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NOT PON1 L55M BUT ACE I/D VARIANT MIGHT BE A RISK FACTOR FOR OSCC IN THE TURKISH POPULATION

Year 2025, Volume: 8 Issue: 1, 15 - 20, 04.03.2025
https://doi.org/10.26650/JARHS2025-1579437

Abstract

Objective: Oral squamous cell carcinoma (OSCC) covers more than 90% of the malignant neoplasms in the mouth. It has been shown that angiotensin-converting enzyme (ACE) and paraoxonase (PON1) gene variants were associated with several cancers. Therefore, we investigated the possible association between ACE insertion/deletion (I/D)-PON1 L55M variants and OSCC development risk in a Turkish population.

Material and Methods: A total of 155 people (104 healthy controls and 51 OSCC patients) made up the study population. These variants were genotyped using polymerase chain reaction (PCR) and/or restriction fragment length polymorphism (RFLP) assays.

Results: ACE I/D allele frequencies were significantly different between patients and controls. The ACE D allele was higher in the patient group compared to the control group, while the I allele was more prevalent in controls than patients (p˂0.0000001). When the patients and controls were examined based on the II+ID vs. DD genotype and II: ID vs. DD, a statistically significant correlation was found (p = 0.0000001 and p = 0.008691, respectively). The genotype and allele distribution of PON1 L55M did not significantly differ between the groups.

Conclusion: In conclusion, our study showed that the ACE I/D variant D allele is a risk factor for the development of OSCC in Turkey. This study contributes to more studies to confirm that ACE I/D plays a role as a genetic risk factor for OSCC.

