Mide, Kolon ve Rektum Kanserlerinde Mir146a Polimorfizmi

Abstract

MikroRNA ailesinin bir üyesi olan Mir146a, hematopoietik hücrelerin düzenlenmesi ve farklılaşması gibi birçok biyolojik yolun düzenlenmesinde önemli bir rol oynar. Türk popülasyonunda mir146a polimorfizmi ile mide, kolon, rektum kanserleri arasındaki ilişki araştırılmıştır. Real-Time PCR ile 212 hasta (mide:73, kolon:76 ve rektum:63) ve 77 sağlıklı kontrolde mir146a geni rs2961920 ve rs2910164'te polimorfizm belirlendi. Bulgular lojistik regresyon ve ki-kare (χ2) testleri ile değerlendirildi. Mide, kolon ve rektum kanserli hastalar ile kontrollerin karşılaştırılmasında alkollü içki tüketimi açısından istatistiksel olarak anlamlı bir ilişki saptandı (p<0,05). İncelenen Türk popülasyonunda mir146a rs2961920 polimorfizmi ile mide ve kolon kanserleri arasında istatistiksel olarak anlamlı ilişki vardı (p<0,05). Ancak rektum kanseri ile kontrol arasında anlamlı bir ilişki yoktu (p>0.05). mir146a rs2910164 polimorfizmi ile mide, kolon ve rektum kanserleri arasında istatistiksel olarak anlamlı bir ilişki bulunmadı (p>0,05). Ancak mide kanseri hastaları ve kontrol grubu mir146a rs2910164 polimorfizmi açısından değerlendirildiğinde GG+CG ve CC genotiplerinde bu polimorfizm ile mide kanseri arasında istatistiksel olarak anlamlı bir ilişki vardı (χ2: 5,49 p: 0,019). Benzer şekilde GG+CC ve CG genotiplerinde de bu polimorfizm ile mide kanseri arasında istatistiksel olarak anlamlı ilişki vardı (χ2:5,39, p: 0,020). Bu çalışmada, mikroRNA'ların kanserdeki fonksiyonları ve rollerinin araştırılmasının, kanserin moleküler patolojisinin anlaşılmasında ve moleküler hedefli tedavilerin geliştirilmesinde umut verici olabileceği düşünülmektedir.

Keywords

• Mide Kanseri
• Kolon Kanseri
• Rektum Kanseri
• Polimorfizm
• MİR146A
• Türk Popülasyonu

Mir146a Polymorphism in Gastric, Colon and Rectum Cancers

Abstract

mir146a, a member of the microRNA family, plays an important role in the regulation of many biological pathways such as the regulation and differentiation of hematopoietic cells. The relationship between mir146a polymorphism and gastric, colon, rectum cancers have been investigated in Turkish population. Polymorphism in mir146a gene rs2961920 and rs2910164 have been determined in 212 patients (gastric: 73, colon:76 and rectum:63) and in 77 healthy controls by Real-Time PCR. Findings were evaluated by logistic regression and Khi (χ2) tests. The comparison of gastric, colon and rectum cancer patients and controls determined a statistically significant relationship for alcoholic drink consumption (p<0,05). There was statistically significant relationship between mir146a rs2961920 polymorphism and gastric and colon cancers in the investigated Turkish population (p<0,05). But, there was no significant relationship between rectum cancer and control (p>0.05). There was no statistically significant relationship between mir146a rs2910164 polymorphism and gastric, colon and rectum cancers (p>0.05). However, there was statistically significant relationship between this polymorphism and gastric cancer in GG+CG and CC genotypes when the gastric cancer patients and control group were evaluated for mir146a rs2910164 polymorphism (χ2: 5,49 p: 0,019). Similarly, there was statistically significant relationship between this polymorphism and gastric cancer in GG+CC and CG genotypes (χ2:5,39, p: 0,020). In this study, it is thought that by investigating the functions of microRNAs and their role in cancer, it may be promising in understanding the molecular pathology of cancer and in developing molecular targeted therapies.

Keywords

• Gastric Cancer
• Colon Cancer
• Rectum Cancer
• Polymorphism
• mir146a
• Turkish population

References

1. Akkız, H., Sümbül, A. T., Bayram, S., Bekar, A., and Akgöllü, E. (2010). MDM2 promoter polymorphism is associated with increased susceptibility to hepatocellular carcinoma in Turkish population. Cancer epidemiology, 34(4), 448-452.
2. Calin, G.A., and Croce, C.M. (2006). MiRNA signatures in human cancers. Nature reviews cancer, 6(11), 857-866.
3. Calin, G.A., Sevignani, C., Dumitru, C.D., Hyslop, T., Noch, E., Yendamuri, S., and
4. Croce, C. M. (2004). Human miRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proceedings of the National academy of Sciences of the United States of America, 101(9), 2999-3004.
5. Chae, Y.S., Kim, J.G., Lee, S.J., Kang, B.W., Lee, Y.J., Park, J.Y., and Choi, G.S. (2013). A mir146a polymorphism (rs2910164) predicts risk of and survival from colorectal cancer. Anticancer research, 33(8), 3233-3239.
6. Cheng, A.M., Byrom, M.W., Shelton, J., and Ford, L.P. (2005). Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic acids research, 33(4), 1290-1297.
7. Farber, E. (1984). Cellular biochemistry of the stepwise development of cancer with chemicals: GHA Clowes memorial lecture. Cancer Research, 44 (12 Part 1), 5463-5474.
8. Dedikodu, V., Tramacere, I., Bagnardi, V., Rota, M., Scotti, L., Islami, F., and Boffetta, P. (2011). Alcohol drinking and colorectal cancer risk: an overall and dose response meta-analysis of published studies. Annals of oncology, 22(9), 1958-1972.

