Hye-Rim Song

Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer in a Korean population

BackgroundThis study was designed to investigate an association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer in the Korean population.MethodsWe conducted a population-based large-scale case-control study involving 2,213 patients with newly diagnosed gastric cancer, 1,829 patients with newly diagnosed colorectal cancer, and 1,700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. The statistical significance was estimated by logistic regression analysis.ResultsThe MTHFR C677T frequencies of CC, CT, and TT genotypes were 35.2%, 47.5%, and 17.3% among stomach cancer, 34%, 50.5%, and 15.5% in colorectal cancer, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677TT genotype showed a weak opposite association with colorectal cancer compared to the homozygous CC genotype [adjusted age and sex odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.638-0.984, P = 0.035]. Subjects with the MTHFR 677CT showed a significantly reduced risk of gastric cancer compared whose with the 677CC genotype (age- and sex-adjusted OR = 0.810; 95% CI = 0.696-0.942, P = 0.006). We also observed no significant interactions between the MTHFR C677T polymorphism and smoking or drinking in the risk of gastric and colorectal cancer.ConclusionsThe T allele was found to provide a weak protective association with gastric cancer and colorectal cancer.

Association of a common genetic variant in prostate stem‐cell antigen with gastric cancer susceptibility in a Korean population

A recent genome wide association study (GWAS) indentified a significant association between rs2294008 (C > T) polymorphism in prostate stem‐cell antigen (PSCA) and increased risk of gastric cancer in Japanese and Korean populations. The aim of this study was to determine whether rs2294008 polymorphism is associated with risk of gastric cancer in a Korean population. We conducted a large‐scale case–control study of 3,245 gastric cancer patients and 1,700 controls. The frequencies of the CC, CT, and TT genotypes of rs2294008 polymorphism were 17.8%, 49.9%, and 32.3% in the gastric cancer patients; and 24.4%, 48.1%, and 27.5% in the controls, respectively. We found that the CT and TT genotypes were associated with a significantly increased risk of gastric cancer (ORCT = 1.50, 95% confidence intervals, 95% CI: 1.28–1.76; ORTT = 1.71, 95% CI: 1.43–2.04), compared with the CC genotype. Further, stratified by tumor location and histological type, the effect of the rs2294008 T allele was larger in cardia (ORTT = 2.62, 95% CI = 1.42–4.85) than non‐cardia (ORTT = 1.67, 95% CI = 1.40–2.00), in diffuse‐type (ORTT = 2.00, 95% CI: 1.55–2.59) than in intestinal‐type (ORTT = 1.51, 95% CI: 1.22–1.86). Our study showed that rs2294008 in the PSCA gene was associated with increased risks of gastric cancer in a Korean population, suggests that rs2294008 might play an important role in gastric carcinogenesis.

p53 codon 72 polymorphism and the risk of lung cancer in a Korean population.

The aim of this study was to assess whether p53 codon 72 polymorphism is associated with an increased risk of lung cancer (LC) in a South Korean population. We conducted a population-based, large-scale, case-control study including 3939 patients with LC and 1700 controls. P53 codon 72 polymorphism was determined by real-time polymerase chain reaction (PCR). The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in LC were 37.0%, 46.2%, and 16.7%, respectively; frequencies in the controls were 43.2%, 45.6%, and 11.2%, respectively (p<0.01). The Arg/Pro and Pro/Pro genotype were significantly associated with increased risk of LC (odds ratio (OR)=1.22, 95% confidence interval (CI)=1.06-1.14 and OR=1.83, 95% CI=1.48-2.26, respectively) compared with the Arg/Arg genotype. Risk was compared in different subgroups. The OR of Pro/Pro genotype was significantly higher in small cell lung cancer (SCC) and squamous cell carcinoma (SQC) than in adenocarcinoma (ADC). Higher OR of Pro/Pro genotype was also seen among males. However, relationships between gender, age, smoking, and genotypes were not found. P53 codon 72 polymorphism was associated with an increased risk of LC in this Korean population; the association was especially noteworthy in SQC, SCC, and males.

