RESUMO
BACKGROUND/AIM: Programmed cell death 6 (PDCD6) is up-regulated and highly expressed in early apoptotic cells. In several types of cancer, such as cervical, breast and lung cancers, the association of PDCD6 genotypes have been investigated. However, the contribution of PDCD6 variant genotypes to oral cancer has never been examined. The current study aimed to evaluate the contribution of the PDCD6 rs4957014 and rs3756712 genotypes to the risk of oral cancer in Taiwan. PATIENTS AND METHODS: The contribution of PDCD6 genotypes to oral cancer risk was examined among 958 patients with lung cancer and 958 age- and sex-matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP). RESULTS: The data showed that the hetero-variant GT and homo-variant GG genotypes of PDCD6 rs4957014 were associated with a decreased risk of oral cancer [odds ratio (OR)=0.81 and 0.39, 95% confidence interval (CI)=0.67-0.97 and 0.27-0.56, respectively]. The recessive and dominant models also showed that G carriers have protective effects (OR=0.43 and 0.72, 95% CI=0.30-0.61 and 0.61-0.87, respectively). The analysis of allelic frequency distributions showed that the G allele of PDCD6 rs4957014 was associated with reduced oral cancer risk (OR=0.71, 95% CI=0.62-0.82). There was no significant association between any PDCD6 rs3756712 genotype and oral cancer risk. In addition, the GG genotype at PDCD6 rs4957014 significantly decreased the risk of oral cancer among both males (adjusted OR=0.31, 95%CI=0.24-0.56) and females (adjusted OR=0.44, 95% CI=0.22-0.91). Furthermore, the GG genotype at PDCD6 rs4957014 significantly decreased the risk of oral cancer among smokers (adjusted OR=0.35, 95% CI=0.22-0.58), alcohol drinkers (adjusted OR=0.33, 95% CI=0.18-0.49), non-betel quid chewers (adjusted OR=0.33, 95% CI=0.17- 0.81), betel quid chewers (adjusted OR=0.34, 95% CI=0.21- 0.59), but not among never-smokers and non-alcohol drinkers. CONCLUSION: The G allele carriers of PDCD6 rs4957014 may have protective effects on oral cancer risk and serve as a practical marker for early detection of oral cancer in Taiwan.
Assuntos
Proteínas Reguladoras de Apoptose , Proteínas de Ligação ao Cálcio , Neoplasias Bucais , Proteínas Reguladoras de Apoptose/genética , Proteínas de Ligação ao Cálcio/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , TaiwanRESUMO
BACKGROUND/AIM: Accumulating evidence shows that caspase-8 (Cas-8) rs3834129 genotypes determine susceptibility to various cancers, but their association with nasopharyngeal carcinoma (NPC) has not been examined. We aimed at investigating the association of Cas-8 rs3834129 with NPC risk. MATERIALS AND METHODS: Cas-8 rs3834129 genotypes and their associations with NPC risk were investigated among 176 NPC patients and 352 non-cancer subjects by the PCR-RFLP method. Additionally, the interaction of Cas-8 rs3834129 genotypes with smoking was examined. RESULTS: The II, ID and DD frequencies were 56.8, 36.9 and 6.3% among NPC patients and 54.8, 38.1 and 7.1% among control subjects (ptrend=0.8830). Allelic frequency distribution analysis also indicated that the D allele is not a risk factor for NPC (p=0.6183). There was no interaction between Cas-8 rs3834129 and smoking and NPC risk (p=0.8305). CONCLUSION: Cas-8 rs3834129 genotypes play a minor role in the risk for NPC.
Assuntos
Caspase 8/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Carcinoma Nasofaríngeo/genética , Alelos , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/epidemiologia , Carcinoma Nasofaríngeo/patologia , Polimorfismo de Fragmento de Restrição/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Fatores de Risco , Fumar , TaiwanRESUMO
Pipoxolan HCl (5,5-diphenyl-2-(2'-piperidino-ethyl)-1,3-dioxolane-4-one hydrochloride) is a compound containing a dioxolan moiety that was reported to induce apoptosis in cancer cells. In this study, we investigated the anti-leukemia effects of pipoxolan on U937 leukemia cells both in vivo and in vitro. Cell viability, reactive oxygen species (ROS) production, mitochondrial membrane potential, apoptosis and caspases-9 and -3 activity were examined following treatment of U937 leukemia cells with 10 µM pipoxolan by flow cytometry and caspase-activity assay. The apoptosis-associated Bcl-2 family proteins, Bax, Bcl-2 and Bcl-xL, were examined by Western blotting. We found that pipoxolan inhibited U937 cell proliferation in a dose- and time-dependent manner. Morphological assessment and cell cycle analysis indicated that pipoxolan induced the apoptosis of the U937 cells. Pipoxolan (10 µM) increased ROS production and decreased mitochondrial membrane potential 1 h after pipoxolan treatment. Pre-treatment of pipoxolan-treated cells with N-acetyl-L-cysteine (a ROS chelator) inhibited the increase in ROS production. After treatment with 10 µM pipoxolan for 24 h, there was an increase in pro-apoptotic Bax and a decrease in anti-apoptotic Bcl-2 and Bcl-xL proteins. In vivo, we found that pipoxolan significantly suppressed tumor growth in BALB/cnu-/nu- mice inoculated with U937 cells. Taken together, the data from our studies indicate that pipoxolan possesses potent anti-leukemia activity and is a potential novel alternative cancer therapeutic agent for human leukemia.
