• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3325-3328
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• 2012

Aim: To evaluate the association of glutathione S-transferases gene polymorphisms with the risk of gastric cancer, with reference to smoking and Helicobacter pylori infection. Methods: We conducted a 1:1 matched case-control study with 410 gastric cancer cases and 410 cancer-free controls. Polymorphisms of GSTM1, GSTT1 and GSTP1 were determined using PCR-CTPP. Results: The GSTM1 and GSTT1 null genotypes were significantly associated with the risk of gastric cancer after adjusting for potential confounding factors (OR=1.68, 95% CI=1.32-2.23 for null GSTM1, OR=1.73; 95% CI=1.24-2.13 for null GSTT1). The combination of null GSTM1 and null GSTT1 conferred an elevated risk (OR=2.54, 95% CI=1.55-3.39). However, no association was found for GSTP1 polymorphism The smoking modified the association of GSTM1 and GSTT1 null genotypes with the risk of gastric cancer. Conclusion: GSTM1 and GSTT1 null genotypes are associated with increased risk of gastric cancer, and smoking modifies the association.

• Journal of Gastric Cancer
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• v.1 no.1
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• pp.24-31
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• 2001

Purpose: Despite knowledge of the adverse effects of resection-line disease, surgeons continue to perform inadequate resections. This demonstrates the need for a more aggressive approach to assessment of resection margins at operation. Materials and Methods: Seven hundred fifteen gastric cancer patients who were operated on at our hospital from 1992 to 1998 were included in this analysis. Various clinicopathological factors, including resection-line involvement, were ascertained from the surgical and histopathological records. Results: Of the 715 evaluable patients, 27 patients ($3.8\%$) had involvement of one or both resection lines; in 10 patients the proximal resection line only, in 16 the distal resection line only, and 1 both resection lines were involved. Presence of resection-line involvement was significantly associated with T3 and T4 stage, N (+) stage, M (+) stage, type of operation (total gastrectomy), tumor location (entire stomach), size$\geq$11 cm), and gross type of tumor (Borrmann 4 type). When performing a distal subtotal gastrectomy, no involvement was found when the cranial and caudal distances between the lesion and the line of transection was equal to or greater than 2 cm and 3 cm, respectively, for early cancer and 7 cm and 3 cm, respectively, for advanced cancer. When performing a total gastrectomy for upper 1/3 or middle 1/3 gastric cancer, no involvement was found when the cranial distances between the lesion and the line of transection were equal to or greater than 3 cm and 4 cm, respectively, without distinction of the presence of serosal invasion. Conclusions: The difference in survival between positive and negative margin patients is limited to the group of patients with curative surgery. An important principle of treatment is that the entire tumor must be removed with a 3 cm distal margin and a 2- to 7 cm margin depending on the location and the depth of wall invasion of the tumor, to provide histologically negative margins.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.945-951
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• 2012

Objective: FAS/FASL gene promoter polymorphisms have been repeatedly associated with gastric cancer risk, but findings are inconclusive across studies. To address a more precise estimation of the relationship, a meta-analysis was performed. Methods: Data were collected from the Pubmed, Medline and EMBASE databases, with the last report up to 1 December, 2011. Crude ORs with 95% CIs were used to assess the strength of the association by (1) the additive, (2) the codominant, (3) the dominant, and (4) the recessive models. Results: A total of seven studies, including six studies on FAS -1377G>A polymorphism, five studies on FAS -670A>G polymorphism, and six studies on FASL -844T>C polymorphism, were identified in the current meta-analysis. Overall, an association of FAS -1377G>A (AA versus GG: OR = 1.313, 95% CI = 1.045-1.650, Ph = 0.347, $I^2$ = 10.8) and FASL -844T>C (CC versus TT: OR = 1.352, 95% CI = 1.043-1.752, Ph = 0.461, $I^2$ = 0.0) polymorphisms with gastric cancer was found in the codominant model. However, we did not detect any association between gastric cancer and the FAS -670A>G polymorphism. In the subgroup analysis by ethnicity, similar elevated risks were also observed in Asian population for FAS -1377G>A (AA versus GG: OR = 1.309, 95% CI = 1.041-1.646, Ph = 0.240, $I^2$ = 27.3) and FASL -844T>C (CC versus TT: OR = 1.420, 95% CI = 1.081-1.865, Ph = 0.524, $I^2$ = 0.0) polymorphisms. Conclusions: This meta-analysis indicated that FAS -1377G>A and FASL -844T>C polymorphisms might be associated with gastric cancer risk.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7763-7768
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• 2014