Methylenetetrahydrofolate reductase C677T polymorphism in patients with lung cancer in a Korean population

BackgroundThis study was designed to investigate an association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of lung cancer in a Korean population.MethodsWe conducted a large-scale, case-control study involving 3938 patients with newly diagnosed lung cancer and 1700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. Statistical significance was estimated by logistic regression analysis.ResultsThe MTHFR C677T frequencies of CC, CT, and TT genotypes were 34.5%, 48.5%, and 17% among lung cancer patients, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677CT and TT genotype showed a weak protection against lung cancer compared with the homozygous CC genotype, although the results did not reach statistical significance. The age- and gender-adjusted odds ratio (OR) of overall lung cancer was 0.90 (95% confidence interval (CI), 0.77-1.04) for MTHFR 677 CT and 0.88 (95% CI, 0.71-1.07) for MTHFR 677TT. However, after stratification analysis by histological type, the MTHFR 677CT genotype showed a significantly decreased risk for squamous cell carcinoma (age- and gender-adjusted OR, 0.78; 95% CI, 0.64-0.96). The combination of 677 TT homozygous with 677 CT heterozygous also appeared to have a protection effect on the risk of squamous cell carcinoma. We observed no significant interaction between the MTHFR C677T polymorphism and age and gender or smoking habit.ConclusionsThis is the first reported study focusing on the association between MTHFR C677T polymorphisms and the risk of lung cancer in a Korean population. The T allele was found to provide a weak protective association with lung squamous cell carcinoma.

Genetic variations in the PRKAA1 and ZBTB20 genes and gastric cancer susceptibility in a Korean population.

A recent genome‐wide association study (GWAS) identified new susceptibility single‐nucleotide polymorphisms (SNPs) rs13361707 (PRKAA1 and PTGER4 gene on 5p13.1) and rs9841504 (ZBTB20 gene on 3q13.31) that were significantly associated with non‐cardia gastric cancer. The aim of this study was to determine whether rs13361707 and rs9841504 polymorphisms are associated with the risk of gastric cancer in a Korean population. We conducted a large‐scale case–control study of 3245 gastric cancer patients and 1700 controls. The allele frequencies for rs13361707 C and rs9841504 G were 53.5% and 18.3% among gastric cancer cases, compared with 47.1% and 17.2% among controls, respectively. We found that rs13361707 TC and CC genotypes were associated with increased risk for gastric cancer (odds ratios [OR] = 1.29; 95% confidence interval [CI] = 1.11–1.51 for TC vs. TT and 1.68; 1.41–2.01 for CC vs. TT). However, we found no significant association between rs9841504 and gastric cancer risk (OR = 1.11; 0.97–1.28 for CG vs. CC; OR = 1.09; 0.77–1.53 for GG vs. CC). We observed no significant interactions between rs13361707 and rs9841504 polymorphisms and age, gender, smoking habit, alcohol consumption, and clinicopathologic characteristics such as anatomical tumor location and histological type. Our study showed that the rs13361707 polymorphism was associated with increased risk of gastric cancer in a Korean population. This finding provides further evidence that genetic variant of PRKAA1 and PTGER4 genes may contribute to the gastric carcinogenesis. However, we found no association between rs9841504 and gastric cancer risk.

High Prevalence of Vitamin D Deficiency in Adults Aged 50 Years and Older in Gwangju, Korea: the Dong-gu Study

Vitamin D plays an important role in bone metabolism and maintaining bone health. Recently, new evidence has revealed that vitamin D affects chronic diseases such as autoimmune diseases, cardiovascular diseases and certain cancers. The aim of this study was to evaluate the vitamin D status and the prevalence of vitamin D deficiency in an urban Korean population. This study included 8,976 participants (3,587 men and 5,389 women) aged 50 yr and older. Serum 25(OH)D level was measured by chemiluminescent microparticle immunoassay. The prevalence of vitamin D deficiency [25(OH)D < 20 ng/mL] was 59.7% and 86.5% in men and women, respectively. The prevalence of vitamin D deficiency increased significantly with age in men, but not in women and it decreased from April to July, more prominently in men than in women. These results suggest that sun exposure, intake of vitamin D supplement, and regular physical activities is recommended in an urban Koreans, especially in women.

Association between total bilirubin and hemoglobin A1c in Korean type 2 diabetic patients.

