Advertisement

Breast Cancer

, Volume 26, Issue 5, pp 602–611 | Cite as

C677T and A1298C methylenetetrahydrofolate reductase polymorphisms and breast cancer susceptibility among Latinos: a meta-analysis

  • Perla Meneses-Sanchez
  • Samantha C. Garcia-Hernandez
  • Leonardo M. Porchia
  • Ricardo Pérez-Fuentes
  • Enrique Torres-Rasgado
  • Alejandra Del Angel Soto
  • M. Elba Gonzalez-MejiaEmail author
Original Article

Abstract

Background

Previous meta-analyses have shown an ethnic dependency of the C677T and the A1298C methylenetetrahydrofolate reductase (MTHFR) polymorphisms, with no focus on the Latino population. For Latinos, many studies have examined these polymorphisms and breast cancer susceptibility, yielding no concise result. Therefore, we undertook this meta-analysis to determine the effect these polymorphisms have on breast cancer risk for Latinos.

Methods

PubMed, EBSCO, LILACS, Scopus, and Latin American-specific databases were searched for studies exploring the association between the MTHFR polymorphisms and breast cancer susceptibility in Latinos until January 2019. Genotype distributions were extracted and, depending on the level heterogeneity determined by the ψ2-based Q test and the I2 test, fixed-effects or random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. No publication bias was detected by the Begg–Mazumdar’s test and Egger’s test.

Results

Of the 280 retrieved publications, 9 studies were included: 9 for the C677T polymorphism and 5 for the A1298C polymorphism. For the C677T polymorphism, there was an elevated risk for the homozygous (OR 1.42, 95% CI 1.05–1.92), the dominant (OR 1.16, 95% CI 1.02–1.31), the recessive (OR 1.33, 95% CI 1.01–1.75), and the allelic model (OR 1.17, 95% CI 1.03–1.33, p < 0.01). No association between the A1298C polymorphism and the risk to develop breast cancer was determined.

Conclusion

The results indicated that, for Latinos, the C677T polymorphism is associated with a significant risk for developing breast cancer, whereas the A1289C polymorphism does not.

Keywords

MTHFR Mutation Carcinogenesis Latin America 

Notes

Acknowledgements

The authors would like to express their gratitude to Mtro. Ricardo Villegas Tovar, Coordinator of Scientific Production and International Visibility, BUAP.

Funding

This study was supported by grants from Programa para el Desarrollo Profesional Docente (to CA-160 FACMED) and Vicerrectorıa de Investigacion, Benemerita Universidad Autonoma de Puebla, Mexico (to TORE-SAL18-G, PEFR-SAL18-G, and GOMM-SAL18-I).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

12282_2019_961_MOESM1_ESM.pdf (287 kb)
Supplementary material 1 (PDF 286 KB)

