Year 2022,
, 1025 - 1031, 30.12.2022
Ahmet İyibozkurt
,
Bedia Çakmakoğlu
,
Baris Ertugrul
,
Elif Sinem İplik
Supporting Institution
İstanbul Üniversitesi Bilimsel Araştırma Proje
References
- [1] Gultekin M, Kucukyildiz I, Karaca MZ, Dundar S, Boztas
G, Turan SH, Hacikamiloglu E, Keskinkilic B. Trends of
gynecological cancers in Turkey: Toward Europe or Asia? Int
J Gynecol Cancer. 2017; 27 (7): 1525-1533. DOI: 10.1097/
IGC.000.000.0000001026.
- [2] Hall M, Peters G. Genetic alterations of cyclins, cyclin dependent kinases, and Cdk inhibitors in human cancer. Adv Cancer Res 1996;68:67–108. DOI: 10.1016/s0065-230x(08)60352-8.
- [3] Prat J, Oliva E, Lerma E, Matias-Guiu X. Uterine papillary
serous adenocarcinoma. A 10-case study of p53 and c-erbB-2
expression and DNA content. Cancer 1994;74 (16):1778–1783.
- [4] Feldman I, Feldman GM, Mobarak C, Dunkelberg JC, Leslie
KK. Identification of proteins within the nuclear factor-kappa
B transcriptional complex including estrogen receptor-alpha.
Am J Obstet Gynecol. 2007;196(4):394.e1-11; discussion 394.
e11-3. DOI: 10.1016/j.ajog.2006.12.033.
- [5] Modugno F, Ness RB, Chen C, Weiss NS. Inflammation
and endometrial cancer: A hypothesis. Cancer Epidemiol
Biomarkers Prev 2005;14 (12):2840–2847. DOI: 10.1158/1055-
9965.EPI-05-0493.
- [6] Pallares J, Martínez-Guitarte JL, Dolcet X, Llobet D, Rue M, Palacios J, Prat J, Matias-Guiu X. Abnormalities in the NF kappaB family and related proteins in endometrial carcinoma. J Pathol. 2004;204(5):569-577. DOI: 10.1002/path.1666.
- [7] Oh JH, Kim JH, Ahn HJ, Yoon JH, Yoo SC, Choi DS, Lee IS, Ryu HS,
Min CK. Syndecan-1 enhances the endometrial cancer invasion
by modulating matrix metalloproteinase-9 expression through
nuclear factor kappaB. Gynecol Oncol. 2009;114(3):509-515.
DOI: 10.1016/j.ygyno.2009.05.027.
- [8] Tong BJ, Tan J, Tajeda L, Das SK, Chapman JA, DuBois RN,
Dey SK. Heightened expression of cyclooxygenase-2 and
peroxisome proliferator-activated receptor-delta in human
endometrial adenocarcinoma. Neoplasia. 2000; 2(6): 483-490.
DOI: 10.1038/sj.neo.7900119.
- [9] Lambropoulou M, Alexiadis G, Limberis V, Nikolettos N,
Tripsianis G. Clinicopathologic and prognostic significance of
cyclooxygenase-2 expression in endometrial carcinoma. Histol
Histopathol. 2005;20(3):753-759. DOI: 10.14670/HH-20.753.
- [10] Lambropoulou M, Papadopoulos N, Tripsianis G, Alexiadis G,
Pagonopoulou O, Kiziridou A, Liberis V, Kakolyris S, Chatzaki
E. Co-expression of survivin, c-erbB2, and cyclooxygenase-2
(COX-2): prognostic value and survival of endometrial cancer
patients. J Cancer Res Clin Oncol. 2010; 136 (3): 427-435. DOI:
10.1007/s00432.009.0673-6.
- [11] St-Germain ME, Gagnon V, Parent S, Asselin E. Regulation of
COX-2 protein expression by Akt in endometrial cancer cells is
mediated through NF-kappaB/IkappaB pathway. Mol Cancer.
2004 11;3:7. DOI: 10.1186/1476-4598-3-7.
- [12] Domenyuk VP, Litovkin KV, Verbitskaya TG, Dubinina VG,
Bubnov VV. Identification of new DNA markers of endometrial
cancer in patients from the Ukrainian population. Exp Oncol.