Recent studies have shown that bilirubin is negatively associated with hemoglobin A1c (HbA1c) in the general population. The association between bilirubin and HbA1c in serum of diabetes patients has not yet been studied. The aim of the present study was to evaluate the association between total bilirubin and HbA1c in Korean patients with type 2 diabetes. A total of 690 of the 1,275 type 2 diabetes patients registered with the public health centers in Seo-gu, Gwangju and Gokseong-gun, Jeollanam-do participated in this study. Following an overnight fast, venous blood and urine samples were collected and analyzed. The mean HbA1c values differed significantly according to total bilirubin (≤ 0.4 mg/dL, 7.6%; 0.5 mg/dL, 7.3%; 0.6-0.7 mg/dL, 7.2%; and ≥ 0.8 mg/dL, 7.1%; P for trend = 0.016) after we adjusted for other confounding factors. When the odds ratio (OR) was adjusted for other confounding factors, there was a significant association between total bilirubin and HbA1c (OR, 0.4 [95% confidence interval, 0.2-0.8] for total bilirubin ≥ 0.8 mg/dL versus ≤ 0.4 mg/dL. In conclusion, total bilirubin concentrations in serum are negatively associated with HbA1c levels after adjustment for sex, age, and other confounding factors in type 2 diabetes patients.

p53 codon 72 polymorphism and the risk of esophageal cancer: a Korean case-control study

The aim of this study was to assess whether p53 codon 72 polymorphism is associated with an increased risk of esophageal cancer (EC) in South Korea. We conducted a case-control study including 340 patients with EC, and 1700 controls. P53 codon 72 polymorphism was determined by real-time polymerase chain reaction. The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in EC were 39.4%, 45.6%, and 15.0%, respectively; frequencies in the controls were 43.2%, 45.6%, and 11.2%, respectively. Compared with the Arg/Arg genotype, the OR of the Arg/Pro genotype was 1.09 (95% CI = 0.85-1.41) and that of the Pro/Pro genotype was 1.47 (95% CI = 1.02-2.11) for EC overall. When adjusted by age, gender, and smoking status, the OR of the Arg/Pro genotype was 1.24 (95% CI = 0.92-1.67) and that of the Pro/Pro genotype was 1.77 (95% CI = 1.15-2.74) for EC overall. In never-smokers and ever-smokers, the OR of the Arg/Pro genotype was 0.59 (95% CI = 0.37-0.95) and 1.39 (95% CI = 1.00-1.91), respectively, and there was a significant difference in the homogeneity test (P= 0.011). We observed that the p53 codon 72 polymorphism was associated with an increased risk of EC in this Korean case-control study, and smoking status modified the association between the p53 codon 72 polymorphism and the risk of EC.

APOE polymorphism and carotid atherosclerosis in Korean population: The Dong-gu Study and the Namwon Study

OBJECTIVE We evaluated the association between APOE polymorphism and carotid atherosclerosis in two large independent cohorts from South Korea. METHODS The datasets were from the Dong-gu Study (N = 9056) and the Namwon Study (N = 10,158). Carotid ultrasonography was performed to measure carotid intima-media thickness (IMT) and the presence of carotid plaques. The APOE polymorphism was determined by PCR-RFLP. We performed combined and separate analyses for the two datasets. RESULTS In the combined analysis, individuals with E2E2 or E2E3 genotype had a lower common carotid IMT compared with individuals with E3E3 genotype (0.684 mm vs. 0.736 mm, p = 0.007; 0.718 mm vs. 0.736 mm, p < 0.001, respectively). This association was very slightly attenuated but remained statistically significant after adjustment for blood lipids (0.690 mm vs. 0.736 mm, p = 0.033; 0.725 mm vs. 0.736 mm, p = 0.005, respectively). Compared with individuals with E3E3 genotype, individuals with E2E3 genotype had lower risk for carotid plaque (odds ratio (OR) = 0.83, 95% confidence interval (CI) = 0.75-0.93), while individuals with E3E4 genotype had a higher risk for carotid plaque (OR = 1.09, 95% CI = 1.00-1.20). After adjustment for blood lipids, ORs of E2E3 genotype for carotid plaque was slightly attenuated but remained significant (OR = 0.87 95% CI = 0.78-0.97), while OR of E3E4 genotype were slightly attenuated and not significant (OR = 1.08, 95% CI, 0.99-1.18). CONCLUSIONS We found that APOE polymorphism is associated with carotid atherosclerosis and this association was partly mediated through blood lipid. Our results suggest that APOE polymorphism may influence atherosclerosis through non-lipid pathways.

Replication of results of genome‐wide association studies on esophageal squamous cell carcinoma susceptibility loci in a Korean population

Two recent genome-wide association studies have identified that the rs2274223 single-nucleotide polymorphism inphospholipase C epsilon 1 and the single-nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high-resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.08-3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR=0.71, 95% CI=0.52-0.97) and no significant association in the older group (OR=1.19, 95% CI=0.87-1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case-control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.