Abstract
Aim: Colorectal cancer, the most widely seen type of cancer of the gastrointestinal system, is also the fourth most common cause of death among cancer diseases. Early diagnosis of this type of cancer is important for prognosis and it is reported that the use of inflammatory cytokines in circulation might be useful as a prognostic biomarker. For this purpose, in this study, association of interleukin-6 (IL-6)-174 G/C and interleukin-18 (IL-18) -607 C/A polymorphisms and plasma levels with colorectal cancer was investigated. Method: This study was consist of 96 patients with colorectal cancer and 96 healthy individuals as control group. The polymorphisms of the patients and healthy volunteers groups were investigated by Real-Time PCR. The plasma levels of IL-6 and IL-18 were determined by ELISA method. Results: Upon comparison of the genotype rates of IL-6 G/C (rs1800795) and IL-18 C/A (rs1946518) polymorphisms, a statistically significant difference was found between the patient and the control groups (p<0.001). Plasma levels of IL-6 were significantly higher in the group of patients with colorectal cancer (p<0.001). However, no statistically significant difference was found among the plasma levels of IL-18 in the control group (p<0.966). In order to determine the likelihood of developing CRC due to the combined effects of IL-6 and IL-18 genotypes, the association of genotype combinations of both genes in patients and control group with CRC development was investigated. In such cases that GC- CA and CC-CA genotype combinations exist and both genes are heterozygous, it was determined that there might be a risk of CRC development. Conclusion: Interleukin-6 and interleukin-18 may play a role in the development of colorectal cancer. In addition, the plasma levels of these cytokines can be used for early diagnosis
References
- Büyükdoğan M. Kolorektal Kanserde Genetik ve Etyolojik Faktörler. Selçuk Tıp Derg 2009;25 (3):171-80.
- Walter V, Jansen L, Hoffmeister M, Brenner H. Smoking and survival of colorectal cancer patients: systematic review and meta-analysis. Annals of Oncology 2014; 25(8):1517-25.
- Durko L, Malecka-Panas E. Lifestyle Modifications and Colorectal Cancer. Curr Colorectal Cancer Rep 2014;10:45–54.
- Saygılı G. Kolorektal Karsinomlarda Siklooksijenaz–2 Boyanma
- Prognostik Parametrelerle Karşılaştırılması. Şişli Etfal Eğitim ve Araştırma Hastanesi. Uzmanlık tezi. İstanbul, 2007. Enziminin Paterni
- Yaygınlığının 5. Heike K, Rainer P. Serum interleukin-6 level in colorectal cancer patients- a summary of published results. Int. Journal Colorectal Dis 2010; 25(2): 135-40.
- Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso M A. Chronic Inflammation and Cytokines in the Tumor Microenvironment. Journal of Immunology Research 2014;2014:149-85.
- Bidwell J, Keen L, Gallagher G. Cytokine gene polymorphism in human disease. Genes and Immunity 1999; 1(1): 3-19.
- Kemik Ö, Kemik A.S, Dülger A.C, Hasırcı İ, Daştan E, Bartın MK, Purisa S, Tüzün S. Karaciğer
- Hastalarda İnterlökin-6 Düzeyleri. Van Tıp Dergisi 2010;17 (2): 42-5. Kolon
- Kanserli 9. Lesina M, Wörmann S. M, Neuhöfer P, Song
- inflammatory and malignant diseases of the pancreas. 2014;26(1): 80–7. Interleukin-6 in Seminars in
- Immunology 10. Neurath MF, Finotto S. IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated
- Growth Factor Rev.2011; 22(2): 83-9.
- cancer.Cytokine 11. Palma G, Barbieri A, Bimonte S, Zappavigna
- PA, Ciliberto G, Arra C. Interleukin 18: Friend or foe in cancer. Biochimica et Biophysica Acta 2013;1836(2):296–303.