References

  1. 1.
    Cancer Key Facts. Publisher WHO Geneva, Headquarters in Geneva. 2018. http://www.unesco.org/new/en/unesco/worldwide/latin-america-and-the-caribbean/. Accessed 11 May 2018.
  2. 2.
    Partanen T, Monge P, Wesseling C. Causes and prevention of occupational cancer. Acta Médica Costarricense. 2009;51(4):195–205.Google Scholar
  3. 3.
    Yan W, Zhang Y, Zhao E, Zhang S. Association between the MTHFR C677T polymorphism and breast cancer risk: a meta-analysis of 23 case–control studies. Breast J. 2016;22(5):593–4.CrossRefGoogle Scholar
  4. 4.
    Kim Y-I. Nutritional epigenetics: impact of folate deficiency on DNA methylation and colon cancer susceptibility. J Nutr. 2005;135(11):2703–9.CrossRefGoogle Scholar
  5. 5.
    Crider KS, Yang TP, Berry RJ, Bailey LB. Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate’s role. Adv Nutr. 2012;3(1):21–38.CrossRefGoogle Scholar
  6. 6.
    Shrubsole MJ, Gao YT, Cai Q, Shu XO, Dai Q, Hebert JR, et al. MTHFR polymorphisms, dietary folate intake, and breast cancer risk: results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomark Prev. 2004;13(2):190–6.CrossRefGoogle Scholar
  7. 7.
    Gao CM, Tang JH, Cao HX, Ding JH, Wu JZ, Wang J, et al. MTHFR polymorphisms, dietary folate intake and breast cancer risk in Chinese women. J Hum Genet. 2009;54(7):414–8.CrossRefGoogle Scholar
  8. 8.
    van der Put NM, Gabreels F, Stevens EM, Smeitink JA, Trijbels FJ, Eskes TK, et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998;62(5):1044–51.CrossRefGoogle Scholar
  9. 9.
    He L, Shen Y. MTHFR C677T polymorphism and breast, ovarian cancer risk: a meta-analysis of 19,260 patients and 26,364 controls. OncoTargets Ther. 2017;10:227.CrossRefGoogle Scholar
  10. 10.
    Kumar P, Yadav U, Rai V. Methylenetetrahydrofolate reductase gene C677T polymorphism and breast cancer risk: Evidence for genetic susceptibility. Meta Gene. 2015;6:72–84.CrossRefGoogle Scholar
  11. 11.
    Zhu X-L, Liu Z-Z, Yan S-X, Wang W, Chang R-X, Zhang C-Y, et al. Association between the MTHFR A1298C polymorphism and risk of cancer: evidence from 265 case–control studies. Mol Genet Genom. 2016;291(1):51–63.CrossRefGoogle Scholar
  12. 12.
    Liu W, Li Y, Li R, Han X, Ma Y, Liu B, et al. Association of MTHFR A1298C polymorphism with breast cancer and/or ovarian cancer risk: an updated meta-analysis. Afr J Tradit Complement Altern Med. 2016;13(5):72–86.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Zhang J, Zhang L, Li G. Association between MTHFR gene 1298A> C polymorphism and breast cancer susceptibility: a meta-analysis based on 38 case–control studies with 40,985 subjects. World J Surg Oncol. 2016;14(1):230.CrossRefGoogle Scholar
  14. 14.
    Xie S-Z, Liu Z-Z, Yu J-h, Liu L, Wang W, Xie D-L, et al. Association between the MTHFR C677T polymorphism and risk of cancer: evidence from 446 case–control studies. Tumor Biol. 2015;36(11):8953–72.CrossRefGoogle Scholar
  15. 15.
    Batschauer AP, Cruz NG, Oliveira VC, Coelho FF, Santos IR, Alves MT, et al. HFE, MTHFR, and FGFR4 genes polymorphisms and breast cancer in Brazilian women. Mol Cell Biochem. 2011;357(1–2):247–53.CrossRefGoogle Scholar
  16. 16.
    Calderón-Garcidueñas AL, Cerda-Flores RM, Lilia A. SNP C677T del gen metilentetrahidrofolato-reductasa y cáncer de mama en mujeres mexicanas. Rev Med Inst Mex Seguro Soc. 2017;55(6):720–4.PubMedGoogle Scholar
  17. 17.
    Ramos-Silva A, Figuera LE, Soto-Quintana OM, Puebla-Perez AM, Ramirez-Patino R, Gutierrez-Hurtado I, et al. Association of the C677T polymorphism in the methylenetetrahydrofolate reductase gene with breast cancer in a Mexican population. Genet Mol Res. 2015;14(2):4015–26.CrossRefGoogle Scholar
  18. 18.
    Zara-Lopes T, Gimenez-Martins AP, Nascimento-Filho CH, Castanhole-Nunes MM, Galbiatti-Dias AL, Padovani-Junior JA, et al. Role of MTHFR C677T and MTR A2756G polymorphisms in thyroid and breast cancer development. Genet Mol Res. 2016;15(2):;gmr8222.  https://doi.org/10.4238/gmr.15028222.CrossRefGoogle Scholar
  19. 19.
    Stang A. Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.CrossRefGoogle Scholar
  20. 20.
    Miller JJ. The inverse of the Freeman–Tukey double arcsine transformation. Am Stat. 1978;32(4):138-.Google Scholar
  21. 21.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clin Trials. 1986;7(3):177–88.CrossRefGoogle Scholar
  22. 22.
    Carvalho Barbosa RDC, Menezes DC, Freire TF, Sales DC, Alencar VH, Rabenhorst SH. Associations of polymorphisms of folate cycle enzymes and risk of breast cancer in a Brazilian population are age dependent. Mol Biol Rep. 2012;39(4):4899–907.CrossRefGoogle Scholar
  23. 23.
    Le Marchand L, Haiman CA, Wilkens LR, Kolonel LN, Henderson BE. MTHFR polymorphisms, diet, HRT, and breast cancer risk: the multiethnic cohort study. Cancer Epidemiol Biomark Prev. 2004;13(12):2071–7.Google Scholar
