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Objectives: The expression levels of two DNA repair genes ( CHAF1A and CHAF1B) and a chromosome segregation gene ( AURKA) were susceptible to arecoline exposure, a major alkaloid of areca nut. We hypothesize that genetic variants of these genes might also be implicated in the risk of oral cancer and could be modified by substance use of betel quid or alcohol and cigarettes. Material and methods: A case-control study, which included 507 patients with oral cancer and 717 matched controls, was performed in order to evaluate the cancer susceptibility by the tagging single-nucleotide polymorphisms (tagSNPs) in AURKA, CHAF1A, and CHAF1B using a genotyping assay and gene-environment interaction analysis. Results: The Phe31Ile polymorphism (rs2273535, T91A) of AURKA was significantly associated with an increased risk of oral cancer (odds ratio (OR) = 2.1, 95 % confidence interval (CI) 1.2-3.5). The gene dosage of the 91A allele also showed a significant trend in risk of oral cancer ( P = 0.008). Furthermore, we found the AURKA 91AA homozygote was modifiable by substance use of alcohol, betel quid, and cigarettes (ABC), leading to increased risk of oral cancer in an additive or a multiplicative model (combined effect indexes = 1.2-4.0 and 1.5-2.2, respectively). However, no association was observed between the genetic variants of CHAF1A or CHAF1B and oral cancer risk in the study. Conclusion: These findings reveal the functional Phe31Ile polymorphism tagSNP of AURKA may be a strong susceptibility gene in ABC-related oral cancer occurrence. Clinical relevance: The results of this betel-related oral cancer study provide the evidence of environment-gene interaction for early prediction and molecular diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to investigate the predictive role of pretreatment metabolic volume (MTV) in pharyngeal cancer (PC) patients treated with definitive (chemo) radiotherapy. Methods: This retrospective analysis enrolled 64 patients with PC treated with (chemo) radiotherapy. All patients received pretreatment fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Four PET segmentation methods were used, namely applying an isocontour at a standardized uptake value (SUV) of either 2.5 or 3.0 (MTV2.5 and MTV3.0) or using fixed thresholds of either 40 or 50 % (MTV40 %, MTV50 %) of the maximum intratumoural FDG activity. Disease-free survival (DFS) and primary relapse-free survival (PRFS) were examined according to cutoffs of the median values for each MTV and the gross tumour volume (GTVp). Independent prognosticators were identified by Cox regression analysis. Results: With a median follow-up of 24 months, 19 patients died, and 26 patients experienced tumour relapse at primary sites. Multivariate analysis of the DFS showed that MTV2.5 > 13.6 ml was the only predictor of relapse [ p = 0.011, hazard ratio = 2.69, 95 % confidence interval (CI) 1.25-5.76]. The independent predictor for PRFS was MTV2.5 > 13.6 ml ( p = 0.003, hazard ratio = 3.76, 95 % CI 1.57-8.92), whereas GTVp > 15.5 ml had a marginal impact on PRFS ( p = 0.06, hazard ratio = 3.54, 95 % CI 0.97-11.85). Patients having tumours with MTV2.5 > 13.6 ml had a significantly inferior 2-year PRFS compared with patients who had lower MTV2.5 tumours (39 vs 72 %, respectively, p = 0.001). Conclusion: For PC patients treated with definitive (chemo)radiotherapy, pretreatment MTV2.5 volume achieved the best predictive value for primary recurrence, and the same value was also a prognosticator for DFS. [ABSTRACT FROM AUTHOR]

Background: Caveolin-1, which has been proposed as a candidate tumor suppressor, plays a regulatory role in several signaling pathways. The aim of this study was to evaluate the association between oral cancer susceptibility and Cav-1 genotypes. In this hospital-based case-control study, the association of Cav-1 polymorphisms with oral cancer risk in a central Taiwanese population was investigated. Methods: Six hundred patients with oral cancer and 620 age- and sex-matched healthy control subjects were genotyped and analyzed by polymerase chain reaction-restriction fragment length polymorphism. Results: There were significant differences between oral cancer and control groups in the distributions of their genotypes ( P = 1.7 × 10 and 2.6 × 10) and allelic frequencies ( P = 3.3 × 10 and 9.5 × 10) in the Cav-1 G14713A (rs3807987) and T29107A (rs7804372) polymorphisms, respectively. As for the combined genotype analysis, those who had GG/AT or GG/AA at Cav-1 G14713A/T29107A showed a 0.72-fold (95% confidence interval = 0.52-0.99) decreased risk of oral cancer compared to those with GG/TT, while those of any other combinations were of increased risk. The presence of metastasis was also correlated to both Cav-1 G14713A AA and Cav-1 T29107A TT genotypes. Conclusions: Cav-1 is involved in oral cancer, the A allele of the Cav-1 G14713A is risky, the A allele of the Cav-1 T29107A is protective, and AA/TT on these two polymorphisms may be the most risky combined genotype for the development of oral cancer and may be novel risk markers for early detection and prediction of distant metastasis. [ABSTRACT FROM AUTHOR]