McKay James D, McCullough Marjorie L, Ziegler Regina G, Kraft Peter, Saltzman Barbara S, Riboli Elio, Barricarte Aurelio, Berg Christine D, Bergland Goran, Bingham Sheila, Brustad Magritt, Bueno-de-Mesquita H Bas, Burdette Laurie, Buring Julie, Calle Eugenia E, Chanock Stephen J, Clavel-Chapelon Françoise, Cox David G, Dossus Laure, Feigelson Heather Spencer, Haiman Christopher A, Hankinson Susan E, Hoover Robert N, Hunter David J, Husing Anika, Kaaks Rudolph, Kolonel Laurence N, Le Marchand Loic, Linseisen Jakob, McCarty Catherine A, Overvad Kim, Panico Salvatore, Purdue Mark P, Stram Daniel O, Stevens Victoria L, Trichopoulos Dimitrios, Willett Walter C, Yuenger Jeffrey, Thun Michael J
IARC, Lyon, France.
Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):297-305. doi: 10.1158/1055-9965.EPI-08-0539.
Vitamin D is hypothesized to lower the risk of breast cancer by inhibiting cell proliferation via the nuclear vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs1544410 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR, and reduced risk has been reported for the BsmI BB genotype, a SNP in strong linkage disequilibrium with a 3'-untranslated region, which may influence VDR mRNA stability.
We pooled data from 6 prospective studies in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium to examine associations between these SNPs and breast cancer among >6,300 cases and 8,100 controls for each SNP using conditional logistic regression.
The odds ratio (OR) for the rs2228570 (FokI) ff versus FF genotype in the overall population was statistically significantly elevated [OR, 1.16; 95% confidence interval (95% CI), 1.04-1.28] but was weaker once data from the cohort with previously published positive findings were removed (OR, 1.10; 95% CI, 0.98-1.24). No association was noted between rs1544410 (BsmI) BB and breast cancer risk overall (OR, 0.98; 95% CI, 0.89-1.09), but the BB genotype was associated with a significantly lower risk of advanced breast cancer (OR, 0.74; 95% CI, 0.60-0.92).
Although the evidence for independent contributions of these variants to breast cancer susceptibility remains equivocal, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status.
维生素D被认为可通过核维生素D受体（VDR）抑制细胞增殖，从而降低患乳腺癌的风险。VDR基因中的两种常见单核苷酸多态性（SNP），即rs1544410（BsmI）和rs2228570（FokI），与乳腺癌风险的关联并不一致。据报道，编码转录活性较低的VDR异构体的FokI ff基因型会增加风险，而与3'非翻译区处于强连锁不平衡状态的SNP即BsmI BB基因型与风险降低有关，该SNP可能影响VDR mRNA的稳定性。
我们汇总了美国国立癌症研究所乳腺癌和前列腺癌队列联盟6项前瞻性研究的数据，以使用条件逻辑回归分析这两种SNP与6300多例病例和8100例对照中每种SNP的乳腺癌之间的关联。
总体人群中，rs2228570（FokI）ff基因型与FF基因型相比，优势比（OR）在统计学上显著升高[OR，1.16；95%置信区间（95%CI），1.04 - 1.28]，但去除先前发表有阳性结果队列的数据后，该关联变弱（OR，1.10；95%CI，0.98 - 1.24）。总体而言，未发现rs1544410（BsmI）BB与乳腺癌风险之间存在关联（OR，0.98；95%CI，0.89 - 1.09），但BB基因型与晚期乳腺癌风险显著降低有关（OR，0.74；95%CI，0.60 - 0.92）。
尽管这些变体对乳腺癌易感性的独立贡献证据仍不明确，但未来的大型研究应将VDR基因变异与维生素D状态生物标志物结合起来。
