Studies Of HLA-DPB1 Polymorphisms In Population At The High And Low Risk Of Gastric Cancer

PrefaceGastric cancer is the major malignant tumor in our country, which is the critical risk factor of population health. In the past years, most of scholars recognized that multiple factors were involved in carcinogenesis of gastric cancer , especially coaction of environmental factors and hereditary factors. The infection of H. pylori is closely associated with precancerous gastric lesions and gastric cancer, and clinic symptoms of H. pylori + positive persons are various,which are association with not only H. pylori virulence but also inherit ingredient.. HLA locates on chromosome 6p21,composed with Ⅰ, Ⅱ,Ⅲ, and that is the most complicated heredity system. HLA class II genes comprise of DR DQ DP,DR has the most polymorphisms (DRA1,DRB1,DRB2 and so on ) ,DP polymorphisms is inferior to DR, composed with DPA1,A2,DPB1,B2. In the recent years,some researches have indicated that DR DQ polymorphisms are associated with gastric diseases. But the report about relationship of DPB1 polymorphisms and gastric diseases is lack, and the study is much less in which research objects are the cases of the high and low area of gastric cancer. Based on the population data of the high and low area of gastric cancer, our study analyses distribution difference of HLA — DPB1 polymorphisms, and explores the relationship between distribution difference and the risk of gastric cancer and the infection of H. pylori. In order to further look for the cautelous signal of gastric cancer genetic susceptibility , and definitude the coaction of environmental and inherit factors in the development of gastric cancer as well as the possible action mechanism.Materials and MethodsPeripheral venous blood were drawn from study objects. Genomic DNA was isolated from peripheral blood using conventional hydroxybenzene - chloroform technique. The second DPB1 exon was amplified using the oligonucleotide primer , the amplified DNA were digested with restriction endonucleases for 3 ~ 4 hour in 371. The digested DNA samples were run in 4% agarose gels at 160v for 40min . The DNA fragment were revealed by BET( bromoethidium chlorid) coloration. ELISA detected serum H. pylori - IgG,and higher than 42EIU for positive, or else for negative. Then 4 biopsy tissue took from corpusN angle^antrum and focus of infection by gastroscopy were carried out pathohistology diagnosis for case subgroup.Results1. The DNA typing of HLA - DPB1 polymorphisms: Four HLA - DPB1 polymorphisms were detected : The most predominant DPB1 allele was DPB1 * 1401 with the frequency of 64. 99% , followed by DPB1 * 1701 (5. 8% ) , * 0901(3.6%), * 0301 (1.0%);2. Distribution difference between the high and low area of gastric cancer;alleles were found significantly different in population between the high and low area of gastric carcinoma, population of the high area has a lower allele frequency of DPB1 * 0901 (OR = 0.25 95% CI = 0. 144 ~ 0.431;P = 0) and higher allele frequency of DPB1 * 1701 (OR = 4. 212 95% CI = 2. 463 ~ 7. 202;P = 0 ) compared with population of the low area;3. The relationship between HLA -DPB1 polymorphisms and gastric diseases and the infection of H. pylori: No significant difference was found among DPB1 *0901, * 1401, * 1701 alleles in the gastric cases. No significant difference was found among DPB1 * 0901, * 1401, * 1701 alleles between Hp + positive and Hp - negative population;analysed coaction of HLA - DPB1 polymorphisms and the infection of H. pylori for gastric cancer ,no significant differencewas found.Conclusions1. HLA - DPB1 polymorphisms ( DPB1 * 0901, * 1701) has significant difference in the frequency of carriers between the high and low area of gastric carcinoma.2. No association was found between distribution difference and gastric cancer susceptibility and the infection of H. pylori.