Lajin Bassam, Alhaj Sakur Amir, Ghabreau Lina, Alachkar Amal
Department of Analytical Chemistry, Faculty of Pharmacy, University of Aleppo, Aleppo, Syria.
Tumour Biol. 2012 Aug;33(4):1133-9. doi: 10.1007/s13277-012-0354-y. Epub 2012 Feb 29.
Dietary folate status as well as polymorphisms in one-carbon metabolism genes may affect the risk of breast cancer through aberrant DNA methylation and altered nucleotide synthesis and DNA repair. A large number of studies investigated the role of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms in breast cancer with inconsistent results. Association between multiple polymorphisms in one-carbon metabolism genes and breast cancer was not studied before in an Arab population. The purpose of the present study is to test the hypothesis that polymorphisms in one-carbon metabolism genes are associated with breast cancer susceptibility in Syrian breast cancer women patients. A total of 245 subjects (119 breast cancer women patients and 126 healthy controls) were genotyped for MTHFR C677T and A1298C and MTRR A66G polymorphisms. Association was tested for under numerous genetic models. A statistically significant association was found for MTHFR A1298C polymorphism especially under the allele contrast model (odds ratio (OR) = 1.68, 95% confidence interval (CI) (1.16-2.45), P = 0.006). On the other hand, no significant association was found for MTHFR C677T or MTRR A66G under any of the genetic models tested. The effects of the compound genotypes were also examined. The 66GG genotype was found to be protective against breast cancer when combined with the 677CT or 1298AC genotype (OR = 0.18, 95% CI (0.04-0.82), P = 0.014; OR = 0.3, 95% CI (0.08-1.11), P = 0.058). In conclusion, our study supports the hypothesis that polymorphisms in one-carbon gene metabolisms modulate the risk for breast cancer, particularly the A1298C polymorphism of the MTHFR gene.
膳食叶酸状态以及一碳代谢基因中的多态性可能通过异常的DNA甲基化、核苷酸合成改变和DNA修复影响乳腺癌风险。大量研究调查了亚甲基四氢叶酸还原酶（MTHFR）和甲硫氨酸合酶还原酶（MTRR）多态性在乳腺癌中的作用，但结果不一致。此前尚未在阿拉伯人群中研究一碳代谢基因中的多个多态性与乳腺癌之间的关联。本研究的目的是检验一碳代谢基因中的多态性与叙利亚乳腺癌女性患者的乳腺癌易感性相关这一假设。对总共245名受试者（119名乳腺癌女性患者和126名健康对照）进行了MTHFR C677T和A1298C以及MTRR A66G多态性的基因分型。在众多遗传模型下测试了关联性。发现MTHFR A1298C多态性存在统计学显著关联，尤其是在等位基因对比模型下（优势比（OR）=1.68，95%置信区间（CI）（1.16 - 2.45），P = 0.006）。另一方面，在任何测试的遗传模型下，MTHFR C677T或MTRR A66G均未发现显著关联。还检查了复合基因型的影响。发现66GG基因型与677CT或1298AC基因型组合时对乳腺癌具有保护作用（OR = 0.18，95% CI（0.04 - 0.82），P = 0.014；OR = 0.3，95% CI（0.08 - 1.11），P = 0.058）。总之，我们的研究支持一碳基因代谢中的多态性调节乳腺癌风险这一假设，特别是MTHFR基因的A1298C多态性。
