Genetic G2548A polymorphism of leptin gene and risk of cancer: a meta-analysis of 6860 cases and 7956 controls

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.