2007;29(2):152-155.
- [13] Gonzalez-Ramos R, Defrere S, Devoto L. Nuclear factor kappaB: A main regulator of inflammation and cell survival in endometriosis pathophysiology. Fertil Steril. 2012;98(3):520-528. DOI: 10.1016/j.fertnstert.2012.06.021.
- [14] Elwood PC, Gallagher AM, Duthie GG, Mur LA, Morgan G.
Aspirin, salicylates, and cancer. Lancet 2009;373 (9671) :1301-
1309. DOI: 10.1016/S0140-6736(09)60243-9.
- [15] Andersen V, Christensen J, Overvad K, Tjonneland A, Vogel U.
Polymorphisms in NF-қB, PXR, LXR and risk of colorectal cancer
in a prospective study of Danes. BMC Cancer 2010;10:484.
DOI: 10.1186/1471-2407-10-484.
- [16] Vaskivuo TE, Stenback F, Tapanainen JS. Apoptosis and
apoptosis related factors Bcl-2, Bax, Tumor necrosis factor alfa,
and NF-kB in human endometrial hyperplasia and carcinoma.
Cancer 2002;95(7):1463-1471. DOI: 10.1002/cncr.10876.
- [17] de Martin R, Schmid JA, Hofer-Warbinek R. The NF-kappaB/rel
family of transcription factors in oncogenic transformation and
apoptosis. Mutat Res 1999;437 (3): 231-243. DOI: 10.1016/
s1383-5742(99)00089-7.
- [18] Nagata S. Apoptosis by death factor. Cell 1997;8 (3)8 :355-365.
DOI: 10.1016/s0092-8674(00)81874-7.
- [19] Kalkoven E, Wissink S, van der Saag PT, van der BB. Negative
interaction between the RelA(p65) subunit of NF-kappaB and
the progesterone receptor. J Biol Chem. 1996;271(11): 6217-
6224. DOI: 10.1074/jbc.271.11.6217.
- [20] Higgins KA, Perez JR, Coleman TA, Dorshkind K, McComas WA,
Sarmiento UM, Rosen CA, Narayanan R. Antisense inhibition
of the p65 subunit of NF-kappa B blocks tumorigenicity and
causes tumor regression. Proc Natl Acad Sci U S A. 1993;
1;90(21):9901-9905. DOI: 10.1073/pnas.90.21.9901.
- [21] Tang Z, Nie ZL, Pan Y, Zhang L, Gao L, Zhang Q, Lili Qu,
Bangshun He, Song G, Zhang Y and Wang S. The Cox-2
1195G>A polymorphism and cancer risk: A meta-analysis of 25
case-control studies. Mutagenesis 2011;26(6):729-734. DOI:
10.1093/mutage/ger040.
- [22] Hoff JH, te Morsche RHM, Roelofs HMJ, van der Logt EMJ,
Nagengast FM, Peters WHM. COX-2 polymorphisms 765G>C
and 1195A>G and colorectal cancer risk. World J Gastroenterol
2009;15(36):4561-4565. DOI: 10.3748/wjg.15.4561.
- [23] Zhang X, Miao X, Tan W, Ning B, Liu Z, Hong Y, Song W, Guo
Y, Zhang X, Shen Y, Qiang B, Kadlubar FF, Lin D. Identification
of functional genetic variants in cyclooxygenase-2 and their
association with risk of esophageal cancer. Gastroenterology
2005;129 (2):565-576. DOI: 10.1016/j.gastro.2005.05.003.
- [24] Fujiwaki R, Iida K, Kanasaki H, Ozaki T, Hata K, Miyazaki
K. Cyclooxygenase-2 expression in endometrial cancer:
correlation with microvessel count and expression of vascular
endothelial growth factor and thymidine phosphorylase. Hum
Pathol. 2002;33(2):213-219. DOI: 10.1053/hupa.2002.31292.
- [25] Liang JT, Huang KC, Jeng YM, Lee PH, Lai HS, Hsu HC. Microvessel
density, cyclooxygenase 2 expression, K-ras muıtation and p53
overexpression in colonic cancer. Br J Surg 2004;91(3):355-
361. DOI: 10.1002/bjs.4447.
- [26] Yoshimatsu K, Golijanin D, Paty PB, Soslow RA, Jakobsson
PJ, DeLellis RA, Subbaramaiah K, Dannenberg AJ. Inducible
microsomal prostaglandin E synthase is overexpressed in
colorectal adenomas and cancer. Clin Cancer Res. 2001;
7(12):3971-3976.
