Association of LEP A19G polymorphism with cancer risk: a systematic review and pooled analysis

Abstract

The results from the published studies on the association between leptin (LEP) genetic polymorphism and cancer risk are conflicting. The common A19G (rs2167270) genetic polymorphism has been reported to be functional and may contribute to genetic susceptibility to cancers. However, the association between LEP A19G (rs2167270) genetic polymorphism and cancer risk remains inconclusive. To better understand the role of LEP A19G (rs2167270) genetic polymorphism in global cancer, we conducted this comprehensive meta-analysis encompassing 5,679 cases and 7,443 controls. Overall, the LEP A19G (rs2167270) genetic polymorphism was associated with lower cancer risk. In the stratified analysis, significant associations were found between the LEP A19G (rs2167270) genetic polymorphism and colorectal cancer and non-Hodgkin's lymphoma. For colorectal cancer, there was no significant association of LEP A19G (rs2167270) variant with this disease under heterozygous codominant model [odds ratio (OR) = 1.11 (0.97-1.27)], dominant genetic model [OR = 1.03 (0.91-1.17)], and additive genetic model [OR = 0.94 (0.86-1.03)]; however, there was a marginal association under homozygous codominant model [OR = 0.80 (0.66-0.97)] and recessive genetic model [OR = 0.75 (0.63-0.90)]. For non-Hodgkin's lymphoma, there was a significant association of LEP A19G (rs2167270) variant with the disease under homozygous codominant model [OR = 0.74 (0.59-0.94)], recessive genetic model [OR = 0.76 (0.61-0.94)], and additive genetic model [OR = 0.89 (0.80-0.99)], but not under heterozygous codominant model [OR = 0.95 (0.82-1.10)] and dominant genetic model [OR = 0.91 (0.79-1.04)]. Moreover, a significantly decreased cancer risk was found in recessive genetic model among Latin American population. When stratified by study design, significantly elevated susceptibility to cancer was not found among any studies. No significantly differences in genotype method and sample size in cases were found among genotypes. These findings suggest that the LEP A19G (rs2167270) genetic polymorphism may decrease the susceptibility to cancers in colorectal cancer and non-Hodgkin's lymphoma, when assuming a homozygote codominant model and a recessive genetic model among Latin American population. The phenomenon also indicates that the SNP functions as a recessive mutation, which needs to be verified or linked with functional studies.

Leptin gene variants and colorectal cancer risk: Sex-specific associations

“…Some studies have observed associations of the A allele of LEP rs2167270 –the reference allele in our study–with elevated leptin levels [ 24 , 55 ]. Contradictory to what we would then expect given the proposed directional effect, several studies have reported significant association of the A allele of this variant with decreased CRC risk [ 39 , 40 ]. Consistent with these observations, our study observed that the G allele of this variant was associated with a modest increased CRC risk among women.…”

Gender Differences in Adipocyte Metabolism and Liver Cancer Progression

“…DNA polymorphism in the leptin gene is associated with tumorigenesis of multiple cancer types, such as lung cancer, lymphoma, thyroid cancer, and colon cancer ( Slattery et al, 2008 ; Liu et al, 2014 ; Unsal et al, 2014 ; Marcello et al, 2015 ). LEP is primarily expressed in differentiated adipocytes of white adipose tissue, and the hormone leptin it encodes for, plays a role in the regulation of food intake and the expression of energy-regulating peptides.…”

Investigation of <em>LEP </em>and <em>LEPR </em>polymorphisms with the risk of hepatocellular carcinoma: a case&ndash;control study in Eastern Chinese Han population

“…Some previous meta-analyses suggested that LEP rs7799039 A>G and rs2167270 G>A variants conferred risk to cancer. 15 – 17 However, the association of LEP rs7799039 A>G and rs2167270 G>A polymorphisms with HCC risk is unknown.…”