Skip to main content Skip to main navigation menu Skip to site footer

Hubungan Polimorfisme Gen Matriks Metalloproteinase-9 (MMP-9) rs3918242 (C-1562T) dengan Metastasis Kanker Payudara

Abstract

Introduction: Breast cancer, constituting 16.6% of all cancer cases in Indonesia, involves uncontrolled cell growth in the breast epithelium. Diagnostic delays contribute to decreased survival rates. Despite screening efforts, treatment delays persist, necessitating effective early detection markers. The MMP-9 rs3918242 gene polymorphism's link to breast cancer risk remains inconclusive. This study investigates the association between MMP-9 gene polymorphism rs3918242 (C-1562T) and breast cancer metastasis, aiming to enhance understanding and early detection strategies.

Method: This analytical descriptive research with a cross-sectional design was carried out for 6 months at the Biochemistry Laboratory, Faculty of Medicine and Integrated Biomedical Laboratory, Udayana University. The samples for this research were 46 stored biological materials from venous blood samples. Identification of the MMP-9 rs3918242 polymorphism was carried out by DNA isolation, PCR, and sequencing. Data were analyzed using software tools in the form of univariate and bivariate analysis to determine the relationship between the MMP-9 rs3918242 gene polymorphism and breast cancer metastasis.

Results: In 46 research samples, metastatic cases were found in 18 samples (37%) and non-metastatic cases in 29 samples (63%). The distribution of polymorphisms was found to be dominant in the CC (60.8%), CT (19.6%) and TT (19.6%) genotypes. There is a significant relationship between the MMP-9 gene polymorphism rs3918242 CT + TT genotype and breast cancer metastasis with a p-value of 0.036 (<0.05) and a prevalence ratio of 2.132 (95% CI: 1.047-4.343).

Conclusion: There is a significant relationship between the MMP-9 rs3918242 gene polymorphism and breast cancer metastasis.

 

Pendahuluan: Kanker payudara merupakan pertumbuhan sel secara abnormal dan tidak terkontrol pada epitel payudara. Prevalensi kanker payudara mencapai 16,6% dari seluruh jenis kanker di Indonesia. Keterlambatan diagnosis sampai saat ini masih menjadi permasalahan dalam penatalaksanaan kanker payudara sehingga survival rate pasien menurun. Upaya screening dan diagnostik sudah dilakukan, namun keterlambatan penanganan masih tinggi, sehingga diperlukan marker yang efektif sebagai deteksi dini risiko kanker payudara. Beberapa studi telah mengkaji mengenai hubungan polimorfisme gen MMP-9 rs3918242 dengan risiko kanker payudara namun hasil yang didapatkan masih bervariasi. Tujuan dari penelitian ini adalah untuk mengetahui hubungan antara polimorfisme gen MMP-9 rs3918242 (C-1562T) dengan metastasis pada kanker payudara.

Metode: Penelitian deskriptif analitik dengan desain potong lintang ini dilaksanakan selama   6 bulan berloaksi di Laboratorium Biokimia Fakultas Kedokteran dan Laboratorium Biomedik Terpadu, Universitas Udayana. Sampel penelitian ini adalah bahan biologi tersimpan sampel darah vena berjumlah 46. Identifikasi polimorfisme MMP-9 rs3918242 dilakukan isolasi DNA, PCR dan sequensing. Data dianalisis menggunakan piranti perangkat lunak berupa analisis univariat dan bivariat untuk mengetahui hubungan polimorfisme gen MMP-9 rs3918242 dengan metastasis kanker payudara.

Hasil: Pada 46 sampel penelitian ditemukan kasus metastasis sebanyak 18 sampel (37%) dan non-metastasis sebanyak 29 sampel (63%). Distribusi polimorfisme ditemukan dominan pada genotipe CC (60,8%), CT (19,6%) dan TT (19,6%). Terdapat hubungan signifikan antara polimorfisme gen MMP-9 rs3918242 genotipe CT + TT terhadap metastasis kanker payudara dengan nilai p 0.036 (<0.05) dan prevalence ratio sebesar 2.132 (95% CI: 1.047-4.343).

Kesimpulan: Terdapat hubungan yang signifikan dan bermakna antara polimorfisme gen MMP-9 rs3918242 dengan metastasis kanker payudara.

