Gastric cancer is ranked as the most common cancer in Koreans. A recent molecular biological study about the folate pathway gene revealed the correlation with a couple of cancer types. In the folate pathway, several genes are involved, including methylenetetrahydrofolate reductase (MTHFR), methyltet...
Gastric cancer is ranked as the most common cancer in Koreans. A recent molecular biological study about the folate pathway gene revealed the correlation with a couple of cancer types. In the folate pathway, several genes are involved, including methylenetetrahydrofolate reductase (MTHFR), methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), and methyltetrahydrofolate-homocysteine methyltransferase (MTR). The MTHFR gene has been reported several times for the correlation with gastric cancer risk. However, the association of the MTRR or MTR gene has not been reported to date. In this study, we investigated the association between the single nucleotide polymorphisms (SNPs) of the MTHFR, MTRR, and MTR genes and the risk of gastric cancer in Koreans. To identify the genetic association with gastric cancer, we selected 17 SNPs sites in folate pathway-associated genes of MTHFR, MTR, and MTRR and tested in 1,261 gastric cancer patients and 375 healthy controls. By genotype analysis, estimating odds ratios and 95% confidence intervals (CI), rs1801394 in the MTRR gene showed increased risk for gastric cacner, with statistical significance both in the codominant model (odds ratio [OR], 1.39; 95% CI, 1.04 to 1.85) and dominant model (OR, 1.34; 95% CI, 1.02 to 1.75). Especially, in the obese group (body mass index ${\geq}25kg/m^2$), the codominant (OR, 9.08; 95% CI, 1.01 to 94.59) and recessive model (OR, 3.72; 95% CI, 0.92 to 16.59) showed dramatically increased risk (p < 0.05). In conclusion, rs1801394 in the MTRR gene is associated with gastric cancer risk, and its functional significance need to be validated.
Gastric cancer is ranked as the most common cancer in Koreans. A recent molecular biological study about the folate pathway gene revealed the correlation with a couple of cancer types. In the folate pathway, several genes are involved, including methylenetetrahydrofolate reductase (MTHFR), methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), and methyltetrahydrofolate-homocysteine methyltransferase (MTR). The MTHFR gene has been reported several times for the correlation with gastric cancer risk. However, the association of the MTRR or MTR gene has not been reported to date. In this study, we investigated the association between the single nucleotide polymorphisms (SNPs) of the MTHFR, MTRR, and MTR genes and the risk of gastric cancer in Koreans. To identify the genetic association with gastric cancer, we selected 17 SNPs sites in folate pathway-associated genes of MTHFR, MTR, and MTRR and tested in 1,261 gastric cancer patients and 375 healthy controls. By genotype analysis, estimating odds ratios and 95% confidence intervals (CI), rs1801394 in the MTRR gene showed increased risk for gastric cacner, with statistical significance both in the codominant model (odds ratio [OR], 1.39; 95% CI, 1.04 to 1.85) and dominant model (OR, 1.34; 95% CI, 1.02 to 1.75). Especially, in the obese group (body mass index ${\geq}25kg/m^2$), the codominant (OR, 9.08; 95% CI, 1.01 to 94.59) and recessive model (OR, 3.72; 95% CI, 0.92 to 16.59) showed dramatically increased risk (p < 0.05). In conclusion, rs1801394 in the MTRR gene is associated with gastric cancer risk, and its functional significance need to be validated.
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제안 방법
The iPLEX extension was performed in a total volume of 9 μL with 50 μM dNTP/dideoxynucleotide phosphate (ddNTP) each, 0.063 unit/μL Thermo Sequenase (Sequenom, Inc.), and 625 nM to 1.25 μM extension primers.
대상 데이터
Buffy coat samples of 1,261 patients (69.4%) who had undergone surgery at the Gastric Cancer Center, National Cancer Center (NCC) of Korea, between September 2001 and December 2005 were included as cases. Most of the selected gastric cancer patients possessed distal stomach tumors.
Seventeen SNPs in MTHFR, MTRR, and MTR were selected, covering previously studied SNPs, such as C677T (rs1801133) and A1298C (rs1801131) in MTHFR [29] and A66G (rs1801394) in MTR [27]. The SNP information, including nucleic acid sequences, was collected from dbSNP (http://www.
이론/모형
Genotyping was carried out using the iPLEX assay on the MassARRAY Platform (Sequenom, Inc.). The iPLEX extension was performed in a total volume of 9 μL with 50 μM dNTP/dideoxynucleotide phosphate (ddNTP) each, 0.
The chi-square test for association was used to test differences of genotype frequencies between normal and gastric cancer patients. Odds ratios (OR) and their 95% confidence intervals (CI) in relation to MTHFR, MTTRR, and MTR genotypes were calculated.
성능/효과
05). Also, the recessive model showed significantly higher risk (OR, 3.72; 95% CI, 0.92 to 16.59). Additionally, we analyzed the correlation among family history, H.
05) only among obese subjects. For the dominant model, the OR was also increased with statistical significance (OR, 1.98; 95% CI, 1.06 to 3.49; p ＜ 0.05). Also, the recessive model showed significantly higher risk (OR, 3.
후속연구
Here, we report the association of genetic variations in MTRR with the risk of gastric cancer for the first time. In further studies, we need to validate our finding in a larger population, considering detailed clinical information, and study the functional relevance of polymorphisms with cancer development more. Also, we need to consider other genes in the folate pathway and investigate gastric cancer susceptibility with epidemiological and environmental factors (e.
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