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Review
. 2019 Sep;21(9):e3114.
doi: 10.1002/jgm.3114. Epub 2019 Aug 6.

Methylenetetrahydrofolate reductase polymorphisms and colorectal cancer prognosis: A meta-analysis

Xin-Lin Chen  1 , Yu-Mei Wang  2 , Fei Zhao  1 , Zheng Chen  3 , Xiaofei Yang  4 , Cong Sun  5 , Yunpeng Gao  6 , Tian-Ge Yang  7 , Guo Tian  7 , Yi-Ming Chen  1 , Shui-Lian Zhu  8 , Xiao-Bing Lin  9 , Feng-Bin Liu  8
Affiliations
Review

Methylenetetrahydrofolate reductase polymorphisms and colorectal cancer prognosis: A meta-analysis

Xin-Lin Chen et al. J Gene Med. 2019 Sep.

Abstract

Background: The present study focused on understanding the prognostic value of the methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms rs1801133 (C667T) and rs1801131 (A1298C) in patients with colorectal cancer (CRC).

Methods: A systematic literature search was conducted in March 2016. Databases, including Medline, EMBASE, Cochrane and Chinese databases (including CNKI, Wanfang and VIP), were searched to identify the relevant articles describing MTHFR polymorphisms in patients with CRC. Data regarding overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were collected and analysed.

Results: Twenty-four studies with 5423 patients with CRC were included. Significant differences in OS, PFS and DFS were not observed among the different comparisons of patients carrying different alleles of the MTHFR rs1801133 polymorphism (including TT versus CC, TT versus CT + CC, CT + TT versus CC and CT versus CC). Compared with patients with the rs1801131 CA + AA genotypes, patients with the CC genotype had a shorter OS (hazard ratio = 1.85; 95% confidence interval = 1.30-2.65) and DFS (hazard ratio = 2.16; 95% confidence interval= 1.19-3.93). Significant differences in OS, PFS and DFS were not observed among the other patient groups (including CC versus AA, CC + CA versus AA and CA versus AA). Subgroup analysis of rs1801133 and rs1801131 showed that patients with CRC from Asian regions and Western regions demonstrated similar results.

Conclusions: The MTHFR rs1801133 polymorphism was not associated with the prognosis of patients with CRC; however, rs1801131 may be associated with the prognosis of patients with CRC. Well-designed prospective studies are necessary to obtain a better understanding of the prognostic value of rs1801133 and rs1801131.

Keywords: colorectal cancer; gene polymorphism; meta-analysis; methylenetetrahydrofolate reductase; prognosis.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Flow chart of the search strategy
Figure 2
Figure 2
Meta‐analysis plots of the HRs for survival in the comparison of patients with the CC genotype and patients with the AA + CA genotypes of rs1801131. OS, overall survival; PFS, progression‐free survival; DFS, disease‐free survival
See this image and copyright information in PMC

References

    1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11‐30. - PubMed
    1. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383:1490‐1502. - PubMed
    1. Torres Stone RA, Waring ME, Cutrona SL, Kiefe CI, Allison J, Doubeni CA. The association of dietary quality with colorectal cancer among normal weight, overweight and obese men and women: a prospective longitudinal study in the USA. BMJ Open. 2017;7:e015619. - PMC - PubMed
    1. Asteria CR, Pucciarelli S, Gerard L, et al. The impact of colorectal screening program on the detection of right‐sided colorectal cancer. A 5‐year cohort study in the Mantua District. Int J Colorectal Dis. 2015;30:1627‐1637. - PubMed
    1. Stern LL, Mason JB, Selhub J, Choi SW. Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene. Cancer Epidemiol Biomarkers Prev. 2000;9:849‐853. - PubMed

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