References

  • Rao SVK, Mejia G, Roberts-Thomson K, Logan R. Epidemiology of oral cancer in Asia in the past decade-an update (2000-2012). Asian Pac J Cancer Prev 2013;14(10):5567-77. google scholar
  • Yang W-H, Wang S-J, Chang Y-S, Su C-M, Yang S-F, Tang C-H. Association of resistin gene polymorphisms with oral squamous cell carcinoma progression and development. Biomed Res Int 2018;14(9531315). google scholar
  • Lee C-F, Chiang N-N, Lu Y-H, Huang Y-S, Yang J-S, Tsai S-C, et al. Benzyl isothiocyanate (BITC) triggers mitochondria-mediated apoptotic machinery in human cisplatin-resistant oral cancer CAR cells. Biomedicine 2018;8(3). google scholar
  • Yaren A, Turgut S, Kursunluoglu R, Oztop I, Turgut G, Degirmencioglu S, et al. Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients with breast cancer and effects on prognostic factors. J Investig Med 2007;55(5):255-61. google scholar
  • Gan L, Liu X, Wu Z, Huang M, Zhang X, Guo W. Angiotensin-converting enzyme insertion/deletion polymorphism and gastric cancer: a systematic review and meta-analysis. Int J Clin Exp Med 2015;8(4):5788-93. google scholar
  • Hubert C, Houot A-M, Corvol P, Soubrier F. Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene. J Biol Chem 1991;266(23):15377-83. google scholar
  • Lin C, Yang H-Y, Wu C-C, Lee H-S, Lin Y-F, Lu K-C, et al. Angiotensin-converting enzyme insertion/deletion polymorphism contributes high risk for chronic kidney disease in Asian male with hypertension-a meta-regression analysis of 98 observational studies. PloS one 2014;9(1):e87604. google scholar
  • Precourt L-P, Amre D, Denis M-C, Lavoie J-C, Delvin E, Seidman E, et al. The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis 2011;214(1):20-36. google scholar
  • Pan X, Huang L, Li M, Mo D, Liang Y, Liu Z, et al. The association between PON1 (Q192R and L55M) gene polymorphisms and risk of cancer: A meta-analysis based on 43 studies. Biomed Res Int 2019;2019. google scholar
  • Brophy VH, Jarvik GP, Richter RJ, Rozek LS, Schellenberg GD, Furlong CE. Analysis of paraoxonase (PON1) L55M status requires both genotype and phenotype. Pharmacogenet Genomics 2000;10(5):453-60. google scholar
  • Inanır A, Yigit S, Tural S, Ozturk SD, Akkanet S, Habiboğlu A. Significant association between insertion/deletion polymorphism of the angiotensin-convertig enzyme gene and ankylosing spondylitis. Mol Vis 2012;18:2107. google scholar
  • Basol N, Karakus N, Savas AY, Karakus K, Kaya İ, Karaman S, et al. The evaluation of two genetic polymorphisms of paraoxonase 1 in patients with pulmonary embolism. J Clin Lab Anal 2018;32(7):e22455. google scholar
  • Abram MH, van Heerden WF, Rheeder P, Girdler-Brown BV, van Zyl AW. Epidemiology of oral squamous cell carcinoma. Sadj. 2012;67(10):550-3. google scholar
  • Wegman-Ostrosky T, Soto-Reyes E, Vidal-Millân S, Sânchez-Corona J. The renin-angiotensin system meets the hallmarks of cancer. J Renin Angiotensin Aldosterone Syst 2015;16(2):227-33. google scholar
  • Matsushima-Otsuka S, Fujiwara-Tani R, Sasaki T, Ohmori H, Nakashima C, Kishi S, et al. Significance of intranuclear angiotensin-II type 2 receptor in oral squamous cell carcinoma. Oncotarget 2018;9(93):36561. google scholar
  • de Carvalho Fraga CA, Farias LC, Jones KM, Batista de Paula AM, Guimaraes AL. Angiotensin-converting enzymes (ACE and ACE2) as potential targets for malignant epithelial neoplasia: review and bioinformatics analyses focused in oral squamous cell carcinoma. Protein Pept Lett 2017;24(9):784-92. google scholar
  • Vairaktaris E, Yapijakis C, Tsigris C, Vassiliou S, Derka S, Nkenke E, et al. Association of angiotensin-converting enzyme gene insertion/ deletion polymorphism with increased risk for oral cancer. Acta Oncol 2007;46(8):1097-102. google scholar
  • Xie Y, You C, Chen J. An updated meta-analysis on association between angiotensin I-converting enzyme gene insertion/deletion polymorphism and cancer risk. Tumour Biol 2014;35(7):6567-79. google scholar
  • Zhang Y, He J, Deng Y, Zhang J, Li X, Xiang Z, et al. The insertion/ deletion (I/D) polymorphism in the Angiotensin-converting enzyme gene and cancer risk: a meta-analysis. BMC Med Genet 2011;12(1):1-10. google scholar
  • Raba G, Zawlik I, Braun M, Paszek S, Potocka N, Skrzypa M, et al. Evaluation of the association between angiotensin converting enzyme insertion/deletion polymorphism and the risk of endometrial cancer in and characteristics of Polish women. Adv Clin Exp Med 2020;29(5):581-5. google scholar
  • Chen J, Sun M, Zhou M, Lu R. Associations between I/D polymorphism in the ACE gene and lung cancer: an updated systematic review and a meta-analysis. BMC cancer 2021;21(1):1-9. google scholar
  • Elabd NS, Montaser B, Gohar S, Makboul K, Elhamoly M. Association Between the ACE (I/D) Gene Polymorphism and Hepatocellular Carcinoma Risk in Egyptian HCV Patients. Int J Cancer Res 2020;4(3):159-67. google scholar
  • Yigit B, Bozkurt N, Narter F, Yilmaz H, Yucebas E, Isbir T. Effects of ACE I/D polymorphism on prostate cancer risk, tumor grade and metastatis. Anticancer Res 2007;27(2):933-6. google scholar
  • Chung F, Yang Y, Chen C, Lin C, Shieh T. Angiotensin-converting enzyme gene insertion/deletion polymorphism is associated with risk of oral precancerous lesion in betel quid chewers. Br J Cancer 2005;93(5):602-6. google scholar
  • Cejas P, Casado E, Belda-Iniesta C, De Castro J, Espinosa E, Redondo A, et al. Implications of oxidative stress and cell membrane lipid peroxidation in human cancer (Spain). Cancer Causes Control 2004;15(7):707-19. google scholar
  • Uluocak N, Atılgan D, Parlaktaş BS, Erdemir F, Ateş Ö. A pilot study assessing the association between paraoxonase 1 gene polymorphism and prostate cancer. Turk J Urol 2017;43(3):279. google scholar
  • Hashim Z, Zarina S. Assessment of paraoxonase activity and lipid peroxidation levels in diabetic and senile subjects suffering from cataract. Clin Biochem 2007;40(9-10):705-9. google scholar
  • Dantoine TF, Debord J, Charmes J-P, Merle L, Marquet P, Lachatre G, et al. Decrease of serum paraoxonase activity in chronic renal failure. J Am Soc Nephrol 1998;9(11):2082-8. google scholar
  • Baskol G, Karakucuk S, Oner AO, Baskol M, Kocer D, Mirza E, et al. Serum paraoxonase 1 activity and lipid peroxidation levels in patients with age-related macular degeneration. Ophthalmologica 2006;220(1):12-6. google scholar
  • Raiszadeh F, Solati M, Etemadi A, Azizi F. Serum paraoxonase activity before and after treatment of thyrotoxicosis. Clin Endocrinol 2004;60(1):75-80. google scholar
  • Malik UU, Siddiqui IA, Hashim Z, Zarina S. Measurement of serum paraoxonase activity and MDA concentrations in patients suffering with oral squamous cell carcinoma. Clin Chim Acta 2014;430:38-42. google scholar
  • Metin ZB, Aydin S, Unur M, Cakmakoglu B, Toptas B, Hafiz G, et al. Oral squamous cell carcinoma and serum paraoxonase 1. J Laryngol Otol 2013;127(12):1208-13. google scholar
  • Hu P, Ma Y, Zhang L, Ma S. PON1 L55M polymorphism might contribute to the risk of cancer. Panminerva Med 2016;59(1):107-13. google scholar
  • Santana ITS, Dos Santos JNA, de Almeida VL, Ferreira WNS, Santos EM, de Almeida Freitas R, et al. Association of PON1, TNF-a and TGF-Ş gene polymorphisms with prognosis in oral and oropharyngeal squamous cell carcinoma. Acta Odontol Scand 2021;79(5):327-34. google scholar

