title: Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis.
abstract: BACKGROUND
  Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations.
  
  
  METHODS
  We searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A) and rs1137101 (Q223R) in normal cell lines derived from 270 subjects with different ethnicities.
  
  
  RESULTS
  The final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41). Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51) but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity.
  
  
  CONCLUSIONS
  Despite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies.
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China ; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.forename: Bo
authors.initials: B
authors.lastname: Xi
authors.forename: Rikje
authors.initials: R
authors.lastname: Ruiter
authors.forename: Ting-Yan
authors.initials: TY
authors.lastname: Shi
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Zhu
authors.forename: Meng-Yun
authors.initials: MY
authors.lastname: Wang
authors.forename: Qiao-Xin
authors.initials: QX
authors.lastname: Li
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhou
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Qiu
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Wei
mesh_terms: D016022:Case-Control Studies; D016206:Databases, Bibliographic; D020022:Genetic Predisposition to Disease; D060148:HapMap Project; D006801:Humans; D020738:Leptin / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D009369:Neoplasms / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D044469:Racial Groups; D054411:Receptors, Leptin / Q000235:genetics*
chemical_list: D020738:Leptin; D012333:RNA, Messenger; D054411:Receptors, Leptin