title: Association between LMP2 and LMP7 gene polymorphisms and the risk of gastric cancer: A case-control study.
abstract: The integrality of low molecular weight protein (LMP)2/LMP7 function plays an important role in the processing of GC cell antigens. The purpose of the present hospital-based case-control study was to estimate the effect of polymorphisms in the LMP2 and LMP7 genes on the risk of GC. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to distinguish the Arg to His substitution at codon 60 of LMP2 (LMP2-60) and the Gln to Lys substitution at codon 145 of LMP7 (LMP7-145) in 502 gastric cancer patients and 502 age and gender-matched cancer-free control individuals. The Lys allele of the LMP7-145 variant was more frequent in GC patients compared with control individuals [P=0.004; adjusted odds ratio (OR), 1.39; 95% confidence interval (CI), 1.11-1.74]. The Gln/Lys and Lys/Lys genotypes increased the risk of GC compared with the Gln/Gln genotype (P=0.049 and P=0.041, respectively; adjusted OR, 1.32 and 2.13, respectively; 95% CI, 1.00-1.73 and 1.03-4.39, respectively). Compared with the Gln/Gln genotype, the LMP7-145 Gln/Lys and Lys/Lys variants of the LMP7 gene were also associated with increased susceptibility to GC (P=0.017; adjusted OR, 1.38; 95% CI, 1.06-1.80). Haplotype analysis revealed that the LMP2 (Arg)-LMP7 (Lys) haplotype was associated with increased risk of GC (P=0.013, adjusted OR=1.34, 95% CI=1.06-1.70). Stratified analysis revealed that the association between the risk of GC and the variant genotypes of LMP7-145 was stronger in older individuals (>59 years), males and non-smokers. However, no association between the LMP2-60 polymorphism and the risk of GC was observed. The present results suggest that the LMP7-145 genetic variant contributes to increased susceptibility to GC, and the Lys allele is an independent risk factor for GC.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Zekuan
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Younan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China ; Jiangsu Province Academy of Clinical Medicine, Institute of Tumor Biology, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: L I
authors.initials: LI
authors.lastname: Yang
keywords: LMP2/LMP7; gastric cancer; gene polymorphism