Association between LMP2 and LMP7 gene polymorphisms and the risk of gastric cancer: A case-control study

Abstract

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.

The Immunoproteasome in oxidative stress, aging, and disease

“…For example, polymorphisms within LMP7 shows a higher prevalence in gastric cancer (GC), whereas LMP2 polymorphisms, within the same cancer, were not associated with promoting GC (Ma et al, 2015). Conversely, polymorphisms within LMP2 were found to play a key role in the development of acute myeloid leukemia and multiple myelomas, whereas polymorphisms within LMP7 were not considered a risk factor (Yu et al, 2013).…”

Lack of association between ERCC5 gene polymorphisms and gastric cancer risk in a Chinese population

“…However, not all individuals exposed to such risk factors develop this disease, suggesting that genetic factors may contribute to its development. Indeed, many previous studies have reported that certain genes are involved in gastric cancer risk, includingmiR-146a, IL-17A, LMP2, LMP7, IGF1, and GSTM1 (Farahani et al, 2015;Hou and Yang, 2015;Ma et al, 2015;Wei et al, 2015;Zhang and Cui, 2015).…”

LMP2 immunoproteasome promotes lymphocyte survival by degrading apoptotic BH3‐only proteins

“…Similarly in mice, genetic loss of LMP7 mice causes accumulation of polyubiquitinated proteins and oxidative stress . Strikingly, several human diseases, including multiple myeloma, gastric cancer, Huntington's Disease, Alzheimer's Disease and amyotrophic lateral sclerosis, have increased IP levels or are associated with subunit polymorphisms . These observations are also hard to reconcile with the canonical role of IPs in antigen presentation.…”