1
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 stan- dard procedures. Fifteen-twenty five metaphases were analyzed. Results: Twenty five tumors were analysed: 8 malignant (4 squa- mous cell carcinoma, 1 Merkell cell carcinoma, 1 Ewing sarcoma, 1 rhabomyosarcoma and 1 myofibrosarcoma) and 17 benign (1 kerato- cyst, 3 pleomorphic adenoma, 2 central giant cell granuloma, 2 sol- itary 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 granu- loma, ameloblastoma, hemangiopericytoma and solitary fibrous tumor showed abnormal clones with either few or multiple chromo- somal changes. The cytogenetic differences between malignant and benign tumors and its significance will be discussed. Conclusions: Cytogenetic analysis is recommended as a comple- mentary 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 Univer- sity, Taichung, Taiwan, ROC Alpha B-Crystallin (CRYAB) is an extremely stable protein func- tions as ‘‘molecular chaperone” in preservation intracellular archi- tecture, cell membrane and highly antiapoptotic. Lack or lower CRYAB expression is a prognostic biomarker for head and neck can- cer, while its genomic variations and the association with carcino- genesis 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 Tai- wanese 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 geno- types, between the oral cancer and control groups. The G allele CRY- AB 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). 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 polymor- phisms 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 Euro- pean population. Methods: Functional DNA polymorphisms in 32 genes that en- code 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 be- tween the two groups. A series of multivariate logistic regression models (adjusted for age and gender) was constructed in order to as- sess the contribution of homozygous or heterozygous variant poly- morphic 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 ac- count, 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 b Tufts University School of Medicine, United States c Tufts University Sackler School of Biomedical Sciences, United States d Tufts Medical Center, United States Poster session III / Oral Oncology Supplement 3 (2009) 201–236 203 Committee Listings Welcome IAOO Program Keynote Bios. Keynote Abs. Pan. Disc. & Symp. Abs. Orals List Poster List Oral Abstracts Poster Abstracts

P3.07. The association of Alpha B-Crystallin polymorphisms with oralcancer susceptibility in Taiwan

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Page 1: P3.07. The association of Alpha B-Crystallin polymorphisms with oralcancer susceptibility in Taiwan

Cytogenetic analysis is an important diagnostic and prognostictool 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 stan-dard procedures. Fifteen-twenty five metaphases were analyzed.

Results: Twenty five tumors were analysed: 8 malignant (4 squa-mous cell carcinoma, 1 Merkell cell carcinoma, 1 Ewing sarcoma, 1rhabomyosarcoma and 1 myofibrosarcoma) and 17 benign (1 kerato-cyst, 3 pleomorphic adenoma, 2 central giant cell granuloma, 2 sol-itary fibrous tumor, 1 granular cell tumor, 1 angiomyoma,1 fibroma,3 lipoma, 1 intraosseous schwannoma, 1 hemangiopericytoma and 1ameloblastoma).

Among the malignant tumors, the squamous cell carcinoma andmyofibrosarcoma showed normal karyotype, while the Merkel cellcarcinoma, Ewing sarcoma and rhabdomyosarcoma showed multipleand complex chromosomal changes. Among the benign tumors,pleomorphic adenoma, lipoma, fibroma, central giant cell granu-loma, ameloblastoma, hemangiopericytoma and solitary fibroustumor showed abnormal clones with either few or multiple chromo-somal changes.

The cytogenetic differences between malignant and benigntumors and its significance will be discussed.

