Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, 06510, USA.
Cancer Causes Control. 2013 Oct;24(10):1875-84. doi: 10.1007/s10552-013-0264-3. Epub 2013 Aug 3.
Genetic polymorphisms in one-carbon metabolizing pathway genes have been associated with risk of malignant lymphoma. However, the results have been inconsistent. The objectives of this study were to examine the potential relationship between gene-nutrient interactions and the risk of non-Hodgkin lymphoma (NHL).
We examined 25 polymorphisms in 16 one-carbon metabolism genes for their main effect and gene-nutrient interactions in relation to NHL risk among 518 incident cases and 597 population-based controls of Connecticut women enrolled between 1996 and 2000.
A significantly reduced risk of NHL was associated with the homozygous TT genotype in CBS (rs234706, Ex9+33C>T) (OR = 0.51, 95 % CI 0.31-0.84), the homozygous CC genotype in MBD2 (rs603097, -2176C>T) (OR = 0.37, 95 % CI 0.17-0.79), the heterozygote AG genotype in FTHFD (rs1127717, Ex21+31A>G) (OR = 0.73, 95 % CI 0.55-0.98), and a borderline significantly reduced risk of NHL was observed for the homozygous CC genotype in MTRR (rs161870, Ex5+136T>C) (OR = 0.23, 95 % CI 0.05-1.04). The reduced risk of NHL associated with these genotypes was predominately in those with higher dietary vitamin B6 and methionine intakes, as well as with higher dietary folate intake although results were less stable. A borderline significantly increased risk of NHL was also observed for CBS (rs1801181, Ex13+41C>T), FTHFD (rs2305230, Ex10-40G>T), SHMT1 (rs1979277, Ex12+138C>T), and SHMT1 (rs1979276, Ex12+236T>C), and these associations appeared to be contingent on dietary nutrient intakes.
Our results suggest that variation in several one-carbon metabolizing pathway genes may influence the risk of NHL through gene-nutrient interactions involving dietary nutrient intakes.
研究表明，一碳代谢途径基因中的遗传多态性与恶性淋巴瘤的风险有关。然而，结果并不一致。本研究的目的是探讨基因-营养素相互作用与非霍奇金淋巴瘤（NHL）风险之间的潜在关系。
我们在 1996 年至 2000 年间招募的康涅狄格州女性的 518 例新发病例和 597 例基于人群的对照组中，检查了 16 个一碳代谢基因中 25 个基因的多态性与 NHL 风险之间的主要作用和基因-营养素相互作用。
CBS（rs234706，Ex9+33C>T）中的纯合 TT 基因型（OR=0.51，95%CI 0.31-0.84）、MBD2（rs603097，-2176C>T）中的纯合 CC 基因型（OR=0.37，95%CI 0.17-0.79）、FTHFD（rs1127717，Ex21+31A>G）中的杂合 AG 基因型（OR=0.73，95%CI 0.55-0.98）与 NHL 的风险显著降低相关，MTRR（rs161870，Ex5+136T>C）中的纯合 CC 基因型与 NHL 的风险呈临界显著降低相关（OR=0.23，95%CI 0.05-1.04）。与这些基因型相关的 NHL 风险降低主要见于较高的膳食维生素 B6 和蛋氨酸摄入量以及较高的膳食叶酸摄入量，但结果不太稳定。CBS（rs1801181，Ex13+41C>T）、FTHFD（rs2305230，Ex10-40G>T）、SHMT1（rs1979277，Ex12+138C>T）和 SHMT1（rs1979276，Ex12+236T>C）也观察到 NHL 的风险临界显著增加，这些关联似乎取决于膳食营养素的摄入量。
我们的结果表明，一碳代谢途径中几个基因的变异可能通过涉及膳食营养素摄入的基因-营养素相互作用影响 NHL 的风险。