Background: Gastritis and gastric cancer are the most common diseases in the Kazakh population. Polymorphisms in genes coding of cytokines have been played important role with gastric disease risk. The risk alleles of cytokines in patients with gastritis can predict the risk of developing gastric cancer. The aim of this study was to investigate cytokine gene polymorphisms as risk factors for the development of gastritis in a case-control study with gastritis patients and healthy individuals from the Kazakh ethnic group, living in North Kazakhstan. Materials and Methods: The polymerase chain reaction followed by direct sequencing were used for detection of two functional polymorphisms in the IL1 gene family, and TaqMan SNP Genotyping Assay Sets were applied for three potentially functional polymorphisms in the IL10 gene, and one in the TNFA promoter. Results: Association analysis of studied allelic variants and the development of gastritis in H. pylori-positive patients showed that IL1B -31C/C, IL1B -511T/T and IL1RN -2/2 allelic variants were associated with development of gastritis (OR=1.8 (1.07-3.16), p=0.025; OR=1.7 (1.04-2.99), p=0.035, and OR=4.92 (2.45-9.85), p<0.001) respectively. Haplotype C-Т that combines both homozygous allelic variants of IL1B gene also had a statistically significant association with slightly higher OR (OR: 1.43, 95% CI: 1.08-1.88). Conclusions: The data from the current study showed that the genotype IL-1B -511Т/-31C-IL1-RN-2 and H. pylori infection increase risk of gastritis in the Kazakh population. That genotype combination might be a factor increasing the risk of developing gastric cancer.

• Journal of Gastric Cancer
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• v.11 no.1
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• pp.64-68
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• 2011

A 54 year old man was referred to our hospital with gastric cancer. The patient had a history of splenectomy and a left nephrectomy as a result of a traffic accident 15 years earlier. The endoscopic findings were advanced gastric cancer at the lower body of the stomach. Abdominal ultrasonography (USG) and magnetic resonance imaging demonstrated a metastatic nodule in the S2 segment of the liver. Eventually, the clinical stage was determined to be cT2cN1cM1 and a radical distal gastrectomy, lateral segmentectomy of the liver were performed. The histopathology findings confirmed the diagnosis of intrahepatic splenosis, omental splenosis. Hepatic splenosis is not rare in patients with a history of splenic trauma or splenectomy. Nevertheless, this is the first report describing a patient with gastric cancer and intrahepatic splenosis that was misinterpreted as a liver metastatic nodule. Intra-operative USG guided fine needle aspiration should be considered to avoid unnecessary liver resections in patients with a suspicious hepatic metastasis.

• Journal of Gastric Cancer
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• v.3 no.3
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• pp.151-157
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• 2003

Purpose: In this study, we attempted to ascertain the proton magnetic resonance spectroscopy (${1}^H$ MRS) peak characteristics of human gastric tissue layers and finally to use the metabolic peaks of MRS to distinguish between normal and abnormal gastric specimens. Materials and Methods: Ex-vivo ${1}^H$ MRS examinations of thirty-five gastric specimens were performed to distinguish abnormal gastric tissues invaded by carcinoma cells from normal stomach-wall tissues. High-resolution 400-MHz (9.4-T) ${1}^H$ nuclear magnetic resonance (NMR) spectra of two gastric layers, a proper muscle layer, and a composite mucosasubmucosa layer were compared with those of clinical 64- MHz (1.5-T) MR spectra. Three-dimensional spoiled gradient recalled (SPGR) images were used to determine the size and the position of a voxel for MRS data collection. Results: For normal gastric tissue layers, the metabolite peaks of 400-MHz ${1}^H$ MRS were primarily found to be as follows: lipids at 0.9 ppm and 1.3 ppm; alanine at 1.58 ppm; N-acetyl neuraminic acid (sialic acid) at 2.03 ppm; and glutathione at 2.25 ppm in common. The broad and featureless featureless spectral peaks of the 64-MHz MRS were bunched near 0.9, 1.3, and 2.0, and 2.2 ppm in human specimens without respect to layers. In a specimen (Borrmmann type III) with a tubular adenocarcinoma, the resonance peaks were measured at 1.26, 1.36 and 3.22 ppm. All the peak intensities of the spectrum of the normal gastric tissue were reduced, but for gastric tumor tissue layers, the lactate peak split into 1.26 and 1.39 ppm, and the peak intensity of choline at 3.21 ppm was increased. Conclusion: We found that decreasing lipids, an increasing lactate peak that split into two peaks, 1.26 ppm and 1.36 ppm, and an increasing choline peak at 3.22 ppm were markers of tumor invasion into the gastric tissue layers. This study implies that MR spectroscopy can be a useful diagnostic tool for gastric cancer.