9. Giovannucci, E. (2001). An updated review of the epidemiological evidence that cigarette smoking increases risk of colorectal cancer. Cancer Epidemiology and Prevention Biomarkers, 10(7), 725-731.
10. Giovannucci, E. (2004). Alcohol, one-carbon metabolism, and colorectal cancer: recent insights from molecular studies. The Journal of nutrition, 134(9), 2475S-2481S.
11. Gong, J., Tong, Y., Zhang, H.M., Wang, K., Hu, T., Shan, G., and Guo, A.Y. (2012). Genome‐wide identification of SNPs in miRNA genes and the SNP effects on miRNA target binding and biogenesis. Human mutation, 33(1), 254-263.
12. Haggar, F.A., and Boushey, R.P. (2009). Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clinics in colon and rectal surgery, 22(04), 191-197.
13. Hauptman, N., and Glavac, D. (2013). MiRNAs and long non-coding RNAs: prospects in diagnostics and therapy of cancer. Radiology and oncology, 47(4), 311-318.
14. Hu, Z., Liang, J., Wang, Z., Tian, T., Zhou, X., Chen, J., and Shen, H. (2009). Common genetic variants in pre‐miRNAs were associated with increased risk of breast cancer in Chinese women. Human mutation, 30(1), 79-84.
15. Jazdzewski, K., Murray, E.L., Franssila, K., Jarzab, B., Schoenberg, D.R., and de la Chapelle, A. (2008). Common SNP in pre-mir146a decreases mature mir expression and predisposes to papillary thyroid carcinoma. Proceedings of the National Academy of Sciences, 105(20), 7269-7274.
16. Karahasanoğlu T. (2011). Kolorektal Kanserler: Tanı ve Cerrahi Tedavi. İ.Ü Cerrahpaşa Tıp Fak. Sürekli Tıp Eğitimi Etkinlikleri, 271–279.
17. Kim, V.N. (2005). Small RNAs: classification, biogenesis, and function. Mol cells, 19(1), 1-15.
18. Miller S.A, Dykes D.D and Polesky H.F. (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16, 1215.
19. Moskal, A., Norat, T., Ferrari, P., and Riboli, E. (2007). Alcohol intake and colorectal cancer risk: A dose–response meta_analysis of published cohort studies. International journal of cancer, 120(3), 664-671.
20. Murray K.R. (1996). Harper’ın Biyokimyası, Zenobiyotiklerin Metabolizması, 799–806, ISBN:975–953–1–1.
21. Ruvkun, G. (2001). Glimpses of a tiny RNA world. Science, 294(5543), 797-799. Saydam F, Değirmenci İ, Güneş H.V. (2011). MikroRNA’lar ve kanser. Dicle Medical Journal, 38(1):113-20.
22. Shen, J., Ambrosone, C.B., Dicioccio, R.A., Odunsi, K., Lele, S.B., and Zhao, H. (2008). A functional polymorphism in the mir146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis, 29(10), 1963-1966.
23. Su, R., Li, W., and Luo, R. (2016). Association between mir146a, mir149, mir196a2 and mir499 gene polymorphisms and the susceptibility to gastric cancer in a Chinese population. Int. J. Clin. Exp. Med, 9, 2192-2199.
24. Tanno, B., Cesi, V., Vitali, R., Sesti, F., Giuffrida, M.L., Mancini, C., and Raschella, G. (2005).
25. Silencing of endogenous IGFBP-5 by micro RNA interference affects proliferation, apoptosis and differentiation of neuroblastoma cells. Cell Death and Differentiation, 12(3), 213-223.
26. Tsong, W.H., Koh, W.P., Yuan, J.M., Wang, R., Sun, C.L., and Yu, M.C. (2007). Cigarettes and alcohol in relation to colorectal cancer: the Singapore Chinese Health Study. British journal of cancer, 96(5), 821-827.
27. Wijnhoven, B.P., Michael, M.Z., and Watson, D.I. (2007). MiRNAs and cancer. British journal of surgery, 94(1), 23-30.
28. Xu, T., Zhu, Y., Wei, Q.K., Yuan, Y., Zhou, F., Ge, Y.Y., and Zhuang, S.M. (2008). A functional polymorphism in the mir146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis, 29(11), 2126-2131.