Regular Multivitamin Supplement Use, Single Nucleotide Polymorphisms in ATIC, SHMT2, and SLC46A1, and Risk of Ovarian Carcinoma.
Regular Multivitamin Supplement Use, Single Nucleotide Polymorphisms in ATIC, SHMT2, and SLC46A1, and Risk of Ovarian Carcinoma.
复制标题
DOI：
10.3389/fgene.2012.00033
复制
发表时间：
2012
影响因子：
3.7
通讯作者：
Sellers TA
中科院分区：
文献类型：
--
作者：
Kelemen LE;Wang Q;Dinu I;Vierkant RA;Tsai YY;Cunningham JM;Phelan CM;Fridley BL;Amankwah EK;Iversen ES;Berchuck A;Schildkraut JM;Goode EL;Sellers TA
ATIC、SHMT2和SLC46A1在单碳（1-C）转移中起重要作用。作者在两项美国病例对照研究的高加索参与者中检查了卵巢癌与这些基因的15种变异之间的关系是否通过定期使用多种维生素（1-C供体的来源）而改变。采用阶段性研究设计，对多种维生素之间的相互作用进行了测试，并根据多种维生素补充剂的使用对变体与卵巢癌之间的关联进行了分层报道。在655例病例和920例对照（第一阶段）中，使用复合维生素改变了6个变异的每等位基因风险关联。在968例病例和1265例对照（第一和第二阶段）的更大样本中，两种变异的相互作用显著（P≤0.03），特别是在常规多种维生素使用者中：ATIC rs7586969[比值比(OR) = 0.7, 95%置信区间(CI) = 0.6-0.9]和ATIC rs16853834 （OR = 1.5, 95% CI = 1.1-2.0）。两个ATIC单核苷酸多态性（snp）不具有相同的单倍型；然而，他们组成的单倍型反映了经常服用多种维生素补充剂的人的SNP风险关联。通过比较有和没有两个ATIC变量-多种维生素相互作用项的调整模型中观察到的似然比检验统计量与由病例状态排列10,000次产生的检验统计量的零分布，还进行了多变量分析。相应的观察到的P值0.001比排列衍生的P值0.009更为极端，表明拒绝无关联的原假设。总之，几乎没有统计证据表明这15种变异与卵巢癌的风险独立相关。然而，当在SNP和基因水平上进行评估时，ATIC变异与常规多种维生素摄入的统计相互作用可能支持这些与卵巢健康和疾病过程相关的发现。
ATIC, SHMT2, and SLC46A1 have essential roles in one-carbon (1-C) transfer. The authors examined whether associations between ovarian carcinoma and 15 variants in these genes are modified by regular multivitamin use, a source of 1-C donors, among Caucasian participants from two US case–control studies. Using a phased study design, variant-by-multivitamin interactions were tested, and associations between variants and ovarian carcinoma were reported stratified by multivitamin supplement use. Per-allele risk associations were modified by multivitamin use at six variants among 655 cases and 920 controls (Phase 1). In a larger sample of 968 cases and 1,265 controls (Phases 1 and 2), interactions were significant (P ≤ 0.03) for two variants, particularly among regular multivitamin users: ATIC rs7586969 [odds ratio (OR) = 0.7, 95% confidence interval (CI) = 0.6–0.9] and ATIC rs16853834 (OR = 1.5, 95% CI = 1.1–2.0). The two ATIC single nucleotide polymorphisms (SNPs) did not share the same haplotype; however, the haplotypes they comprised mirrored their SNP risk associations among regular multivitamin supplement users. A multi-variant analysis was also performed by comparing the observed likelihood ratio test statistic from adjusted models with and without the two ATIC variant-by-multivitamin interaction terms with a null distribution of test statistics generated by permuting case status 10,000 times. The corresponding observed P value of 0.001 was more extreme than the permutation-derived P value of 0.009, suggesting rejection of the null hypothesis of no association. In summary, there is little statistical evidence that the 15 variants are independently associated with risk of ovarian carcinoma. However, the statistical interaction of ATIC variants with regular multivitamin intake, when evaluated at both the SNP and gene level, may support these findings as relevant to ovarian health and disease processes.