DOI QR코드

DOI QR Code

Association between MTHFR C677T Polymorphism and Risk of Prostate Cancer: Evidence from 22 Studies with 10,832 Cases and 11,993 Controls

  • Abedinzadeh, Mehdi (Department of Urology, Shahid Rahnamoun Hospital) ;
  • Zare-Shehneh, Masoud (Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences and Health Services) ;
  • Neamatzadeh, Hossein (Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences and Health Services) ;
  • Abedinzadeh, Maryam (Department of Biology, Art and Science University) ;
  • Karami, Hormoz (Department of Urology, Shahid Rahnamoun Hospital)
  • 발행 : 2015.06.26

초록

Background: The MTHFR C677T polymorphism is a genetic alteration affecting an enzyme involved in folate metabolism, but its relationship to host susceptibility to prostate cancer remains uncertain. The aim of this study was to investigate the association between MTHFR C677T polymorphism and prostate cancer by performing a meta-analysis. Materials and Methods: Pubmed and Web of Science databases were searched for case-control studies investigating the association between MTHFR C677T polymorphism and prostate cancer. Odds ratios (OR) and 95% confidence intervals (95%CI) were used to assess any link. Results: A total of 22 independent studies were identified, including 10,832 cases and 11,993 controls. Meta-analysis showed that there was no obvious association between MTHFR C677T polymorphism and risk of prostate cancer under all five genetic models. There was also no obvious association between MTHFR C677T polymorphism and risk of prostate cancer in the subgroup analyses of Caucasians. In contrast, MTHFR C677T polymorphism was associated with increased risk for prostate cancer in Asians with the allele model (C vs G: OR=1.299, 95 %CI =1.121-1.506, P=0.001, $P_{heterogeneity}=0.120$, $I^2=45%$), additive genetic model (CC vs TT: OR =1.925, 95 % CI= 1.340-2.265, P=0.00, $P_{heterogeneity}=0.587$, $I^2=0.00%$), recessive model (CC vs TT+TC: OR= 1.708, 95 % CI=1.233-2.367, P=0.001, $P_{heterogeneity}=0.716$, $I^2=0.00%$), and heterozygote genetic model (CT vs TT: OR=2.193, 95 % CI =1.510-3.186, P=0.000, $P_{heterogeneity}=0.462$, $I^2=0.00%$). Conclusions: These results suggest that the MTHFR C677T polymorphism does not contribute to the risk of prostate cancer from currently available evidence in populations overall and Caucasians. However, the meta analysis indicates that it may play a role in prostate cancer development in Asians.