TÜRK POPÜLASYONUNDA ACE I/D VARYANTI OSCC İÇİN BİR RİSK FAKTÖRÜ OLABİLİR FAKAT PON1 L55M RİSK FAKTÖRÜ DEĞİLDİR

Year 2025, Volume: 8 Issue: 1, 15 - 20, 04.03.2025
https://doi.org/10.26650/JARHS2025-1579437

Abstract

Amaç: Oral skuamöz hücreli karsinom (OSCC), ağızdaki malign neoplazm ların %90’ından fazlasını kapsar. Anjiyotensin dönüştürücü enzim (ACE) ve paraoksonaz (PON1) gen varyantlarının birçok kanserle ilişkili olduğu gös terilmiştir. Bu nedenle, Türk popülasyonunda ACE I/D-PON1 L55M var yantları ile OSCC gelişim riski arasındaki olası ilişkiyi araştırmayı amaçladık.

Gereç ve Yöntemler: Çalışma popülasyonu toplam 155 bireyden oluşmak taydı (51 OSCC hastası ve 104 sağlıklı kontrol). ACE I/D - PON1 L55M var yantları, PCR ve RFLP analizleri kullanılarak genotiplendi.

Bulgular: ACE I/D alel frekansları hastalar ve kontroller arasında anlamlı şekilde farklılık göstermiştir. ACE D aleli, hasta grubunda kontrol grubuna kıyasla daha yüksek iken, I aleli kontrollerde hastalara kıyasla daha fazlaydı (p˂0,0000001). Hastalar ile kontroller, II+ID vs. DD genotipine (p=0,0000001) ve II: ID vs. DD’ye (p=0,008691) göre karşılaştırıldığında istatistiksel olarak anlamlı bir ilişki gözlendi. PON1 L55M genotipi veya alel dağılımı açısından hastalar ve kontroller arasında anlamlı bir fark buluna madı (p>0,05).

Sonuç: Sonuç olarak çalışmamız ACE I/D varyant D alelinin Türkiye’de OSCC gelişimi için risk faktörü olduğunu gösterdi. Bu çalışma, ACE I/D’nin OSCC için genetik bir risk faktörü olarak rol oynadığını doğrulamak amacıyla yapılacak daha fazla araştırmaya katkı sağlamaktadır.

