Investigation of Leptin and its receptor (LEPR) for single nucleotide polymorphisms in colorectal cancer: A case-control study involving 2,306 subjects.

Abstract

e16100 Background: Colorectal cancer is a leading cause of cancer deaths, with poor prognosis. Some studies have reported that obesity and overweight are risk factor for the development of CRC. Leptin ( LEP) and its receptor ( LEPR) single nucleotide polymorphisms (SNPs) might regulate energy balance and be implicated in the development of CRC. The aim of this case-control study was to assess the association of LEP rs2167270 G > A, rs7799039 A > G, LEPR rs6588147 G > A, rs1137100 G > A and rs1137101 G > A SNPs with susceptibility to CRC in Eastern Chinese Han population. Methods: 1,003 CRC cases and 1,303 matched controls was compared. Five functional SNPs in LEP and LEPR genes were chosen to evaluate the correlation of these chosen SNPs with CRC susceptibility. We used the SNPscan genotyping assay to genotype LEP and LEPR SNPs. Results: A significantly decreased risk of CRC was found to be associated with the LEPR rs6588147 polymorphism (GA vs. GG: crude P= 0.007 and GA/AA vs. GG: crude P= 0.018). With adjustments for risk factors (e.g. age, gender, drinking, BMI and smoking), these associations were not changed. In subgroup analyses, the association of LEP rs2167270 with a decreased risk of CRC was found in the ≥61 years old subgroup. For LEPR rs1137100, the association of this SNP with an increased susceptibility of CRC was found in the BMI < 24 kg/m2 subgroup. In subgroup analyses for LEPR rs6588147, we identified that this locus also decreased the susceptibility of CRC in the male subgroup, < 61 years old subgroup, never smoking subgroup and never drinking subgroup. For LEPR rs1137101, the relationship of this polymorphism with a decreased susceptibility to CRC was found in the never drinking subgroup. Conclusions: The present study highlights that LEPR rs6588147, rs1137101 and LEP rs2167270 may decrease the risk of CRC. However, LEPR rs1137100 is associated with susceptibility to CRC. Further case-control studies with larger sample sizes should be conducted to validate our findings.