- Tangkijvanich P, Thong-ngam D, Mahachai V, Theamboonlers A, Poovorawan Y. Role of serum interleukin-18 as a prognostic hepatocellular
- Gastroenterol. 2007; 13(32): 4345-9. with World
- J Kun-Yun Y, Ying-Ying L, Ling-Ling H, Jim-Ray C, Rei-Ping Tang. The −174 G/C Polymorphism in Interleukin-6 (IL-6) Promoter Region is Associated with Serum IL-6 and Carcinoembryonic Antigen Levels in Patients with Colorectal Cancers in Taiwan. J Clain Immunol 2010;30(1): 53-9.
- Slattery ML, Wolff RK, Herrick JS, Caan BJ, Potter JD. IL6 genotypes and colon and rectal cancer. Cancer Causes Control 2007;18(10): 1095–105.
- Gangwar R, Mittal B, Mittal RD. Association
- promoter polymorphism with risk of cervical cancer. Int J Biol Markers 2009; 24(1): 11-58.
- interleukin-6-174G>C 16.Noqueira de Souza NC, Brenna SM, Campos F, Syrjänen KJ, Baracat EC, Silva ID. Interleukin-6 polymorphisms and the risk of cervical cancer. Int J Gynecol Cancer .2006; 16(3): 1278-82.
- Vairaktaris E, Yiannopoulos A, Vylliotis A, Yapijakis C, Derka S, Vassiliou S, Nkenke E, Serefoglou Z, Ragos V, Tsigris C, Vorris E, Critselis E, Avgoustidis D,Neukam FW, Patsouris interleukin-6-174
- polymorphism with increased risk of oral cancer. Int J Biol Markers 2006; 21(4): 246- 50. association of G>C
- promoter 18. Grivennikov SI, Michael K. Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage. Ann Rheum Dis 2011;(70): 104-8.
- Samur M, Akbulut H. Kolorektal Karsingenes
- Hematoloji- Onkoloji 2003;5(3): 115-21. Herediter
- Durumlar. 20. Lopez PS, Vazquez RCF, Martin J, Sánchez E, Tallada M, Garrido F, Cózar JM, Ruiz-Cabello F. Impact of interleukin-18 polymorphisms-607 and -137 on clinical characteristics of renal cell carcinoma patients. Human Immunology 2010; (71): 309–13. 21. Chatzıtheofylaktou
- Heterozygosity for Interleukin-18 –607 A/C A,
- Polymorphism is Associated with Risk for Colorectal Cancer. Antıcancer Research 2007; (27): 3849-54. Yannopoulos A, C. Tsıgrıs
- Qin AQ, Li RK, Yang CM, Li RK, Yang CM, Huang
- Association of the IL-18 gene polymorphism with susceptibility to colorectal cancer. Zhonghua Wei Chang Wai Ke Za Zhi. 2012;15(4): 400-3. ZY, Guo
- HJ. Farjadfar A, Mojtahedı Z, Ghayumı M A, Erfani
- Interleukin-18 promoter polymorphism is associated with lung cancer: A case-control study. Acta Oncologica 2009;48(7): 971- 6.
- Wang Q, Zheng L, Yang HL, Bao J. Correlation of serum IL-18 level and IL-18 gene promoter polymorphisms to the risk of cervical cancer. Nan Fang Yi Ke Da Xue Xue Bao. 2008;28(5): 754-7.
- Merendino RA, Ruello A, Cascinu S, Ferlazzo B, Bene A, Bonanno D, Quattrocchi P, Caristi N, Gangemi S. Influence of 5- fluorouracil and folinic acid on interleukin- 18 production in colorectal cancer patients. Int J Biol Markers 2002;17(1): 63-6.
