P07: Gastric cancer risks among atomic-bomb survivors differ by HLA class I genotype

Abstract

Since radiation exposure affects the immune system as well as risk of various cancers, we have commenced an “immunogenome” study to look at genetic susceptibility to radiation-associated cancers. HLA class I molecules are known to regulate various immune and inflammatory responses. In this study, we examined effects of radiation exposure on individual susceptibility to gastric cancer based on HLA Class I ( HLA-A, -B, -C ) polymorphisms. This study comprised 150 gastric cancer patients and 300 controls. HLA genotype distribution among the controls not exposed to atomic-bomb radiation was almost identical to that in the general Japanese population. Comparison between non-exposed gastric cancer patients and non-exposed controls showed no statistically significant relationship between gastric cancer risk and HLA-B or HLA-C genotypes. However, frequency of HLA-A*2601 , one of the HLA-A genotypes, was significantly lower among cases (3.7%) than controls (18.3%), with P HLA-A*2601 among the gastric cancer patients (average radiation dose: 0.8 Gy) (18.8%) was almost the same as frequency among the controls (15.8%). Risk elevation by radiation was most prominent in HLA-A*2601 , compared with other genotypes. These results suggest that HLA-A*2601 may be involved in decreased gastric cancer risk among non-exposed people and that, among those with the HLA-A*2601 allele, radiation exposure may increase gastric cancer risk. On the basis of this finding, we conducted further analysis of association between the HLA-A*2601 allele and plasma levels of various inflammatory markers along with analyses of pathological typing and H. pylori infection.