Gene polymorphisms involved in folate and methionine metabolism and increased risk of sporadic colorectal adenocarcinoma

Guimarães, José Augusto Chaves; Ayrizono, Maria de Lurdes; Coy, Cláudio Saddy Rodrigues; Lima, Carmen Sílvia Passos

doi:10.1007/s13277-011-0185-2

Cited by 21 publications

(19 citation statements)

References 34 publications

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“…For the MTHFR A1298C , MTRR A66G , MTR A2756G analyses, 12, 6, and 7 studies were conducted in Caucasians, respectively, while 5, 3, and 3 studies were in Asians. Genotype distributions in the controls of all studies were in HWE except for 8 studies for MTHFR C677T polymorphism 29, 31, 37, 40, 44, 48-50, 4 studies for A1298C polymorphism 14, 17, 28, 41, 1 study for MTRR A66G polymorphism 47, and 1 study for MTR A2756G polymorphism 17. The detailed characteristics of the included studies were shown in the supplementary Table 1 .…”

Section: Resultsmentioning

confidence: 99%

The Polymorphisms in Methylenetetrahydrofolate Reductase, Methionine Synthase, Methionine Synthase Reductase, and the Risk of Colorectal Cancer

Zhou¹,

Mei²,

Luo³

et al. 2012

Int. J. Biol. Sci.

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Polymorphisms in genes involved in folate metabolism may modulate the risk of colorectal cancer (CRC), but data from published studies are conflicting. The current meta-analysis was performed to address a more accurate estimation. A total of 41 (17,552 cases and 26,238 controls), 24(8,263 cases and 12,033 controls), 12(3,758 cases and 5,646 controls), and 13 (5,511 cases and 7,265 controls) studies were finally included for the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1289C, methione synthase reductase (MTRR) A66G, methionine synthase (MTR) A2756G polymorphisms and the risk of CRC, respectively. The data showed that the MTHFR 677T allele was significantly associated with reduced risk of CRC (OR = 0.93, 95%CI 0.90-0.96), while the MTRR 66G allele was significantly associated with increased risk of CRC (OR = 1.11, 95%CI 1.01-1.18). Sub-group analysis by ethnicity revealed that MTHFR C677T polymorphism was significantly associated with reduced risk of CRC in Asians (OR = 0.80, 95%CI 0.72-0.89) and Caucasians (OR = 0.84, 95%CI 0.76-0.93) in recessive genetic model, while the MTRR 66GG genotype was found to significantly increase the risk of CRC in Caucasians (GG vs. AA: OR = 1.18, 95%CI 1.03-1.36). No significant association was found between MTHFR A1298C and MTR A2756G polymorphisms and the risk of CRC. Cumulative meta-analysis showed no particular time trend existed in the summary estimate. Probability of publication bias was low across all comparisons illustrated by the funnel plots and Egger's test. Collectively, this meta-analysis suggested that MTHFR 677T allele might provide protection against CRC in worldwide populations, while MTRR 66G allele might increase the risk of CRC in Caucasians. Since potential confounders could not be ruled out completely, further studies were needed to confirm these results.

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Section: Resultsmentioning

confidence: 99%

The Polymorphisms in Methylenetetrahydrofolate Reductase, Methionine Synthase, Methionine Synthase Reductase, and the Risk of Colorectal Cancer

Zhou¹,

Mei²,

Luo³

et al. 2012

Int. J. Biol. Sci.

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“…The MTHFR C677T, MTHFR A1298C, and MTR A2756G single nucleotide polymorphisms have been found to alter levels of folate and homocysteine, which changes the functionality of expressed proteins [25]. The MTHFR and MTR genes have been widely studied, and the MTHFR C677T, MTHFR A1298C, and MTR A2756G polymorphisms are associated with risk of several cancers [10,[26][27][28][29][30]. Lopez-Cortes et al found that the MTHFR C677T polymorphism has significant effects on susceptibility to prostate cancer in an Ecuadorian population [10].…”

Section: Discussionmentioning

confidence: 99%

Association of methylenetetrahydrofolate reductase and methionine synthase polymorphisms with breast cancer risk and interaction with folate, vitamin B6, and vitamin B12 intakes

Qiao

De-chuang

et al. 2014

Tumor Biol.

