The Roles of MTRR and MTHFR Gene Polymorphisms in Colorectal Cancer Survival
Background: Paradoxically epidemiological data illustrate a negative relationship between dietary folate intake and colorectal cancer (CRC) risk. The occurrence and progression of CRC may be influenced by variants in some key enzyme coding genes in the folate metabolic pathway. We investigated the c...
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ftdoajarticles:oai:doaj.org/article:ed6f5217afc34c1e8fbcde467a1a3b95 2023-05-15T17:22:49+02:00 The Roles of MTRR and MTHFR Gene Polymorphisms in Colorectal Cancer Survival Yu Wang Meizhi Du Jillian Vallis Matin Shariati Patrick S. Parfrey John R. Mclaughlin Peizhong Peter Wang Yun Zhu 2022-11-01T00:00:00Z https://doi.org/10.3390/nu14214594 https://doaj.org/article/ed6f5217afc34c1e8fbcde467a1a3b95 EN eng MDPI AG https://www.mdpi.com/2072-6643/14/21/4594 https://doaj.org/toc/2072-6643 doi:10.3390/nu14214594 2072-6643 https://doaj.org/article/ed6f5217afc34c1e8fbcde467a1a3b95 Nutrients, Vol 14, Iss 4594, p 4594 (2022) MTRR MTHFR gene polymorphism haplotype folate colorectal cancer survival Nutrition. Foods and food supply TX341-641 article 2022 ftdoajarticles https://doi.org/10.3390/nu14214594 2022-12-30T21:26:32Z Background: Paradoxically epidemiological data illustrate a negative relationship between dietary folate intake and colorectal cancer (CRC) risk. The occurrence and progression of CRC may be influenced by variants in some key enzyme coding genes in the folate metabolic pathway. We investigated the correlation between genetic variants in methionine synthase reductase ( MTRR ) and methylenetetrahydrofolate reductase ( MTHFR ) and CRC survival. Methods: This study used data collected from the Newfoundland Familial Colorectal Cancer Study. A total of 532 patients diagnosed with CRC for the first time from 1999 to 2003 were enrolled, and their mortality were tracked until April 2010. DNA samples were genotyped by Illumina’s integrated quantum 1 million chip. Cox models were established to assess 33 tag single-nucleotide polymorphisms in MTRR and MTHFR in relation to overall survival (OS), disease-free survival (DFS) and CRC-specific survival. Results: The MTRR and MTHFR genes were associated with DFS and CRC-specific survival in CRC patients at the gene level. After multiple comparison adjustment, MTRR rs1801394 A (vs. G) allele was associated with increased DFS ( p = 0.024), while MTHRT rs3737966 (G vs. A), rs4846049 (T vs. G), rs1476413 (A vs. G), rs1801131 (C vs. A), rs12121543 (A vs. C), rs1801133 (C vs. T), rs4846052 (T vs. C), rs2066471 (A vs. G) and rs7533315 (T vs. C) were related to worse CRC-specific survival. Additionally, significant interactions were seen among pre-diagnostic alcohol consumption with MTRR rs1801394, rs3776467, rs326124, rs162040, and rs3776455, with superior OS associated with those protective variant alleles limited to patients with alcohol consumption under the median. The MTHFR rs3737966 (G vs. A) allele seemed to be detrimental to CRC survival only among subjects with fruit intake below the median. Conclusions: Polymorphic variants in MTRR and MTHFR genes that code for key enzymes for folate metabolism may be associated with survival in patients with CRC. The gene-CRC outcome ... Article in Journal/Newspaper Newfoundland Directory of Open Access Journals: DOAJ Articles Nutrients 14 21 4594 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
topic |
MTRR MTHFR gene polymorphism haplotype folate colorectal cancer survival Nutrition. Foods and food supply TX341-641 |
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MTRR MTHFR gene polymorphism haplotype folate colorectal cancer survival Nutrition. Foods and food supply TX341-641 Yu Wang Meizhi Du Jillian Vallis Matin Shariati Patrick S. Parfrey John R. Mclaughlin Peizhong Peter Wang Yun Zhu The Roles of MTRR and MTHFR Gene Polymorphisms in Colorectal Cancer Survival |