References

  • Rao SVK, Mejia G, Roberts-Thomson K, Logan R. Epidemiology of oral cancer in Asia in the past decade-an update (2000-2012). Asian Pac J Cancer Prev 2013;14(10):5567-77. google scholar
  • Yang W-H, Wang S-J, Chang Y-S, Su C-M, Yang S-F, Tang C-H. Association of resistin gene polymorphisms with oral squamous cell carcinoma progression and development. Biomed Res Int 2018;14(9531315). google scholar
  • Lee C-F, Chiang N-N, Lu Y-H, Huang Y-S, Yang J-S, Tsai S-C, et al. Benzyl isothiocyanate (BITC) triggers mitochondria-mediated apoptotic machinery in human cisplatin-resistant oral cancer CAR cells. Biomedicine 2018;8(3). google scholar
  • Yaren A, Turgut S, Kursunluoglu R, Oztop I, Turgut G, Degirmencioglu S, et al. Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients with breast cancer and effects on prognostic factors. J Investig Med 2007;55(5):255-61. google scholar
  • Gan L, Liu X, Wu Z, Huang M, Zhang X, Guo W. Angiotensin-converting enzyme insertion/deletion polymorphism and gastric cancer: a systematic review and meta-analysis. Int J Clin Exp Med 2015;8(4):5788-93. google scholar
  • Hubert C, Houot A-M, Corvol P, Soubrier F. Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene. J Biol Chem 1991;266(23):15377-83. google scholar
  • Lin C, Yang H-Y, Wu C-C, Lee H-S, Lin Y-F, Lu K-C, et al. Angiotensin-converting enzyme insertion/deletion polymorphism contributes high risk for chronic kidney disease in Asian male with hypertension-a meta-regression analysis of 98 observational studies. PloS one 2014;9(1):e87604. google scholar
  • Precourt L-P, Amre D, Denis M-C, Lavoie J-C, Delvin E, Seidman E, et al. The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis 2011;214(1):20-36. google scholar
  • Pan X, Huang L, Li M, Mo D, Liang Y, Liu Z, et al. The association between PON1 (Q192R and L55M) gene polymorphisms and risk of cancer: A meta-analysis based on 43 studies. Biomed Res Int 2019;2019. google scholar
  • Brophy VH, Jarvik GP, Richter RJ, Rozek LS, Schellenberg GD, Furlong CE. Analysis of paraoxonase (PON1) L55M status requires both genotype and phenotype. Pharmacogenet Genomics 2000;10(5):453-60. google scholar
  • Inanır A, Yigit S, Tural S, Ozturk SD, Akkanet S, Habiboğlu A. Significant association between insertion/deletion polymorphism of the angiotensin-convertig enzyme gene and ankylosing spondylitis. Mol Vis 2012;18:2107. google scholar
  • Basol N, Karakus N, Savas AY, Karakus K, Kaya İ, Karaman S, et al. The evaluation of two genetic polymorphisms of paraoxonase 1 in patients with pulmonary embolism. J Clin Lab Anal 2018;32(7):e22455. google scholar
  • Abram MH, van Heerden WF, Rheeder P, Girdler-Brown BV, van Zyl AW. Epidemiology of oral squamous cell carcinoma. Sadj. 2012;67(10):550-3. google scholar
  • Wegman-Ostrosky T, Soto-Reyes E, Vidal-Millân S, Sânchez-Corona J. The renin-angiotensin system meets the hallmarks of cancer. J Renin Angiotensin Aldosterone Syst 2015;16(2):227-33. google scholar
  • Matsushima-Otsuka S, Fujiwara-Tani R, Sasaki T, Ohmori H, Nakashima C, Kishi S, et al. Significance of intranuclear angiotensin-II type 2 receptor in oral squamous cell carcinoma. Oncotarget 2018;9(93):36561. google scholar
  • de Carvalho Fraga CA, Farias LC, Jones KM, Batista de Paula AM, Guimaraes AL. Angiotensin-converting enzymes (ACE and ACE2) as potential targets for malignant epithelial neoplasia: review and bioinformatics analyses focused in oral squamous cell carcinoma. Protein Pept Lett 2017;24(9):784-92. google scholar
  • Vairaktaris E, Yapijakis C, Tsigris C, Vassiliou S, Derka S, Nkenke E, et al. Association of angiotensin-converting enzyme gene insertion/ deletion polymorphism with increased risk for oral cancer. Acta Oncol 2007;46(8):1097-102. google scholar
  • Xie Y, You C, Chen J. An updated meta-analysis on association between angiotensin I-converting enzyme gene insertion/deletion polymorphism and cancer risk. Tumour Biol 2014;35(7):6567-79. google scholar
