Investigation Between MTHFR A1298C polymorphism and Oral Squamous Cell Carcinoma Risk in Turkish Population

Abstract

DOI: 10.26650/experimed.2019.19009

Objective: Oral squamous cell carcinoma (OSCC) with its poor survival rates and rising number of incidences arises through several etiological factors including environmental, genetic and epigenetic alterations. Several studies have established an association between cancer susceptibility and polymorphisms of methylenetetrahydrofolate reductase (MTHFR), the key enzyme involved in folate metabolism and, therefore in DNA synthesis, methylation and repair. The aim of the present study was to establish any association between MTHFR A1298C variants and alcohol and/or tobacco consumption, gender or age in respect to clinical histopathological parameters, and the risk of OSCC development in the Turkish population.

Material and Method: MTHFR A1298C genotyping in 107 OSCC patients and 107 cancer-free healthy controls was performed using the PCR-RFLP method.

Results: The study groups were age-matched with higher frequencies in the male gender. In the patients group, the distribution of MTHFR A1298C variants was not significant. Smoking was not found to be a risk factor: in non-smokers the frequency of the MTHFR A1298 allele was higher than the 1298C allele, and the A1298 allele carriers possessed moderately or well differentiated tumors with a diameter of <4 cm. However, these associations were not detected in smokers.

Conclusion: The present study alone did not demonstrate any association between the MTHFR A1298C polymorphism and the risk of OSCC in the Turkish population, however the prognosis of OSCC may be influenced by MTHFR A1298C variants.

Cite this article as: Küçükhüseyin Ö, Kayhan KB, Ünür M, Yılmaz Aydoğan H. Investigation Between MTHFR A1298C polymorphism and Oral Squamous Cell Carcinoma Risk in Turkish Population. Experimed 2019; 9(2): 44-52.

Keywords

• OSCC,MTHFR,polymorphism,gene,oral cancer

Türk Toplumunda MTHFR A1298C Polimorfizmi ile Oral Sküamoz Hücre Karsinom Gelişim Riski Arasındaki İlişkinin Araştırılması

Abstract

DOI: 10.26650/experimed.2019.19009

Amaç: Düşük yaşam süresi ile karakterize olan ve çevresel faktörlerin yanı sıra genetik ve epigenetik değişimlerin katkılarının bulunduğu oral sküamoz hücre karsinomu (OSHK) gün geçtikçe yükselen insidansıyla dikkati çekmektedir. Günümüze kadar, folat metabolizmasının önemli enzimlerinden biri olan ve dolayısıyla DNA sentezi, metilasyonu ve tamir mekanizmalarında rol oynayan metilen tetrahidrofolat redüktaz (MTHFR) enzimine ait genetik varyantlar ile kanser yatkınlığı arasındaki ilişkinin araştırıldığı birçok çalışma yapılmıştır. Çalışmamızda, Türk popülasyonundaki MTHFR A1298C varyantları ile alkol ve/veya sigara kullanımı, cinsiyet, yaş veya klinik parametreler esasında oral sküamoz hücre karsinomu gelişim riskinin araştırılması hedeflenmiştir.

Gereç ve Yöntem: MTHFR varyantları PCR-RFLP yöntemleri kullanılarak aynı yaş grubundaki 107 hasta ile 107 sağlıklı bireyde analiz edilmiştir.

Bulgular: Hasta ve kontrol grubu arasında MTHFR A1298C genotip ve allel dağılımı bakımdan anlamlı bir fark elde edilmemiştir. Sigara-içmeyen hastalarda, A1298 allel frekansı mutant allele göre yüksek olup, bu alleli taşıyanlarda tümör çapının 4cm’den büyük olduğu ve bu tümörlerin orta veya iyi diferansiasyona sahip olduğu tespit edilmiştir. Ancak bu durum sigara içen hastalarda tespit edilmemiştir.

Sonuç: Çalışmamız sonucunda MTHFR A1298C polimorfizminin hastalık gelişiminde bir risk faktörü olmadığı, ancak hastalığın prognozunda özellikte mutant varyantın etkili olabileceği kanaatine varılmıştır.

Cite this article as: Küçükhüseyin Ö, Kayhan KB, Ünür M, Yılmaz Aydoğan H. Investigation Between MTHFR A1298C polymorphism and Oral Squamous Cell Carcinoma Risk in Turkish Population. Experimed 2019; 9(2): 44-52.