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We assessed the association between dietary intake of folate and the MTHFR genotype with breast cancer in a Chinese population, with additional analysis of the interactions of gene polymorphisms and dietary intake of folate, vitamin B6, and vitamin B12. A case-control study was performed, and 535 patients with newly diagnosed breast cancer and 673 controls were enrolled into this study. The MTHFR 667TT genotype (odds ratio (OR) = 1.82, 95 % confidence interval (CI) = 1.24-2.97) and T allele (OR 0= 1.48, 95 % CI = 1.15-1.78) were correlated with a moderately significant increased risk of breast cancer when compared with the CC genotype. Individuals carrying the MTR 2756GG genotype (OR = 1.66, 95 % CI = 1.16-2.56) and G allele (OR = 1.42, 95 % CI = 1.26-1.81) had a higher risk of breast cancer when compared with subjects with the AA genotype. The MTHFR 667 T allele and MTR 2756 G allele were associated with a higher risk of breast cancer in individuals with low folate intake, vitamin B6, and vitamin B12, but the association disappeared among subjects with moderate and high intake of folate, vitamin B6, and vitamin B12. This case-control study found that the MTHFR C677T and MTR A2756G polymorphisms are associated with risk of breast cancer, and folate, vitamin B6, and vitamin B12 intakes influence these associations.

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“…In addition, Le Marchand et al (77) observed that the MTHFR 1298C allele was weakly protective against CRC. However, Guimarães et al (69) reported that the carriers of the combined variants MTHFR 1298AC+CC and 677CT+TT exhibited an increased risk of CRC, whether in isolation or in combination. According to Shannon et al (14) Figure 2.…”

Section: Discussionmentioning

confidence: 99%

“…The conflicting conclusions among the studies mentioned above may be attributed to several causes. First, the sample sizes of the populations included in several studies were relatively small (19,27,69), which may result in false-positive or false-negative outcomes. Second, the eligibility criteria for inclusion of control subjects differed among the studies.…”

Section: Discussionmentioning

confidence: 99%

Association of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms with colorectal cancer risk: A meta-analysis

Zhao

Xing

et al. 2013

Biomedical Reports

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Abstract. Colorectal cancer (CRC) is one of the most common types of cancer worldwide and a leading cause of cancer-related mortality. This meta-analysis was conducted to determine the effect of methylenetetrahydrofolate reductase (MTHFR) mutants on the risk of CRC. A literature search was conducted on PubMed, Medline and the China National Knowledge Infrastructure (CNKI) databases. Eligible studies were collected based on rigorous criteria of inclusion. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by the fixed-or random-effects model. After all the studies were pooled, the OR of CRC for individuals carrying the MTHFR 677TT genotype, compared to the CC genotype, was 0.89 (95% CI: 0.82-0.97). When analyzed by ethnicity, Asians with the MTHFR 1298CC genotype exhibited a decreased risk of CRC (OR=0.69; 95% CI: 0.54-0.89). In a mixed population, a significantly reduced risk of CRC was observed among carriers of the 677TT (OR=0.86; 95% CI: 0.76-0.96) and the 1298CC (OR=0.82; 95% CI: 0.69-0.98) genotypes, compared to the wild-type homozygous genotype. In the subgroup of colon cancer, the OR of 677TT vs. CC+CT was 0.83 (95% CI: 0.72-0.96) and the OR of 1298CC vs. AA+AC was 0.81 (95% CI: 0.69-0.96). In the rectal cancer subgroup, the OR of 677TT vs. CC+CT was 0.86 (95% CI: 0.77-0.97). Therefore, this meta-analysis suggested that the MTHFR 677T and 1298C alleles were associated with a low risk of CRC.

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Gene polymorphisms involved in folate and methionine metabolism and increased risk of sporadic colorectal adenocarcinoma

Cited by 21 publications

References 34 publications

The Polymorphisms in Methylenetetrahydrofolate Reductase, Methionine Synthase, Methionine Synthase Reductase, and the Risk of Colorectal Cancer

The Polymorphisms in Methylenetetrahydrofolate Reductase, Methionine Synthase, Methionine Synthase Reductase, and the Risk of Colorectal Cancer

Association of methylenetetrahydrofolate reductase and methionine synthase polymorphisms with breast cancer risk and interaction with folate, vitamin B6, and vitamin B12 intakes

Association of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms with colorectal cancer risk: A meta-analysis

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