Preliminary Study on the Single Nucleotide Polymorphism (SNP) of XRCC1 Gene Identificationto Improve the Outcomes of Radiotherapy for Cervical Cancer

Devita Tetriana, Wiwin Mailana, Iin Kurnia, Mukh Syaifudin

Abstract


Cervical cancer is the most fatal disease among Indonesian women. In recognition of the substantial variation in the intrinsic response of individuals to radiation, an effort had been done to identify the genetic markers, primarily Single Nucleotide polymorphisms (SNPs), which are associated with responsiveness of cancer cells to radiation therapy. One of these SNPs is X-ray repair cross-complementing protein 1 (XRCC1) that is one of the most important genes in deoxyribonucleic acid (DNA) repair pathways. Meta-analysis in the determination of the association of XRCC1 polymorphisms with cervical cancer revealed the potential role of XRCC1 polymorphisms in predicting cell response to radiotherapy.Our preliminary study with real-time polymerase chain reaction (RT-PCR) showed that radiotherapy affected the XRCC1 gene analyzed in blood of cervical cancer patient. Other published study found three SNPs of XRCC1 (Arg194Trp, Arg280His, and Arg399Gln) that cause amino acid substitutions. Arg194Trp is only SNPs that associated with high risk of cervical cancer but not others. Additionally, structure and function of this protein can be altered by functional SNPs, which may lead to the susceptibility of individuals to cancers. Anotherstudy found G399A polymorphisms. We concluded that SNP of this DNA repair genes have been found to be good predictors of efficacy of radiotherapy.

Kanker serviks adalah penyakit yang paling fatal pada perempuan di Indonesia. Untuk memahami variasi substansial respon intrinsik individual terhadap radiasi, suatu usaha telah dilakukan untuk mengidentifikasi petanda genetik, terutama Single Nucleotide polymorphism (SNP), yang berkaitan dengan responsel kanker terhadap terapi radiasi. Satu dari SNP tersebut adalah X-ray repair cross-complementing protein 1 (XRCC1) yang merupakan satu dari gen paling penting dalam lajur perbaikan asam deoksiribonukleat (DNA). Meta-analysis dalam penentuan hubungan polimorfisme XRCC1 dengan kanker serviks menemukan adanya peranan potensial polimorfisme XRCC1 dalam memprediksi respon sel terhadap radioterapi. Studi awal kami menggunakan real-time polymerase chain reaction (RT-PCR) menunjukkan bahwa radioterapi mempengaruhi gen XRCC1yang dianalisis dalam darah pasien kanker serviks. Studi yang telah dipublikasi menemukan tiga SNP dari XRCC1 (Arg194Trp, Arg280His, dan Arg399Gln) yang menyebabkan substitusi asam amino. Arg194Trp merupakan satu-satunya SNP yang berkaitan dengan tingginya risiko kanker serviks, tetapi tidak pada yang lain. Di samping itu, strukturdan fungsi protein ini dapat berubah oleh SNP fungsional, yang mengarah ke kerentanan individu untuk menderita kanker. Studi lain menemukan polimorfisme G399A. Kami menyimpulkan bahwa SNP dari gen perbaikan DNA ini merupakan prediktor yang baik dari keberhasilan radioterapi.


Keywords


cervical cancer; radiotherapy outcome; SNPs; XRCC1

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References


Alsbeih,G, Al-Harbi, N, El-Sebaie, M & Al-Badawi I. (2013). HPV prevalence and genetic predisposition to cervical cancer in Saudi Arabia. Infectious Agents and Cancer. 8:15.

Barbisan, G, Prez, LO, Difranza, L, Fernndez, CJ, Ciancio, NE, Golijow, CD. (2011). XRCC1 Arg399Gln polymorphism and risk for cervical cancer development in Argentine women. Eur J Gynaecol Oncol. 32(3):274-9.

Barnett, GC, West, CM, Dunning, AM, Elliott RM, Coles, CE, Pharoah, PD, Burnet, NG. (2009). Normal Tissue Reactions to Radiotherapy: Towards Tailoring Treatment Dose by Genotype. Nat Rev Cancer. 9:134-142.

Bentzen, SM, Heeren, G, Cottier, B, Slotman, B, Glimelius, B, Lievens, Y, & Van den Bogaert, W. (2005). Towards Evidence-based Guidelines for Radiotherapy Infrastructure and Staffing Needs in Europe: the ESTRO QUARTS project. Radiotherapy Oncology. 75:355-365.

Cheng, X-D, Lu, W-G, Ye, F, Wan, X-Y & Xie, X. (2009). The association of XRCC1 gene single nucleotide polymorphisms with response to neoadjuvant chemotherapy in locally advanced cervical carcinoma. Journal of Experimental & Clinical Cancer Research. 28:91.

Delaney, G, Jacob, S, Featherstone, C, & Barton, M. (2005). The Role of Radiotherapy in Cancer Treatment: Estimating Optimal Utilization from a Review of Evidence-based Clinical Guidelines. Cancer. 104:1129-1137.

Jung, H, Beck-Bornholdt, HP, Svoboda, V, Alberti, W, & Herrmann, T. (2001). Quantification of late complications after radiation therapy. Radiother Onco. 61:233-246.

