Gastric Cancer, 2015, 18(3):495-503.

Gene polymorphisms in the ornithine decarboxylase–polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations

Lisa Y. Cho, Jae Jeong Yang, et al

Department of Preventive MedicineSeoul National University College of MedicineSeoulRepublic of Korea; et al

BACKGROUND:

The study aimed to examine the association between genes encoding molecules in the ornithine decarboxylase (ODC)-polyamine pathway (ODC1, AMD1, NQO1, NOS2A, and OAZ2) and gastric cancer risk and whether the gene-phytoestrogen interaction modifies gastric cancer risk.

METHODS:

Among 76 gastric cancer cases and their 1:4 matched controls within the Korean Multi-center Cancer Cohort, a total of 30 SNPs in five genes involved in the ODC pathway were primarily analyzed. The second-stage genotyping in 388 matched case-control sets was conducted to reevaluate the significant SNPs interacting with phytoestrogens during the primary analysis. The summary odds ratios (ORs) [95 % confidence intervals (CIs)] for gastric cancer were estimated. Interaction effects between the SNPs and plasma concentrations of phytoestrogens (genistein, daidzein, equol, and enterolactone) were evaluated.

RESULTS:

In the pooled analysis, NQO1 rs1800566 showed significant genetic effects on gastric cancer without heterogeneity [OR 0.83 (95 % CI 0.70-0.995)] and a greater decreased risk at high genistein/daidzein levels [OR 0.36 (95 % CI 0.15-0.90) and OR 0.26 (95 % CI 0.10-0.64), respectively; p interaction < 0.05]. Risk alleles of AMD1 rs1279599, AMD1 rs7768897, and OAZ2 rs7403751 had a significant gene-phytoestrogen (genistein and daidzein) interaction effect to modify the development of gastric cancer. They had an increased gastric cancer risk at low isoflavone levels, but a decreased risk at high isoflavone levels (p interaction < 0.01).

CONCLUSIONS:

Our findings suggest that common variants in the genes involved in the ODC pathway may contribute to the risk of gastric cancer possibly by modulating ODC polyamine biosynthesis or by interaction between isoflavones and NQO1, OAZ2, and AMD1.

日本《胃癌》，2014年7月

在鸟氨酸脱羧酶-多胺途径中的基因多态性通过与异黄酮浓聚物的相互作用改变胃癌风险

丽莎 Y 秋，杨载正，等

韩国首尔国立大学医学院预防医学系；等

背景︰

这项研究旨在探讨在鸟氨酸脱羧酶 (ODC)-聚多胺途径（ODC1、 AMD1、 NQO1，NOS2A 和 OAZ2）上基因编码分子与胃癌风险之间的关联，以及基因-植物雌激素之间的相互作用是否改变胃癌的患病风险。

方法︰

在韩国多重中心癌症人群 的76 例胃癌病例以及1:4 匹配对照病例中，主要分析了参与 ODC 通路的五个基因共 30 个 SNPs位点。在 388个 配对病例-对照组中进行第二阶段的基因分型，在初步分析阶段重新评估单核苷酸多态性与植物雌激素之间重要的相互作用。估算了胃癌比值 (ORs) [95%可信区间 （CIs）]。对单核苷酸多态性与植物雌激素血浆浓度（金雀异黄素、 大豆黄酮、 雌马酚和 肠内酯） 之间的相互作用进行了评价。

结果︰

汇总分析，NQO1 rs1800566对胃癌表现出没有非均质性的显著遗传影响 [OR 0.83 (95%CI 0.70 0.995)] ，并且有明显降低的风险在高水平的金雀异黄素/大豆黄酮 [OR 0.36 (95% CI 0.15-0.90) 和 OR 0.26 (95% CI 0.10-0.64)，分别；p 相互作用< 0.05]。AMD1 rs1279599，AMD1 rs7768897 和 OAZ2 rs7403751 的风险等位基因拥有明显的基因-植物雌激素（金雀异黄素和大豆黄酮）之间的相互作用来修改胃癌的发展过程。他们发现异黄酮的水平低时胃癌风险增加，而异黄酮水平高时风险降低 (p 相互作用< 0.01)。

结论︰

我们的研究结果表明，参与 ODC 通路基因的共同变异可能有助于胃癌的风险是可能通过调节 ODC 多胺生物合成或通过异黄酮和 NQO1、 OAZ2 和 AMD1 之间的相互作用。