Amaç: Böbrek hücreli karsinom (BHK) dünya genelinde kansere bağlı ölümlerin %3’ünü oluşturan önemli bir hastalıktır. Genetik ve çevresel faktörlerin BHK oluşumu ve gelişimi üzerinde etkili olduğu ileri sürülmekle birlikte risk faktörleri yeterince bilinmemektedir. Siklooksijenaz-2 (COX-2) prostoglandinlerin sentezinde rol alan bir enzimdir. Normal dokuda genellikle bulunmazken, yapılan çalışmalarda COX-2 düzeylerinin çeşitli kanser türlerinde arttığı ileri sürülmektedir. Çalışmamızda, Türk toplumunda COX-2 geninin promoter bölgesindeki -765 G/C polimorfizmi ile BHK’nin oluşumu ve gelişimi arasındaki ilişkiyi incelemeyi planladık. Gereç ve Yöntem: Çalışmamıza 2015-2017 yılları arasında klinik ve histopatolojik olarak BHK tanısı konan 88 hasta ile kontrol grubu olarak sistemik hastalığı bulunmayan 157 sağlıklı kişi dahil edildi. Hasta ve sağlıklı kişilerden elde edilen DNA örneklerinde polimeraz zincir reaksiyonu- restriksiyon fragman uzunluk polimorfizmi tekniği (PZR-RFUP) ile COX-2 G-765C gen polimorfizmi incelendi. Elde edilen sonuçlar Mann-Whitney U, Pearson ki-kare testleri ve lojistik regresyon analizi yapılarak istatistiksel olarak değerlendirildi. Bulgular: Türk toplumunda, COX-2 G-765C gen polimorfizminde GG genotip dağılımı ve G allel sıklığı daha yüksek bulundu. COX-2 G-765C gen polimorfizminde genotip dağılımı ve allel sıklığı bakımından BHK’li hasta ve kontrol grubu arasında anlamlı bir farklılık bulunmadı. Buna ek olarak, hastalığın derece ve evreleri açısından incelendiğinde COX-2 G-765C gen polimorfizminde genotip dağılımı ve allel sıklığı açısından istatistiksel olarak anlamlı bir ilişki saptanmadı. Sonuç: Türk toplumunda COX2 G-765C gen polimorfizminin BHK oluşumu ve gelişimi için bir risk faktörü olmadığı ileri sürülebilir. Anahtar Kelimeler: Böbrek hücreli karsinom, COX2, Türk toplumu,
1.Ridge CA, Pua BB, Madoff DC. Epidemiology
and staging of renal cell carcinoma. Semin Intervent
Radiol 2014; 31: 3-8.
2.Siegel RL, Miller KD, Jemal A. Cancer statistics,
2015.CA Cancer J Clin 2015; 65: 5-29.
3.Linehan WM, Srinivasan R, SchmidtLS. The
genetic basis of kidney cancer: a metabolic disease.
Nat Rev Urol 2010; 7: 277-285.
4Yao T, Wang Q, Zhang W, Bian A, Zhang J.
Identification of gene sassociated with renal cell
carcinoma using gene expression profiling analysis
Oncol Lett. 2016; 12: 73-78.
5.Li D, Hao SH, Sun Y, Hu CM, Ma ZH, Wang ZM,
Liu J, Liu HB, Ye M, Zhang YF, Yang DS, Shi G.
Functional Polymorphisms in COX-2 Gene Are
Correlated with the Risk of Oral Cancer. Biomed
Res Int 2015; 2015: 580652.
6.Coskunpinar E, Eraltan IY, Turna A, Agachan B.
Cyclooxygenase-2 gene and lung carcinoma risk.
Med Oncol 2011; 28: 1436-1440.
7.Mandal RK, Mittal RD. Polymorphisms in COX-
2 gene influence prostate cancer susceptibility in
a northern Indian cohort. Arch Med Res 2011; 2:
620-626.
8.Cossiolo DC, Costa HCM, Fernandes KBP,
Laranjeira LLS, Fernandes MTP, Poli-Frederico RC.
Polymorphism of the cox-2 gene and susceptibility
to colon and rectal cancer. Arq Bras Cir Dig 2017;
30: 114-117.
9.Chang WS, Tsai CW, Ji HX, Wu HC, Chang YT,
Lien CS, Liao WL, Shen WC, Tsai CH, BauDT.
Associations of cyclooxygenase 2 polymorphic
genotypes with bladder cancer risk in Taiwan.
Anticancer Res 2013; 33: 5401-5405.
