Methylenetetrahydrofolate Reductase C677T Distribution among Cervical Cancer Patients at Dr. Hasan Sadikin General Hospital

Ani Melani Maskoen, Cynthia Kurniawan, Herman Susanto, Edhyana Sahiratmadja


Cervical cancer is the second most common cancer among women in the world. Persistent infection with high risk human papillomavirus (HPV) is one of the necessary causes of cervical cancer development. However, host genetic factors may also play a role in cervical cancer carcinogenesis. Methylenetetrahydrofolate reductase enzyme, encoded by the MTHFR gene, regulates folate metabolism which is important for genetic expression and stability. Single nucleotide polymorphism (SNP) C677T in MTHFR gene may produce a thermo-labile enzyme, resulting in a reduced enzyme activity. The aim of this study was to explore the SNP C677T of MTHFR gene and the susceptibility to cervical cancer among cancer patients visiting Dr. Hasan Sadikin General Hospital, Bandung, Indonesia. This descriptive quantitative study involved cervical cancer patients recruited in 2010 and their control group. Genomic DNA was extracted from patients’ blood. MTHFR C677T genotype was performed using BeadXpress Reader Illumina® and some samples were re-genotyped for confirmation using conventional PCR-RFLP. The distribution of MTHFR C677T genotype in cervical cancer patients was 71.6%, 25.4%, and 3%, and 44%, 36%, and 20% in control group for CC, CT, and TT, respectively. This yielded a statistical significant difference of CC vs CT+TT (p 0.014 with OR 3.22 and CI 95% 1.24 – 8.33). Taken together, this result indicates that T allele has a protective effect against cervical cancer development. Further studies to confirm this effect in bigger population is warranted. [MKB. 2016;48(4):216–21]

Key words: Cervical cancer, MTHFR C677T, polymorphism, Bandung


Distribusi C677T gen Methylenetetrahydrofolate Reductase pada Pasien Kanker Serviks di Rumah Sakit Dr. Hasan Sadikin Bandung

Kanker serviks menduduki peringkat kedua sebagai kanker yang paling sering ditemukan pada wanita di dunia. Infeksi persisten oleh human papillomavirus (HPV) tipe risiko tinggi merupakan salah satu penyebab utama kanker serviks. Selain itu, factor genetic juga turut berperan dalam proses perkembangan kanker serviks. Enzim methylenetetrahydrofolate reductase yang disandi oleh gen MTHFR berfungsi meregulasi metabolism folat. Polimorfisme C677T pada gen MTHFR dapat membuat produksi enzim menjadi termolabil sehingga terjadi penurunan aktivitas. Distribusi folat yang abnormal dapat mengganggu proses metilasi, sintesis, dan perbaikan DNA yang dikaitkan dengan perkembangan kanker serviks. Tujuan penelitian ini adalah mengetahui distribusi polimorfisme C677T gen MTHFR pada pasien kanker serviks di Rumah Sakit Umum Dr. Hasan Sadikin Bandung, Indonesia. Penelitian deskriptif kuantitatif ini melibatkan pasien kanker serviks yang diinklusi tahun 2010 dan sebagai control adalah wanita yang datang untuk pemeriksaan PAPsmear. DNA genomic diisolasi dari darah pasien dan dihibridisasi dengan menggunakan system BeadXpress Reader Illumina® untuk menentukan jenis genotipenya. Genotipe beberapa sampel dikonfirmasi dengan metode PCR-RFLP. Hasil distribusi polimorfisme C677T gen MTHFR dengan genotipe CC, CT, dan TT pada pasien kanker serviks adalah 71,6%, 25,4%, dan 3% dan pada kontrol adalah 44%, 36%, and 20%. Hasil ini menunjukkan perbedaan yang signifikan antara pasien kanker serviks dan kontrolnya, dengan genotipe CC vs CT+TT menunjukkan nilai p=0,014 (OR 3.22 dan IK 95% 1,24–8,33). Simpulan, alel T menunjukkan efek yang protektif pada perkembangan kanker serviks. Penelitian harus dilanjutkan untuk membuktikan efek protektif alel pada kanker serviks.[MKB. 2016;48(4):216–21]

Kata kunci: Kanker serviks, MTHFR C677T, polimorfisme, Bandung


DOI: 10.15395/mkb.v48n4.754


cervical cancer, MTHFR C677T, polymorphism

Full Text:



GLOBOCAN 2012. Cancer incidence and mortality worldwide [internet]. International Agency for Research on Cancer. [cited 02/03/2014]. Available from:

Lai CH, Huang HJ, Hsueh S, Chao A, Lin CT, Huang SL, et al. Human papillomavirus genotype in cervical cancer: a population-based study. Int J Cancer. 2007;120(9):1999–2006.

