Lu Qing, Jiang Ke, Li Qiong, Ji Ya-Jie, Chen Wei-Li, Xue Xiao-Hong
Department of Breast Surgery, Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No.110, Ganhe Road, Shanghai, 200437, China.
Tumour Biol. 2015 May;36(5):3757-62. doi: 10.1007/s13277-014-3016-4. Epub 2015 Jan 8.
Breast cancer is the most common cancer affecting women in China and the world. Folate supplementation is proven to be effective in reducing the risk of breast cancer or improving its prognosis. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism and DNA synthesis. This study aims to examine whether single nucleotide polymorphisms (SNP) in the MTHFR gene are associated with risk and survival of breast cancer and serum folate levels in healthy controls. We genotyped nine tagging SNPs in the MTHFR gene in a case-control study, including 560 breast cancer cases and 560 healthy controls in China. We found that TT genotype of rs1801133 had significant increased risk of breast cancer [adjusted odds ratio (OR) = 1.60, 95 % confidence interval (CI) 1.12-2.28] compared with CC genotype, and CC genotype of rs9651118 conferred significant reduced risk of breast cancer (adjusted OR = 0.65, 95 % CI 0.45-0.95) compared to TT genotype. Haplotype analysis also showed that MTHFR CACCAA and AGTCAC haplotypes (rs12121543-rs13306553-rs9651118-rs1801133-rs4846048-rs1801131) had significant reduced risk of breast cancer (adjusted OR = 0.70, 95 % CI 0.58-0.86; adjusted OR = 0.57, 95 % CI 0.40-0.80) compared with CATTAA haplotype. Besides, MTHFR rs9651118 CC genotype was significantly associated with survival in breast cancer cases (adjusted hazard ratio (HR) = 0.63, 95 % CI 0.40-0.99). But none of the SNPs in the MTHFR gene was associated with serum folate level in healthy controls. These findings suggest that variants in the MTHFR gene may influence the risk and prognosis of breast cancer.
乳腺癌是中国和全球影响女性的最常见癌症。补充叶酸已被证明可有效降低患乳腺癌的风险或改善其预后。亚甲基四氢叶酸还原酶（MTHFR）是参与叶酸代谢和DNA合成的一种重要酶。本研究旨在探讨MTHFR基因中的单核苷酸多态性（SNP）是否与乳腺癌的风险、生存率以及健康对照者的血清叶酸水平相关。在一项病例对照研究中，我们对MTHFR基因中的9个标签SNP进行了基因分型，研究对象包括560例中国乳腺癌患者和560名健康对照者。我们发现，与CC基因型相比，rs1801133的TT基因型使乳腺癌风险显著增加[调整优势比（OR）= 1.60，95%置信区间（CI）1.12 - 2.28]，而与TT基因型相比，rs9651118的CC基因型使乳腺癌风险显著降低（调整OR = 0.65，95%CI 0.45 - 0.95）。单倍型分析还显示，与CATTAA单倍型相比，MTHFR CACCAA和AGTCAC单倍型（rs12121543 - rs13306553 - rs9651118 - rs1801133 - rs4846048 - rs1801131）使乳腺癌风险显著降低（调整OR = 0.70，95%CI 0.58 - 0.86；调整OR = 0.57，95%CI 0.40 - 0.80）。此外，MTHFR rs9651118的CC基因型与乳腺癌患者的生存率显著相关（调整风险比（HR）= 0.63，95%CI 0.40 - 0.99）。但MTHFR基因中的SNP均与健康对照者的血清叶酸水平无关。这些发现表明，MTHFR基因变异可能影响乳腺癌的风险和预后。