Conclusions: Cytogenetic analysis is recommended as a comple-mentary diagnostic and prognostic tool in oral tumors. It canstrengthen our understanding of the tumorogenesis process of theselesions.

doi:10.1016/j.oos.2009.06.532

P3.07. The association of Alpha B-Crystallin polymorphisms withoralcancer susceptibility in TaiwanC.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 UniversityHospital, Taiwanb Department of Biochemistry, School of Medicine, China MedicalUniversity, Taiwanc Department of Biological Science and Technology, China MedicalUniversity, Taiwand Graduate Institute of Chinese Medical Science, China Medical Univer-sity, Taichung, Taiwan, ROC

Alpha B-Crystallin (CRYAB) is an extremely stable protein func-tions as ‘‘molecular chaperone” in preservation intracellular archi-tecture, cell membrane and highly antiapoptotic. Lack or lowerCRYAB expression is a prognostic biomarker for head and neck can-cer, while its genomic variations and the association with carcino-genesis are not well studied. Therefore, we hypothesized thatsingle nucleotide polymorphisms (SNPs) in CRYAB may be associatedwith risk of oral cancer. In this hospital-based study, the associationof CRYAB A-1215G (rs2228387), C-802G (rs14133) and intron2(rs2070894) polymorphisms with oral cancer risk in a central Tai-wanese population was investigated. In total, 496 patients with oralcancer and 496 age- and gender-matched healthy controls recruitedfrom the China Medical Hospital in central Taiwan were genotyped.A significantly different distribution was found in the frequency ofthe CRYAB C-802G genotype, but not in A-1215G and intron2 geno-types, between the oral cancer and control groups. The G allele CRY-AB C-802G conferred a significant (P = 0.000142) increased risk oforal cancer. Patients carrying CG or GG of their CRYAB C-802G werealso of lower 5-year survival and higher metastasis rates (P < 0.05).

Our results provide the first evidence that the G allele of the CRYABC-802G may be associated with the development of oral cancer andmay be a novel useful marker for oral cancer detection anddiagnosis.

doi:10.1016/j.oos.2009.06.533

P3.08. Gene expression polymorphisms of inflammation-relatedfactors are associated with risk for oral squamous cell carcinomain EuropeansC. Yapijakis *, D. Avgoustidis, Z. Serefoglou, A. Vylliotis, S.Spyridonidou, E. Critselis

University of Athens, GreeceUniversity of Erlangen, Germany

Introduction: Recent genetic association studies performed byour group and others have indicated that functional DNA polymor-phisms in genes of factors related to inflammation, angiogenesisand thrombosis are associated with increased risk for oral squamouscell carcinoma (OSCC). Here we present the combinatory effect ofgene polymorphisms using multivariate logistic regression analysisin an attempt to predict the occurrence of OSCC in the studied Euro-pean population.

Methods: Functional DNA polymorphisms in 32 genes that en-code cytokines and their receptors, matrix metalloproteinases andtheir inhibitors, platelet glycoproteins and coagulation factors wereinvestigated in blood DNA samples isolated from 330 Europeans(Greeks and Germans). They included a group of 162 OSCC patientsand a group of 168 healthy controls with comparable age, gender,and ethnicity. Detected genotype distributions were compared be-tween the two groups. A series of multivariate logistic regressionmodels (adjusted for age and gender) was constructed in order to as-sess the contribution of homozygous or heterozygous variant poly-morphic genotypes upon overall, early and advanced stages ofOSCC development.

Results: In all regression models, the contribution of TNF-a andIL-6 polymorphisms was consistently significant. Furthermore, whenthe mode of inheritance of each variant allele was taken into ac-count, five polymorphisms emerged as primary predictors for allOSCC 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 summay be used for prediction of OSCC for any given combination ofgenotypes in the five inflammation-related genes.

Conclusion: The present regression analysis of 32 studied DNApolymorphisms revealed that five of them, which influence geneexpression and quantity of inflammation-related factors, stronglycontribute 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 ofepithelialto mesenchymal transitionL.W. Solomon a,*, M. Carlson b, T.M. DesRochers c, N. Laver b,d

a Tufts University School of Dental Medicine, United Statesb Tufts University School of Medicine, United Statesc Tufts University Sackler School of Biomedical Sciences, United Statesd Tufts Medical Center, United States

Poster session III / Oral Oncology Supplement 3 (2009) 201–236 203

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