Association of XRCC2 rs2040639 with the survival of patients with oral squamous cell carcinoma undergoing concurrent chemoradiotherapy.

OBJECTIVE: To investigate the association between the variants of DNA double-strand break repair genes and the clinical outcomes of patients with oral squamous cell carcinoma (OSCC) undergoing concurrent chemoradiotherapy. METHODS: Five variants of DNA double-strand break repair genes in samples from 319 patients with OSCC were genotyped using the Sequenom iPLEX MassARRAY system. Kaplan-Meier curves and Cox proportional hazards analysis were used to identify the factors associated with patient survival. RESULTS: The XRCC2 rs2040639 (G3063A) polymorphism in the codominant model was associated with decreased recurrence risk (hazard ratio [HR] = 0.55, 95% confidence interval [CI] = 0.31-0.98; p = 0.042). A marginally significant interaction was observed between XRCC2 rs2040639 and PRKDC rs7003908 in patients carrying the AA and AA genotypes; these patients showed reduced recurrence risk (HR = 0.36, 95% CI = 0.17-0.79; p = 0.010). CONCLUSION: The A-allele of XRCC2 rs2040639 is a favorable prognostic factor for disease-free survival. Patients with these genotypes may benefit from concurrent chemoradiotherapy. Additional confirmation from studies with larger samples or other ethnic populations is warranted.

Predictive value of genetic variants XRCC1 rs1799782, APEX1 rs1760944, and MUTYH rs3219489 for adjuvant concurrent chemoradiotherapy outcomes in oral squamous cell carcinoma patients.

Genetic variations in DNA base excision repair (BER) genes may affect tumor sensitivity to chemotherapy and radiotherapy. Thus, we investigated the effects of single-nucleotide polymorphisms (SNPs) in key BER pathway genes on clinical outcomes in male patients who received concurrent chemoradiotherapy (CCRT). Seven SNPs from XRCC1, OGG1, APEX1, and MUTYH were genotyped using the Sequenom iPLEX MassARRAY system in samples from 319 men with advanced oral squamous cell carcinoma. The disease-free survival (DFS) rates of the MUTYH rs3219489 genotypes and those of the other genotypes differed significantly (log-rank test p = 0.027). Multivariate Cox proportional hazard analysis showed that the MUTYH rs3219489 GG genotype was associated with poor DFS (recessive model: hazard ratio [HR] = 2.01, 95% confidence interval [CI] = 1.31-3.10; p = 0.002). The CT + TT genotypes of XRCC1 rs1799782 (dominant model: HR = 0.65, 95% CI = 0.43-0.99; p = 0.044) and GG genotype of APEX1 rs1760944 (recessive model: HR = 1.64, 95% CI = 1.00-2.70; p = 0.050) were associated with overall survival (OS). Carrying the two risk genotypes, CC and GG of XRCC1 rs1799782 and APEX1 rs1760944, respectively, (HR = 2.95, 95% CI = 1.47-5.88; p = 0.002) increased mortality risk. Our findings showed that carrying the two risk genotypes of XRCC1 rs1799782 and APEX1 rs1760944 was associated with poor OS, while the GG genotype of MUTYH rs3219489 was associated with poor DFS. Patients carrying the risk genotypes may not benefit from CCRT; therefore, they will need alternative treatments.

Estilos de aprendizaje de preferencia entre estudiantes de Medicina en La Gambia / Learning styles proffered by medical students in The Gambia

Introducción: En las últimas tres décadas, la proposición de que los estudiantes aprenden siguiendo diferentes estilos se ha convertido en un prominente tema en pedagogía a nivel mundial. En La Gambia no se conoce cuáles son los estilos de aprendizaje en estudiantes de Medicina. Objetivo: Caracterizar los estilos de aprendizaje de preferencia en estudiantes de la Escuela de Medicina y Ciencias Afines de la Salud en La Gambia. Métodos: Se aplicó un diseño transversal mediante el cuestionario estandarizado VARK para la recolección de datos, cuyo análisis se realizó con el uso del software SPSS. Resultados: La mayoría de los estudiantes prefirieron variantes multimodales de aprendizaje; la variante bimodal se escogió con más frecuencia. No se obtuvieron asociaciones significativas entre las puntuaciones VARK y el sexo o la edad de los estudiantes (p > 0,05). Se alcanzaron diferencias significativas para las puntuaciones kinestésicas entre estudiantes de preclínica y clínica (p = 0,031). Además, se logró una asociación significativa con relación a las variantes unimodales preferidas entre los estudiantes de preclínica y clínica. No fueron encontradas diferencias significativas en cuanto al rendimiento académico entre estudiantes con preferencias unimodales o multimodales (p > 0,05). Conclusiones: La aplicación del cuestionario VARK permitió la identificación de los estilos preferidos de aprendizaje para modos particulares de presentación de la información en estudiantes de Medicina en La Gambia. Los estilos de aprendizaje difirieron entre los estudiantes, la mayoría de los cuales tuvieron preferencia por los estilos multimodales, que incluían la variante kinestésica. Estos hallazgos pudieran emplearse para mejorar la calidad de la enseñanza(AU)

