Effect of thrombosis-related gene polymorphisms upon oral cancer: a regression analysis
Antonis Vylliotis, Christos Yapijakis, Emeka Nkenke, Themistoklis Nisyrios, Dimitrios Avgoustidis, Maria Adamopoulou, Vasilios Ragos, Stavros Vassiliou, Nikolas Koronellos, Eleftherios Vairaktaris
It is well-known that there is an interplay between hemostasis, thrombosis and cancer. Functional DNA polymorphisms in genes encoding factors related to thrombosis have been associated with increased risk for oral squamous cell carcinoma (OSCC). The present study investigated the possible combinatory effect of 10 such polymorphisms as primary risk predictors for OSCC in a European population. Two groups including 160 patients with OSCC and 168 healthy controls of Greek and German origin were studied. The patient and control groups were comparable regarding ethnicity, age and gender. For all studied individuals, 10 genotypes of functional polymorphisms were investigated: 5,10-methylene tetrahydrofolate reductase (MTHFR) C677T, coagulation factor V (F5) Leiden, coagulation factor II (F2, also known as prothrombin) G20210A, coagulation factor XII (F12) C46T, coagulation factor XIII A1 subunit (F13A1) Val34Leu, serpine1 (SERPINE1, also known as plasminogen activator inhibitor-1) 4G/5G, protein Z (PROZ) -A13G, angiotensin I-converting enzyme (ACE) I/D, angiotensinogen (AGT) Met325Thr, and carboxypeptidase B2 (CPB2, also known as thrombin-activatable fibrinolysis inhibitor) C1040T. Multivariate logistic regression models were used in order to evaluate the relation and contribution of homozygous and heterozygous variant polymorphisms upon overall, early and advanced stages of OSCC. Five out of the studied polymorphisms, influencing the expression of SERPINE1 and ACE genes, as well as the activity of CPB2, F12 and F13 proteins, were recognized as significant predictive factors for OSCC. The ‘mode of inheritance’ regression model, in particular, revealed the low expression I allele of ACE to be a primary predictor in overall, early and advanced stages of oral cancer. Comparing the present findings with previous knowledge, possible interactions of these factors and their relation to the risk for OSCC development are discussed.
Prevalence of human papillomavirus in saliva and cervix of sexually active women
Maria Adamopoulou, Eleftherios Vairaktaris, Emeka Nkenke, Dimitrios Avgoustidis, Petros Karakitsos, Vasilios Sioulas, Themistoklis Nisyrios, Christos Yapijakis
Objective: Human papillomavirus (HPV) is strongly associated with cervical cancer and possibly with some oropharyngeal cancers. However, the relation between oral and cervical HPV infection is not fully understood. This study evaluates the prevalence rate and type-concordance of HPVs in these areas.
Methods: HPV DNA typing was performed in saliva and cervical specimens of 43 sexually active women, with the use of general consensus PCR and nested PCR (NPCR) tests.
Results: The prevalence rate of HPV DNA in cervical and saliva samples was 51.2% and 11.6% with general PCR, and 60.5% and 44.2% with NPCR, respectively. The probability of HPV DNA detection with general PCR in saliva was about 8 times lower compared to the cervix (P<0.001, OR: 0.13, 95% CI: 0.04-0.37), but showed no difference when the more sensitive NPCR method was applied (P=0.139, OR: 0.52, 95% CI: 0.22-1.21). The distribution of HPV variants according to their oncogenic potential revealed no statistically significant difference, regardless to the PCR method used for both sites. All general PCR HPV DNA positive saliva specimens belonged to women with cytology findings (n=5). These women had also 8.5 times higher risk for presenting with positive HPV detection in saliva with the NPCR method (P=0.009, OR=8.50, 95% CI: 1.74-39.70).
Conclusions: Women with genital HPV infection are at higher risk for asymptomatic oral HPV infection. Prophylactic HPV-vaccination may reduce the burden of HPV-related diseases in both cervix and oropharynx.
Copyright © 2013 Elsevier Inc. All rights reserved.
Oral carcinogenesis is not achieved in different carcinogen-treated PAI-1 transgenic and wild-type mouse models
Dimitris Avgoustidis, Themistoklis Nisyrios, Emeka Nkenke, Roger Lijnen, Vassilis Ragos, Despina Perrea, Ismini Donta, Apostolia Vaena, Christos Yapijakis, Eleftherios Vairaktaris
Aim: In an effort to assess the role of plasminogen activator inhibitor-1 (PAI-1) in oral squamous cancer development and progression, two different carcinogen treatment protocols were conducted.
Materials and methods: Protocol I included mice from a PAI-1 transgenic (Tg) breed (n=56) and their wild-type (WT) counterparts (n=56), divided into one control group and two main experimental groups, treated with 7,12-dimethylbenz[a]anthracene (DMBA) for 8 and 16 weeks, respectively. Protocol II included the same number and types of animals and groups, which were similarly treated with 4-Nitroquinoline 1-oxide (4-NQO) in drinking water. Two drugs that affect plasma PAI-1 levels, enalapril and pravastatin, were administered to certain subgroups of animals in both protocols.
Results: None of the animals developed macroscopically-visible oral cancer lesions. Eleven animals under Protocol I and 52 animals under Protocol II died. Skin lesions were noted only in DMBA-treated animals (n=9). Almost all animals administered with 4-NQO developed alopecia and lost weight, while two of them developed stomach tumours, and one female mouse developed a large ovarian cyst.
Conclusion: Transgenic mice may respond differently when used in well-established carcinogen models and oral carcinogenesis is hard to achieve in these rodents.
