P3.08. Gene expression polymorphisms of inflammation-related factors are associated with risk for oral squamous cell carcinoma in Europeans

P3.08. Gene expression polymorphisms of inflammation-related factors are associated with risk for oral squamous cell carcinoma in Europeans

Cytogenetic analysis is an important diagnostic and prognostic tool in most malignant tumors. Cytogenetic findings of oral solid tumors are still limit...

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Cytogenetic analysis is an important diagnostic and prognostic tool in most malignant tumors. Cytogenetic findings of oral solid tumors are still limited. Here we present cytogenetic results of 25 cases of oral tumors. Methods: Fresh tissue specimens were rinsed and cultured. Cells were fixed after 3–12 days of culture and analyzed following standard procedures. Fifteen-twenty five metaphases were analyzed. Results: Twenty five tumors were analysed: 8 malignant (4 squamous cell carcinoma, 1 Merkell cell carcinoma, 1 Ewing sarcoma, 1 rhabomyosarcoma and 1 myofibrosarcoma) and 17 benign (1 keratocyst, 3 pleomorphic adenoma, 2 central giant cell granuloma, 2 solitary fibrous tumor, 1 granular cell tumor, 1 angiomyoma,1 fibroma, 3 lipoma, 1 intraosseous schwannoma, 1 hemangiopericytoma and 1 ameloblastoma). Among the malignant tumors, the squamous cell carcinoma and myofibrosarcoma showed normal karyotype, while the Merkel cell carcinoma, Ewing sarcoma and rhabdomyosarcoma showed multiple and complex chromosomal changes. Among the benign tumors, pleomorphic adenoma, lipoma, fibroma, central giant cell granuloma, ameloblastoma, hemangiopericytoma and solitary fibrous tumor showed abnormal clones with either few or multiple chromosomal changes. The cytogenetic differences between malignant and benign tumors and its significance will be discussed. Conclusions: Cytogenetic analysis is recommended as a complementary diagnostic and prognostic tool in oral tumors. It can strengthen our understanding of the tumorogenesis process of these lesions. doi:10.1016/j.oos.2009.06.532

P3.07. The association of Alpha B-Crystallin polymorphisms with oralcancer susceptibility in Taiwan C.C. Lin a,*, C.N. Wen a,b, T.H. Chang a, T.Y. An a, H.C. Hung a, K.Y. Shun a,c,d a Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taiwan b Department of Biochemistry, School of Medicine, China Medical University, Taiwan c Department of Biological Science and Technology, China Medical University, Taiwan d Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan, ROC

Alpha B-Crystallin (CRYAB) is an extremely stable protein functions as ‘‘molecular chaperone” in preservation intracellular architecture, cell membrane and highly antiapoptotic. Lack or lower CRYAB expression is a prognostic biomarker for head and neck cancer, while its genomic variations and the association with carcinogenesis are not well studied. Therefore, we hypothesized that single nucleotide polymorphisms (SNPs) in CRYAB may be associated with risk of oral cancer. In this hospital-based study, the association of CRYAB A-1215G (rs2228387), C-802G (rs14133) and intron2 (rs2070894) polymorphisms with oral cancer risk in a central Taiwanese population was investigated. In total, 496 patients with oral cancer and 496 age- and gender-matched healthy controls recruited from the China Medical Hospital in central Taiwan were genotyped. A significantly different distribution was found in the frequency of the CRYAB C-802G genotype, but not in A-1215G and intron2 genotypes, between the oral cancer and control groups. The G allele CRYAB C-802G conferred a significant (P = 0.000142) increased risk of oral cancer. Patients carrying CG or GG of their CRYAB C-802G were also of lower 5-year survival and higher metastasis rates (P < 0.05).

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Our results provide the first evidence that the G allele of the CRYAB C-802G may be associated with the development of oral cancer and may be a novel useful marker for oral cancer detection and diagnosis. doi:10.1016/j.oos.2009.06.533

P3.08. Gene expression polymorphisms of inflammation-related factors are associated with risk for oral squamous cell carcinoma in Europeans C. Yapijakis *, D. Avgoustidis, Z. Serefoglou, A. Vylliotis, S. Spyridonidou, E. Critselis University of Athens, Greece University of Erlangen, Germany Introduction: Recent genetic association studies performed by our group and others have indicated that functional DNA polymorphisms in genes of factors related to inflammation, angiogenesis and thrombosis are associated with increased risk for oral squamous cell carcinoma (OSCC). Here we present the combinatory effect of gene polymorphisms using multivariate logistic regression analysis in an attempt to predict the occurrence of OSCC in the studied European population. Methods: Functional DNA polymorphisms in 32 genes that encode cytokines and their receptors, matrix metalloproteinases and their inhibitors, platelet glycoproteins and coagulation factors were investigated in blood DNA samples isolated from 330 Europeans (Greeks and Germans). They included a group of 162 OSCC patients and a group of 168 healthy controls with comparable age, gender, and ethnicity. Detected genotype distributions were compared between the two groups. A series of multivariate logistic regression models (adjusted for age and gender) was constructed in order to assess the contribution of homozygous or heterozygous variant polymorphic genotypes upon overall, early and advanced stages of OSCC development. Results: In all regression models, the contribution of TNF-a and IL-6 polymorphisms was consistently significant. Furthermore, when the mode of inheritance of each variant allele was taken into account, five polymorphisms emerged as primary predictors for all OSCC stages: TIMP-2 ( 418C/G) OR = 26.33, 95%CI = 12.39–55.95; TNF-a ( 308G/A) OR = 15.27, 95%CI = 7.30–31.96; IL-6 ( 174G/C) OR = 8.33, 95%CI = 3.95–17.58; IL-8 ( 251A/T) OR = 3.54, 95%CI = 1.69–7.43 and IL-10 ( 1082A/G) OR = 2.65, 95%CI = 1.28– 5.46. Based on these results, an algorithm of estimated risk sum may be used for prediction of OSCC for any given combination of genotypes in the five inflammation-related genes. Conclusion: The present regression analysis of 32 studied DNA polymorphisms revealed that five of them, which influence gene expression and quantity of inflammation-related factors, strongly contribute in increasing the risk for OSCC occurrence. doi:10.1016/j.oos.2009.06.534

P3.09. Spindle cell squamous carcinoma: An in-vivo example of epithelialto mesenchymal transition L.W. Solomon a,*, M. Carlson b, T.M. DesRochers c, N. Laver b,d a

Tufts University School of Dental Medicine, United States Tufts University School of Medicine, United States c Tufts University Sackler School of Biomedical Sciences, United States d Tufts Medical Center, United States b

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Poster session III / Oral Oncology Supplement 3 (2009) 201–236