Kerns, SL, Ostrer, H, Stock, R, Li, W, Moore, J, Pearlman, A, Campbell, C, Shao, Y, Stone, N, Kusnetz, L & Rosenstein, BS. (2010). Genome-wide Association Study to Identify Single Nucleotide Polymorphisms (SNPs) Associated with the Development of Erectile Dysfunction in African-American Men after Radiotherapy for Prostate Cancer. International Journal of Radiation Oncology Biologyand Physics.78:1292-1300.

Khanna, S. (1992). Implementation of Cancer Management in Indonesia. Proceeding National Seminar on the Implementation of Cancer Management in Indonesia.

Kurnia, I, Siregar,B, Soetopo,S, Ramli, I, Kurjana, T, Tetrian, D, Hernowo, B, Andrijono, A & Tobing, M.D.M. (2014). The utilization of biomarkers for predicting the response of cervical cancer cells to radiotherapy. Annual Research Report of The Center for Technology of Radiation Safety and Metrology, National Nuclear Energy Agency.

Li, H, You, Y, Lin, C, Zheng, M, Hong, C, Chen, J, Li, D, Au, WW & Chen, Z. (2013). XRCC1 codon 399Gln polymorphism is associated with radiotherapy-induced acute dermatitis and mucositis in nasopharyngeal carcinoma patients.Radiation Oncology.8:31.

Li, Y, Liu, F, Tan, SQ, Wang, Y, Li, SW. (2012). X-Ray Repair Cross-Complementing Group 1 (XRCC1) Genetic Polymorphisms and Cervical Cancer Risk: A HuGE Systematic Review and Meta-Analysis. PLoS ONE 7(9): e44441. doi:10.1371/journal.pone.0044441.

Mangunkusumo, R. (1998). Frequency of Malignant Tumors in Indonesia, a Pathological Base Observation. Proceeding 4-th Continuing Medical Education on Early Detection and Prevention of Cancer.

Mao, X, Young, BD & Yong-Jie Lu. (2007). YJ.The Application of Single Nucleotide Polymorphism Microarrays in Cancer Research. Curr Genomics. 8(4): 219228.

Mulyadi, B. (1998). Cancer Control Programme in Indonesia. Proceeding of the 4-th Continuing Medical Education on Early Detection and Prevention of Cancer. Jakarta.

National Cancer Institute.What Is Cancer? (on line) (2013).http://www.cancer.gov/cancertopics/ cancerlibrary/what-is-cancer. [accessed on July 2013].

National Center for Biotechnology Information, U.S. National Library of Medicine 8600 Rockville Pike, Bethesda MD, 20894USA. http://www.ncbi.nlm.nih.gov/gene/7515

Rapley, R & Harbron, S. (Eds.). (2004). Molecular Analysis and Genome Discovery. Chichester: John Wiley & Sons Ltd.

Rosenstein, BS. (2011). Identification of SNPs Associated with Susceptibility for Development of Adverse Reactions to Radiotherapy.Pharmacogenomics 12(2): 267275.

Ryu, JS, Hong, YC, Han, HS, Lee, JE, Kim, S, Park, YM, Kim, YC, Hwang, TS. (2004). Association between polymorphisms of RECC1 and XPD and survival in non-small-cell lung cancer patients treated with cisplatin combination chemotherapy. Lung Cancer 44:311-316.

Shuai, H-L, Luo, X, Yan, R-L, Li, J, Chen, D-L. (2012). XRCC1 Polymorphisms are Associated with Cervical Cancer Risk and Response to Chemotherapy: a Systematic Review and Meta-analysis. Asian Pacific J Cancer Prev. 13(12): 6423-6427.

Soedarmo, PS & Suhardi. (1992). Trend and Case of Cancer Diseases.Proceeding National Seminar on the Implementation of Cancer Management in Indonesia.

Terrazzino, S, La Mattina, P, Gambaro, G, Masini, L, Franco, P, Canonico, PL, Genazzani, AA, & Krengli, M. (2011). Common variants of GSTP1, GSTA1, and TGFb1 are associated with the risk of radiation-induced fibrosis in breast cancer patients. International Journal of Radiation Oncology, Biology and Physics 1-8. doi:10.1016/j.ijrobp.2011.06.2012.

Tjindarbumi, D & Mangunkusumo, R. (2002). Cancer in Indonesia, Present and Future. Japanese Journalof Clinical Oncology, 32 (suppl 1): S17-S21.

Tudek B. (2007). Base excision repair modulation as a risk factor for human cancers. Mol Aspects Med 28: 258-275.

Wasisto, B. (1991). The National Cancer Control Programme in Indonesia. WHO Meeting on National Cancer Programme. Geneva.Switzerland.

Whitehouse, CJ, Taylor, RM, Thistlethwaite, A, Zhang,H, Karimi-Busheri,F, Lasko, D, Weinfeld, M & Caldecott, KW. (2001). XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 104: 107-117.

World Health Organization Report [WHO Report]. (2012). United Nations, The World Bank, IARC Globocan (on line) http://www.who.int/hpvcentre/statistics/en/[accessed on 2012].

XingMing, EN. (2009). Single nucleotide polymorphisms in XRCC1 and outcome in esophagus cancer receiving cisplatin based concurrent chemoradiotherapy. J. Acta Metallurgica Sinica. 21(1): 20-22.




DOI: https://doi.org/10.15294/biosaintifika.v7i2.3949

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