Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Relationship between Genetic Polymorphisms in MTHFR (C677T, A1298C and their Haplotypes) and the Incidence Of Breast Cancer among Jordanian Females - Case-Control Study

  • Awwad, Nemah (Biopharmaceutics and Clinical Pharmacy, Department of Pharmacy, The University of Jordan) ;
  • Yousef, Al-Motassem (Biopharmaceutics and Clinical Pharmacy, Department of Pharmacy, The University of Jordan) ;
  • Abuhaliema, Ali (Biopharmaceutics and Clinical Pharmacy, Department of Pharmacy, The University of Jordan) ;
  • Abdalla, Ihab (Biopharmaceutics and Clinical Pharmacy, Department of Pharmacy, The University of Jordan) ;
  • Yousef, Muhammad (Biopharmaceutics and Clinical Pharmacy, Department of Pharmacy, The University of Jordan)
  • Published : 2015.07.13
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Breast cancer is a major cause of morbidity and mortality in Jordan and worldwide. Abnormality of DNA methylation is a possible mechanism for the development of cancer. Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation. Our aim was to study the association between genetic polymorphisms of MTHFR at two sites (C677T and A1298C) and their haplotypes and the risk of breast cancer among Jordanian females. Materials and Methods: A case-control study involving 150 breast cancer cases and 150 controls was conducted. Controls were age-matched to cases. Polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique and sequencing were conducted to determine the genotypes. Results: There was a significant difference in genotype frequency of C677T in the 41-60 year age category [cases: CC (37.4%), CT (49.5%) and TT (13.2%); controls: CC (56.3%), CT (35.6%) and TT (8%), p= 0.04; $OR_{TT\;vs.\;CC}$: 2.5, 95% CI: (0.9-6.9); $OR_{at\;least\;on\;T$: 2.1, 95%CI: (1.2-3.9)]. There was no significant difference in genotype frequency of A1298C between cases and controls [cases: AA (46.6%), AC (41.8%) and CC (11.6%); controls: AA (43%), AC (47.4%) and CC (9.6%); p= 0.6]. There was a significant difference of MTHFR genetic polymorphism haplotypes among breast cancer cases and controls [cases/control: CA: 38.3/45.4%; CC: 28.9/25.2%; TA: 29.2/21; TC: 3.6/8.3; p value= 0.01; $OR_{TA\;vs.\;CA}=1.6$; 95% CI (1.1-2.5); p= 0.02]. Conclusions: Genetic polymorphism of MTHFR C677T may modulate the risk of breast cancer especially in the 41-60 year age group. Additionally, TA haplotype amends the risk of breast cancer. Future studies with a larger sample size are needed to validate the role of MTHFR genetic polymorphisms in breast cancer.

