Authors' Affiliations: Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Departments of Nutrition, and Biostatistics, Harvard School of Public Health; Department of Medicine, and Channing Division of Network Medicine, Brigham and Women's Hospital; Division of Gastroenterology, Massachusetts General Hospital; Department of Medicine, Harvard Medical School; Gastrointestinal Malignancy Program, and Medical-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Public Health Sciences Division, Fred Hutchinson Cancer Research Center; Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington; Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Divisions of Cancer Epidemiology and Genetics, and Cancer Control and Population Sciences, National Cancer Institute, NIH, Bethesda; University of Maryland, School of Medicine, Baltimore, Maryland; Service de Génétique Médicale, CHU Nantes, Nantes, France; Divisions of Clinical Epidemiology and Aging Research and Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; Division of Research, Kaiser Permanente Medical Care Program, Oakland; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Translational Genomics Research Institute, Phoenix, Arizona; Department of Surgery, Toronto General Hospital; Ontario Institute for Cancer Research; Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto; Faculty of Medicine, The University of Ottawa, Ottawa, Ontario, Canada; Department of Environmental Medicine, Division of Epidemiology, New York University School of Medicine, New York; Department of Social and Preventive Medicine, University of Buffalo, Buffalo, New York; Melborne School of Population Health, The University of Melbourne, Melbourne, Victoria, Australia; Epidemiology Pro
Cancer Epidemiol Biomarkers Prev. 2013 Nov;22(11):2037-46. doi: 10.1158/1055-9965.EPI-13-0209. Epub 2013 Aug 27.
Experimental evidence has demonstrated an antineoplastic role for vitamin D in the colon, and higher circulating 25-hydroxyvitamin D [25(OH)D] levels are consistently associated with a lower risk of colorectal cancer. Genome-wide association studies have identified loci associated with levels of circulating 25(OH)D. The identified single-nucleotide polymorphisms (SNPs) from four gene regions collectively explain approximately 5% of the variance in circulating 25(OH)D.
We investigated whether five polymorphisms in GC, CYP2R1, CYP24A1, and DHCR7/NADSYN1, genes previously shown to be associated with circulating 25(OH)D levels, were associated with colorectal cancer risk in 10,061 cases and 12,768 controls drawn from 13 studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR). We conducted a meta-analysis of crude and multivariate-adjusted logistic regression models to calculate odds ratios and associated confidence intervals for SNPs individually, SNPs simultaneously, and for a vitamin D additive genetic risk score (GRS).
We did not observe a statistically significant association between the 25(OH)D-associated SNPs and colorectal cancer marginally, conditionally, or as a GRS, or for colon or rectal cancer separately.
Our findings do not support an association between SNPs associated with circulating 25(OH)D and risk of colorectal cancer. Additional work is warranted to investigate the complex relationship between 25(OH)D and colorectal cancer risk.
There was no association observed between genetic markers of circulating 25(OH)D and colorectal cancer. These genetic markers account for a small proportion of the variance in 25(OH)D.
实验证据表明维生素 D 在结肠中具有抗肿瘤作用，循环中 25-羟维生素 D [25(OH)D] 水平较高与结直肠癌风险降低相关。全基因组关联研究已经确定了与循环 25(OH)D 水平相关的基因座。从四个基因区域确定的单核苷酸多态性 (SNP) 共同解释了循环 25(OH)D 中约 5%的变异。
我们研究了先前与循环 25(OH)D 水平相关的 GC、CYP2R1、CYP24A1 和 DHCR7/NADSYN1 基因中的五个多态性是否与 10061 例病例和 12768 例对照的结直肠癌风险相关，这些病例和对照来自包括在遗传学和结直肠癌流行病学联盟 (GECCO) 和结肠癌家族登记处 (CCFR) 中的 13 项研究。我们对原始和多变量调整的逻辑回归模型进行了荟萃分析，以计算 SNP 个体、SNP 同时和维生素 D 附加遗传风险评分 (GRS) 的比值比和相关置信区间。
我们没有观察到与循环 25(OH)D 相关的 SNP 与结直肠癌之间存在统计学显著关联，无论是边缘、条件还是作为 GRS，或者是结肠或直肠癌分别。
我们的研究结果不支持与循环 25(OH)D 相关的 SNP 与结直肠癌风险之间的关联。需要进一步的研究来调查 25(OH)D 与结直肠癌风险之间的复杂关系。
没有观察到循环 25(OH)D 的遗传标记与结直肠癌之间存在关联。这些遗传标记仅占 25(OH)D 变异的一小部分。