키워드

참고문헌

  1. Albright F, Stephenson RA, Agarwal N, et al (2015). Prostate cancer risk prediction based on complete prostate cancer family history. Prostate, 75, 390-8. https://doi.org/10.1002/pros.22925
  2. Ashton LJ, Gifford AJ, Kwan E, et al (2009). Reduced folate carrier and methylenetetrahydrofolate reductase gene polymorphisms: associations with clinical outcome in childhood acute lymphoblastic leukemia. Leukemia, 23, 1348-51. https://doi.org/10.1038/leu.2009.67
  3. Bai JL, Zheng MH, Xiac X, et al (2009). MTHFR C677T polymorphism contributes to prostate cancer risk among Caucasians: A meta-analysis of 3511 cases and 2762 controls. Eur J Cancer, 45, 1443-9. https://doi.org/10.1016/j.ejca.2009.01.020
  4. Berger SH, Pittman DL (2008), Wyatt MD. Uracil in DNA: consequences for carcinogenesis and chemotherapy. Biochem Pharmacol, 76, 697-706. https://doi.org/10.1016/j.bcp.2008.05.019
  5. Cai D, Ning L, Pan C, et al (2010). Association of polymorphisms in folate metabolic genes and prostate cancer risk: a casecontrol study in a Chinese population. J Genet, 89, 263-7. https://doi.org/10.1007/s12041-010-0037-7
  6. Cicek MS, Nock NL, Li L, et al (2004). Relationship between methylenetetrahydrofolate reductase C677T and A1298C genotypes and haplotypes and prostate cancer risk and aggressiveness. Cancer Epidemiol Biomarkers Prev, 13, 1331-6.
  7. Collin SM, Metcalfe C, Zuccolo L, et al (2009) Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev, 18, 2528-39. https://doi.org/10.1158/1055-9965.EPI-09-0223
  8. DerSimonian RLN (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88. https://doi.org/10.1016/0197-2456(86)90046-2
  9. de Vogel S, Meyer K, Fredriksen Å, et al (2013). Serum folate and vitamin B12 concentrations in relation to prostate cancer risk--a Norwegian population-based nested case-control study of 3000 cases and 3000 controls within the JANUS cohort. Int J Epidemiol, 42, 201-10. https://doi.org/10.1093/ije/dys199
  10. Eeles RA, Kote-Jarai Z, Giles GG, et al (2008). Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet, 40, 316-21. https://doi.org/10.1038/ng.90
  11. Fard-Esfahani P, Mohammadi Torbati P, Hashemi Z, et al (2012). Analysis of relationm between C677T genotype in MTHFR gene and prostatic cancer in Iranian males. Acta Med Iran, 50, 657-63.
  12. Ghasemi S, Tavakoli A, Moghadam M, et al (2014). Risk of prostate cancer and thrombosis-related factor polymorphisms. Biomed Rep, 2, 53-56. https://doi.org/10.3892/br.2013.180
  13. Goovaerts P, Xiao H (2011). Geographical, temporal and racial disparities in late-stage prostate cancer incidence across Florida: A multiscale joinpoint regression analysis. Int J Health Geogr, 5, 63.
  14. Heijmans BT, Boer JM, Suchiman HE, et al (2003). A common variant of the methylenetetrahydrofolate reductase gene (1p36) is associated with an increased risk of cancer. Cancer Res, 63, 1249-53.
  15. Johansson M, Van Guelpen B, Hultdin J, et al (2007). The MTHFR C677T polymorphism and risk of prostate cancer: results from the CAPS study. Cancer Causes Control, 18, 1169-74. https://doi.org/10.1007/s10552-007-9055-z
  16. Kimura F, Franke KH, Steinhoff C, et al (2000). Methyl group metabolism gene polymorphisms and susceptibility to prostatic carcinoma. Prostate, 45, 225-31. https://doi.org/10.1002/1097-0045(20001101)45:3<225::AID-PROS4>3.0.CO;2-7
  17. Kobayashi LC, Limburg H, Miao Q, et al (2012). Folate intake, alcohol consumption, and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism: influence on prostate cancer risk and interactions. Front Oncol, 2, 100.
  18. Kreile M, Rots D, Piekuse L, et al (2014). Lack of Association between polymorphisms in genes MTHFR and MDR1 with risk of childhood acute lymphoblastic leukemia. Asian Pac J Cancer Prev, 15, 9707-11. https://doi.org/10.7314/APJCP.2014.15.22.9707
  19. Kucukhuseyin O, Kurnaz O, Akadam-Teker B, et al (2011). Effects of the MTHFR C677T polymorphism on prostate specific antigen and prostate cancer. Asian Pac J Cancer Prev, 12, 2275-8.