10.Agachan Cakmakoglu B, Attar R, Kahraman
OT, Dalan AB, Iyibozkurt AC, Karateke A, Attar
E. Cyclooxygenase-2 gene and epithelial ovarian
carcinoma risk. Mol Biol Rep 2011; 38: 3481-3486.
11.Chang WS, Liao CH, Miao CE, Wu HC, Hou
LL, Hsiao CL, Ji HX, Tsai CW, Bau DT. The role
of functional polymorphisms of cyclooxygenase 2
in renal cell carcinoma. Anticancer Res 2014; 34:
5481-5486.
12.Siddiqi A, Saidullah B, Sultana S. Anticarcinogenic effect of hesperidin against renal cell
carcinoma by targeting COX-2/PGE2 pathway in
Wistar rats. Environ Toxicol 2018; 33: 1069-1077.
13.Zhu W, Wei BB, Shan X, Liu P. -765G>C and
8473T>C polymorphisms of COX-2 and cancer
risk: a meta-analysis based on 33 case-control
studies. Mol Biol Rep 2010; 37: 277-288.
14.Mittal M, Kapoor V, Mohanti BK, Das SN.
Functional variants of COX-2 and risk of tobaccorelated oral squamous cell carcinoma in high-risk
Asian Indians. Oral Oncol 2010; 46: 622-626.
15.Gharib AF, Karam RA, Abd El Rahman TM,
Elsawy WH.COX-2 polymorphisms 765G→C and
-1195A→G and hepatocellular carcinoma risk.
Gene 2014; 543: 234-236.
16.Hou L, Grillo P, Zhu ZZ, Lissowska J, Yeager
M, Zatonski W, Zhu G, Baccarelli A, Chanock
SJ, Fraumeni JF Jr, Chow WH. COX1 and COX2
polymorphisms and gastric cancer risk in a Polish
population. Anticancer Res 2007; 27: 4243-4247.
17.Van Nes JG, de Kruijf EM, Faratian D, van
de Velde CJ, Putter H, Falconer C, Smit VT, Kay
C, van de Vijver MJ, Kuppen PJ, Bartlett JM.
COX2 expression in prognosis and in prediction to
endocrine therapy in early breast cancer patients.
Breast Cancer Res Treat 2011; 125: 671-685.
18.Vogel U, Christensen J, Wallin H, Friis S, Nexo
BA, Tjonneland A. Polymorphisms in COX-2,
NSAID use and risk of basal cell carcinoma in a
prospective study of Danes. Mutat Res 2007; 617:
138-146.
19.Souza RF, Shewmake K, Beer DG,
Cryer B, Spechler SJ. Selective inhibition of
cyclooxygenase-2 suppresses growth and induces
apoptosis in human esophageal adenocarcinoma
cells. Cancer Res 2000; 60: 5767-5772.
20.Kujubu DA, Reddy ST, Fletcher BS and
Herschman HR. Expression of the protein product
of the prostaglandin synthase- 2/TIS10 gene in
mitogen-stimulated Swiss 3T3 cells. J Biol Chem
1993; 268: 5425-5430.
21.Kawata R, Reddy ST, Wolner B and Herschman
HR. Prostaglandin synthase 1 and prostaglandin
synthase 2 both participate in activation-induced
prostaglandin D2 production in mast cells. J
Immunol 1995; 155: 818-825.
22.Reddy ST and Herschman HR. Ligand-induced
prostaglandin synthesis requires expression of
the TIS10/PGS-2 prostaglandin synthase gene in
murine fibroblasts and macrophages. J Biol Chem
1994; 269: 15473-15480.
23.Güçer H , Şahan E, Akyıldız İğdem A, Tetikkurt
Ü.S., Erdoğan N. Cox-2 Expression and Microvessel
Density in Clear Cell Type Renal Cell Carcinoma
Turkish Journal of Pathology 2009; 25:13-19.
24.Yoshimura R, Matsuyama M, Kawahito Y,
Tsuchida K, Kuratsukuri K, Takemoto Y, Mitsuhashi
M, Sano H, Nakatani T. Study of cyclooxygenase-2
in renal cell carcinoma. Int J Mol Med 2004;13:
229-233.
25.Cho DS, Joo HJ, Oh DK, Kang JH, Kim YS, Lee
KB, Kim SJ. Cyclooxygenase-2 and p53 expression
as prognostic indicators in conventional renal cell
carcinoma. Yonsei Med J. 2005; 46: 133-140.
26.Papafili A, Hill MR, Brull DJ, McAnulty RJ,
Marshall RP, Humphries SE, LaurentGJ. Common
promoter variant in cyclooxygenase-2 represses
gene expression: evidence of role in acute-phase
inflammatory response. Arterioscler Thromb Vasc
Biol 2002; 22: 1631-1636.
