Section of Gastroenterology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois, United States of America.
PLoS One. 2011;6(10):e26123. doi: 10.1371/journal.pone.0026123. Epub 2011 Oct 27.
Low vitamin D levels are associated with an increased incidence of colorectal cancer (CRC) and higher mortality from the disease. In the US, African Americans (AAs) have the highest CRC incidence and mortality and the lowest levels of vitamin D. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been previously associated with CRC, but few studies have included AAs. We studied 795 AA CRC cases and 985 AA controls from Chicago and North Carolina as well as 1324 Caucasian cases and 990 Caucasian controls from Chicago and Spain. We genotyped 54 tagSNPs in VDR (46586959 to 46521297 Mb) and tested for association adjusting for West African ancestry, age, gender, and multiple testing. Untyped markers were imputed using MACH1.0. We analyzed associations by gender and anatomic location in the whole study group as well as by vitamin D intake in the North Carolina AA group. In the joint analysis, none of the SNPs tested was significantly associated with CRC. For four previously tested restriction fragment length polymorphisms, only one (referred to as ApaI), tagged by the SNP rs79628898, had a nominally significant p-value in AAs; none of these polymorphisms were associated with CRC in Caucasians. In the North Carolina AAs, for whom we had vitamin D intake data, we found a significant association between an intronic SNP rs11574041 and vitamin D intake, which is evidence for a VDR gene-environment interaction in AAs. In summary, using a systematic tagSNP approach, we have not found evidence for significant associations between VDR and CRC in AAs or Caucasians.
维生素 D 水平低与结直肠癌（CRC）发病率增加和疾病死亡率升高有关。在美国，非裔美国人（AA）的 CRC 发病率和死亡率最高，而维生素 D 水平最低。维生素 D 受体（VDR）基因中的单核苷酸多态性（SNP）先前与 CRC 相关，但很少有研究包括 AA。我们研究了来自芝加哥和北卡罗来纳州的 795 名 AA CRC 病例和 985 名 AA 对照，以及来自芝加哥和西班牙的 1324 名白种人病例和 990 名白种人对照。我们在 VDR 中对 54 个标记 SNP 进行了基因分型（46586959 至 46521297 Mb），并通过调整西非血统、年龄、性别和多重检验来检测关联。未分型的标记物使用 MACH1.0 进行了推断。我们在整个研究组中按性别和解剖位置以及在北卡罗来纳州 AA 组中按维生素 D 摄入量分析了关联。在联合分析中，测试的 SNP 均与 CRC 无显著关联。对于四个先前测试的限制性片段长度多态性，只有一个（称为 ApaI），由 SNP rs79628898 标记，在 AA 中具有名义上显著的 p 值；这些多态性在白种人中均与 CRC 无关。在北卡罗来纳州 AA 中，我们有维生素 D 摄入量数据，我们发现内含子 SNP rs11574041 与维生素 D 摄入量之间存在显著关联，这证明了 AA 中 VDR 基因-环境相互作用。总之，使用系统的标记 SNP 方法，我们没有发现 VDR 与 AA 或白种人 CRC 之间存在显著关联的证据。
