Yang Yunji, Liu Pengcheng, Guo Feng, Liu Run, Yang Yong, Huang Changjia, Shu Hexi, Gong Jinpeng, Cai Ming
Department of Orthopedics , Shanghai Tenth People's Hospital , Tongji University, School of Medicine , Shanghai, China.
J BUON. 2014 Oct-Dec;19(4):1096-104.
The results from the published studies on the association between LEP (leptin) genetic polymorphism and cancer risk are conflicting. The common G2548A genetic polymorphism has been reported to be functional and may contribute to genetic susceptibility to cancers. However, the association between LEP G2548A genetic polymorphism and cancer risk remains inconclusive.
To better understand the role of LEP G2548A genetic polymorphism in global cancer, we conducted this comprehensive meta-analysis encompassing 6860 cases and 7956 controls.
Overall, the LEP G2548A genetic polymorphism was associated with higher cancer risk in three genetic models (AA vs GG, AA vs AG/GG, A vs G). In the stratified analysis, there was significant association of LEP G2548A variant with non-Hodgkin's lymphoma (NHL) under homozygous co-dominant model (OR=1.27, 95% CI 1.01-1.60) and additive genetic model (OR=1.14, 95% CI 1.01-1.28). Moreover, a significantly increased cancer risk was found in three genetic models (AA vs GG, AA vs AG/GG, A vs G) among Caucasian population. For Asians, no significant associations were observed in any genetic model tested.
These findings suggest that the LEP G2548A genetic polymorphism may increase the susceptibility of cancers in NHL, especially in the homozygote co-dominant model and the additive genetic model among Caucasian populations. The phenomenon also indicates that the SNP functions as a recessive mutation, which needs to be verified or linked with functional studies.
已发表的关于瘦素(LEP)基因多态性与癌症风险之间关联的研究结果相互矛盾。常见的G2548A基因多态性据报道具有功能性,可能会导致癌症的遗传易感性。然而,LEP G2548A基因多态性与癌症风险之间的关联仍无定论。
为了更好地理解LEP G2548A基因多态性在全球癌症中的作用,我们进行了这项综合荟萃分析,纳入了6860例病例和7956例对照。
总体而言,在三种遗传模型(AA与GG、AA与AG/GG、A与G)中,LEP G2548A基因多态性与较高的癌症风险相关。在分层分析中,在纯合共显性模型(OR = 1.27,95% CI 1.01 - 1.60)和加性遗传模型(OR = 1.14,95% CI 1.01 - 1.28)下,LEP G2548A变异与非霍奇金淋巴瘤(NHL)存在显著关联。此外,在白种人群中,三种遗传模型(AA与GG、AA与AG/GG、A与G)均发现癌症风险显著增加。对于亚洲人,在任何测试的遗传模型中均未观察到显著关联。
这些发现表明,LEP G2548A基因多态性可能会增加NHL中癌症的易感性,尤其是在白种人群的纯合子共显性模型和加性遗传模型中。这一现象还表明该单核苷酸多态性起隐性突变的作用,这需要通过功能研究进行验证或关联。