Keywords

References

  1. American Cancer Society. 2012. Cancer Facts and Figures 2012 [Online]. Available: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-031941.pdf [Accessed 25-3-2015 2015].
  2. Butterworth AS, Higgins JP, Pharoah P (2006). Relative and absolute risk of colorectal cancer for individuals with a family history: a meta-analysis. Eur J Cancer, 42, 216-27. https://doi.org/10.1016/j.ejca.2005.09.023
  3. Chad M. Barnett, Laura Boehnke Michaud, Francisco J. Esteva (2014). Bresat cancer. In 'Pharmacotherapy: A Pathophysiologic Approach', Eds Mc Graw Hill education,
  4. Cochran G (1954). Some methods for strengthening the common $\chi$ tests. Biometrics, 10.
  5. Collaborative Group on Hormonal Factors in Breast Cancer (2001). Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet, 358, 1389-99. https://doi.org/10.1016/S0140-6736(01)06524-2
  6. Diakite B, Tazzite A, Hamzi K, et al (2012). Methylenetetrahydrofolate reductase C677T polymorphism and breast cancer risk in Moroccan women. African Health Sciences, 12, 204-9.
  7. Eliassen AH, Colditz GA, Rosner B, et al (2006). Adult weight change and risk of postmenopausal breast cancer. JAMA, 296, 193-201. https://doi.org/10.1001/jama.296.2.193
  8. Food Fortification Initiative. 2014. Middle East - Fortification Status [Online]. Available: http://www.ffinetwork.org/regional_activity/middle_east.php#middle_east.php?s=2&_suid=142601829808809411473741271781 [Accessed 10-3-2015 2015].
  9. Foulkes WD (2008). Inherited susceptibility to common cancers. N Eng J Med, 359, 2143-53. https://doi.org/10.1056/NEJMra0802968
  10. Frosst P, Blom HJ, Milos R, et al (1995). A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genetics, 10, 111-3. https://doi.org/10.1038/ng0595-111
  11. Gaughan DJ, Barbaux S, Kluijtmans LA, et al (2000). The human and mouse methylenetetrahydrofolate reductase (MTHFR) genes: genomic organization, mRNA structure and linkage to the CLCN6 gene. Gene, 257, 279-89. https://doi.org/10.1016/S0378-1119(00)00392-9
  12. Hosseini M, Houshmand M, Ebrahimi A (2011). MTHFR polymorphisms and breast cancer risk. Arch Medical Science, 7, 134-7.
  13. Jiang Y, Hou J, Zhang Q, et al (2013). The MTHFR C677T polymorphism and risk of acute lymphoblastic leukemia: an updated meta-analysis based on 37 case-control studies. Asian Pac J Cancer Prev, 14, 6357-62. https://doi.org/10.7314/APJCP.2013.14.11.6357
  14. Jiao Z, Li D (2013). Lack of association between MHTFR Glu429Ala polymorphism and breast cancer susceptibility: a systematic review and meta-analysis of 29 research studies. Tumour Biology, 34, 1225-33. https://doi.org/10.1007/s13277-013-0665-7
  15. Jordan ministry of health. 2010. Annual Incidence of cancer in Jordan [Online]. Available: http://www.moh.gov.jo/EN/Pages/Periodic-Newsletters.aspx [Accessed 21-1-2015 2015].
  16. Kruk J (2014). Lifestyle Components and Primary Breast Cancer Prevention. Asian Pac J Cancer Prev, 15, 10543-55.
  17. Liew S, Gupta ED (2015). Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: Epidemiology, metabolism and the associated diseases. Eur J Medical Genetics, 58, 1-10. https://doi.org/10.1016/j.ejmg.2014.10.004
  18. Luo B, Repalli J, Yousef AM, et al (2011). Human thymidylate synthase with loop 181-197 stabilized in an inactive conformation: ligand interactions, phosphorylation, and inhibition profiles. Protein Science, 20, 87-94. https://doi.org/10.1002/pro.539
  19. Marie A., Barbara G., Terry L., et al 2013. Pharmacotherapy Principles and Practice.
  20. National cancer institute. 2014. BRCA1 and BRCA2: Cancer Risk and Genetic Testing [Online]. Available: http://www.cancer.gov/cancertopics/genetics/brca-fact-sheet [Accessed 6-3-2015 2015].
  21. 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
  22. Pharoah PD, Day NE, Duffy S, et al (1997). Family history and the risk of breast cancer: a systematic review and meta-analysis. Intl J Cancer, 71, 800-9. https://doi.org/10.1002/(SICI)1097-0215(19970529)71:5<800::AID-IJC18>3.0.CO;2-B
  23. Rai V (2014a). Methylenetetrahydrofolate Reductase A1298C Polymorphism and Breast Cancer Risk: A Meta-analysis of 33 Studies. Ann Medical Health Sciences Res, 4, 841-51. https://doi.org/10.4103/2141-9248.144873
  24. Rai V (2014b). The methylenetetrahydrofolate reductase C677T polymorphism and breast cancer risk in Asian populations. Asian Pac J Cancer Prev, 15, 5853-60. https://doi.org/10.7314/APJCP.2014.15.14.5853
  25. Rodriguez S, Gaunt TR, Day IN (2009). Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol, 169, 505-14. https://doi.org/10.1093/aje/kwn359
  26. Shiovitz S, Korde LA (2015). Genetics of breast cancer: a topic in Evolution. Ann Oncol. [Epub ahead of print]
  27. Siegel R, Naishadham D, Jemal A (2012). Cancer statistics, 2012. CA: a Cancer J Clin, 62, 10-29. https://doi.org/10.3322/caac.20138
  28. Walker SE, Lorsch J (2013). Sanger dideoxy sequencing of DNA. Method Enzymol, 529, 171-84. https://doi.org/10.1016/B978-0-12-418687-3.00014-8
  29. Welcsh PL, King MC (2001). BRCA1 and BRCA2 and the genetics of breast and ovarian cancer. Human Molecular Genetics, 10, 705-13. https://doi.org/10.1093/hmg/10.7.705
  30. Xu X, Gammon MD, Zeisel SH, et al (2008). Choline metabolism and risk of breast cancer in a population-based study. FASEB J, 22, 2045-52. https://doi.org/10.1096/fj.07-101279
  31. 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
  32. Yousef AM, Shomaf M, Berger S, et al (2013). Allele and genotype frequencies of the polymorphic methylenetetrahydrofolate reductase and colorectal cancer among Jordanian population. Asian Pac J Cancer Prev, 14, 4559-65. https://doi.org/10.7314/APJCP.2013.14.8.4559
  33. Zhang, Qiu LX, Wang ZH, et al (2010). MTHFR C677T polymorphism associated with breast cancer susceptibility: a meta-analysis involving 15,260 cases and 20,411 controls. Breast Cancer Res Treatment, 123, 549-55. https://doi.org/10.1007/s10549-010-0783-5
  34. Zhong S, Chen Z, Yu X, et al (2014). A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate reductase gene polymorphisms in breast cancer. Molec Cell Biochem, 41, 5775-85.
  35. Zintzaras E (2006). Methylenetetrahydrofolate reductase gene and susceptibility to breast cancer: a meta-analysis. Clinical Genetics, 69, 327-36. https://doi.org/10.1111/j.1399-0004.2006.00605.x
  36. Zintzaras E, Koufakis T, Ziakas PD, et al (2006). A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate reductase gene polymorphisms in acute lymphoblastic leukemia. Eur J Epidemiol, 21, 501-10. https://doi.org/10.1007/s10654-006-9027-8
  37. Zintzaras E, Lau J (2008). Synthesis of genetic association studies for pertinent gene-disease associations requires appropriate methodological and statistical approaches. J Clin Epidemiol, 61, 634-45. https://doi.org/10.1016/j.jclinepi.2007.12.011