- [27] Ma X, Hui Y, Lin L, Wu Y, Zhang X, Liu P. Clinical significance
of COX-2, GLUT-1 and VEGF expressions in endometrial cancer
tissues. Pak J Med Sci. 2015;31(2):280-284. DOI: 10.12669/
pjms.312.6604.
- [28] Lupi LA, Cucielo MS, Silveira HS, Gaiotte LB, Cesário RC, Seiva
FRF, de Almeida Chuffa LG. The role of Toll-like receptor
4 signaling pathway in ovarian, cervical, and endometrial
cancers. Life Sci. 2020;15; 247:117435 DOI:10.1016/j.
lfs.2020.117435.
- [29] Cavalcanti V, Ponce TG, Mafra FA, André GM, Christofolini
DM, Barbosa CP, Bianco B. Evaluation of the frequency of
G-765C polymorphism in the promoter region of the COX-2
gene and its correlation with the expression of this gene in the
endometrium of women with endometriosis. Arch Gynecol
Obstet. 2016;293(1):109-115. DOI: 10.1007/s00404.015.3808-9
NF-қB and COX-2 Relation Between Endometrial Cancer and the Clinicopathological Parameters
Year 2022,
, 1025 - 1031, 30.12.2022
Ahmet İyibozkurt
,
Bedia Çakmakoğlu
,
Baris Ertugrul
,
Elif Sinem İplik
Abstract
Objective: Our study examines nuclear factor kappa B (NF-қB) and cyclooxygenase-2 (COX-2) polymorphisms in the most common gynecological cancer type, endometrial cancer, and the relationship between disease parameters and these polymorphisms.
Methods: In our patient group; while 109 endometrial cancer patients were examined and treated in the Department of Gynecology and Obstetrics, Istanbul Medical Faculty, and 106 healthy women without the disease were included in the control group. DNA of blood samples taken from all groups were isolated; COX-2 765C> G and COX-2 1195A> G polymorphisms were studied with NF-қB-94 ins / delATTG. Genotypes analyzed using the PCR-based restriction fragment length polymorphisms (RFLP) method were investigated in terms of the relationship between endometrial cancer susceptibility and endometrial cancer disease parameters. Results in SPSS 17 program; Student’s t-tests were analyzed
using Anova, Fisher’s exact, and Chi-square tests.
Results: NF-қB D + and DD genotype, COX-2 765 G + and GG genotype, and COX-2 1195 AA genotype were found to be significantly more common in the endometrial cancer group compared to the control group (p <0.05). However, no significant relationship was found between polymorphisms and disease parameters.
Conclusion: NF-қB and COX-2 polymorphisms are more common in women with endometrial cancer. However, the absence of a link between these polymorphisms and the prevalence or violence of the disease suggests that they often trigger cancer development.
References
- [1] Gultekin M, Kucukyildiz I, Karaca MZ, Dundar S, Boztas
G, Turan SH, Hacikamiloglu E, Keskinkilic B. Trends of
gynecological cancers in Turkey: Toward Europe or Asia? Int
J Gynecol Cancer. 2017; 27 (7): 1525-1533. DOI: 10.1097/
IGC.000.000.0000001026.
- [2] Hall M, Peters G. Genetic alterations of cyclins, cyclin dependent kinases, and Cdk inhibitors in human cancer. Adv Cancer Res 1996;68:67–108. DOI: 10.1016/s0065-230x(08)60352-8.
- [3] Prat J, Oliva E, Lerma E, Matias-Guiu X. Uterine papillary
serous adenocarcinoma. A 10-case study of p53 and c-erbB-2
expression and DNA content. Cancer 1994;74 (16):1778–1783.
- [4] Feldman I, Feldman GM, Mobarak C, Dunkelberg JC, Leslie
KK. Identification of proteins within the nuclear factor-kappa
B transcriptional complex including estrogen receptor-alpha.
