Association of polymorphisms in genes related to cell cycle (ERP29, LEF1, MCC and PTCH1) and DNA transcription factors (IKBKAP and ZNF415) with base of tongue squamous cell carcinoma risk.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6073-6073
Author(s):  
Carmen Silvia Passos Lima ◽  
Benilton Carvalho ◽  
Renata Pellegrino ◽  
Leticia Khater ◽  
Carlos Takahiro Chone ◽  
...  

6073 Background: Recently, we found 6.609 genetic single nucleotide polymorphisms (SNPs) with distinct frequencies between base of tongue squamous cell carcinoma (BTSCC) patients and controls. The study was performed using high-resolution DNA microarrays genotyping (Affymetrix). The SNPs identified never have been previously described with BTSCC risk. Some SNPs of interest were located in genes related to cell cycle (ERP29, LEF1, MCC and PTCH1) and DNA transcription (IKBKAP and ZNF415) and they were selected to validation process. Objective: Validate the SNPs ERP29 c.*293A>G (rs7114); LEF1 c.*1213A>G (rs2107028) and g.127267A>G (rs4245926); MCC c.*5077A>G (rs7033); PTCH1 g.27369025G>A (rs16909856) and g.27369324G>A (rs16909859); IKBKAP c.3214T>A (rs3204145) and ZNF415 c.*443A>G (rs3814) associated to BTSCC risk. Methods: Genomic DNA from 49 BTSCC patients and 49 controls was genotyping by TaqMan assays (Applied Biosystems). The differences between groups were analyzed by logistic regression model. Power analysis (PA) was used to verify the effect of sample size on the results obtained. Results: Eight SNPs identified by Affymetrix were validated by TaqMan assays. The frequencies of ERP29 c.*293AG+GG (30 vs 11%, P=0.03; PA=65%), LEF1 c.*1213AA+AG (95 vs 80%, P=0.02; PA=61%) and g.127267AA+AG (93 vs 78%, P=0.02; PA=56%), MCC c.*5077AA+AG (85 vs 64%, P=0.008; PA=67%), PTCH1 g.27369025GG+GA (90 vs 73%, P=0.005; PA=58%) and g.27369324GG+GA (90 vs 73%, P=0.008; PA=58%), IKBKAP c.3214TT+TA (90 vs 72%, P=0.01; PA=62%) and ZNF415 c.*443AA+AG (59 vs 41%, P=0.02; PA=43%) were more common in patients than in controls. Individuals with these genotypes were at 2.9(CI95%: 1.1-8.4), 3.9 (CI95%: 1.4-11.2), 4.0 (CI95%: 1.2-14.7), 3.5 (CI95%: 1.2-11.9), 5.0 (CI95%: 1.7-16.9), 4.5 (CI95%: 1.5-15.2), 4.1 (CI95%: 1.4-12.9), and 3.9 (CI95%: 1.2-13.7)-fold increased risks for BTSCC than others, respectively. Conclusions: Our data present for the first time evidence that inherited abnormalities in ERP29, MCC, LEF1, PTCH1, IKBKAP, and ZNF415 genes may be important determinants of BTSCC. Financial support: FAPESP and FINEP.

2015 ◽  
Vol 12 (3) ◽  
pp. 3958-3964 ◽  
Author(s):  
WEI REN ◽  
PANFENG LIAN ◽  
LONG CHENG ◽  
PEIYUN DU ◽  
XIN GUAN ◽  
...  

2017 ◽  
Vol 127 (7) ◽  
pp. 1589-1594 ◽  
Author(s):  
Kaitlin Christopherson ◽  
Christopher G. Morris ◽  
Jessica M. Kirwan ◽  
Robert J. Amdur ◽  
Peter T. Dziegielewski ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16041-e16041
Author(s):  
Carmen Silvia Passos Lima ◽  
Benilton Carvalho ◽  
Renata Pellegrino ◽  
Leticia Khater ◽  
Carlos Takahiro Chone ◽  
...  

