| Background Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related death worldwide. Epidemiological studies have identified many risk factors for gastric cancer, such as Helicobacter pylori (H. pylori) infection, low fiber intake, and tobacco smoking, however, only a fraction of individuals exposed to these factors develop gastric cancer during their lifetime, which suggests that genetic susceptibility plays an important role in gastric carcinogenesis. It has been reported that polymorphisms in prostate stem cell antigen (PSCA), mucin1gene(MUC1), Selenoprotein S(SEPS1) and tumor necrosis factor-a(TNF-a)genes were associated with the risk of gastric cancer, and polymorphism in mothers against decapentaplegic homolog7(SMAD7)gene was associated with colorectal cancer in a Western population.Objective (1) Analyzed the clinical and pathological data of300gastric cancers by comparing the cardia and non-cardia gastric cancers in clinicopathological profiles, in order to give a better understanding of the profiles of gastric cancer in our region.(2) Analyzed the relationship of single nucleotide polymorphisms in PSCA rs2294008, MUC1rs2070803, SMAD7rsl2953717, TNF-a rs361525, SEPS1rs28665122and susceptibility to gastric cancer with different clinic pathological profiles in a population from Hunan province.Methods300pathologically confirmed gastric cancer patients were enrolled at the Xiangya Hospital of Central South University, The Second-Xiangya Hospital of Central South University and Tumor Hospital of Hunan Province, between June2011and November2011.300healthy controls were selected randomly from the same geographic region as the patients with gastric cancer. First analyze the clinical and pathological data of gastric cancer, then300cases of gastric cancer and300controls were genetyped for PSCA rs2294008, MUC1rs2070803, SMAD7rsl2953717, TNF-a rs361525, SEPS1rs28665122by means of Matrix-assisted laser desorptionionization time-of-flight mass spectrometry(MALDI-TOF-MS). Chi-square test was used to compare demographic distributions and pathological profiles between cases and controls. Hardy-Weinberg equilibrium was checked for controls using the goodness-of-fit χ2test. The associations between the genotypes and risk of gastric cancer were estimated by calculating the odds ratios (ORs) with95%confidence intervals (CIs) using unconditional logistic regression analyses adjusted for age and gender. All tests were conducted at the P=0.05level of significance, using SPSS13.0software package (SPSS, Chicago, IL).Results (1) The main clinicopathological profiles of gastric cancer in our region:gastric cardia canceraccounted for26.3%, while non-cardia cancer accounted for73.7%of total300patients. There was a significant difference in the gender composition between cardia and non-cardia cancer, the male/female ratio was significantly higher in cardia cancer than that of non-cardia gastric cancer (2.7/1vsl.5/1, P=0.04). There was no significant difference on average age between cardia cancer patients (51.2±12.2years) and non-cardia gastric cancer group(52.5±11.4years). The proportion of patients over65years of age in cardia cancer group was significantly higher than that of non-cardia gastric cancer group (24.1%vs12.7%, P=0.020). According to Lauren classification, the proportion of intestinal-type gastric cancer in cardia cancer was significantly higher than that of non-cardia gastric cancer(82.4%vs70.1%, P=0.035). Classification according to the degree of differentiation, the proportion of poorly differentiated type in cardia cancer was significantly lower than that of non-cardia gastriccancer (56.0%vs74.5%, P<0.001). The cases are mostly advanced gastric cancer and TNM staging were not significant different between cardia and non-cardia gastric cancer(P=0.160). To compare the findings with other studies in othe countries or regions, we found that the proportion of gastric cardia cancer was consistent with the results from Shanxi, Shenyang, Portugal and England (21.5%-29.5%), but higher than results from SouthKorea and Japan, which was reported to be less than10%. Consistent results in gender composition and age of onset were observed in them(2.7/1VS1.66-3.7/1, the average age of onset:52.1-63.0y). This study was more consistent with Portugal and England with respect to the Lauren classification and TNM staging, as both were mainly intestinal type and with advanced TNM stages(Ⅲ-Ⅳ), whose proportions were significantly higher than Shenyang, SouthKorea and Japan (62.1%VS41.3%-56.4%).Conclusion (1) The main clinic pathological profiles of gastric cancer in our region were susceptible with men, late age of onset, intestinal type, poorly differentiated and late TNM staging; compared with non-cardia gastric cancer, cardia cancer tends to be male-dominated, more inclined to well-differentiated and intestinal type.(2) PSCA rs2294008was associated with increased risk of gastric cancer. TT genotype increased gastric cancer risk to an odd of2.26(95%CI1.25-4.07, P=0.007), TC to1.72(95%CI1.23-2.42, P=0.002) compared with CC genetype. Further stratification analysis revealed that rs2294008TT and TC genotypes had a consistently increased risk on both intestinal and diffuse-type gastric cancer.(3) MUC1rs2070803was associated with the susceptibility to gastric cancer. GA genotype was associated with decreased gastric cancer risk to an odd of0.42(95%CI0.28-0.62) compared with GG genetype. Further stratification analysis revealed that the effect of rs2070803in MUC1was consistent in both intestinal and diffuse-subtypes.(4) There were no statistical differences on SMAD7 rs12953717genotypes frequencies between gastric cancer cases and controls, and between the two pathologic subtypes of gastric cancer.(5) TNF-a rs361525AA genotype was significantly associated with increased gastric cancer risk (OR=2.15,95%CI1.06-4.37, P=0.035). AA genotype was significantly associated with decreased intestinal-type gastric cancer risk (OR=0.42,95%CI:0.20-0.89, P=0.023), however, there were no statistical differences on TNF-a rs361525genotype frequencies between intestinal gastric cancer and controls.(6) SEPS1rs28665122GA genotype was significantly associated with decreased gastric cancer risk (OR=0.63,95%CI:0.40-0.99, P=0.044). AA genotype was significantly associated with increased intestinal-type gastric cancer risk (OR=1.71,95%CI:1.02-2.84, P=0.041), however, there were no statistical differences on genotypes frequencies between intestinal gastric cancer and controls. |
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