Am J Obstet Gynecol. 2007;196(4):394.e1-11; discussion 394.
e11-3. DOI: 10.1016/j.ajog.2006.12.033.
- [5] Modugno F, Ness RB, Chen C, Weiss NS. Inflammation
and endometrial cancer: A hypothesis. Cancer Epidemiol
Biomarkers Prev 2005;14 (12):2840–2847. DOI: 10.1158/1055-
9965.EPI-05-0493.
- [6] Pallares J, Martínez-Guitarte JL, Dolcet X, Llobet D, Rue M, Palacios J, Prat J, Matias-Guiu X. Abnormalities in the NF kappaB family and related proteins in endometrial carcinoma. J Pathol. 2004;204(5):569-577. DOI: 10.1002/path.1666.
- [7] Oh JH, Kim JH, Ahn HJ, Yoon JH, Yoo SC, Choi DS, Lee IS, Ryu HS,
Min CK. Syndecan-1 enhances the endometrial cancer invasion
by modulating matrix metalloproteinase-9 expression through
nuclear factor kappaB. Gynecol Oncol. 2009;114(3):509-515.
DOI: 10.1016/j.ygyno.2009.05.027.
- [8] Tong BJ, Tan J, Tajeda L, Das SK, Chapman JA, DuBois RN,
Dey SK. Heightened expression of cyclooxygenase-2 and
peroxisome proliferator-activated receptor-delta in human
endometrial adenocarcinoma. Neoplasia. 2000; 2(6): 483-490.
DOI: 10.1038/sj.neo.7900119.
- [9] Lambropoulou M, Alexiadis G, Limberis V, Nikolettos N,
Tripsianis G. Clinicopathologic and prognostic significance of
cyclooxygenase-2 expression in endometrial carcinoma. Histol
Histopathol. 2005;20(3):753-759. DOI: 10.14670/HH-20.753.
- [10] Lambropoulou M, Papadopoulos N, Tripsianis G, Alexiadis G,
Pagonopoulou O, Kiziridou A, Liberis V, Kakolyris S, Chatzaki
E. Co-expression of survivin, c-erbB2, and cyclooxygenase-2
(COX-2): prognostic value and survival of endometrial cancer
patients. J Cancer Res Clin Oncol. 2010; 136 (3): 427-435. DOI:
10.1007/s00432.009.0673-6.
- [11] St-Germain ME, Gagnon V, Parent S, Asselin E. Regulation of
COX-2 protein expression by Akt in endometrial cancer cells is
mediated through NF-kappaB/IkappaB pathway. Mol Cancer.
2004 11;3:7. DOI: 10.1186/1476-4598-3-7.
- [12] Domenyuk VP, Litovkin KV, Verbitskaya TG, Dubinina VG,
Bubnov VV. Identification of new DNA markers of endometrial
cancer in patients from the Ukrainian population. Exp Oncol.
2007;29(2):152-155.
- [13] Gonzalez-Ramos R, Defrere S, Devoto L. Nuclear factor kappaB: A main regulator of inflammation and cell survival in endometriosis pathophysiology. Fertil Steril. 2012;98(3):520-528. DOI: 10.1016/j.fertnstert.2012.06.021.
- [14] Elwood PC, Gallagher AM, Duthie GG, Mur LA, Morgan G.
Aspirin, salicylates, and cancer. Lancet 2009;373 (9671) :1301-
1309. DOI: 10.1016/S0140-6736(09)60243-9.
- [15] Andersen V, Christensen J, Overvad K, Tjonneland A, Vogel U.
Polymorphisms in NF-қB, PXR, LXR and risk of colorectal cancer
in a prospective study of Danes. BMC Cancer 2010;10:484.
DOI: 10.1186/1471-2407-10-484.
- [16] Vaskivuo TE, Stenback F, Tapanainen JS. Apoptosis and
apoptosis related factors Bcl-2, Bax, Tumor necrosis factor alfa,
and NF-kB in human endometrial hyperplasia and carcinoma.
Cancer 2002;95(7):1463-1471. DOI: 10.1002/cncr.10876.
- [17] de Martin R, Schmid JA, Hofer-Warbinek R. The NF-kappaB/rel
family of transcription factors in oncogenic transformation and
apoptosis. Mutat Res 1999;437 (3): 231-243. DOI: 10.1016/
s1383-5742(99)00089-7.
