ABSTRACT
BACKGROUND: Gastric carcinoma is one of the most common gastrointestinal malignancies worldwide. Some studies have suggested that it has a worse prognosis in non-elderly than in elderly patients. The aim of the present study was to clarify whether the patient's age is an independent prognostic factor. METHODS: A total of 742 patients with gastric carcinoma, who had registered in our cancer registry center between years 2001- 2006 were reviewed to investigate the prognostic significance of age. They were divided into the following two groups: non-elderly (under 70 years) and elderly (70 years or older). The clinicopathological features were reviewed retrospectively and a multivariate analysis was carried out. RESULTS: Lymph node metastasis and differentiated type were more frequently observed in non-elderly than in elderly patients (P<0.0001) and older patients diagnosed with more advanced stages compared with those younger than 70 years old (P=0.015). 5-year survival rates were 27.2 and 15.2% in non-elderly and elderly patients, respectively, the difference being statistically significant (P<0.001). Multivariate analysis showed that age and wall penetration were independent prognostic factors CONCLUSIONS: Age clinically serves as an important predictor of survival in patients with gastric carcinoma and elderly patients with gastric carcinoma have a worse prognosis than nonelderly patients.
Subject(s)
Adenocarcinoma/secondary , Stomach Neoplasms/pathology , Adenocarcinoma/surgery , Adult , Age Factors , Aged , Aged, 80 and over , Cross-Sectional Studies , Feasibility Studies , Female , Humans , Iran , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Risk Factors , Stomach Neoplasms/surgery , Survival Rate , Young AdultABSTRACT
PURPOSE: The aim of the present study was to determine the profile of mismatch repair (MMR) defects in Iranian colorectal cancer patients by using immunohistochemical staining for products of four MMR genes: MLH1, MSH2, PMS2, and MSH6. METHODS: Tissue samples of 343 patients were immunostained for MLH1, MSH2, PMS2, and MSH6. Clinical and family history and survival data were compared between normal and abnormal staining patterns. RESULTS: Fourteen percent of the patients had abnormal nuclear staining for MMR proteins. MLH1 was absent in four, MLH1/PMS2 in 15, PMS2 in five, MSH2 in 12, and MSH2/MSH6 in 12 patients. These tumors were more proximal, had a nonsignificant better survival, and were more associated with positive family history. Estimation of this study of prevalence of hereditary nonpolyposis colorectal cancer in Iran was 5.5% of the total colorectal cancers. CONCLUSIONS: Along with the recommendations of the National Institute of Cancer, we recommend immunohistochemistry staining for MLH1, MSH2, PMS2, and MSH6 for determining the eligibility of patients for mutation analysis of MMR genes.
Subject(s)
Colorectal Neoplasms/pathology , DNA Mismatch Repair , Nuclear Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adenosine Triphosphatases/metabolism , Aged , DNA Repair Enzymes/metabolism , DNA-Binding Proteins/metabolism , Female , Humans , Immunohistochemistry , Iran , Logistic Models , Male , Middle Aged , Mismatch Repair Endonuclease PMS2 , Multivariate Analysis , MutL Protein Homolog 1 , MutS Homolog 2 Protein/metabolism , Staining and Labeling , Survival AnalysisABSTRACT
BACKGROUND AND AIM: The present study was designed to consider whether amino acid substitution polymorphisms in O6-methylguanine-DNA methyltransferase (MGMT) and DNA methyl transferase 1 (DNMT1) genes may be associated with the genetic susceptibility to sporadic colorectal cancer. PATIENTS AND METHODS: We assessed eight non-synonymous polymorphisms of these two genes by PCR/pyrosequencing. Our population consisted of 208 individuals with sporadic colorectal cancer and 213 controls. Allele frequencies and genotypes were compared between the two groups. RESULTS: The calculated odds ratios indicated no association between DNMT1 and colorectal cancer. However, there was a significant association between two polymorphisms in MGMT with sporadic colorectal cancer: Arg128Gln (OR, 5.53; 95% CI) and Gly160Arg (OR, 3.04; 95% CI). CONCLUSIONS: These findings could be indicative of factors contributing to high occurrence of Iranian colorectal cancer patients.
Subject(s)
Amino Acid Substitution , Colorectal Neoplasms/genetics , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Polymorphism, Single Nucleotide , Repressor Proteins/genetics , Tumor Suppressor Proteins/genetics , Adult , Case-Control Studies , Colorectal Neoplasms/epidemiology , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Iran/epidemiology , Male , Middle Aged , Polymerase Chain ReactionABSTRACT
BACKGROUND: Gastric cancer is one of the most common malignant tumors in Iran. Hypomethylation and/or hypermethylation of DNA has been described in gastric cancer and is presumed to be an early event in carcinogeneisis. OBJECTIVE: We therefore hypothesized that single nucleotide polymorphisms of the DNMT1 gene may be associated with the genetic susceptibility to gastric cancer. METHODS: Totals of 200 patients and 200 controls, both of Iranian origin, were studied. Three polymorphisms were genotyped by PCR-RFLP and allele frequencies and genotypes were compared between the cases and controls. Odds ratios were calculated and the interactions between the polymorphisms, age and sex were examined. RESULTS: There were no significant associations between the DNMT1 polymorphisms and gastric cancer. CONCLUSION: We could not show any association between DNMT1 polymorphisms and gastric cancer. Larger sets of polymorphisms and sample sizes are required for future testing of possible associations.
Subject(s)
Polymorphism, Single Nucleotide , Repressor Proteins/genetics , Stomach Neoplasms/genetics , Adult , Case-Control Studies , DNA Methylation , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Iran/epidemiology , Male , Middle Aged , Odds Ratio , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Sequence Analysis, DNAABSTRACT
BACKGROUND: It has been proposed that folate and polymorphisms of the enzyme methylenetetrahydrofolate reductase (MTHFR), which regulates influx of folate for methylation reactions for DNA synthesis and repair, are involved in colorectal cancer. This study was designed to determine the influence of a genetic variant (MTHFR G1793A) and folate on colon cancer in Iran. MATERIALS AND METHODS: We analyzed 227 cases and 239 normal unmatched controls using pyrosequencing. Odds ratios and 95% confidence intervals (95% CI) were calculated to evaluate associations of the MTHFR gene polymorphism with colorectal cancer risk. RESULTS: A significantly reduced risk of recurrence was observed in patients heterozygous for the MTHFR G1793A polymorphism (OR: 0.17; 95% CI, 0.05-0.52). The frequency of GG, GA and AA genotypes of MTHFR among the colorectal cancer patients were 98%, 2% and 0% respectively, while the frequencies among controls were 90%, 10% and 0%, respectively. Furthermore, a significant reduction in recurrence risk was seen in MTHFR G1793A heterozygotes limited to those who received folate supplements. CONCLUSION: Our study is compatible with previous findings concerning a reverse association between the MTHFR 1793G> A genotype with cancers in different populations.