  24. 24.
    Lopez-Cortes A, Echeverria C, Ona-Cisneros F, Sanchez ME, Herrera C, Cabrera-Andrade A, et al. Breast cancer risk associated with gene expression and genotype polymorphisms of the folate-metabolizing MTHFR gene: a case–control study in a high altitude Ecuadorian mestizo population. Tum Biol J Int Soc Oncodev Biol Med. 2015;36(8):6451–61.CrossRefGoogle Scholar
  25. 25.
    Ma E, Iwasaki M, Junko I, Hamada GS, Nishimoto IN, Carvalho SM, et al. Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case–control study in Brazilian women. BMC Cancer. 2009;9:122.CrossRefGoogle Scholar
  26. 26.
    Rezende LM, Marson FAL, Lima CSP, Bertuzzo CS. Can. MTHFR C677T and a1298c polymorphisms alter the risk and severity of sporadic breast cancer in Brazilian women? Clin Breast Cancer. 2017;17(4):e199–208.CrossRefGoogle Scholar
  27. 27.
    Duthie SJ, Narayanan S, Brand GM, Pirie L, Grant G. Impact of folate deficiency on DNA stability. J Nutr. 2002;132(8):2444S-9S.CrossRefGoogle Scholar
  28. 28.
    Santilli F, Davì G, Patrono C. Homocysteine, methylenetetrahydrofolate reductase, folate status and atherothrombosis: a mechanistic and clinical perspective. Vasc Pharmacol. 2016;78:1–9.CrossRefGoogle Scholar
  29. 29.
    Moreno-Estrada A, Gravel S, Zakharia F, McCauley JL, Byrnes JK, Gignoux CR, et al. Reconstructing the population genetic history of the Caribbean. PLoS Genet. 2013;9(11):e1003925.CrossRefGoogle Scholar
  30. 30.
    Ramos BRDA, D’Elia MPB, Amador MAT, Santos NPC, Santos SEB, da Cruz Castelli E, et al. Neither self-reported ethnicity nor declared family origin are reliable indicators of genomic ancestry. Genetica. 2016;144(3):259–65.CrossRefGoogle Scholar
  31. 31.
    McLean E, de Benoist B, Allen LH. Review of the magnitude of folate and vitamin B12 deficiencies worldwide. Food Nutr Bull. 2008;29(2_suppl1):38–51.CrossRefGoogle Scholar
  32. 32.
    Marchetta CM, Hamner HC. Blood folate concentrations among women of childbearing age by race/ethnicity and acculturation, NHANES 2001–2010. Maternal Child Nutr. 2016;12(1):39–50.CrossRefGoogle Scholar
  33. 33.
    Brito A, Mujica-Coopman MF, Olivares M, Lopez de Romana D, Cori H, Allen LH. Folate and vitamin B12 status in Latin America and the Caribbean: an update. Food Nutr Bull. 2015;36(2_suppl):109-S18.CrossRefGoogle Scholar
  34. 34.
    Ramakrishnan U. Prevalence of micronutrient malnutrition worldwide. Nutr Rev. 2002;60(suppl_5):46–52.CrossRefGoogle Scholar
  35. 35.
    Bae S, Ulrich CM, Bailey LB, Malysheva O, Brown EC, Maneval DR, et al. Impact of folic acid fortification on global DNA methylation and one-carbon biomarkers in the Women’s Health Initiative Observational Study cohort. Epigenetics. 2014;9(3):396–403.CrossRefGoogle Scholar
  36. 36.
    Naushad SM, Divya C, Janaki Ramaiah M, Hussain T, Alrokayan SA, Kutala VK. Population-level diversity in the association of genetic polymorphisms of one-carbon metabolism with breast cancer risk. J Community Genet. 2016;7(4):279–90.CrossRefGoogle Scholar
  37. 37.
    Ergul E, Sazci A, Utkan Z, Canturk NZ. Polymorphisms in the MTHFR gene are associated with breast cancer. Tum Biol J Int Soc Oncodev Biol Med. 2003;24(6):286–90.CrossRefGoogle Scholar
  38. 38.
    Maruti SS, Ulrich CM, Jupe ER, White E. MTHFR C677T and postmenopausal breast cancer risk by intakes of one-carbon metabolism nutrients: a nested case–control study. Breast Cancer Res BCR. 2009;11(6):R91.CrossRefGoogle Scholar
  39. 39.
    Suzuki T, Matsuo K, Hirose K, Hiraki A, Kawase T, Watanabe M, et al. One-carbon metabolism-related gene polymorphisms and risk of breast cancer. Carcinogenesis. 2008;29(2):356–62.CrossRefGoogle Scholar
  40. 40.
    Platek ME, Shields PG, Marian C, McCann SE, Bonner MR, Nie J, et al. Alcohol consumption and genetic variation in methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase in relation to breast cancer risk. Cancer Epidemiol Biomark Prev. 2009;18(9):2453–9.CrossRefGoogle Scholar

Copyright information

© The Japanese Breast Cancer Society 2019

Authors and Affiliations

  • Perla Meneses-Sanchez
    • 1
  • Samantha C. Garcia-Hernandez
    • 1
  • Leonardo M. Porchia
    • 2
  • Ricardo Pérez-Fuentes
    • 2
    • 3
  • Enrique Torres-Rasgado
    • 3
  • Alejandra Del Angel Soto
    • 1
  • M. Elba Gonzalez-Mejia
    • 1
    Email author
  1. 1.Departamento de GenéticaFacultad de Medicina, Benemérita Universidad Autónoma de PueblaPueblaMexico
  2. 2.Laboratorio de Investigación en Fisiopatología de Enfermedades Crónicas, Centro de Investigación Biomédica de OrienteIMSSAtlixcoMexico
  3. 3.Facultad de Medicina, Benemérita Universidad Autónoma de PueblaPueblaMexico

Personalised recommendations