• Journal of Gastric Cancer
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• v.10 no.3
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• pp.91-98
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• 2010

Purpose: Silent mating-type information regulation 2 homologue 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. SIRT1 plays an important role in the regulation of cell death/survival and stress response in mammals. The aim of this study was to investigate whether the SIRT1 gene is involved in the development or progression of gastric cancers. Materials and Methods: SIRT1 and p53 genes in 86 gastric cancers were examined for genetic alterations by PCR-single strand conformation polymorphism sequencing, as well as SIRT1 protein expression in 170 gastric cancers by immunohistochemistry. Results: In the genetic analysis, we found SIRT1 and p53 mutations in two and 12 cases, respectively. Two missense mutations, c.599 C>T (T200I) and c.1258 G>A (E420K), were detected in the SIRT1 gene coding region. The SIRT1 and p53 mutation were found in mutually exclusive gastric cancers. The immunohistochemistry revealed that SIRT1 overexpression was found in 95 (55.9%) of 170 gastric cancers. Altered SIRT1 expression was not statistically associated with clinicopathological parameters, including tumor differentiation, location, lymph node metastasis, or p53 expression. Two cases with an SIRT1 mutation showed increased SIRT1 expression. Conclusions: These results suggest that genetic alterations and overexpression of the SIRT1 gene may contribute to gastric cancer development.

• Journal of Gastric Cancer
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• v.4 no.3
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• pp.137-142
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• 2004

Purpose: There have been some controversies over the therapeutic principles of advanced gastric cancer, and the results of treatment have been variable, especially for stage III disease. This study was conducted to define the prognostic factors of stage III gastric cancer. Materials and Methods: This retrospective study was based on the medical records of 179 patients with stage III disease who received a gastrectomy from January 1990 to December 1994. The 5-year survival rate was analyzed according to the age, sex, tumor location, tumor size, Borrmann's type, depth of invasion, lymph-node metastasis, ratio of metastatic lymph nodes, type of surgical resection, extent of lymphnode dissection, curability of resection, postoperative chemotherapy, and pathological stage. The statistical analysis was done by using the Kaplan-Meier method, the log-rank test, and the Cox proportional hazards model. Results: The overall 5-year survival rate was $61.6\%$ the 5-year survival rates according to subgroup were $69.7\%$ for stage IIIa ($100\%$ for $T_{2}N_{2}$, $70.0\%$ for $T_{3}N_{1}$, $68.6\%$ for $T_{4}N_{0}$), and $54.1\%$ for stage IIIb ($T_{3}N_{2}$) (P<0.05). Among various clinicopathologic factors of stage III gastric cancer, the age of the patient, the tumor location, the gross type of tumor, the type of gastric resection, the extent of lymph-node dissection, the curability of resection, and the subgroups of stage III were statistically significant in the univariate survival analysis. The multivariate analysis defined the curability of resection, the extent of lymph-node dissection, the type of operation, the stage of disease, and the age of the patient as independent prognostic factors. Conclusion: A curative surgical resection and an extended lymph-node dissection are thought to be most important for improving the survival rate in stage III gastric cancer patients.

• Journal of Gastric Cancer
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• v.10 no.3
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• pp.141-148
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• 2010

We have always attempted to create a standard treatment protocol for patients with gastric cancer. However, many debates still exist regarding gastric cancer treatment. For the past 2 years, at the Annual Congress of the Korean Gastric Cancer Association, we have presented a grand symposium on the "Debates on the strategy for treating gastric cancer". In 2008, four major topics were discussed and voted on after discussion. The four major topics were proximal location treatment for early gastric cancer, management choices for pyloric obstruction with advanced gastric cancer, management of liver metastasis, and reconstruction methods after a distal gastrectomy. The opinions of the audience for six minor topics were expressed by an electronic voting system. In 2009, the four main topics were treatment for submucosal tumor sized around 2 cm, laparoscopic gastrectomy in T2N1 gastric cancer, choices for managing gastric lymphoma, and application of a pylorus preserving procedure for early gastric cancer at the antrum. The opinions of the audience for these six minor topics were expressed by an electronic voting system, as was conducted in 2008. It was good opportunity to identify a point of contact about the debates on managing gastric cancer. The results of these debates and studies will identify the best methods to treat patients with gastric cancer.

• Journal of Gastric Cancer
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• v.6 no.2
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• pp.114-119
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• 2006

Purpose: The purpose of this study is to determine whether it is possible to evaluate patients with pN2 or pN3 early gastric cancer (EGC) as being in an advanced stage before and during the operation. Materials and Methods: 4,430 patients underwent a gastrectomy for cancer from 1990 to 2003. Eight of the 552 patients with EGC included pN2 or pN3. The estimated clinical and surgical stage before and during the operation were compared to the pathological results, and a follow-up of progression was done. Results: The patients were evenly distributed among all age groups with seven men and one woman. The pre-operative estimate of T1 by CT was 25% (2/8). In the main, the cT stage was over estimated. The estimate of over N2 was 50% (4/8). One patient was preoperatively staged as la sT1 during operation was 57.1% (4/7), and the estimate of over N2 was 67% (4/6). Two patients were intraoperatively evaluated as Ia. Only one patient survived over 5 years, and the mean survival of these patients was 15 months $(95%\;Cl:\;0{\sim}35.5)$. Conclusion: It was generally possible to evaluate patients with EGC of over pN2 as being in an advanced stage before and during the operation. Although very rare (2/552, 0.04%), there were EGC patients whose stages were not predictable at all. Therefore, more precise preoperative and intraoperative staging methods are warranted.