Introduction: In the last three decades, the proposition that students learn by following different styles has become a prominent topic in pedagogy worldwide. In The Gambia, learning styles in medical students are not known. Objective: To characterize the learning styles preferred by the students of the School of Medicine and Allied Health Sciences of The Gambia. Methods: A cross-sectional design was applied using the standardized VARK questionnaire for data collection, the analysis of which was performed using the SPSS software. Results: Most students preferred multimodal variants of learning; the bimodal variant was chosen more frequently. No significant associations were obtained between VARK scores and the sex or age of the students (p>0.05). Significant differences were reached for kinesthetic scores between preclinical and clinical students (p=0.031). In addition, a significant association was achieved in relation to the preferred unimodal variants among preclinical and clinical students. No significant differences were found regarding academic performance among students with unimodal or multimodal preferences (p>0.05). Conclusions: The application of the VARK questionnaire allowed the identification of preferred learning styles for particular ways of presenting information among medical students in The Gambia. Learning styles differed among students, most of whom had a preference for multimodal styles, which included the kinesthetic variant. These findings could be used to improve the quality of teaching(AU)

Polymorphisms of Mismatch Repair Pathway Genes Predict Clinical Outcomes in Oral Squamous Cell Carcinoma Patients Receiving Adjuvant Concurrent Chemoradiotherapy.

BACKGROUND: We aimed to investigate the association between single-nucleotide polymorphisms (SNP) in mismatch repair (MMR) pathway genes and survival in patients with oral squamous cell carcinoma (OSCC) who received adjuvant concurrent chemoradiotherapy (CCRT). METHODS: Using the Sequenom iPLEX MassARRAY system, five SNPs in four major MMR genes were genotyped in 319 patients with OSCC who received CCRT treatment. Kaplan-Meier survival curves and Cox proportional hazard regression models were used to assess overall survival (OS) and disease-free survival (DFS) among MMR genotypes. RESULTS: The results of Kaplan-Meier survival analysis revealed that the MutS homolog 2 (MSH2) rs3732183 polymorphism showed a borderline significant association with DFS (log-rank p = 0.089). Participants with the MSH2 rs3732183 GG genotype exhibited a relatively low risk of recurrence (hazard ratio (HR) = 0.45; 95% confidence interval (CI) = 0.22-0.96; p = 0.039). In addition, the MutL homolog 1 (MLH1) rs1800734 GG genotype carriers exhibited higher OS (HR = 0.52, 95% CI = 0.27-1.01; p = 0.054) and DFS (HR = 0.49, 95% CI = 0.26-0.92; p = 0.028) rates. CONCLUSIONS: Our results indicated that the GG genotypes of MSH2 rs3732183 and MLH1 rs1800734 are associated with relatively high survival in OSCC patients treated using adjuvant CCRT. These polymorphisms may serve as prognosis predictors in OSCC patients.

Polymorphisms in ERCC5 rs17655 and ERCC1 rs735482 Genes Associated with the Survival of Male Patients with Postoperative Oral Squamous Cell Carcinoma Treated with Adjuvant Concurrent Chemoradiotherapy.

