TNF‐&agr; (−308G>A) and TNF‐R1 (36A>G) single nucleotide polymorphisms are strong risk factors for odontogenic keratocystic tumor development

BACKGROUND Polymorphisms in genes encoding tumor necrosis factor-α (TNF-α) and its receptor TNF-R1 have been shown to affect one person's susceptibility to develop certain neoplastic diseases. The aim of the present association study was to investigate whether single nucleotide polymorphisms (SNPs) in TNF-α (-308G>A) and TNF-R1 (36A>G) genes modulate the susceptibility for keratocystic odontogenic tumors (KCOTs) development in Serbian patients. METHODS Genotyping was performed in 60 KCOT patients and 125 healthy individuals, using polymerase chain reaction/restriction fragment length polymorphism analysis. RESULTS A significant difference in genotype and allele frequencies was found between patients and controls for both SNPs (P < 0.05). Carriers of the TNF-α A variant had an eightfold increase of KCOT risk (OR = 8.12, 95% CI = 3.98-16.56, P < 0.0001), while carriers of the TNF-R1 G variant had approximately a fourfold increase of KCOT risk (OR=3.65, CI: 1.60-8.40, P = 0.001). CONCLUSIONS Our findings suggest that the two polymorphisms are strong risk factors for KCOT development in Serbian population.

[1]  R. Freitas,et al.  Immunoexpression of tumour necrosis factor‐&agr;, interleukin‐1&agr; and interleukin‐10 on odontogenic cysts and tumours , 2017, International endodontic journal.

[2]  I. Soldatovic,et al.  Survivin, cyclin D1, and p21hras in keratocystic odontogenic tumors before and after decompression. , 2016, Oral diseases.

[3]  V. Patel,et al.  P53 polymorphism at codon 72 is associated with keratocystic odontogenic tumors in the Thai population. , 2015, Asian Pacific journal of cancer prevention : APJCP.

[4]  F. Chen,et al.  Underestimated PTCH1 mutation rate in sporadic keratocystic odontogenic tumors. , 2015, Oral oncology.

[5]  Mingyan Zhang,et al.  Tumor necrosis factor-alpha gene −308G > A polymorphism alters the risk of hepatocellular carcinoma in a Han Chinese population , 2014, Diagnostic Pathology.

[6]  Shao-Yi Huang,et al.  The association between the polymorphisms of TNF-α and non-Hodgkin lymphoma: a meta-analysis , 2014, Tumor Biology.

[7]  J. N. dos Santos,et al.  Transcriptional profiles of SHH pathway genes in keratocystic odontogenic tumor and ameloblastoma. , 2014, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[8]  D. Pang,et al.  Association of TNF-α, TNFRSF1A and TNFRSF1B Gene Polymorphisms with the Risk of Sporadic Breast Cancer in Northeast Chinese Han Women , 2014, PloS one.

[9]  F. Chen,et al.  PTCH1 Gene Mutations in Keratocystic Odontogenic Tumors: A Study of 43 Chinese Patients and a Systematic Review , 2013, PloS one.

[10]  V. Jurišić,et al.  Keratocystic Odontogenic Tumors – Clinical and Molecular Features , 2013 .

[11]  A. Amirzargar,et al.  Gene polymorphism of interleukin-1 alpha and beta in keratocystic odontogenic tumors. , 2012, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[12]  A. Kolokythas,et al.  Does cytokine profiling of aspirate from jaw cysts and tumors have a role in diagnosis? , 2012, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[13]  B. Miličić,et al.  Survivin gene promoter polymorphism -31G/C as a risk factor for keratocystic odontogenic tumor development. , 2012, European journal of oral sciences.

[14]  A. Guimarães,et al.  Association of -308 TNF-α promoter polymorphism with clinical aggressiveness in patients with head and neck squamous cell carcinoma. , 2011, Oral oncology.

[15]  V. Olgac,et al.  The Role of RANK/RANKL/OPG Signalling Pathways in Osteoclastogenesis in Odontogenic Keratocysts, Radicular Cysts, and Ameloblastomas , 2011, Head and neck pathology.

[16]  B. McKnight,et al.  Genetic variation in proinflammatory cytokines IL6, IL6R, TNF-region, and TNFRSF1A and risk of breast cancer , 2011, Breast Cancer Research and Treatment.

[17]  B. Dozic,et al.  Survivin expression in odontogenic keratocysts and correlation with cytomegalovirus infection. , 2010, Oral diseases.

[18]  I. van der Waal,et al.  Biological pathways involved in the aggressive behavior of the keratocystic odontogenic tumor and possible implications for molecular oriented treatment - an overview. , 2010, Oral oncology.

[19]  M. Vered,et al.  The immunoprofile of odontogenic keratocyst (keratocystic odontogenic tumor) that includes expression of PTCH, SMO, GLI-1 and bcl-2 is similar to ameloblastoma but different from odontogenic cysts. , 2009, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[20]  E. Nkenke,et al.  Association of polymorphisms in Tumor Necrosis Factor Alpha and Beta genes with increased risk for oral cancer. , 2009, Anticancer research.

[21]  F. Balkwill.  Tumour necrosis factor and cancer , 2009, Nature Reviews Cancer.

[22]  V. Jurišić,et al.  The inflammatory radicular cysts have higher concentration of tnf-alpha in comparison to odontogenic keratocysts (odontogenic tumour). , 2007, Acta medica.

[23]  V. Jurišić,et al.  The Inflammatory Radicular Cysts Have Higher Concentration of TNF-α in Comparison to Odontogenic Keratocysts (Odontogenic Tumour). , 2007, Acta medica.

[24]  L. Barnes,et al.  Pathology and genetics of head and neck tumours , 2005 .

[25]  T. Day,et al.  Oral Cancer and Precancerous Lesions , 2002, CA: a cancer journal for clinicians.

[26]  M. Shear,et al.  The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm? Part 1. Clinical and early experimental evidence of aggressive behaviour. , 2002, Oral oncology.

[27]  P. Stoelinga,et al.  Long-term follow-up on keratocysts treated according to a defined protocol. , 2001, International journal of oral and maxillofacial surgery.

[28]  S. Targan,et al.  Tumor necrosis factor: biology and therapeutic inhibitors. , 2000, Gastroenterology.

[29]  J. Steer,et al.  Effects of stimulus and cell type on the expression of the -308 tumour necrosis factor promoter polymorphism. , 2000, Cytokine.

[30]  S. Jones,et al.  TNF recruits TRADD to the plasma membrane but not the trans-Golgi network, the principal subcellular location of TNF-R1. , 1999, Journal of immunology.

[31]  Y. Bando,et al.  Interleukin-1: the principal osteolytic cytokine produced by keratocysts. , 1992, Archives of oral biology.