Assessment of myeloperoxidase (Mpo) gene polymorphism in cervical cancer

Yasemen Adalı; Sacide Pehlivan; Sibel Oğuzkan Balcı; Meral Koyuncuoğlu

doi:10.28982/josam.916187

Authors

Yasemen Adalı https://orcid.org/0000-0002-8004-7364
Sacide Pehlivan https://orcid.org/0000-0003-1272-5845
Sibel Oğuzkan Balcı https://orcid.org/0000-0003-0537-3028
Meral Koyuncuoğlu https://orcid.org/0000-0003-1347-8110

DOI:

https://doi.org/10.28982/josam.916187

Keywords:

Cervical cancer, Myeloperoxidase, MPO, Gene polymorphism

Abstract

Background/Aim: Cervical cancer (CC) is the most common gynecological malignancy in women. In spite of a variety of treatment protocols, it is necessary to carefully investigate all factors that play a role in the pathogenesis of these tumors which may have mortal progression. In this context, in our study we aimed to assess the myeloperoxidase (MPO) gene polymorphism, an important inflammatory enzyme, among cervix cancer cases. Methods: In this cross-sectional study, 79 cases diagnosed as cervical carcinoma between 1992-2012 is included. The cases without archival paraffin blocks and clinical follow-ups are excluded. All slides with tumor involvement are reviewed and the ones which demonstrate tumor’s characteristics are determined. After block determination 3 sections with 10-micron thickness obtained from paraffin blocks and MPO gene polymorphism was shown using acil restriction endonuclease enzyme with the restriction fragment length polymorphism (RFLP) method after polymerase chain reaction (PCR). The histopathological parameters including tumor stage and type, lymph node metastasis, ovary and endometrium involvement, recurrence and late metastasis are compared with genotype using chi-square and Fisher’s exact test. Results: The mean age of cases was 51.3 (10.9) years. Of 79 cases, 29 (36.7%) had AG (adenine-guanine) and 50 (633%) had GG (guanine-guanine) genotypes. Only endometrium involvement was identified to have a statistically difference with MPO gene polymorphism among the assessed histopathologic parameters (P=0.015). When clinical parameters are assessed, there was no difference identified between genotype and mortality (P=0.622). Conclusion: Cervical cancer is thought to have progressive and regressive characteristics of tumor development due to the inflammatory response of the host. Within this framework, in our study assessing gene polymorphism of one of the inflammatory response foundation stones of MPO, we identified more endometrial involvement for cases with AG genotype. We believe this significance will be encountered for more parameters in broad case series.

Downloads

Download data is not yet available.

References

Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health. 2020 Feb;8(2):e191-e203. doi: 10.1016/S2214-109X(19)30482-6.

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015 Mar;65(2):87-108. doi: 10.3322/caac.21262. 3.

Vinh-Hung V, Bourgain C, Vlastos G, Cserni G, De Ridder M, Storme G, et al. Prognostic value of histopathology and trends in cervical cancer: a SEER population study. BMC Cancer. 2007 Aug 23;7:164. doi: 10.1186/1471-2407-7-164.

Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000 Apr;18(8):1606-13. doi: 10.1200/JCO.2000.18.8.1606.

Pinto AP, Tulio S, Cruz OR. Hpv cofactors in cervical carcinogenesis. Rev Assoc Med Bras (1992). 2002 Jan- Mar;48(1):73-8. Portuguese. doi: 10.1590/s0104-42302002000100036.

Lages EL, Belo AV, Andrade SP, Rocha MÂ, de Freitas GF, Lamaita RM, et al. Analysis of systemic inflammatory response in the carcinogenic process of uterine cervical neoplasia. Biomed Pharmacother. 2011 Oct;65(7):496-9. doi: 10.1016/j.biopha.2011.06.010.

Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T, McDermott MF, et al. Cytokine gene polymorphism in human disease: on-line databases. Genes Immun. 1999 Sep;1(1):3-19. doi: 10.1038/sj.gene.6363645.

Hulkkonen J, Pertovaara M, Antonen J, Lahdenpohja N, Pasternack A, Hurme M. Genetic association between interleukin-10 promoter region polymorphisms and primary Sjögren's syndrome. Arthritis Rheum. 2001 Jan;44(1):176-9. doi: 10.1002/1529-0131(200101)44:1<176::AID-ANR23>3.0.CO;2-K.

Winterbourn CC, Kettle AJ. Biomarkers of myeloperoxidase-derived hypochlorous acid. Free Radic Biol Med. 2000 Sep 1;29(5):403-9. doi: 10.1016/s0891-5849(00)00204-5.

Winterbourn CC, Vissers MC, Kettle AJ. Myeloperoxidase. Curr Opin Hematol. 2000 Jan;7(1):53-8. doi: 10.1097/00062752-200001000-00010.

Stocker R, Keaney JF Jr. Role of oxidative modifications in atherosclerosis. Physiol Rev. 2004 Oct;84(4):1381-478. doi: 10.1152/physrev.00047.2003.

Johnson KR, Nauseef WM. Molecular biology of myeloperoxidase. In: Everse J, Everse K., Grisham M, eds. Peroxidases in Chemistry and Biology., Boca Raton, FL: CRC Press;1991. Pp. 63–82.

Dally H, Gassner K, Jäger B, Schmezer P, Spiegelhalder B, Edler Let al. Myeloperoxidase (MPO) genotype and lung cancer histologic types: the MPO -463 A allele is associated with reduced risk for small cell lung cancer in smokers. Int J Cancer. 2002 Dec 10;102(5):530-5. doi: 10.1002/ijc.10756.