- [18] Nagata S. Apoptosis by death factor. Cell 1997;8 (3)8 :355-365.
DOI: 10.1016/s0092-8674(00)81874-7.
- [19] Kalkoven E, Wissink S, van der Saag PT, van der BB. Negative
interaction between the RelA(p65) subunit of NF-kappaB and
the progesterone receptor. J Biol Chem. 1996;271(11): 6217-
6224. DOI: 10.1074/jbc.271.11.6217.
- [20] Higgins KA, Perez JR, Coleman TA, Dorshkind K, McComas WA,
Sarmiento UM, Rosen CA, Narayanan R. Antisense inhibition
of the p65 subunit of NF-kappa B blocks tumorigenicity and
causes tumor regression. Proc Natl Acad Sci U S A. 1993;
1;90(21):9901-9905. DOI: 10.1073/pnas.90.21.9901.
- [21] Tang Z, Nie ZL, Pan Y, Zhang L, Gao L, Zhang Q, Lili Qu,
Bangshun He, Song G, Zhang Y and Wang S. The Cox-2
1195G>A polymorphism and cancer risk: A meta-analysis of 25
case-control studies. Mutagenesis 2011;26(6):729-734. DOI:
10.1093/mutage/ger040.
- [22] Hoff JH, te Morsche RHM, Roelofs HMJ, van der Logt EMJ,
Nagengast FM, Peters WHM. COX-2 polymorphisms 765G>C
and 1195A>G and colorectal cancer risk. World J Gastroenterol
2009;15(36):4561-4565. DOI: 10.3748/wjg.15.4561.
- [23] Zhang X, Miao X, Tan W, Ning B, Liu Z, Hong Y, Song W, Guo
Y, Zhang X, Shen Y, Qiang B, Kadlubar FF, Lin D. Identification
of functional genetic variants in cyclooxygenase-2 and their
association with risk of esophageal cancer. Gastroenterology
2005;129 (2):565-576. DOI: 10.1016/j.gastro.2005.05.003.
- [24] Fujiwaki R, Iida K, Kanasaki H, Ozaki T, Hata K, Miyazaki
K. Cyclooxygenase-2 expression in endometrial cancer:
correlation with microvessel count and expression of vascular
endothelial growth factor and thymidine phosphorylase. Hum
Pathol. 2002;33(2):213-219. DOI: 10.1053/hupa.2002.31292.
- [25] Liang JT, Huang KC, Jeng YM, Lee PH, Lai HS, Hsu HC. Microvessel
density, cyclooxygenase 2 expression, K-ras muıtation and p53
overexpression in colonic cancer. Br J Surg 2004;91(3):355-
361. DOI: 10.1002/bjs.4447.
- [26] Yoshimatsu K, Golijanin D, Paty PB, Soslow RA, Jakobsson
PJ, DeLellis RA, Subbaramaiah K, Dannenberg AJ. Inducible
microsomal prostaglandin E synthase is overexpressed in
colorectal adenomas and cancer. Clin Cancer Res. 2001;
7(12):3971-3976.
- [27] Ma X, Hui Y, Lin L, Wu Y, Zhang X, Liu P. Clinical significance
of COX-2, GLUT-1 and VEGF expressions in endometrial cancer
tissues. Pak J Med Sci. 2015;31(2):280-284. DOI: 10.12669/
pjms.312.6604.
- [28] Lupi LA, Cucielo MS, Silveira HS, Gaiotte LB, Cesário RC, Seiva
FRF, de Almeida Chuffa LG. The role of Toll-like receptor
4 signaling pathway in ovarian, cervical, and endometrial
cancers. Life Sci. 2020;15; 247:117435 DOI:10.1016/j.
lfs.2020.117435.
- [29] Cavalcanti V, Ponce TG, Mafra FA, André GM, Christofolini
DM, Barbosa CP, Bianco B. Evaluation of the frequency of
G-765C polymorphism in the promoter region of the COX-2
gene and its correlation with the expression of this gene in the
endometrium of women with endometriosis. Arch Gynecol
Obstet. 2016;293(1):109-115. DOI: 10.1007/s00404.015.3808-9