Pibiri Fabio, Kittles Rick A, Sandler Robert S, Keku Temitope O, Kupfer Sonia S, Xicola Rosa M, Llor Xavier, Ellis Nathan A
Department of Pediatrics and the Institute of Human Genetics, University of Illinois at Chicago, 900 S. Ashland Ave. MC 767, Chicago, IL, 60607, USA.
Cancer Causes Control. 2014 May;25(5):561-70. doi: 10.1007/s10552-014-0361-y. Epub 2014 Feb 23.
Disparities in both colorectal cancer (CRC) incidence and survival impact African Americans (AAs) more than other US ethnic groups. Because vitamin D is thought to protect against CRC and AAs have lower serum vitamin D levels, genetic variants that modulate the levels of active hormone in the tissues could explain some of the cancer health disparity. Consequently, we hypothesized that genetic variants in vitamin D-related genes are associated with CRC risk.
To test this hypothesis, we studied 39 potentially functional single-nucleotide polymorphisms (SNPs) in eight genes (CYP2R1, CYP3A4, CYP24A1, CYP27A1, CYP27B1, GC, DHCR7, and VDR) in 961 AA CRC cases and 838 healthy AA controls from Chicago and North Carolina. We tested whether SNPs are associated with CRC incidence using logistic regression models to calculate p values, odds ratios, and 95 % confidence intervals. In the logistic regression, we used a log-additive genetic model and used age, gender, and percent West African ancestry, which we estimated with the program STRUCTURE, as covariates in the models.
A nominally significant association was detected between CRC and the SNP rs12794714 in the vitamin D 25-hydroxylase gene CYP2R1 (p = 0.019), a SNP that has previously been associated with serum vitamin D levels. Two SNPs, rs16847024 in the GC gene and rs6022990 in the CYP24A1 gene, were nominally associated with left-sided CRC (p = 0.015 and p = 0.018, respectively).
Our results strongly suggest that genetic variation in vitamin D-related genes could affect CRC susceptibility in AAs.
与美国其他种族群体相比，非裔美国人（AAs）在结直肠癌（CRC）发病率和生存率方面的差异更为明显。由于维生素D被认为具有预防CRC的作用，且AAs的血清维生素D水平较低，因此，调节组织中活性激素水平的基因变异可能是造成癌症健康差异的部分原因。因此，我们推测维生素D相关基因的变异与CRC风险相关。
为验证这一假设，我们研究了来自芝加哥和北卡罗来纳州的961例AA CRC病例和838例健康AA对照中8个基因（CYP2R1、CYP3A4、CYP24A1、CYP27A1、CYP27B1、GC、DHCR7和VDR）中的39个潜在功能性单核苷酸多态性（SNP）。我们使用逻辑回归模型计算p值、比值比和95%置信区间来检测SNP是否与CRC发病率相关。在逻辑回归中，我们使用对数加性遗传模型，并将年龄、性别和西非血统百分比（我们用STRUCTURE程序估算）作为模型中的协变量。
在维生素D 25-羟化酶基因CYP2R1中的SNP rs12794714与CRC之间检测到名义上显著的关联（p = 0.019），该SNP先前已与血清维生素D水平相关。GC基因中的两个SNP，rs16847024和CYP24A1基因中的rs6022990与左侧CRC名义上相关（分别为p = 0.015和p = 0.01）。
我们的结果强烈表明维生素D相关基因的遗传变异可能影响AAs对CRC的易感性。
