, NECC) and a nested-case control study of three prospective cohort studies: the Nurses’ Health Study (NHS), NHSII, and the Women’s Health Study (WHS). Data from the cohort studies were combined and analyzed using conditional logistic regression and pooled with the results from the NECC, which were analyzed using unconditional logistic regression, using a random effects model. We obtained genotype data for 1,473 cases and 2,006 controls. We observed a significant positive association between the number of Fok1 f alleles and ovarian cancer risk in the pooled analysis (p-trend=0.03). The odds ratio (OR) for the ff versus FF genotype was 1.26 (95% confidence interval (CI)=1.01-1.57). Neither the Bsm1 (p-trend=0.96) or Cdx2 (p-trend=0.13) SNPs were significantly associated with ovarian cancer risk. Among the prospective studies, the risk of ovarian cancer by plasma vitamin D levels did not clearly vary by any of the genotypes. For example among women with the Fok1 FF genotype, the OR comparing plasma 25-hydroxyvitamin D ≥32 ng/mL versus <32 ng/mL was 0.66 (95%CI=0.34-1.28), and among women with the Ff or ff genotype the OR was 0.71 (95%CI=0.43-1.18). Our results of an association with the Fok1 VDR polymorphism further support a role of the vitamin D pathway in ovarian carcinogenesis.