Polymorphisms in the MTHFR and VDR genes and skin cancer risk
Polymorphisms in the MTHFR and VDR genes and skin cancer risk
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DOI：
10.1093/carcin/bgl156
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发表时间：
2007-02-01
期刊：
影响因子：
4.7
通讯作者：
Hunter, David J.
中科院分区：
文献类型：
--
作者：
Han, Jiali;Colditz, Graham A.;Hunter, David J.
叶酸和维生素D已被证明是受紫外线（UV）辐射。UVA辐射可以分解血浆叶酸，而维生素D可以在UVB暴露的皮肤中合成。叶酸代谢参与DNA合成和修复，维生素D处理抗增殖作用。这两种营养素的功能都与皮肤癌发生有关。我们在护士健康研究的一项巢式病例对照研究中评估了亚甲基四氢叶酸还原酶（MTHFR）基因（C677 T和A1298 C）和维生素D受体（VDR）基因（Fok 1，Bsm 1和Cdx 2）的遗传多态性与皮肤癌风险[219例黑色素瘤，286例鳞状细胞癌（SCC），300例基底细胞癌（BCC）和873例对照]。两个MTHFR多态性与皮肤癌风险之间没有显著相关性。我们观察到C677 T多态性和叶酸摄入量对SCC风险的交互作用（P，交互作用= 0.04）;在TT基因型和低叶酸摄入量的女性中观察到最高风险（OR = 2.14; 95%CI = 1.01-4.50）。VDR Bsm 1 BB基因型与SCC风险增加显著相关（OR = 1.51; 95%CI = 1.00-2.28）。Bsm 1基因多态性与维生素D摄入量之间存在交互作用，BB基因型和维生素D摄入量高的女性患SCC的风险最高（OR = 2.38，95%CI = 1.22-4.62）（P，交互作用= 0.08）。这项研究表明，MTHFR和VDR的多态性与叶酸和维生素D的饮食摄入量相互作用，在皮肤癌的发展，特别是SCC的可能作用。由于大量的比较和测试，可能的关联应谨慎解释，并由其他研究证实。
Folate and vitamin D have been shown to be influenced by ultraviolet (UV) radiation. UVA radiation can break down plasma folate, whereas vitamin D can be synthesized in UVB-exposed skin. Folate metabolism is involved in DNA synthesis and repair, and vitamin D processes anti-proliferative effects. The functions of both nutrients are implicated in skin carcinogenesis. We evaluated genetic polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T and A1298C) and the vitamin D receptor (VDR) gene (Fok1, Bsm1 and Cdx2) with skin cancer risk in a nested case-control study within the Nurses' Health Study [219 melanoma, 286 squamous cell carcinoma (SCC), 300 basal cell carcinoma (BCC) and 873 controls]. No significant associations were observed for the two MTHFR polymorphisms on skin cancer risk. We observed an interaction between the C677T polymorphism and total folate intake on SCC risk (P, interaction = 0.04); the highest risk was observed among women with TT genotype and low folate intake (OR = 2.14; 95% CI = 1.01-4.50). The VDR Bsm1 BB genotype was significantly associated with an increased SCC risk (OR = 1.51; 95% CI = 1.00-2.28). An interaction between the Bsm1 polymorphism and total vitamin D intake on SCC was observed, with the highest risk seen in women with the BB genotype and high vitamin D intake (OR = 2.38; 95% CI = 1.22-4.62) (P, interaction = 0.08). This study suggests a possible role of the polymorphisms in MTHFR and VDR interacting with dietary intakes of folate and vitamin D in skin cancer development, especially for SCC. Due to a large number of comparisons and tests, the possible associations should be interpreted with caution and confirmed by other studies.