Matsuo K, Hamajima N, Shinoda M, Hatooka S, Inoue M, Takezaki T, et al. Possible risk reduction in esophageal cancer associated with MPO -463 A allele. J Epidemiol. 2001 May;11(3):109-14. doi: 10.2188/jea.11.109.

Hung RJ, Boffetta P, Brennan P, Malaveille C, Gelatti U, Placidi D, et al. Genetic polymorphisms of MPO, COMT, MnSOD, NQO1, interactions with environmental exposures and bladder cancer risk. Carcinogenesis. 2004 Jun;25(6):973-8. doi: 10.1093/carcin/bgh080.

Olson SH, Carlson MD, Ostrer H, Harlap S, Stone A, Winters M, et al. Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer. Gynecol Oncol. 2004 Jun;93(3):615-20. doi: 10.1016/j.ygyno.2004.03.027.

Mäkelä S, Hurme M, Ala-Houhala I, Mustonen J, Koivisto AM, Partanen J, et al. Polymorphism of the cytokine genes in hospitalized patients with Puumala hantavirus infection. Nephrol Dial Transplant. 2001 Jul;16(7):1368-73. doi: 10.1093/ndt/16.7.1368.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492.

Blicharski J, Wolska T, Zduńczyk A, Bodzoń A, Lisiewicz J, Piotrowski J, et al. K. Enzymes of neutrophils in women with malignant tumors of reproductive organs. Folia Histochem Cytochem (Krakow). 1980;18(3):173-82.

Van Rensburg CE, Van Staden AM, Anderson R, Van Rensburg EJ. Hypochlorous acid potentiates hydrogen peroxide-mediated DNA-strand breaks in human mononuclear leucocytes. Mutat Res. 1992 Feb;265(2):255-61. doi: 10.1016/0027-5107(92)90054-6.

Klebanoff SJ. Oxygen metabolism and the toxic properties of phagocytes. Ann Intern Med. 1980 Sep;93(3):480-9. doi: 10.7326/0003-4819-93-3-480.

Clark RA, Klebanoff SJ, Einstein AB, Fefer A. Peroxidase-H2O2-halide system: Cytotoxic effect on mammalian tumor cells. Blood. 1975 Feb;45(2):161-70.

Clark RA, Klebanoff SJ. Neutrophil-mediated tumor cell cytotoxicity: role of the peroxidase system. J Exp Med. 1975 Jun 1;141(6):1442-7. doi: 10.1084/jem.141.6.1442.

Terashima M, Maesawa C, Oyama K, Ohtani S, Akiyama Y, Ogasawara S, et al.. Gene expression profiles in human gastric cancer: expression of maspin correlates with lymph node metastasis. Br J Cancer. 2005 Mar 28;92(6):1130-6. doi: 10.1038/sj.bjc.6602429.

Huang SK, Chiu AW, Pu YS, Huang YK, Chung CJ, Tsai HJ, et al. Arsenic methylation capability, myeloperoxidase and sulfotransferase genetic polymorphisms, and the stage and grade of urothelial carcinoma. Urol Int. 2009;82(2):227-34. doi: 10.1159/000200805.

Baek WK, Cho JW, Suh SI, Suh MH, Shin DH, Cho CH, et al. p53 codon 72 polymorphism and risk of cervical carcinoma in Korean women. J Korean Med Sci. 2000 Feb;15(1):65-7. doi: 10.3346/jkms.2000.15.1.65.

Krishnappa P, Kong HM, Mohamad IB, Voon K, Somanath SD. CD40 polymorphism in cervical carcinoma in a subset of Malaysian population. J Obstet Gynaecol Res. 2017 May;43(5):923-928. doi: 10.1111/jog.13277.

Zhang Z, Borecki I, Nguyen L, Ma D, Smith K, Huettner PC, et al. CD83 gene polymorphisms increase susceptibility to human invasive cervical cancer. Cancer Res. 2007 Dec 1;67(23):11202-8. doi: 10.1158/0008-5472.CAN-07-2677.

Matsumoto K, Oki A, Satoh T, Okada S, Minaguchi T, Onuki M, et al. Interleukin-10 -1082 gene polymorphism and susceptibility to cervical cancer among Japanese women. Jpn J Clin Oncol. 2010 Nov;40(11):1113-6. doi: 10.1093/jjco/hyq094.

Sobti RC, Shekari M, Tamandani DM, Malekzadeh K, Suri V. Association of interleukin-18 gene promoter polymorphism on the risk of cervix carcinogenesis in north Indian population. Oncol Res. 2008;17(4):159-66. doi: 10.3727/096504008785114156.

Natter C, Polterauer S, Pils S, Castillo-Tong DC, Zeilinger R, Heinze G, et al. Association of -463G/A MPO gene polymorphism and risk of cervical intraepithelial neoplasia. Arch Gynecol Obstet. 2016 Apr;293(4):865-9. doi: 10.1007/s00404-015-3869-9

Shi X, Li B, Yuan Y, Chen L, Zhang Y, Yang M, et al. The possible association between the presence of an MPO -463 G > A (rs2333227) polymorphism and cervical cancer risk. Pathol Res Pract. 2018 Aug;214(8):1142-1148. doi: 10.1016/j.prp.2018.05.018.