DOI QR코드

DOI QR Code

MTHFR C677T Polymorphism and Colorectal Cancer Risk in Asians, a Meta-analysis of 21 Studies

  • Yang, Zhen (Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University) ;
  • Zhang, Xie-Fu (Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University) ;
  • Liu, Hong-Xiang (Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University) ;
  • Hao, Yong-Shun (Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University) ;
  • Zhao, Chun-Lin (Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University)
  • Published : 2012.04.30

Abstract

Background: Previous studies concerning the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer risk in Asian populations generated conflicting results. A meta-analysis was therefore performed to allow a more reliable estimate of any link. Methods: Relevant studies concerning the association between the MTHFR C677T polymorphism and risk of colorectal cancer were included into this meta-analysis. The quality of the studies was assessed according to a predefined scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for this gene-disease association using fixed or random effect models according to the heterogeneity between included studies. Results: Finally, 21 studies with a total of 6692 cases and 8266 controls were included. Meta-analyses showed that there was an obvious association of the MTHFR 677T allele with decreased risk of colorectal cancer (OR = 0.91, 95%CI=0.85-0.98, P=0.011). Subgroup analyses by country further identified this association, with dietary folate as the main source of heterogeneity. Conclusion: The MTHFR 677T allele is associated with a lower risk of colorectal cancer in Asian populations, and there is effect modification by population plasma folate.