topic_facet |
MTRR MTHFR gene polymorphism haplotype folate colorectal cancer survival Nutrition. Foods and food supply TX341-641 |
description |
Background: Paradoxically epidemiological data illustrate a negative relationship between dietary folate intake and colorectal cancer (CRC) risk. The occurrence and progression of CRC may be influenced by variants in some key enzyme coding genes in the folate metabolic pathway. We investigated the correlation between genetic variants in methionine synthase reductase ( MTRR ) and methylenetetrahydrofolate reductase ( MTHFR ) and CRC survival. Methods: This study used data collected from the Newfoundland Familial Colorectal Cancer Study. A total of 532 patients diagnosed with CRC for the first time from 1999 to 2003 were enrolled, and their mortality were tracked until April 2010. DNA samples were genotyped by Illumina’s integrated quantum 1 million chip. Cox models were established to assess 33 tag single-nucleotide polymorphisms in MTRR and MTHFR in relation to overall survival (OS), disease-free survival (DFS) and CRC-specific survival. Results: The MTRR and MTHFR genes were associated with DFS and CRC-specific survival in CRC patients at the gene level. After multiple comparison adjustment, MTRR rs1801394 A (vs. G) allele was associated with increased DFS ( p = 0.024), while MTHRT rs3737966 (G vs. A), rs4846049 (T vs. G), rs1476413 (A vs. G), rs1801131 (C vs. A), rs12121543 (A vs. C), rs1801133 (C vs. T), rs4846052 (T vs. C), rs2066471 (A vs. G) and rs7533315 (T vs. C) were related to worse CRC-specific survival. Additionally, significant interactions were seen among pre-diagnostic alcohol consumption with MTRR rs1801394, rs3776467, rs326124, rs162040, and rs3776455, with superior OS associated with those protective variant alleles limited to patients with alcohol consumption under the median. The MTHFR rs3737966 (G vs. A) allele seemed to be detrimental to CRC survival only among subjects with fruit intake below the median. Conclusions: Polymorphic variants in MTRR and MTHFR genes that code for key enzymes for folate metabolism may be associated with survival in patients with CRC. The gene-CRC outcome ... |
format |
Article in Journal/Newspaper |
author |
Yu Wang Meizhi Du Jillian Vallis Matin Shariati Patrick S. Parfrey John R. Mclaughlin Peizhong Peter Wang Yun Zhu |
author_facet |
Yu Wang Meizhi Du Jillian Vallis Matin Shariati Patrick S. Parfrey John R. Mclaughlin Peizhong Peter Wang Yun Zhu |
author_sort |
Yu Wang |
title |
The Roles of MTRR and MTHFR Gene Polymorphisms in Colorectal Cancer Survival |
title_short |
The Roles of MTRR and MTHFR Gene Polymorphisms in Colorectal Cancer Survival |
title_full |
The Roles of MTRR and MTHFR Gene Polymorphisms in Colorectal Cancer Survival |
title_fullStr |
The Roles of MTRR and MTHFR Gene Polymorphisms in Colorectal Cancer Survival |
title_full_unstemmed |
The Roles of MTRR and MTHFR Gene Polymorphisms in Colorectal Cancer Survival |
title_sort |
roles of mtrr and mthfr gene polymorphisms in colorectal cancer survival |
publisher |
MDPI AG |
publishDate |
2022 |
url |
https://doi.org/10.3390/nu14214594 https://doaj.org/article/ed6f5217afc34c1e8fbcde467a1a3b95 |
genre |
Newfoundland |
genre_facet |
Newfoundland |
op_source |
Nutrients, Vol 14, Iss 4594, p 4594 (2022) |
op_relation |
https://www.mdpi.com/2072-6643/14/21/4594 https://doaj.org/toc/2072-6643 doi:10.3390/nu14214594 2072-6643 https://doaj.org/article/ed6f5217afc34c1e8fbcde467a1a3b95 |
op_doi |
https://doi.org/10.3390/nu14214594 |
container_title |
Nutrients |
container_volume |
14 |
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21 |
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4594 |
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1766109689917997056 |