  • Zhang Y, He J, Deng Y, Zhang J, Li X, Xiang Z, et al. The insertion/ deletion (I/D) polymorphism in the Angiotensin-converting enzyme gene and cancer risk: a meta-analysis. BMC Med Genet 2011;12(1):1-10. google scholar
  • Raba G, Zawlik I, Braun M, Paszek S, Potocka N, Skrzypa M, et al. Evaluation of the association between angiotensin converting enzyme insertion/deletion polymorphism and the risk of endometrial cancer in and characteristics of Polish women. Adv Clin Exp Med 2020;29(5):581-5. google scholar
  • Chen J, Sun M, Zhou M, Lu R. Associations between I/D polymorphism in the ACE gene and lung cancer: an updated systematic review and a meta-analysis. BMC cancer 2021;21(1):1-9. google scholar
  • Elabd NS, Montaser B, Gohar S, Makboul K, Elhamoly M. Association Between the ACE (I/D) Gene Polymorphism and Hepatocellular Carcinoma Risk in Egyptian HCV Patients. Int J Cancer Res 2020;4(3):159-67. google scholar
  • Yigit B, Bozkurt N, Narter F, Yilmaz H, Yucebas E, Isbir T. Effects of ACE I/D polymorphism on prostate cancer risk, tumor grade and metastatis. Anticancer Res 2007;27(2):933-6. google scholar
  • Chung F, Yang Y, Chen C, Lin C, Shieh T. Angiotensin-converting enzyme gene insertion/deletion polymorphism is associated with risk of oral precancerous lesion in betel quid chewers. Br J Cancer 2005;93(5):602-6. google scholar
  • Cejas P, Casado E, Belda-Iniesta C, De Castro J, Espinosa E, Redondo A, et al. Implications of oxidative stress and cell membrane lipid peroxidation in human cancer (Spain). Cancer Causes Control 2004;15(7):707-19. google scholar
  • Uluocak N, Atılgan D, Parlaktaş BS, Erdemir F, Ateş Ö. A pilot study assessing the association between paraoxonase 1 gene polymorphism and prostate cancer. Turk J Urol 2017;43(3):279. google scholar
  • Hashim Z, Zarina S. Assessment of paraoxonase activity and lipid peroxidation levels in diabetic and senile subjects suffering from cataract. Clin Biochem 2007;40(9-10):705-9. google scholar
  • Dantoine TF, Debord J, Charmes J-P, Merle L, Marquet P, Lachatre G, et al. Decrease of serum paraoxonase activity in chronic renal failure. J Am Soc Nephrol 1998;9(11):2082-8. google scholar
  • Baskol G, Karakucuk S, Oner AO, Baskol M, Kocer D, Mirza E, et al. Serum paraoxonase 1 activity and lipid peroxidation levels in patients with age-related macular degeneration. Ophthalmologica 2006;220(1):12-6. google scholar
  • Raiszadeh F, Solati M, Etemadi A, Azizi F. Serum paraoxonase activity before and after treatment of thyrotoxicosis. Clin Endocrinol 2004;60(1):75-80. google scholar
  • Malik UU, Siddiqui IA, Hashim Z, Zarina S. Measurement of serum paraoxonase activity and MDA concentrations in patients suffering with oral squamous cell carcinoma. Clin Chim Acta 2014;430:38-42. google scholar
  • Metin ZB, Aydin S, Unur M, Cakmakoglu B, Toptas B, Hafiz G, et al. Oral squamous cell carcinoma and serum paraoxonase 1. J Laryngol Otol 2013;127(12):1208-13. google scholar
  • Hu P, Ma Y, Zhang L, Ma S. PON1 L55M polymorphism might contribute to the risk of cancer. Panminerva Med 2016;59(1):107-13. google scholar
  • Santana ITS, Dos Santos JNA, de Almeida VL, Ferreira WNS, Santos EM, de Almeida Freitas R, et al. Association of PON1, TNF-a and TGF-Ş gene polymorphisms with prognosis in oral and oropharyngeal squamous cell carcinoma. Acta Odontol Scand 2021;79(5):327-34. google scholar
There are 34 citations in total.

Details

Primary Language English
Subjects Oral Medicine and Pathology, Medical Genetics (Excl. Cancer Genetics)
Journal Section Research Articles
Authors

Ayşe Feyda Nursal 0000-0001-7639-1122

Özge Gümüşay 0000-0002-6236-9829

Serbülent Yiğit 0000-0002-1019-3964

Nilüfer Kuruca 0000-0001-5601-4952

Mehmet Kemal Tümer 0000-0002-6250-0954

Publication Date March 4, 2025
Submission Date November 18, 2024
Acceptance Date January 25, 2025
Published in Issue Year 2025 Volume: 8 Issue: 1

Cite

MLA Nursal, Ayşe Feyda et al. “NOT PON1 L55M BUT ACE I/D VARIANT MIGHT BE A RISK FACTOR FOR OSCC IN THE TURKISH POPULATION”. Journal of Advanced Research in Health Sciences, vol. 8, no. 1, 2025, pp. 15-20, doi:10.26650/JARHS2025-1579437.