Cited by

  1. Potential biomarker panels in overall breast cancer management: advancements by multilevel diagnostics vol.13, pp.5, 2016, https://doi.org/10.2217/pme-2016-0020
  2. Association between MTHFR gene 1298A>C polymorphism and breast cancer susceptibility: a meta-analysis based on 38 case-control studies with 40,985 subjects vol.14, pp.1, 2016, https://doi.org/10.1186/s12957-016-0978-2
  3. Association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with primary glaucoma in Saudi population vol.16, pp.1, 2016, https://doi.org/10.1186/s12886-016-0337-7
  4. Thymidylate Synthase Polymorphisms and Risk of Lung Cancer among the Jordanian Population: a Case Control Study vol.16, pp.18, 2016, https://doi.org/10.7314/APJCP.2015.16.18.8287
  5. Influence of Genotype and Haplotype of MDR1 (C3435T, G2677A/T, C1236T) on the Incidence of Breast Cancer - a Case-Control Study in Jordan vol.17, pp.1, 2016, https://doi.org/10.7314/APJCP.2016.17.1.261
  6. Population-level diversity in the association of genetic polymorphisms of one-carbon metabolism with breast cancer risk vol.7, pp.4, 2016, https://doi.org/10.1007/s12687-016-0277-1
  7. Significant association between ERCC2 and MTHR polymorphisms and breast cancer susceptibility in Moroccan population: genotype and haplotype analysis in a case-control study vol.18, pp.1, 2018, https://doi.org/10.1186/s12885-018-4214-z