International Collaboration of Epidemiological Studies of Cervical Cancer. Cervical carcinoma and reproductive factors: collaborative reanalysis of individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25epidemiological studies. Int J Cancer. 2006;119(5):1108–24.

Roura E, Travier N, Waterboer T, de Sanjosé S, Bosch FX, Pawlita M, et al. The Influence of Hormonal factors on the risk of developing cervical cancer and pre-cancer: Results from the EPIC cohort. PLoS One. 2016;11(3):e0151427.

Collins S, Rollason TP, Young LS, Woodman CB. Cigarette smoking is an independent risk factor for cervical intraepithelial neoplasia in young women: a longitudinal study. Eur J Cancer. 2010;46(2):405–11.

Couto E, Hemminki K. Heritable and environmental components in cervical tumors. Int J Cancer. 2006;119(11):2699–701.

Wang SS, Gonzalez P, Yu K, Porras C, Li Q, Safaeian M, et al. Common genetic variants and risk for HPV persistence and progression to cervical cancer. PLoS One. 2010;5(1):e8667.

Botezatu A, Socolov D, Iancu IV, Huica I, Plesa A, Ungureanu C, et al. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and promoter methylation in cervical oncogenic lesions and cancer. J Cell Mol Med. 2013;17(4):543–9.

Gruber BM. B-group vitamins: Chemoprevention?. Adv Clin Exp Med. 2016; 25(3):561–8.

Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet. 2009; 105(2):103–4.

Panigoro R, Susanto H, Arrazeen MN, Tobing M, Maskoen AM, Sahiratmadja E. Exploring TLR2 gene polymorphisms in cervical cancer development. MKB. 2013;45(4):257–62

Levin BL, Varga E. MTHFR: Addressing Genetic Counseling Dilemmas Using Evidence-Based Literature. J Genet Couns. 2016;25(5):901–11.

Shekari M, Sobti RC, Kordi Tamandani DM, Suri V. Impact of methylenetetrahydrofolate reductase (MTHFR) codon (677) and methionine synthase (MS) codon (2756) on risk of cervical carcinogenesis in North Indian population. Arch Gynecol Obstet. 2008;278(6):517–24.

Nandan NK, Wajid S, Biswas S, Juneja SS, Rizvi M, Prakash R, et al. Allelic variations in 5, 10-methylenetetrahydrofolate reductase gene and susceptibility to cervical cancer in Indian women. Drug Metab Lett. 2008;2(1):18–22.

Rao GG, Kurien A, Gossett D, Griffith WF, Coleman RL, Muller CY. A case-control study of methylenetetrahydrofolate reductase polymorphisms in cervical carcinogenesis. Gynecol Oncol. 2006;101(2):250–4.

Luo YL, Ye P, Zhang QH, Hu TT, Luo MH, Li MQ, et al. Methylenetetrahydrofolatereductase C677T polymorphism and susceptibility to cervical cancer and cervicalintraepithelial neoplasia: a meta-analysis. PLoS One. 2012; 7(9):e46272.

Hughes LB, Beasley TM, Patel H, Tiwari HK, Morgan SL, Baggott JE, et al. Racial or ethnic differences in allele frequencies of single-nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene and their influence on response to methotrexate in rheumatoid arthritis. Ann Rheum Dis. 2006;65(9):1213–8.

Tong SY, Kim MK, Lee JK, Lee JM, Choi SW, Friso S, et al. Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12. Cancer Causes Control. 2011;22(1):63–72.

Jiménez-Wences H, Peralta-Zaragoza O, Fernández-Tilapa G. Human papilloma virus, DNA methylation and microRNA expression in cervical cancer (Review). Oncol Rep. 2014;31(6):2467–76.

Li L, Xu C, Long J, Shen D, Zhou W, Zhou Q, et al. E6 and E7 gene silencing results in decreased methylation of tumor suppressor genes and induces phenotype transformation of human cervical carcinoma cell lines. Oncotarget. 2015;6(27):23930–43.


  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


This Journal indexed by


Creative Commons License
MKB is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License


View My Stats