27.Appleby SB, Ristimäki A, Neilson K, Narko K,
Hla T. Structure of the human cyclooxygenase-2
gene. Biochem J 1994; 302: 723-727.
28.Yang X, Hou F, Taylor L, Polgar P.
Characterization of human cyclooxygenase 2 gene
promoter localization of a TGF-beta response
element. Biochim Biophys Acta 1997; 1350: 287-
292.
29.Gong Z, Bostick RM, Xie D, Hurley TG,
Deng Z, Dixon DA, Zhang J, Hebert JR. Genetic
polymorphisms in the cyclooxygenase-1 and
cyclooxygenase-2 genes and risk of colorectal
adenoma. Int J Colorectal Dis 2009; 24: 647-654.
30.Chang WS, Yang MD, Tsai CW, Cheng LH,
Jeng LB, Lo WC, Lin CH, Huang CY, Bau DT.
Association of cyclooxygenase 2 single-nucleotide
polymorphisms and hepatocellularcarcinoma in
Taiwan. Chin J Physiol 2012; 55: 1-7.
Year 2018,
Volume: 1 Issue: 3, 22 - 30, 30.11.2018
1.Ridge CA, Pua BB, Madoff DC. Epidemiology
and staging of renal cell carcinoma. Semin Intervent
Radiol 2014; 31: 3-8.
2.Siegel RL, Miller KD, Jemal A. Cancer statistics,
2015.CA Cancer J Clin 2015; 65: 5-29.
3.Linehan WM, Srinivasan R, SchmidtLS. The
genetic basis of kidney cancer: a metabolic disease.
Nat Rev Urol 2010; 7: 277-285.
4Yao T, Wang Q, Zhang W, Bian A, Zhang J.
Identification of gene sassociated with renal cell
carcinoma using gene expression profiling analysis
Oncol Lett. 2016; 12: 73-78.
5.Li D, Hao SH, Sun Y, Hu CM, Ma ZH, Wang ZM,
Liu J, Liu HB, Ye M, Zhang YF, Yang DS, Shi G.
Functional Polymorphisms in COX-2 Gene Are
Correlated with the Risk of Oral Cancer. Biomed
Res Int 2015; 2015: 580652.
6.Coskunpinar E, Eraltan IY, Turna A, Agachan B.
Cyclooxygenase-2 gene and lung carcinoma risk.
Med Oncol 2011; 28: 1436-1440.
7.Mandal RK, Mittal RD. Polymorphisms in COX-
2 gene influence prostate cancer susceptibility in
a northern Indian cohort. Arch Med Res 2011; 2:
620-626.
8.Cossiolo DC, Costa HCM, Fernandes KBP,
Laranjeira LLS, Fernandes MTP, Poli-Frederico RC.
Polymorphism of the cox-2 gene and susceptibility
to colon and rectal cancer. Arq Bras Cir Dig 2017;
30: 114-117.
9.Chang WS, Tsai CW, Ji HX, Wu HC, Chang YT,
Lien CS, Liao WL, Shen WC, Tsai CH, BauDT.
Associations of cyclooxygenase 2 polymorphic
genotypes with bladder cancer risk in Taiwan.
Anticancer Res 2013; 33: 5401-5405.
10.Agachan Cakmakoglu B, Attar R, Kahraman
OT, Dalan AB, Iyibozkurt AC, Karateke A, Attar
E. Cyclooxygenase-2 gene and epithelial ovarian
carcinoma risk. Mol Biol Rep 2011; 38: 3481-3486.
11.Chang WS, Liao CH, Miao CE, Wu HC, Hou
LL, Hsiao CL, Ji HX, Tsai CW, Bau DT. The role
of functional polymorphisms of cyclooxygenase 2
in renal cell carcinoma. Anticancer Res 2014; 34:
5481-5486.
12.Siddiqi A, Saidullah B, Sultana S. Anticarcinogenic effect of hesperidin against renal cell
carcinoma by targeting COX-2/PGE2 pathway in
Wistar rats. Environ Toxicol 2018; 33: 1069-1077.
13.Zhu W, Wei BB, Shan X, Liu P. -765G>C and
8473T>C polymorphisms of COX-2 and cancer
risk: a meta-analysis based on 33 case-control
studies. Mol Biol Rep 2010; 37: 277-288.
14.Mittal M, Kapoor V, Mohanti BK, Das SN.
Functional variants of COX-2 and risk of tobaccorelated oral squamous cell carcinoma in high-risk
Asian Indians. Oral Oncol 2010; 46: 622-626.
