The Central Laboratory of Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, 210006 Jiangsu, China.
Mol Biol Rep. 2012 Mar;39(3):3117-22. doi: 10.1007/s11033-011-1076-8. Epub 2011 Jun 23.
Leptin and leptin receptor have been implicated in processes leading to breast cancer initiation and progression. An A to G transition mutation in codon 223, in exon 6 of the leptin receptor gene (LEPR) can result in glutamine to arginine substitution (Gln223Arg). A variety of case-control studies have been published evaluating the association between LEPR Gln223Arg polymorphism and breast cancer. However, published studies have yielded contradictory conclusions. This meta-analysis enrolled eight studies to estimate the overall risk of LEPR Gln223Arg polymorphism associated with breast cancer. The pooled ORs were performed for codominant model (Arg/Arg versus Gln/Gln; Arg/Gln versus Gln/Gln), dominant model (Arg/Arg + Arg/Gln versus Gln/Gln), recessive model (Arg/Arg versus Arg/Gln + Gln/Gln). Overall significantly elevated breast cancer risk was found for recessive model (OR 1.32, 95% CI 1.03-1.69) and for genotype Arg/Gln versus Gln/Gln (OR 1.16, 95% CI 1.01-1.34). In the stratified analysis by ethnicity, significantly increased risks were also found among Africans for genotype Arg/Arg versus Gln/Gln: OR 1.86, 95% CI 1.28-2.71, Arg/Gln versus Gln/Gln: OR 1.48, 95% CI 1.10-1.99, dominant model: OR 1.60, 95% CI 1.21-2.11 and recessive model: OR 1.48, 95% CI 1.07-2.05; for Asians, Arg/Arg versus Gln/Gln: OR 6.79, 95% CI 3.42-13.47 and dominant model: OR 2.03, 95% CI 1.42-2.90. However, no significantly increased risk was found among Europeans for all genetic models. In conclusion, the LEPR 223Arg is a low-penetrant risk for developing breast cancer, especially for black African women.
瘦素和瘦素受体参与了导致乳腺癌发生和发展的过程。瘦素受体基因（LEPR）外显子 6 第 223 位密码子的 A 到 G 转换突变可导致谷氨酰胺到精氨酸取代（Gln223Arg）。已经发表了许多评估 LEPR Gln223Arg 多态性与乳腺癌之间关联的病例对照研究。然而，已发表的研究得出了相互矛盾的结论。这项荟萃分析纳入了八项研究，以评估 LEPR Gln223Arg 多态性与乳腺癌的总体风险。进行了共显性模型（Arg/Arg 与 Gln/Gln；Arg/Gln 与 Gln/Gln）、显性模型（Arg/Arg+Arg/Gln 与 Gln/Gln）、隐性模型（Arg/Arg 与 Arg/Gln+Gln/Gln）的汇总 OR。总体而言，隐性模型（OR 1.32，95%CI 1.03-1.69）和基因型 Arg/Gln 与 Gln/Gln（OR 1.16，95%CI 1.01-1.34）与乳腺癌风险显著增加。在按种族分层的分析中，非洲人基因型 Arg/Arg 与 Gln/Gln 之间也发现了显著增加的风险：OR 1.86，95%CI 1.28-2.71，Arg/Gln 与 Gln/Gln：OR 1.48，95%CI 1.10-1.99，显性模型：OR 1.60，95%CI 1.21-2.11，隐性模型：OR 1.48，95%CI 1.07-2.05；对于亚洲人，Arg/Arg 与 Gln/Gln：OR 6.79，95%CI 3.42-13.47，显性模型：OR 2.03，95%CI 1.42-2.90。然而，在欧洲人中，所有遗传模型均未发现显著增加的风险。总之，LEPR 223Arg 是一种低外显度的乳腺癌发病风险，尤其是对非洲裔黑人女性。