İnterlökin-6 ve interlökin-18 gen polimorfizmlerinin ve plazma düzeylerinin kolorektal kanser ile ilişkisi
Abstract
Amaç: Gastrointestinal sistemin en sık görülen kanser türlerinden olan kolorektal kanser,
kansere bağlı ölüm nedenleri arasında dördüncü sırada bulunmaktadır. Bu kanser türünde
erken teşhis, tedavinin prognozu açısından önemlidir ve dolaşımdaki inflamatuvar sitokinlerin
prognostik amaçla biyomarker olarak kullanılabileceği bildirilmektedir. Bu amaçla, interlökin-6
(IL-6) -174 G/C ve interlökin-18 (IL-18) -607 C/A polimorfizmleri ve plazma düzeylerinin
kolorektal kanser ile ilişkisi araştırıldı. Yöntem: Çalışma kolorektal kanserli 96 hasta ve kontrol
grubu 96 sağlıklı bireyden oluşmaktadır. Hasta ve kontrol gruplarının polimorfizmleri Real-Time
PZR kullanılarak belirlenmiştir. IL-6 ve IL-18’in plazma düzeyleri ise ELISA yöntemiyle
belirlenmiştir. Bulgular: IL-6 G/C (rs1800795) ve IL-18 C/A (rs1946518) polimorfizmlerine ait
genotip sıklıkları karşılaştırıldığında kolorektal kanser hastaları ile kontrol grubu arasında
anlamlı bir ilişki saptanmıştır (p < 0.001). Plazma düzeyleri açısından ise IL-6 kolorektal kanserli
hastalarda anlamlı olarak yüksek bulunmuştur (p < 0.001). Ancak, IL-18 plazma düzeylerinde
anlamlı bir fark saptanmamıştır (p < 0.966). IL-6 ve IL-18 genotiplerinin kombine etkisiyle KRK
gelişme olasılığını saptamak için, her iki genin hasta ve kontrol gruplarındaki genotip
kombinasyonları ile KRK oluşumu arasındaki ilişki kıyaslanmıştır. GC ve CA (p < 0,0001) ile CC ve
CA (p < 0.023) genotip kombinasyonlarında her iki genin heterozigot olduğu durumlarda KRK
gelişimi açısından risk oluşturabileceği saptanmıştır. Sonuç: İnterlökin-6 ve interlökin-18’in
kolorektal kanser gelişiminde rolü olabilir. Ayrıca bu sitokinlerin plazma düzeyleri erken tanı
için kullanılabilir.
Keywords
References
- Büyükdoğan M. Kolorektal Kanserde Genetik ve Etyolojik Faktörler. Selçuk Tıp Derg 2009;25 (3):171-80.
- Walter V, Jansen L, Hoffmeister M, Brenner H. Smoking and survival of colorectal cancer patients: systematic review and meta-analysis. Annals of Oncology 2014; 25(8):1517-25.
- Durko L, Malecka-Panas E. Lifestyle Modifications and Colorectal Cancer. Curr Colorectal Cancer Rep 2014;10:45–54.
- Saygılı G. Kolorektal Karsinomlarda Siklooksijenaz–2 Boyanma
- Prognostik Parametrelerle Karşılaştırılması. Şişli Etfal Eğitim ve Araştırma Hastanesi. Uzmanlık tezi. İstanbul, 2007. Enziminin Paterni
- Yaygınlığının 5. Heike K, Rainer P. Serum interleukin-6 level in colorectal cancer patients- a summary of published results. Int. Journal Colorectal Dis 2010; 25(2): 135-40.
- Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso M A. Chronic Inflammation and Cytokines in the Tumor Microenvironment. Journal of Immunology Research 2014;2014:149-85.
- Bidwell J, Keen L, Gallagher G. Cytokine gene polymorphism in human disease. Genes and Immunity 1999; 1(1): 3-19.
- Kemik Ö, Kemik A.S, Dülger A.C, Hasırcı İ, Daştan E, Bartın MK, Purisa S, Tüzün S. Karaciğer
- Hastalarda İnterlökin-6 Düzeyleri. Van Tıp Dergisi 2010;17 (2): 42-5. Kolon
- Kanserli 9. Lesina M, Wörmann S. M, Neuhöfer P, Song
- inflammatory and malignant diseases of the pancreas. 2014;26(1): 80–7. Interleukin-6 in Seminars in
- Immunology 10. Neurath MF, Finotto S. IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated
- Growth Factor Rev.2011; 22(2): 83-9.
- cancer.Cytokine 11. Palma G, Barbieri A, Bimonte S, Zappavigna
- PA, Ciliberto G, Arra C. Interleukin 18: Friend or foe in cancer. Biochimica et Biophysica Acta 2013;1836(2):296–303.