15.Gharib AF, Karam RA, Abd El Rahman TM,
Elsawy WH.COX-2 polymorphisms 765G→C and
-1195A→G and hepatocellular carcinoma risk.
Gene 2014; 543: 234-236.
16.Hou L, Grillo P, Zhu ZZ, Lissowska J, Yeager
M, Zatonski W, Zhu G, Baccarelli A, Chanock
SJ, Fraumeni JF Jr, Chow WH. COX1 and COX2
polymorphisms and gastric cancer risk in a Polish
population. Anticancer Res 2007; 27: 4243-4247.
17.Van Nes JG, de Kruijf EM, Faratian D, van
de Velde CJ, Putter H, Falconer C, Smit VT, Kay
C, van de Vijver MJ, Kuppen PJ, Bartlett JM.
COX2 expression in prognosis and in prediction to
endocrine therapy in early breast cancer patients.
Breast Cancer Res Treat 2011; 125: 671-685.
18.Vogel U, Christensen J, Wallin H, Friis S, Nexo
BA, Tjonneland A. Polymorphisms in COX-2,
NSAID use and risk of basal cell carcinoma in a
prospective study of Danes. Mutat Res 2007; 617:
138-146.
19.Souza RF, Shewmake K, Beer DG,
Cryer B, Spechler SJ. Selective inhibition of
cyclooxygenase-2 suppresses growth and induces
apoptosis in human esophageal adenocarcinoma
cells. Cancer Res 2000; 60: 5767-5772.
20.Kujubu DA, Reddy ST, Fletcher BS and
Herschman HR. Expression of the protein product
of the prostaglandin synthase- 2/TIS10 gene in
mitogen-stimulated Swiss 3T3 cells. J Biol Chem
1993; 268: 5425-5430.
21.Kawata R, Reddy ST, Wolner B and Herschman
HR. Prostaglandin synthase 1 and prostaglandin
synthase 2 both participate in activation-induced
prostaglandin D2 production in mast cells. J
Immunol 1995; 155: 818-825.
22.Reddy ST and Herschman HR. Ligand-induced
prostaglandin synthesis requires expression of
the TIS10/PGS-2 prostaglandin synthase gene in
murine fibroblasts and macrophages. J Biol Chem
1994; 269: 15473-15480.
23.Güçer H , Şahan E, Akyıldız İğdem A, Tetikkurt
Ü.S., Erdoğan N. Cox-2 Expression and Microvessel
Density in Clear Cell Type Renal Cell Carcinoma
Turkish Journal of Pathology 2009; 25:13-19.
24.Yoshimura R, Matsuyama M, Kawahito Y,
Tsuchida K, Kuratsukuri K, Takemoto Y, Mitsuhashi
M, Sano H, Nakatani T. Study of cyclooxygenase-2
in renal cell carcinoma. Int J Mol Med 2004;13:
229-233.
25.Cho DS, Joo HJ, Oh DK, Kang JH, Kim YS, Lee
KB, Kim SJ. Cyclooxygenase-2 and p53 expression
as prognostic indicators in conventional renal cell
carcinoma. Yonsei Med J. 2005; 46: 133-140.
26.Papafili A, Hill MR, Brull DJ, McAnulty RJ,
Marshall RP, Humphries SE, LaurentGJ. Common
promoter variant in cyclooxygenase-2 represses
gene expression: evidence of role in acute-phase
inflammatory response. Arterioscler Thromb Vasc
Biol 2002; 22: 1631-1636.
27.Appleby SB, Ristimäki A, Neilson K, Narko K,
Hla T. Structure of the human cyclooxygenase-2
gene. Biochem J 1994; 302: 723-727.
28.Yang X, Hou F, Taylor L, Polgar P.
Characterization of human cyclooxygenase 2 gene
promoter localization of a TGF-beta response
element. Biochim Biophys Acta 1997; 1350: 287-
292.
29.Gong Z, Bostick RM, Xie D, Hurley TG,
Deng Z, Dixon DA, Zhang J, Hebert JR. Genetic
polymorphisms in the cyclooxygenase-1 and
cyclooxygenase-2 genes and risk of colorectal
adenoma. Int J Colorectal Dis 2009; 24: 647-654.
30.Chang WS, Yang MD, Tsai CW, Cheng LH,
Jeng LB, Lo WC, Lin CH, Huang CY, Bau DT.
Association of cyclooxygenase 2 single-nucleotide
polymorphisms and hepatocellularcarcinoma in
Taiwan. Chin J Physiol 2012; 55: 1-7.