Department of Preventive Medicine, Genetic Epidemiology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
Cancer Causes Control. 2011 Apr;22(4):541-52. doi: 10.1007/s10552-011-9726-7. Epub 2011 Jan 28.
Folate-associated one-carbon metabolism (FOCM) is an important pathway in colorectal neoplasia risk but data on genetic variation in this pathway are largely limited to studies of single SNPs in selected genes.
We used a comprehensive tagSNP approach to study the association between genetic variation in 11 genes in the FOCM pathway and risk of incident distal colorectal adenomas in a sigmoidoscopy-based case-control study. We included 655 cases (one or more adenomas) and 695 controls (no adenomas) recruited from one of two Kaiser Permanente clinics between 1991 and 1995. We assessed a total of 159 tagSNPs selected using Haploview Tagger as well as selected non-synonymous SNPs. We used unconditional logistic regression to model the association between SNPs and risk of distal adenomas, assuming a log-additive model.
Five SNPs in the SLC19A1 (RFC1) gene: rs1051266 (G80A), rs283895, rs2236484, rs12482346, and rs2838958 were associated with adenoma risk after correction for multiple testing (all corrected p values ≤ 0.043). The non-synonymous SLC19A1 SNP G80A interacted significantly with the MTHFR C677T genotype (interaction p value = 0.018).
Our data suggest that genetic variation in SLC19A1 may modify the risk of distal colorectal adenoma.
叶酸相关的一碳代谢（FOCM）是结直肠肿瘤风险的重要途径，但该途径中遗传变异的数据在很大程度上仅限于选定基因中单 SNP 的研究。
我们使用综合标签 SNP 方法研究了 FOCM 途径中 11 个基因的遗传变异与基于乙状结肠镜检查的病例对照研究中结直肠远端腺瘤发病风险之间的关系。我们纳入了 1991 年至 1995 年间在两家 Kaiser Permanente 诊所之一招募的 655 例病例（一个或多个腺瘤）和 695 例对照（无腺瘤）。我们评估了使用 Haploview Tagger 选择的总共 159 个标签 SNP 以及选定的非同义 SNP。我们使用无条件逻辑回归模型来模拟 SNP 与远端腺瘤风险之间的关联，假设对数加性模型。
SLC19A1（RFC1）基因中的 5 个 SNP：rs1051266（G80A）、rs283895、rs2236484、rs12482346 和 rs2838958 在经过多次测试校正后与腺瘤风险相关（所有校正后的 p 值均≤0.043）。非同义 SLC19A1 SNP G80A 与 MTHFR C677T 基因型显著相互作用（相互作用 p 值=0.018）。
我们的数据表明，SLC19A1 中的遗传变异可能会改变远端结直肠腺瘤的风险。