Keywords

References

  1. AT (1999). Assessing the influence of a single study in the metaanalysis estimate. Stata Tech Bull, 8, 15-7.
  2. Cao HX, Gao CM, Takezaki T, et al (2008). Genetic polymorphisms of methylenetetrahydrofolate reductase and susceptibility to colorectal cancer. Asian Pac J Cancer Prev, 9, 203-8.
  3. Chang SC, Lin PC, Lin JK, et al (2007). Role of MTHFR polymorphisms and folate levels in different phenotypes of sporadic colorectal cancers. Int J Colorectal Dis, 22, 483-9. https://doi.org/10.1007/s00384-006-0190-x
  4. Cui LH, Shin MH, Kweon SS, et al (2010). Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer in a Korean population. BMC Cancer, 10, 236. https://doi.org/10.1186/1471-2407-10-236
  5. Der Simonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88. https://doi.org/10.1016/0197-2456(86)90046-2
  6. Egger M, Davey Smith G, Schneider M, et al (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629-34. https://doi.org/10.1136/bmj.315.7109.629
  7. Egger M, Smith GD, Phillips AN (1997). Meta-analysis, principles and procedures. BMJ, 315, 1533-7. https://doi.org/10.1136/bmj.315.7121.1533
  8. Frosst P, Blom HJ, Milos R, et al (1995). A candidate genetic risk factor for vascular disease, a common mutation in methylenetetrahydrofolate reductase. Nat Genet, 10, 111-3. https://doi.org/10.1038/ng0595-111
  9. Goyette P, Sumner JS, Milos R, et al (1994). Human methylenetetrahydrofolate reductase, isolation of cDNA, mapping and mutation identification. Nat Genet, 7, 195-200. https://doi.org/10.1038/ng0694-195
  10. Hao L, Tian Y, Zhang F, et al (2002). Variation of plasma folate levels in adults between some areas and different seasons in China]. Zhonghua Yu Fang Yi Xue Za Zhi, 36, 308.
  11. Higgins JP, Thompson SG, Deeks JJ, et al (2003). Measuring inconsistency in meta-analyses. BMJ, 327, 557-60. https://doi.org/10.1136/bmj.327.7414.557
  12. Huang P, Zhou ZY, Ma HT, et al (2003). MTHFR polymorphisms and colorectal cancer susceptibility in Chongging people. Acta Academiae Med Militaris Tertiae, 25, 1710-5.
  13. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  14. Jemal A, Siegel R, Xu J, et al (2010). Cancer statistics. CA Cancer J Clin, 60, 277-300. https://doi.org/10.3322/caac.20073
  15. Jiang DK, Ren WH, Yao L, et al (2010). Meta-analysis of association between TP53 Arg72Pro polymorphism and bladder cancer risk. Urology, 76, 765 e1-7.
  16. Jiang DK, Wang WZ, Ren WH, et al (2011). TP53 Arg72Pro polymorphism and skin cancer risk, a meta-analysis. J Invest Dermatol, 131, 220-8. https://doi.org/10.1038/jid.2010.270
  17. Jiang Q, Chen K, Ma X, et al (2005). Diets, polymorphisms of methylenetetrahydrofolate reductase, and the susceptibility of colon cancer and rectal cancer. Cancer Detect Prev, 29, 146-54. https://doi.org/10.1016/j.cdp.2004.11.004
  18. Jiang QT, Chen K, Ma XY, et al (2004). A case-control study on the polymorphisms of methylenetetrahydrofolate reductases, drinking interaction and susceptibility in colorectal cancer. Zhonghua Liu Xing Bing Xue Za Zhi, 25, 612-6.
  19. Jin XX, Zhu ZZ, Wang AZ, et al (2007). Association of methylenetetrahydrofoIate reductase C677T polymorphism with genetic susceptibility to colorectal cancer. Shijie Huaren Xiao Hua Za Zhi, 15, 2754-7.
  20. Kang BS, Ahn DH, Kim NK, et al (2011). Relationship between metabolic syndrome and MTHFR polymorphism in colorectal cancer. J Korean Soc Coloproctol, 27, 78-82. https://doi.org/10.3393/jksc.2011.27.2.78
  21. Kim DH, Ahn YO, Lee BH, et al (2004). Methylenetetrahydrofolate reductase polymorphism, alcohol intake, and risks of colon and rectal cancers in Korea. Cancer Lett, 216, 199-205. https://doi.org/10.1016/j.canlet.2004.08.014
  22. Kim J, Cho YA, Kim DH, et al (2012). Dietary intake of folate and alcohol, MTHFR C677T polymorphism, and colorectal cancer risk in Korea. Am J Clin Nutr, 95, 405-12. https://doi.org/10.3945/ajcn.111.020255
  23. Kim JW, Park HM, Choi YK, et al (2011). Polymorphisms in genes involved in folate metabolism and plasma DNA methylation in colorectal cancer patients. Oncol Rep, 25, 167-72.
  24. Mantel N, Haenszel W (1959). Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst, 22, 719-48.
  25. Markowitz SD, Bertagnolli MM (2009). Molecular origins of cancer, Molecular basis of colorectal cancer. N Engl J Med, 361, 2449-60. https://doi.org/10.1056/NEJMra0804588
  26. Matsuo K, Hamajima N, Hirai T, et al (2002). Methionine synthase reductase gene A66G polymorphism is associated with risk of colorectal cancer. Asian Pac J Cancer Prev, 3, 353-9.
  27. Matsuo K, Ito H, Wakai K, et al (2005). One-carbon metabolism related gene polymorphisms interact with alcohol drinking to influence the risk of colorectal cancer in Japan. Carcinogenesis, 26, 2164-71. https://doi.org/10.1093/carcin/bgi196
  28. Miao XP, Yang S, Tan W, et al (2005). Association between genetic variations in methylenetetrahydrofolate reductase and risk of colorectal cancer in a Chinese population. Zhonghua Yu Fang Yi Xue Za Zhi, 39, 409-11.
  29. Otani T, Iwasaki M, Hanaoka T, et al (2005). Folate, vitamin B6, vitamin B12, and vitamin B2 intake, genetic polymorphisms of related enzymes, and risk of colorectal cancer in a hospital-based case-control study in Japan. Nutr Cancer, 53, 42-50. https://doi.org/10.1207/s15327914nc5301_5
  30. Park KS, Mok JW, Kim JC (1999). The 677C > T mutation in 5, 10-methylenetetrahydrofolate reductase and colorectal cancer risk. Genet Test, 3, 233-6. https://doi.org/10.1089/gte.1999.3.233
  31. Promthet SS, Pientong C, Ekalaksananan T, et al (2010). Risk factors for colon cancer in Northeastern Thailand: interaction of MTHFR codon 677 and 1298 genotypes with environmental factors. J Epidemiol, 20, 329-38. https://doi.org/10.2188/jea.JE20090140
  32. Stuck AE, Rubenstein LZ, Wieland D (1998). Bias in metaanalysis detected by a simple, graphical test. Asymmetry detected in funnel plot was probably due to true heterogeneity. BMJ, 316, 469; author reply 70-1. https://doi.org/10.1136/bmj.316.7129.469
  33. Thompson SG, Higgins J (2002). How should meta-regression analyses be undertaken and interpreted? Stat Med, 21, 1559-73. https://doi.org/10.1002/sim.1187
  34. Yang XX, Li FX, Yi JP, et al (2010). Association of MTHFR C677T polymorphism and susceptibility of lung cancer, gastric cancer and colorectal cancer risk. Guangdong Yi Xue, 31, 2375-8.
  35. Yin G, Kono S, Toyomura K, et al (2004). Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and colorectal cancer, the Fukuoka Colorectal Cancer Study. Cancer Sci, 95, 908-13. https://doi.org/10.1111/j.1349-7006.2004.tb02201.x
  36. Zhang YL, Yuan XY, Zhang C, et al (2008). Relationship between polymorphisms of thymidylate synthase and methylenetetrahydrofolate reductase and susceptibility in Liaoning Benxi colorectal cancer pafients. Linchuang Zhong Liu Xue Za Zhi, 13, 769-74.
  37. Zhu F, Wang YM, Zhang QM (2010). A case-control study of plasma homocysteine, serum folate, the polymorphism of methylenetetrahydrofolate reductase in colorectai cancer. Dongnan Da Xue Xue Bao, 29, 88-92.
  38. Zhu Q, Jin Z, Yuan Y, et al (2011). Impact of MTHFR gene C677T polymorphism on Bcl-2 gene methylation and protein expression in colorectal cancer. Scand J Gastroenterol, 46, 436-45. https://doi.org/10.3109/00365521.2010.537682