The nucleotide excision repair (NER) pathway plays a major role in the repair of DNA damaged by exogenous agents, such as chemotherapeutic and radiotherapeutic agents. Thus, we investigated the association between key potentially functional single nucleotide polymorphisms (SNPs) in the NER pathway and clinical outcomes in oral squamous cell carcinoma (OSCC) patients treated with concurrent chemoradiotherapy (CCRT). Thirteen SNPs in five key NER genes were genotyped in 319 male OSCC patients using iPLEX MassARRAY. Cox proportional hazards models and Kaplan⁻Meier survival curves were used to estimate the risk of death or recurrence. Carriers of the XPC rs2228000 TT genotype showed a borderline significant increased risk of poor overall survival under the recessive model (hazard ratio (HR) = 1.81, 95% confidence interval (CI) = 0.99⁻3.29). The CC genotypes of ERCC5 rs17655 (HR = 1.54, 95% CI = 1.03⁻2.29) and ERCC1 rs735482 (HR = 1.65, 95% CI = 1.06⁻2.58) were associated with an increased risk of worse disease-free survival under the recessive model. In addition, participants carrying both the CC genotypes of ERCC5 rs17655 and ERCC1 rs735482 exhibited an enhanced susceptibility for recurrence (HR = 2.60, 95% CI = 1.11⁻6.09). However, no statistically significant interaction was observed between them. Our findings reveal that the ERCC5 rs17655 CC and ERCC1 rs735482 CC genotypes were associated with an increased risk of recurrence in male patients with OSCC treated with CCRT. Therefore, CCRT may not be beneficial, and alternative treatments are required for such patients.

Biomarkers of Oxidative Stress Associated with the Risk of Potentially Malignant Oral Disorders.

AIM: To investigate the effect of oxidative stress biomarkers on the risk of potentially malignant oral disorders (PMODs). MATERIALS AND METHODS: A total of 208 male adults with PMODs and an equal number of same-age control patients were enrolled. Plasma biomarkers of oxidative stress, measured with 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-ISO), were determined using enzyme-linked immunosorbent assay (ELISA) kits. PMODs were diagnosed in accordance with the World Health Organization (WHO) guidelines. RESULTS: A significant association between a high level of 8-ISO and an increased risk of PMODs was identified [odds ratio (OR)=1.71, 95% confidence interval (CI)=1.12-2.63; p=0.013]. This positive association was stronger among patients with PMOD subtype of leukoplakia (OR=1.94, 95% Cl=1.24-3.06; p=0.004). However, no significant association was observed between plasma 8-OHdG levels and overall risk of PMODs or subtypes. CONCLUSION: Increased plasma 8-ISO levels may indicate the prominence of lipid peroxidation in the development of PMODs, particularly leukoplakia.

Biomarkers of Oxidative Stress Associated with the Risk of Potentially Malignant Oral Disorders.

AIM: To investigate the effect of oxidative stress biomarkers on the risk of potentially malignant oral disorders (PMODs). MATERIALS AND METHODS: A total of 208 male adults with PMODs and an equal number of same-age control patients were enrolled. Plasma biomarkers of oxidative stress, measured with 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-ISO), were determined using enzyme-linked immunosorbent assay kits. PMODs were diagnosed in accordance with the World Health Organization (WHO) guidelines. RESULTS: A significant association between a high level of 8-ISO and an increased risk of PMODs was identified [odds ratio (OR)=1.71, 95% confidence interval (CI)=1.12-2.63; p=0.013]. This positive association was stronger among patients with PMOD subtype of leukoplakia (OR=1.94, 95% Cl=1.24-3.06; p=0.004). However, no significant association was observed between plasma 8-OHdG levels and overall risk of PMODs or subtypes. CONCLUSION: Our findings suggest that increased plasma 8-ISO levels may indicate the prominence of lipid peroxidation in the development of PMODs, particularly leukoplakia.

Associations Between MTHFR Polymorphisms and the Risk of Potentially Malignant Oral Disorders.

AIM: The study aimed to investigate the role of two polymorphisms of methylenetetrahydrofolate reductase (MTHFR), C677T and A1298C, in the risk of potentially malignant oral disorders (PMODs). MATERIALS AND METHODS: Genotypes of the MTHFR C677T and A1298C polymorphisms were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for 224 PMOD cases and 485 age-matched controls. RESULTS: The C677T T allele-carrying genotypes were significantly associated with a decreased risk of PMODs [odds ratio (OR)=0.62, 95% confidence interval (CI)=0.44-0.86]. Haplotype analysis also indicated that the 677T/1298A haplotype was associated with a decreased risk of PMODs (OR=0.56, 95%CI=0.40-0.80). No significant interaction was observed between MTHFR polymorphisms and lifestyle factors. CONCLUSION: Our findings suggest that the T-allele-carrying MTHFR C677T genotype or haplotype may reduce the risk of PMODs. However, these observations require further confirmation using larger samples.