Keywords

• OSCC,MTHFR,polymorphism,gene,oral cancer

References

1. 1. Johnson NW, Jayasekara P, Amarasinghe AA. Squamous cell carcinoma and precursor lesions of the oral cavity: epidemiology and aetiology. Periodontol 2000 2011; 57: 19-37. [CrossRef] 2. Scully C, Field JK, Tanzawa H. Genetic aberrations in oral or head and neck squamous cell carcinoma (SCCHN): 1. Carcinogen metabolism, DNA repair and cell cycle control. Oral Oncol 2000; 36: 256-63. [CrossRef] 3. Bezerra AM, Sant’Ana TA, Gomes AV, de Lacerda Vidal AK, Muniz MT. Tyms double (2R) and triple repeat (3R) confers risk for human oral squamous cell carcinoma. Mol Biol Rep 2014; 41: 7737-42. [CrossRef] 4. Boccia S, Boffetta P, Brennan P, Ricciardi G, Gianfagna F, Matsuo K, et al. Meta-analyses of the methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and risk of head and neck and lung cancer. Cancer Lett 2009; 273: 55-61. [CrossRef] 5. Galbiatti AL, Ruiz MT, Rodrigues JO, Raposo LS, Maniglia JV, Pavarino EC, et al. Polymorphisms and haplotypes in methylenetetrahydrofolate reductase gene and head and neck squamous cell carcinoma risk. Mol Biol Rep 2012; 39: 635-43. [CrossRef] 6. Moody M, Le O, Rickert M, Manuele J, Chang S, Robinson G, et al. Folic acid supplementation increases survival and modulates high risk HPV-induced phenotypes in oral squamous cell carcinoma cells and correlates with p53 mRNA transcriptional down-regulation. Cancer Cell Int 2012; 12: 10. [CrossRef] 7. Supic G, Jovic N, Kozomara R, Zeljic K, Magic Z. Interaction between the MTHFR C677T polymorphism and alcohol--impact on oral cancer risk and multiple DNA methylation of tumor-related genes. J Dent Res 2011; 90: 65-70. [CrossRef] 8. Cao Y, Miao XP, Huang MY, Deng L, Liang XM, Lin DX, et al. Polymorphisms of methylenetetrahydrofolate reductase are associated with a high risk of nasopharyngeal carcinoma in a smoking population from Southern China. Mol Carcinog 2010; 49: 928-34. [CrossRef] 9. Blank S, Rachakonda S, Keller G, Weichert W, Lordick F, Langer R, et al. A retrospective comparative exploratory study on two methylentetrahydrofolate reductase (MTHFR) polymorphisms in esophagogastric cancer: the A1298C MTHFR polymorphism is an independent prognostic factor only in neoadjuvantly treated gastric cancer patients. BMC Cancer 2014; 14: 58. [CrossRef] 10. Nazki FH, Sameer AS, Ganaie BA. Folate: metabolism, genes, polymorphisms and the associated diseases. Gene 2014; 533: 11-20. [CrossRef] 11. Tan X, Wang YY, Dai L, Liao XQ, Chen MW. Genetic polymorphism of MTHFR A1298C and esophageal cancer susceptibility: a meta-analysis. Asian Pac J Cancer Prev 2013; 14: 1951-5. [CrossRef] 12. Skibola CF, Smith MT, Kane E, Roman E, Rollinson S, Cartwright RA, et al. Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults. Proc Natl Acad Sci USA 1999; 96: 12810-5. [CrossRef] 13. Galeone C, Edefonti V, Parpinel M, Leoncini E, Matsuo K, Talamini R, et al. Folate intake and the risk of oral cavity and pharyngeal cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology Consortium. Int J Cancer 2015; 136: 904-14. [CrossRef] 14. Kingsley K. Potential effects of dietary folate supplementation on oral carcinogenesis, development and progression. J Diet Suppl 2010; 7: 51-9. [CrossRef] 15. Bektas-Kayhan K, Kucukhuseyin O, Yilmaz-Aydogan H, Boy-Metin Z, Ünür M, Isbir T. The Effects of Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphism on Oral Squamous Cell Carcinoma. MOJ 2014; 1: 34-40. 16. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1998; 16: 1215. [CrossRef] 17. Song C, Xing D, Tan W, Wei Q, Lin D. Methylenetetrahydrofolate Reductase Polymorphisms Increase Risk of Esophageal Squamous Cell Carcinoma in a Chinese Population. Cancer Res 2001; 61: 3272-5. 18. Gyorffy B, Kocsis I, Vásárhelyi B. Biallelic genotype distributions in papers published in Gut between1998 and 2003: altered conclusions after recalculating the Hardy-Weinberg equilibrium. Gut 2004; 53: 614-6. 19. Esser C, Tomluk J. Reporting Hardy-Weinberg Tests in Case-Control Studies: Reasons for Caution but not for Panic Reactions. J Invest Dermatol 2005; 124: 1082-3. [CrossRef] 20. Levecque C, Elbaz A, Clavel J, Richard F, Vidal JS, Amouyel P, et al. Association between Parkinson’s disease and polymorphisms in the nNOS and iNOS genes in a community-based case-control study. Hum Mol Genet 2003; 12: 79-86. [CrossRef] 21. Taghavi N, Yazdi I. Prognostic factors of survival rate in oral squamous cell carcinoma: Clinical, histologic, genetic and molecular concepts. Arch Iran Med 2015; 18: 314-9. 22. Neumann AS, Lyons HJ, Shen H, Liu Z, Shi Q, Sturgis EM, et al. Methylenetetrahydrofolate reductase polymorphisms and risk of squamous cell carcinoma of the head and neck: a case-control analysis. Int J Cancer 2005; 115: 131-6. [CrossRef] 23. Suzuki T, Matsuo K, Hasegawa Y, Hiraki A, Wakai K, Hirose K, et al. One-carbon metabolism-related gene polymorphisms and risk of head and neck squamous cell carcinoma: case-control study. Cancer Sci 2007; 98: 1439-46. [CrossRef] 24. Kruszyna L, Lianeri M, Rydzanicz M, Gajecka M, Szyfter K, Jagodzinski PP. Polymorphic variants of folate metabolism genes and the risk of laryngeal cancer. Mol Biol Rep 2010; 37: 241-7. [CrossRef] 25. Niu YM, Shen M, Li H, Ni XB, Zhou J, Zeng XT, et al. No association between MTHFR A1298C gene polymorphism and head and neck cancer risk: a meta-analysis based on 9,952 subjects. Asian Pac J Cancer Prev 2012; 13: 3943-7. [CrossRef]