Published online Aug 28, 2020. doi: 10.3748/wjg.v26.i32.4817
Peer-review started: March 12, 2020
First decision: May 15, 2020
Revised: July 2, 2020
Accepted: August 20, 2020
Article in press: August 20, 2020
Published online: August 28, 2020
Polymorphisms of human leukocyte antigen (HLA) genes are suggested to increase the risk of gastric cancer (GC).
To investigate the HLA allele frequencies of patients with GC relative to a control group in terms of CagA+ multiple (≥ 2) EPIYA-C repeats.
The patient group comprised 94 patients [44 GC and 50 duodenal ulcer (DU) patients], and the control group comprised 86 individuals [(50 non-ulcer dyspepsia patients and 36 people with asymptomatic Helicobacter pylori (H. pylori)]. Polymerase chain reaction was performed for the amplification of the H. pylori cagA gene and typing of EPIYA motifs. HLA sequence-specific oligonucleotide (SSO) typing was performed using Lifecodes SSO typing kits (HLA-A, HLA-B HLA-C, HLA-DRB1, and HLA-DQA1-B1 kits).
The comparison of GC cases in terms of CagA+ multiple (≥ 2) EPIYA-C repeats showed that only the HLA-DQB1*06 allele [odds ratio (OR): 0.37, P = 0.036] was significantly lower, but significance was lost after correction (Pc = 0.1845). The HLA-DQA1*01 allele had a high ratio in GC cases with multiple EPIYA-C repeats, but this was not significant in the univariate analysis. We compared allele frequencies in the DU cases alone and in GC and DU cases together using the same criterion, and none of the HLA alleles were significantly associated with GC or DU. Also, none of the alleles were detected as independent risk factors after the multivariate analysis. On the other hand, in a multivariate logistic regression with no discriminative criterion, HLA-DQA1*01 (OR = 1.848), HLA-DQB1*06 (OR = 1.821) and HLA-A*02 (OR = 1.579) alleles were detected as independent risk factors for GC and DU.
None of the HLA alleles were detected as independent risk factors in terms of CagA+ multiple EPIYA-C repeats. However, HLA-DQA1*01, HLA-DQB1*0601, and HLA-A*2 were independent risk factors with no criterion in the multivariate analysis. We suggest that the association of these alleles with gastric malignancies is not specifically related to cagA and multiple EPIYA C repeats.
Core tip: The development of gastric cancer (GC) is suggested to be related to the interactions of bacterial virulence and host genetic factors with the immune response of the host. The effects of polymorphisms in the human leukocyte antigen (HLA) gene may regulate the degree of the inflammatory response of the host leading to the gastric malignancies. We could not detect any prominent HLA alleles between the patient and control groups in terms of CagA+ multiple (≥ 2) EPIYA-C repeat numbers. HLA-DQA1*01, HLA-DQB1*06, and HLA-A*02 were detected as independent risk factors for the risk of GC and duodenal ulcer with no criterion in multivariate analyses. We suggest that the association of these alleles with gastric malignancies is not specifically related to cagA and multiple EPIYA C repeats.