Studies On Association Of The Overweight/Obesity,Helicobacter Pylori Infection And Gastric Cancer

Gastric cancer is one of the most common malignancies in China. The incidence and mortality of gastric cancer were ranked third and fourth respectively among all the malignant tumors worldwide. Gastric cancer is considered to be affected synthetically by life behavior, genetic factors and environmental factors.With the changes of diet and life style, the number of overweight and obese people increased dramatically worldwide. As a result, the public health problems caused by overweight/obesity have aroused people’s attention. Overweight/obesity not only increased the risk of diabetes and cardiovascular disease, but also closely related to several kinds of malignant tumors including gastric cancer.Among all the environmental factors leading to stomach cancer, helicobacter pylori(Hp) is closely relately to the initiation, progression and prognosis of stomach cancer. There are many reasons for Hp infection. Recent studies have shown that overweight/obesity can lead to depression and poor immune function, as a consequence human body would be easily attacked by bacteria and virus.Among all the genetic factors which play an important role in the development of cancer, especially in stomach cancer,genetic predisposition is the principal one. As an important component of functional genomics, single nucleotide polymorphism(SNP) is one genetic basis for racial diversity and interindividual variation, meanwhile it is an important strategy for studies of tumour genetic susceptibility. The relationship between obesity associated genetic variation and disease has attracted greater attention in recent yearsThe occurrence and development of gastric cancer is a complex pathological process, which cannot be explained and revealed by single factor. We conceive of obesity may make the body susceptible to Hp, Hp infection and obesity to further promote the occurrence of gastric cancer. In this paper, we focused on the three major causes of gastric cancer and discussed the relationships among body mass index (BMI), gastric cancer and Hp infection. Also, the association of gene polymorphism related to obesity and susceptibility to gastric cancer was discussed further. There are three parts to the study.Part I Case-control study on the relationship between gastric cancer and overweight or obesityObjective:Body mass index (BMI) is the internationally diagnosis index for overweight/obesity. There are few research on the relationship between BMI and gastric cancer. The purpose of this study is to investigate whether the incidence of gastric in Gansu province is related to overweight/obesity. In the meantime, the effect of overweight/obesity on clinicopathologic characteristics will be discussed further.Method:A hospital-based case-control study was employed for cross sectional analysis on 546 gastric cancer samples and 632 control samples. The general information of case group and control group was described with frequency, mean and standard deviation. T test and X2 test were used to compare the differences between groups. Multiple linear regressions were used to determine the correlation between level of BMI and prevalence of gastric cancer. We evaluated the correlation between BMI and clinicopathologic characteristics with Pearson correlation test.Results:Gastric cancer patients’BMI is higher than control group (P< 0.05), BMI is an independent disease related factor of age and sex (P< 0.05).Compared with normal weight, overweight and obesity increased risk of gastric cancer, OR values were 1.352,4.109. Patients’BMI with cardia cancer is higher than the non-cardia cancer.Higher BMI is one of the cardia cancer pathogenesis related factors (P< 0.05).Compared with the no-cardia cancer patients, BMI of male patients with cardia cancer is higher than female (P< 0.05). BMI of cadia cancer patients over 60 years old is higher than who are younger than 60. (P< 0.05).Conclusion:The incidence of gastric cancer was significant correlation with overweight/obesity in the area of Gansu. Among people over 60, overweight and obese people are more likely to develop gastric cancer.Part Ⅱ Study on the relationship between Hp infection and overweight or obesityObjective:It has been confirmed in part I that overweight/obesity people are correlated significantly with the risk of gastric cancer. Whether people who is the overweight and obese people has higher risk of gastric cancer are susceptible to the infection of Hp. Here, we studied the relationship between BMI and Hp infection in gastric cancer patients and healthy people to verify the Hp infection in gastric patients is related with overweight/obesity.Method:The infection of Hp was examined by ELISA and improved silver staining method in all the objects, a study population including 378 gastric patients and 498 controls was established. Investigated BMI and the infection of Hp by system analysis. The general information was described with frequency, mean and standard deviation. T test and X2 test were used to compare the BMI differences between patients and controls.Results:The detection rate of Hp in gastric cancer group and control group were 70.6% and 58.2% respectively, a significant difference between the two groups (P<0.05); Overweight and obese people in both patients and controls are at higher risk of Hp infection (P<0.05); The infection rate of overweight people in group over 60 years of age is higher than it in under the age of 60 years group. There was significant difference between groups (P<0.05).Conclusion:The infection rate of Hp in gastric patients is significantly higher than in controls. Overweight and obese people are more likely to be infected by Hp, and the infection of Hp is closely related to overweight/obesity in group over 60 years of age.Part Ⅲ The association study between obese genes polymorphism and gastric cancerObjective:In our previous studies, we have drawn the conclusion that overweight and obese are risk factors for the onset of gastric cancer and Helicobacter pylori infection. Case control study based on the investigations of BMI is only a cross-sectional study and limited to evaluate the causal relationship between overweight/obesity and gastric cancer. Therefore, further studies needed to investigate the relationship between overweight/obesity and the susceptibility of gastric cancer.Methods:A case control study was carried out with the PCR-RFLP and Tagman probes in 546 patients with gastric cancer and 632 healthy controls focused on the SNP sets for the LEP gene rs7799039, rs1161556 and rs2167270 variants; LEPR gene rs1137101 variant; GHRL gene rs1629816 variant and GHSR gene rs509035 variant.Results:The distributions of genotype frequency of all six tested SNPs satisfied with the Hardy-Weinberg Equilibrium. The difference on GG genotype of GHSR gene Rs509035 between case group and control group was statistically significant (P=0.001). Allele G was significantly different between case group and control group(P=0.002).GG genotype frequency was statistically different between patients with gastric cancer and healthy control subjects in male(P=0.012). The distributions of GG genotype frequency and allele G frequency were significantly different between non-cardia gastric cancer and control group(P=0.001 and P=0.002, respectively).For rs1137101 variant, AG genotype frequency was significantly different(P=0.015). The distributions of Rs1629816 AG genotype frequency and allele G frequency were statistically different between cardia gastric cancer and control groups(P=0.022 and 0.027, respectively). No statistically differences were observed on genotypes and alleleic genes frequencies of rs7799039, rs11791556 and rs2167270 variants. MDR analysis dimension reduction method showed, rs509035 loci and BMI independent effect maximum (IG quantity was 1.14% and 3.85%).Conclusions:GHSR rs509035 variant was associated with the susceptibility of gastric cancer, especially non-cardia gastric cancer. GHRL rs1629816 variant was associated with the susceptibility of gastric cancer, especially cardia gastric cancer. No evidences were found in this study that LEP rs7799039, rs17761556 and rs2167270 variants, LEPR rs137101 variant was associated with the susceptibility of gastric cancer.Rs509035 loci and BMI are independent risk factors of gastric cancer. There is no interactions among LEP gene/GHRL signal pathway, BMI and Hp infection on is gastric cancer.