References

  1. Kemenkes RI. Panduan Penatalaksanaan Kanker Payudara (Breast Cancer Treatment Guideline). 2019;1–50. Available from: http://kanker.kemkes.go.id/guidelines/PPKPayudara.pdf
  2. Narisuari IDAPM, Manuaba IBTW. Prevalensi dan gambaran karakteristik penderita kanker payudara di poliklinik bedah onkologi RSUP Sanglah, Bali, Indonesia tahun 2016. Intisari Sains Medis. 2020;11(1):183.
  3. International Agency for Research on Cancer (IARC). Indonesia - Global Cancer Observatory. Globocan. 2020;858:1–2.
  4. SEER Cancer Stat Facts: Oral Cavity and Pharynx Cancer. National Cancer Institute. Bethesda, MD,. 2017; Available from: https://seer.cancer.gov/statfacts/html/oralcav.html
  5. Niell BL, Freer PE, Weinfurtner RJ, Arleo EK, Drukteinis JS. Screening for Breast Cancer. Radiol Clin North Am. 2017;55(6):1145–62. Available from: https://doi.org/10.1016/j.rcl.2017.06.004
  6. Kabel AM. Tumor markers of breast cancer: New prospectives. J Oncol Sci. 2017;3(1):5–11. Available from: http://dx.doi.org/10.1016/j.jons.2017.01.001
  7. Huang H. Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: Recent advances. Sensors (Switzerland). 2018;18(10):5–7.
  8. Dofara SG, Chang SL, Diorio C. Gene polymorphisms and circulating levels of MMP-2 and MMP-9: A review of their role in breast cancer risk. Anticancer Res. 2020;40(7):3619–31.
  9. Rahimi Z, Yari K, Rahimi Z. Matrix Metalloproteinase-9 -1562T allele and its combination with MMP-2 -735 C allele are risk factors for breast cancer. Asian Pacific J Cancer Prev. 2015;16(3):1175–9.
  10. Zahra Dehghan Manshadi, Mohammad Hamid FK, Heidar Tayebinia IK. Metalloproteinase Gene Polymorphisms Metastasis in Women with Breast Cancer in Central Iran. 2018;9(April):123–31.
  11. Xu T, Zhang S, Qiu D, Li X, Fan Y. Association between matrix metalloproteinase 9 polymorphisms and breast cancer risk: An updated meta-analysis and trial sequential analysis. Gene. 2020;759(July):144972. Available from: https://doi.org/10.1016/j.gene.2020.144972
  12. de Oliveira VA, Chagas DC, Amorim JR, Pereira R de O, Nogueira TA, Borges VML, et al. Association between matrix metalloproteinase-9 gene polymorphism and breast cancer in brazilian women. Clinics. 2020;75(7):1–5.
  13. Kalali D. The Role of the Matrix Metalloproteinase-9 Gene in Tumor Development and Metastasis: A Narrative Review. Glob Med Genet. 2023;10(02):048–53.
  14. Felizi RT, Veiga MG, Carelli Filho I, Souto RP Do, Fernandes CE, Oliveira E. Association between Matrix Metallopeptidase 9 Polymorphism and Breast Cancer Risk. Rev Bras Ginecol e Obstet. 2018;40(10):620–4.
  15. Padala C, Tupurani MA, Puranam K, Gantala S, Shyamala N, Kondapalli MS, et al. Synergistic effect of collagenase-1 (MMP1), stromelysin-1 (MMP3) and gelatinase-B (MMP9) gene polymorphisms in breast cancer. PLoS One. 2017;12(9):1–19.
  16. Yan C, Sun C, Lu D, Zhao T, Ding X, Zamir I, et al. Estimation of associations between MMP9 gene polymorphisms and breast cancer: Evidence from a meta-analysis. Int J Biol Markers. 2022;37(1):13–20.
  17. Farina AR, Mackay AR. Gelatinase B/MMP-9 in tumour pathogenesis and progression. Cancers (Basel). 2014;6(1):240–96.
  18. Wu H Di, Bai X, Chen DM, Cao HY, Qin L. Association of genetic polymorphisms in matrix metalloproteinase-9 and coronary artery disease in the Chinese han population: A case-control study. Genet Test Mol Biomarkers. 2013;17(9):707–12.
  19. Heo DS, Choi H, Yeom MY, Song BJ, Oh SJ. Serum levels of matrix metalloproteinase-9 predict lymph node metastasis in breast cancer patients. Oncol Rep. 2014;31(4):1567–72.
  20. Merdad A, Karim S, Schulten HJ, Dallol A, Buhmeida A, Al-Thubaity F, et al. Expression of matrix metalloproteinases (MMPs) in primary human breast cancer: MMP-9 as a potential biomarker for cancer invasion and metastasis. Anticancer Res. 2014;34(3):1355–66.

How to Cite

Kusuma, I. K. W. A., Sutadarma, I. W. G. ., Surudarma, I. W., & Wiryanthini, I. A. D. . (2024). Hubungan Polimorfisme Gen Matriks Metalloproteinase-9 (MMP-9) rs3918242 (C-1562T) dengan Metastasis Kanker Payudara. Intisari Sains Medis, 15(1), 62–78. https://doi.org/10.15562/ism.v15i1.1917

HTML
0

Total
0

Share

Search Panel

I Komang Wira Ananta Kusuma
Google Scholar
Pubmed
ISM Journal


I Wayan Gede Sutadarma
Google Scholar
Pubmed
ISM Journal


I Wayan Surudarma
Google Scholar
Pubmed
ISM Journal


Ida Ayu Dewi Wiryanthini
Google Scholar
Pubmed
ISM Journal