  20. Li D, Tian T, Guo C, et al (2012). No association of the MTHFR gene A1298C polymorphism with the risk of prostate cancer: A meta-analysis. Exp Ther Med, 3, 493-8. https://doi.org/10.3892/etm.2012.445
  21. Lopez-Cortes A, Jaramillo-Koupermann G, Munoz MJ, et al (2013). Genetic polymorphisms in MTHFR (C677T, A1298C), MTR (A2756G) and MTRR (A66G) genes associated with pathological characteristics of prostate cancer in the Ecuadorian population. Am J Med Sci, 346, 447-54. https://doi.org/10.1097/MAJ.0b013e3182882578
  22. Mandal RK, Nissar K, Mittal RD (2012). Genetic variants in metabolizing genes NQO1, NQO2, MTHFR and risk of prostate cancer: a study from North India. Mol Biol Rep. 39, 11145-52. https://doi.org/10.1007/s11033-012-2023-z
  23. Marchal C, Redondo M, Reyes-Engel A, et al (2008). Association between polymorphisms of folate-metabolizing enzymes and risk of prostate cancer. Eur J Surg Oncol, 34, 805-10. https://doi.org/10.1016/j.ejso.2007.09.008
  24. Muslumanoglu MH, Tepeli E, Demir S, et al (2009). The analysis of the relationship between A1298C and C677T polymorphisms of the MTHFR gene with prostate cancer in Eskisehir population. Genet Test Mol Biomarkers, 13, 641-5. https://doi.org/10.1089/gtmb.2009.0046
  25. Ozen F, Sen M, Ozdemir O (2014). Methylenetetrahydrofolate Reductase Gene Germ-Line C677T and A1298C SNPs are associated with colorectal cancer risk in the Turkish population. Asian Pac J Cancer Prev, 15, 7731-5. https://doi.org/10.7314/APJCP.2014.15.18.7731
  26. Safarinejad MR, Shafiei N, Safarinejad S (2010). Relationship between three polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T, A1298C, and G1793A) gene and risk of prostate cancer: a case-control study. Prostate, 70, 1645-57. https://doi.org/10.1002/pros.21200
  27. Singal R, Ferdinand L, Das PM, et al (2004) Polymorphisms in the methylenetetrahydrofolate reductase gene and prostate cancer risk. Int J Oncol, 25, 1465-71.
  28. Stevens VL, Rodriguez C, Sun J, et al (2008). No association of single nucleotide polymorphisms in one-carbon metabolism genes with prostate cancer risk. Cancer Epidemiol Biomarkers Prev, 17, 3612-4. https://doi.org/10.1158/1055-9965.EPI-08-0789
  29. Rai V (2014). Folate pathway gene MTHFR C677T polymorphism and risk of lung cancer in asian populations. Asian Pac J Cancer Prev, 15, 9259-64. https://doi.org/10.7314/APJCP.2014.15.21.9259
  30. Reljic A, Simundic AM, Topic E, et al (2007). The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cancer risk: the Croatian case-control study. Clin Biochem, 40, 981-5. https://doi.org/10.1016/j.clinbiochem.2007.05.005
  31. Van Guelpen BR, Wiren SM, Bergh AR, et al (2006). Polymorphisms of methylenetetrahydrofolate reductase and the risk of prostate cancer: a nested case-control study. Eur J Cancer Prev, 15, 46-50. https://doi.org/10.1097/01.cej.0000186640.19872.4d
  32. Vidal AC, Grant DJ, Williams CD, et al (2012), Associations between intake of folate, methionine, and Vitamins B-12, B-6 and prostate cancer risk in American veterans. J Cancer Epidemiol, 2012, 957467.
  33. Wu HC, Chang CH, Tsai RY, et al (2010). Significant association of methylenetetrahydrofolate reductase single nucleotide polymorphisms with prostate cancer susceptibility in Taiwan. Anticancer Res, 30, 3573-7.
  34. Yang YB, Shang YH, Tan YL, et al (2014) . Methylenetetrahydrofolate reductase polymorphisms and susceptibility to esophageal cancer in chinese populations: a meta-analysis. Asian Pac J Cancer Prev, 15, 1345-9. https://doi.org/10.7314/APJCP.2014.15.3.1345
  35. Yilmaz M, Kacan T, Sari H, Kilickap S (2014). Lack of Association between the MTHFR C677T polymorphism and lung cancer in a Turkish population. Asian Pac J Cancer Prev, 15, 6333-7. https://doi.org/10.7314/APJCP.2014.15.15.6333
  36. Zhang WB, Zhang JH, Pan ZQ, et al (2012). The MTHFR C677T polymorphism and prostate cancer risk: new findings from a meta-analysis of 7306 cases and 8062 controls. Asian Pac J Cancer Prev, 13, 2597-604. https://doi.org/10.7314/APJCP.2012.13.6.2597