Cited by

  1. 5,10-Methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) gene polymorphisms and adult meningioma risk vol.115, pp.2, 2013, https://doi.org/10.1007/s11060-013-1218-z
  2. Folate-Related Nutrients, Genetic Polymorphisms, and Colorectal Cancer Risk: the Fukuoka Colorectal Cancer Study vol.14, pp.11, 2013, https://doi.org/10.7314/APJCP.2013.14.11.6249
  3. Colloid or crystalloid solution on maternal and neonatal hemodynamics for cesarean section: A meta-analysis of randomized controlled trials vol.39, pp.5, 2013, https://doi.org/10.1111/jog.12001
  4. The 677C>T (rs1801133) Polymorphism in the MTHFR Gene Contributes to Colorectal Cancer Risk: A Meta-Analysis Based on 71 Research Studies vol.8, pp.2, 2013, https://doi.org/10.1371/journal.pone.0055332
  5. Methylenetetrahydrofolate Reductase Gene Germ-Line C677T and A1298C SNPs are Associated with Colorectal Cancer Risk in the Turkish Population vol.15, pp.18, 2014, https://doi.org/10.7314/APJCP.2014.15.18.7731
  6. Two DNA repair gene polymorphisms on the risk of gastrointestinal cancers: a meta-analysis vol.35, pp.3, 2014, https://doi.org/10.1007/s13277-013-1320-z
  7. Methylenetetrahydrofolate reductase (MTHFR) polymorphism susceptibility to schizophrenia and bipolar disorder: an updated meta-analysis vol.122, pp.2, 2015, https://doi.org/10.1007/s00702-014-1261-8
  8. Association between folate metabolism-related polymorphisms and colorectal cancer risk vol.3, pp.3, 2015, https://doi.org/10.3892/mco.2015.520
  9. rs1801133 polymorphism and susceptibility to colorectal cancer in Iranian population: evidence of a case–control study and meta-analysis vol.17, pp.17, 2016, https://doi.org/10.2217/pgs-2016-0048
  10. Methylenetetrahydrofolate reductase C677T polymorphism and colorectal cancer susceptibility: a meta-analysis vol.37, pp.6, 2017, https://doi.org/10.1042/BSR20170917
  11. gene polymorphisms and their associations with diseases among Chinese population vol.92, pp.3, 2017, https://doi.org/10.1111/cge.12929
  12. gene polymorphisms in colorectal cancer vol.16, pp.4, 2015, https://doi.org/10.2217/pgs.14.177
  13. Personalized hypertension management in practice vol.12, pp.3, 2015, https://doi.org/10.2217/pme.14.83