- Tangkijvanich P, Thong-ngam D, Mahachai V, Theamboonlers A, Poovorawan Y. Role of serum interleukin-18 as a prognostic hepatocellular
- Gastroenterol. 2007; 13(32): 4345-9. with World
- J Kun-Yun Y, Ying-Ying L, Ling-Ling H, Jim-Ray C, Rei-Ping Tang. The −174 G/C Polymorphism in Interleukin-6 (IL-6) Promoter Region is Associated with Serum IL-6 and Carcinoembryonic Antigen Levels in Patients with Colorectal Cancers in Taiwan. J Clain Immunol 2010;30(1): 53-9.
- Slattery ML, Wolff RK, Herrick JS, Caan BJ, Potter JD. IL6 genotypes and colon and rectal cancer. Cancer Causes Control 2007;18(10): 1095–105.
- Gangwar R, Mittal B, Mittal RD. Association
- promoter polymorphism with risk of cervical cancer. Int J Biol Markers 2009; 24(1): 11-58.
- interleukin-6-174G>C 16.Noqueira de Souza NC, Brenna SM, Campos F, Syrjänen KJ, Baracat EC, Silva ID. Interleukin-6 polymorphisms and the risk of cervical cancer. Int J Gynecol Cancer .2006; 16(3): 1278-82.
- Vairaktaris E, Yiannopoulos A, Vylliotis A, Yapijakis C, Derka S, Vassiliou S, Nkenke E, Serefoglou Z, Ragos V, Tsigris C, Vorris E, Critselis E, Avgoustidis D,Neukam FW, Patsouris interleukin-6-174
- polymorphism with increased risk of oral cancer. Int J Biol Markers 2006; 21(4): 246- 50. association of G>C
- promoter 18. Grivennikov SI, Michael K. Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage. Ann Rheum Dis 2011;(70): 104-8.
- Samur M, Akbulut H. Kolorektal Karsingenes
- Hematoloji- Onkoloji 2003;5(3): 115-21. Herediter
- Durumlar. 20. Lopez PS, Vazquez RCF, Martin J, Sánchez E, Tallada M, Garrido F, Cózar JM, Ruiz-Cabello F. Impact of interleukin-18 polymorphisms-607 and -137 on clinical characteristics of renal cell carcinoma patients. Human Immunology 2010; (71): 309–13. 21. Chatzıtheofylaktou
- Heterozygosity for Interleukin-18 –607 A/C A,
- Polymorphism is Associated with Risk for Colorectal Cancer. Antıcancer Research 2007; (27): 3849-54. Yannopoulos A, C. Tsıgrıs
- Qin AQ, Li RK, Yang CM, Li RK, Yang CM, Huang
- Association of the IL-18 gene polymorphism with susceptibility to colorectal cancer. Zhonghua Wei Chang Wai Ke Za Zhi. 2012;15(4): 400-3. ZY, Guo
- HJ. Farjadfar A, Mojtahedı Z, Ghayumı M A, Erfani
- Interleukin-18 promoter polymorphism is associated with lung cancer: A case-control study. Acta Oncologica 2009;48(7): 971- 6.
- Wang Q, Zheng L, Yang HL, Bao J. Correlation of serum IL-18 level and IL-18 gene promoter polymorphisms to the risk of cervical cancer. Nan Fang Yi Ke Da Xue Xue Bao. 2008;28(5): 754-7.
- Merendino RA, Ruello A, Cascinu S, Ferlazzo B, Bene A, Bonanno D, Quattrocchi P, Caristi N, Gangemi S. Influence of 5- fluorouracil and folinic acid on interleukin- 18 production in colorectal cancer patients. Int J Biol Markers 2002;17(1): 63-6.
Details
| Primary Language | Turkish |
|---|---|
| Journal Section | Articles |
| Authors | |
| Publication Date | May 14, 2015 |
| Submission Date | May 14, 2015 |
| Published in Issue | Year 2014 Volume: 7 Issue: 2 |
Cite
MEU Journal of Health Sciences Assoc was began to the publishing process in 2008 under the supervision of Assoc. Prof. Gönül Aslan, Editor-in-Chief, and affiliated to Mersin University Institute of Health Sciences. In March 2015, Prof. Dr. Caferi Tayyar Şaşmaz undertook the Editor-in Chief position and since then he has been in charge.
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