Ochs-Balcom Heather M, Cicek Mine S, Thompson Cheryl L, Tucker Thomas C, Elston Robert C, J Plummer Sarah, Casey Graham, Li Li
Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, NY, USA.
Carcinogenesis. 2008 Sep;29(9):1788-93. doi: 10.1093/carcin/bgn166. Epub 2008 Jul 14.
Vitamin D receptor (VDR) gene variants have been variably associated with risk of colon cancer in epidemiologic studies. We sought to further clarify the relationship between colon cancer and three single-nucleotide polymorphisms (SNPs) in the VDR gene (Cdx-2, FokI and TaqI) in a population-based case-control study of 250 incident cases and 246 controls. Colon cancer cases were more frequently homozygous for the Cdx-2 A allele (9.2 versus 4.1%, P = 0.06). Cdx-2 AA homozygotes were at increased risk with an unadjusted odds ratio (OR) of 2.47 [95% confidence interval (CI): 1.13-5.37, P = 0.022]; adjustment for age, sex, body mass index (BMI), non-steroidal anti-inflammatory use and family history of colorectal cancer yielded an OR of 2.27 (CI: 0.95-5.41, P = 0.065). Carriers of the FokI TT genotype were also at increased risk with an adjusted OR of 1.87 (CI: 1.03-3.38, P = 0.038). Haplotype analyses showed significant increased colon cancer risk for carriers of the Cdx-2-FokI A-T haplotype and the FokI-TaqI T-G haplotype. The three-SNP Cdx-2-FokI-TaqI (A-T-G) haplotype showed a similar association with an adjusted OR of 3.63 (CI: 1.01-13.07). A strong positive association was observed for the Cdx-2 variant among individuals with low BMI or low waist circumference. Our results suggest that genetic variation at the VDR locus, in particular Cdx-2 and FokI SNPs, may influence colon cancer risk and these associations may be modified by adiposity.
在流行病学研究中，维生素D受体（VDR）基因变异与结肠癌风险的关联各不相同。我们试图在一项基于人群的病例对照研究中，进一步阐明结肠癌与VDR基因中的三个单核苷酸多态性（SNP）（Cdx-2、FokI和TaqI）之间的关系，该研究纳入了250例新发病例和246例对照。结肠癌病例中Cdx-2 A等位基因纯合子的频率更高（9.2%对4.1%，P = 0.06）。Cdx-2 AA纯合子的风险增加，未调整的优势比（OR）为2.47 [95%置信区间（CI）：1.13 - 5.37，P = 0.022]；对年龄、性别、体重指数（BMI）、非甾体抗炎药使用情况和结直肠癌家族史进行调整后，OR为2.27（CI：0.95 - 5.41，P = 0.065）。FokI TT基因型携带者的风险也增加，调整后的OR为1.87（CI：1.03 - 3.38，P = 0.038）。单倍型分析显示，Cdx-2 - FokI A - T单倍型和FokI - TaqI T - G单倍型的携带者患结肠癌的风险显著增加。三个SNP的Cdx-2 - FokI - TaqI（A - T - G）单倍型显示出类似的关联，调整后的OR为3.63（CI：1.01 - 13.07）。在BMI低或腰围小的个体中，观察到Cdx-2变异与结肠癌有很强的正相关。我们的结果表明，VDR基因座的遗传变异，特别是Cdx-2和FokI SNP，可能影响结肠癌风险，并且这些关联可能会受到肥胖的影响。
