Department of Otolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
PLoS One. 2013 Sep 26;8(9):e75367. doi: 10.1371/journal.pone.0075367. eCollection 2013.
O(6)-methylguanine-DNA methyltransferase is one of the few proteins to directly remove alkylating agents in the human DNA direct reversal repair pathway. A large number of case-control studies have been conducted to explore the association between MGMT Leu84Phe polymorphism and cancer risk. However, the results were not consistent.
We carried out a meta-analysis of 44 case-control studies to clarify the association between the Leu84Phe polymorphism and cancer risk.
Overall, significant association of the T allele with cancer susceptibility was verified with meta-analysis under a recessive genetic model (P<0.001, OR=1.30, 95%CI 1.24-1.50) and TT versus CC comparison (P=0.001, OR=1.29, 95% CI 1.12-1.50). In subgroup analysis, a significant increased risk was found for lung cancer (TT versus CC, P=0.027, OR=1.67, 95% CI 1.06-2.63; recessive genetic model, P=0.32, OR=1.64, 95% CI 1.04-2.58), whereas risk of colorectal cancer was significantly low under a dominant genetic model (P=0.019, OR=0.84, 95% CI 0.72-0.97). Additionally, a significant association between TT genetic model and total cancer risk was found in the Caucasian population (TT versus CC, P=0.014, OR=1.29, 95% CI 1.05-1.59; recessive genetic model, P=0.009, OR=1.31, 95% CI 1.07-1.61), but not in the Asian population. An increased risk for lung cancer was also verified in the Caucasian population (TT versus CC, P=0.035, OR=1.62, 95% CI 1.04-2.53; recessive genetic model, P=0.048, OR=1.57, 95% CI 1.01-2.45).
These results suggest that MGMT Leu84Phe polymorphism might contribute to the susceptibility of certain cancers.
O(6)-甲基鸟嘌呤-DNA 甲基转移酶是人类 DNA 直接逆转修复途径中直接去除烷化剂的少数几种蛋白质之一。已经进行了大量的病例对照研究来探讨 MGMT Leu84Phe 多态性与癌症风险之间的关系。然而，结果并不一致。
我们对 44 项病例对照研究进行了荟萃分析，以阐明 Leu84Phe 多态性与癌症风险之间的关系。
总体而言，在隐性遗传模型下（P<0.001，OR=1.30，95%CI 1.24-1.50）和 TT 与 CC 比较（P=0.001，OR=1.29，95%CI 1.12-1.50），荟萃分析证实 T 等位基因与癌症易感性存在显著关联。在亚组分析中，发现肺癌的风险显著增加（TT 与 CC，P=0.027，OR=1.67，95%CI 1.06-2.63；隐性遗传模型，P=0.32，OR=1.64，95%CI 1.04-2.58），而显性遗传模型下结直肠癌的风险显著降低（P=0.019，OR=0.84，95%CI 0.72-0.97）。此外，在高加索人群中发现 TT 遗传模型与总癌症风险之间存在显著关联（TT 与 CC，P=0.014，OR=1.29，95%CI 1.05-1.59；隐性遗传模型，P=0.009，OR=1.31，95%CI 1.07-1.61），但在亚洲人群中没有。在高加索人群中还证实了肺癌的风险增加（TT 与 CC，P=0.035，OR=1.62，95%CI 1.04-2.53；隐性遗传模型，P=0.048，OR=1.57，95%CI 1.01-2.45）。
这些结果表明，MGMT Leu84Phe 多态性可能导致某些癌症的易感性。
