Liu Chibo, Liu Liu
Department of Clinical Laboratory, Taizhou Municipal Hospital, Taizhou, 318000, China.
Tumour Biol. 2011 Dec;32(6):1233-40. doi: 10.1007/s13277-011-0227-9. Epub 2011 Sep 2.
Common genetic variations in the leptin (LEP), leptin receptor (LEPR), and paraoxonase 1 (PON1) genes have been considered to be implicated in the development of breast cancer. However, the results were inconsistent. In this study, a meta-analysis was performed to assess the associations of five polymorphisms, including LEP G2548A, LEPR Q223R, LEPR Lys109Arg, PON1 L55M, and PON1 Q192R polymorphisms, with breast cancer risk. Published literature from PubMed, ISI Web of Science, Embase databases, CNKI, and Wanfang Data were retrieved. All studies evaluating the association between LEP G2548A, LEPR Q223R, LEPR Lys109Arg, PON1 L55M, or PON1 Q192R polymorphism and breast cancer risk were included. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Three studies (2,003 cases and 1,967 controls) for LEP G2548A polymorphism, nine studies (4,627 cases and 5,476 controls) for LEPR Q223R polymorphism, five studies (2,759 cases and 2,573 controls) for LEPR Lys109Arg polymorphism, four studies (1,517 cases and 1,379 controls) for PON1 L55M polymorphism, and five studies (1,575 cases and 2,283 controls) for PON1 Q192R polymorphism were included in the meta-analysis. Overall, the results showed null significant association between LEP G2548A, LEPR Q223R, LEPR Lys109Arg, or PON1 Q192R polymorphism and breast cancer risk; however, PON1 L55M was significantly associated with breast cancer risk overall (MM vs. LL: OR = 2.16; 95% CI, 1.76-2.66). For LEPR Q223R polymorphism, further subgroup analysis suggested that the association was only statistically significant in East Asians (OR = 0.50; 95% CI, 0.36-0.70) but not in Caucasians (OR = 1.06; 95% CI, 0.77-1.45) or Africans (OR = 1.30; 95% CI, 0.83-2.03). The present meta-analysis suggested that LEPR Q223R polymorphism might be implicated in the development of breast cancer in East Asians; PON1 L55M might increase breast cancer risk. However, given the limited sample size, the findings warrant further investigation.
瘦素（LEP）、瘦素受体（LEPR）和对氧磷酶1（PON1）基因的常见遗传变异被认为与乳腺癌的发生有关。然而，结果并不一致。在本研究中，进行了一项荟萃分析，以评估包括LEP G2548A、LEPR Q223R、LEPR Lys109Arg、PON1 L55M和PON1 Q192R多态性在内的五种多态性与乳腺癌风险的关联。检索了来自PubMed、ISI Web of Science、Embase数据库、中国知网和万方数据的已发表文献。纳入了所有评估LEP G2548A、LEPR Q223R、LEPR Lys109Arg、PON1 L55M或PON1 Q192R多态性与乳腺癌风险之间关联的研究。使用固定效应或随机效应模型计算合并比值比（OR）及其95%置信区间（CI）。荟萃分析纳入了三项关于LEP G2548A多态性的研究（2003例病例和1967例对照）、九项关于LEPR Q223R多态性的研究（4627例病例和5476例对照）、五项关于LEPR Lys109Arg多态性的研究（2759例病例和2573例对照）、四项关于PON1 L55M多态性的研究（1517例病例和1379例对照）以及五项关于PON1 Q192R多态性的研究（1575例病例和2283例对照）。总体而言，结果显示LEP G2548A、LEPR Q223R、LEPR Lys109Arg或PON1 Q192R多态性与乳腺癌风险之间无显著关联；然而，PON1 L55M总体上与乳腺癌风险显著相关（MM与LL相比：OR = 2.16；95%CI，1.76 - 2.66）。对于LEPR Q223R多态性，进一步的亚组分析表明，该关联仅在东亚人群中具有统计学意义（OR = 0.50；95%CI，0.36 - 0.70），而在白种人（OR = 1.06；95%CI，0.77 - 1.45）或非洲人（OR = 1.30；95%CI，0.83 - 2.03）中无统计学意义。本荟萃分析表明，LEPR Q223R多态性可能与东亚人群乳腺癌的发生有关；PON1 L55M可能增加乳腺癌风险。然而，鉴于样本量有限，这些发现有待进一步研究。