e16041 Background: Inherited genetic alterations, such as single nucleotide polymorphisms (SNPs), were described in association with oropharyngeal cancer risk in few reports with restrict number of SNPs analyzed. Base of tongue (BT) squamous cell carcinoma (SCC) is a common tumor of oropharynx; however, the association of SNPs and BTSCC risk is not clarified and, therefore, this was the aim of this study. Methods: DNA from 49 BTSCC patients and 49 controls was extracted using the QIamp kit (Qiagen). Each sample was genotyped individually using DNA high-resolution microarrays containing 500.568 SNPs (SNP array 5.0, Affymetrix). Further sample processing, including digestion, adaptor ligation, amplification, fragmentation, labeling, hybridization, washing and scanning was assayed according to the standard protocol. Genotype data were acquired by genotyping calling of samples using crlmm algorithm provided by Bioconductor software. The differences between groups were analyzed by the logistic regression model. The SNPs localized in genes of interest were selected by data base analysis in DAVID and NCBI websites. The validation of selected SNPs was performed by RT-PCR, using TaqMan SNP Genotyping Assays (Applied Biosystems) in all samples studied. Results: We observed 6.609 SNPs with distinct frequencies between BTSCC patients and controls. Fifty-two SNPs (0.8%) were located in coding sequence (CDS), 51 (0.8%) in 3’ and 5’- untranslated regions (UTR), 3.461 (52.4%) in up or downstream regions (DWS) and 3.045 (46.0%) in introns. Ten SNPs were selected and validated in study, including those localized in genes related to cell cycle (3’-UTR: ERP29, rs7114; MCC, rs7033; DWS: LEF1, rs2107028 and rs4245926; PTCH1, rs16909856 and rs16909859), transcription process (CDS: IKBKAP, rs3204145; 3’-UTR: ZNF415, rs3814), and cell adhesion (CDS: COL22A1, rs2292927; DWS: LY6K, rs1995467). Conclusions: Our preliminary results suggest that SNPs in genes involved in tumor development may predispose individuals to BTSCC. However, these results should be confirmed by functional protein studies and validated in larger epidemiological studies. Financial support: FAPESP and FINEP.


2021 ◽  
Author(s):  
Jiamin Ding ◽  
Zuoliang Chen ◽  
Wanlu Chen ◽  
Zhongxiong Ma ◽  
Yunde Xie ◽  
...  

Abstract Background: Qilan preparation, a complex Chinese herbal medicine consisting of ingredients extracted from Radix Astragali, Gynostemma Pentaphyllum, Rhizoma Chuanxiong and selenium- rich green tea and known for ‘fortifying the spleen and boosting qi, quickening the blood and transforming stasis, and resolving toxins and relieving pain, is used for the prevention and management of oral diseases. The aim of this study was to examine the antitumor effects of Qilan preparation on oral squamous cell carcinoma (OSCC) in vitro and to explore its underlying mechanisms of action. Methods: Human Tca8113 tongue squamous cell carcinoma (TSCC) cells were tested. Cell proliferation, cell cycle distribution and apoptosis were examined using cell counting kit-8 (CCK8) and flow cytometry (FCM). The expression of PTEN and PDCD4 were determined by western blot. Changes in miR-21 levels were quantified using TaqMan stem-loop real-time PCR. After miR-21 was transiently transfected into Tca8113 cells using Lipofectamine®3000, cell proliferation, apoptosis and miR-21 and PDCD4 expression levels were measured.Results: Qilan preparation inhibited Tca8113 cell growth in a dose- and time-dependent manner by inducing apoptosis and cell cycle arrest in S-phase, decreasing miR-21 levels and increasing PTEN and PDCD4 expression. MiR-21 overexpression reversed the Qilan preparation-induced suppression of cell proliferation and induction of apoptosis while also blocking the increase in PDCD4.Conclusions: Our study revealed, for the first time, the ability of Qilan preparation to suppress TSCC cell growth and elucidated that Qilan preparation elicits its anti-cancer actions via either the miR-21/PDCD4 or PTEN pathway.


2002 ◽  
Vol 128 (9) ◽  
pp. 1067 ◽  
Author(s):  
Babak Azizzadeh ◽  
Pedram Enayati ◽  
Dinesh Chhetri ◽  
Ellie Maghami ◽  
Babak Larian ◽  
...  

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