Danish Cancer Society Research Center, Copenhagen, Denmark.
Department of Neurology, The Danish Multiple Sclerosis Registry, Rigshospitalet, Glostrup, Denmark.
PLoS One. 2020 Feb 3;15(2):e0228635. doi: 10.1371/journal.pone.0228635. eCollection 2020.
The association between vitamin D and incidence of colorectal cancer has been thoroughly investigated, but the results are conflicting. The objectives in this study were to investigate whether two functional polymorphisms in GC and CYP2R1, respectively, previously shown to predict vitamin D concentrations, were associated with risk of colorectal cancer; and further, to assess gene-environment interaction between the polymorphisms and intake of vitamin D through diet and supplementation in relation to risk of colorectal cancer.
A nested case-cohort study of 920 colorectal cancer cases and 1743 randomly selected participants from the Danish prospective "Diet, Cancer and Health" study was performed. Genotypes CYP2R1/rs10741657 and GC/rs4588 were determined by PCR-based KASP™ genotyping assay. Vitamin D intake from supplements and diet was assessed from a validated food frequency questionnaire. Incidence rate ratios were estimated by the Cox proportional hazards model, and interactions between polymorphisms in GC and CYP2R1 and vitamin D intake in relation to risk of colorectal cancer were assessed.
Neither of the two polymorphisms was associated with risk of colorectal cancer per se. Heterozygote carriage of CYP2R1/rs10741657 and GC/rs4588, and carriage of two risk alleles (estimated by a genetic risk score) were weakly associated with 9-12% decreased risk of colorectal cancer per 3 μg intake of vitamin D per day (IRRCYP2R1/rs10741657 = 0.88, 95% CI: 0.79-0.97; IRRGC/rs4588 = 0.91, 95% CI: 0.82-1.01, IRRGRS2 = 0.90, 95% CI: 0.81-0.99).
The results suggest that genetic variation in vitamin D metabolising genes may influence the association between vitamin D intake, through food and supplementation, and risk of colorectal cancer.
NCT03370432. Registered 12 December 2017 (retrospectively registered).
维生素 D 与结直肠癌发病率之间的关联已得到深入研究，但结果存在争议。本研究的目的是探讨先前显示可预测维生素 D 浓度的 GC 和 CYP2R1 中的两个功能多态性是否与结直肠癌风险相关；进一步评估多态性与通过饮食和补充摄入维生素 D 之间的基因-环境相互作用与结直肠癌风险的关系。
对来自丹麦前瞻性“饮食、癌症与健康”研究的 920 例结直肠癌病例和 1743 名随机选择的参与者进行了巢式病例对照研究。通过基于 PCR 的 KASP™ 基因分型测定法确定 CYP2R1/rs10741657 和 GC/rs4588 的基因型。通过经过验证的食物频率问卷评估补充剂和饮食中维生素 D 的摄入量。使用 Cox 比例风险模型估计发病率比，并评估 GC 和 CYP2R1 中的多态性与维生素 D 摄入量之间的相互作用与结直肠癌风险的关系。
这两种多态性本身均与结直肠癌风险无关。CYP2R1/rs10741657 和 GC/rs4588 的杂合子携带以及两个风险等位基因（通过遗传风险评分估计）的携带与每天 3μg 维生素 D 摄入相关的结直肠癌风险降低 9-12%有关（CYP2R1/rs10741657 的 IRRCYP2R1/rs10741657 = 0.88，95%CI：0.79-0.97；GC/rs4588 的 IRRGC/rs4588 = 0.91，95%CI：0.82-1.01，GRS2 的 IRRGRS2 = 0.90，95%CI：0.81-0.99）。
结果表明，维生素 D 代谢基因的遗传变异可能会影响通过食物和补充摄入的维生素 D 与结直肠癌风险之间的关联。
NCT03370432。2017 年 12 月 12 日注册（追溯注册）。
