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 ageand 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,. 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.Oral cancer is the fourth most common male cancer and the fourth leading cause of male cancer death in Taiwan, where the density of oral cancer is the top of the world (1-3). There are already several environmental factors known to contribute to the development of oral cancer, including 456 *These Authors contributed equally to this study.

Background/Aim: The clinical use of arsenic trioxide (As 2 O 3 ) is hampered due to its cardiotoxicity. Therefore, it is critical to prevent As 2 O 3 -induced loss of endothelial integrity. The purpose of this study was to examine As 2 O 3 -induced endothelial dysfunction and evaluate the efficacy of crocetin on reversing As 2 O 3 -induced cardiotoxicity. Materials and Methods: Cultured human umbilical vein endothelial cells (HUVECs) were used to examine As 2 O 3 -induced oxidative stress, apoptosis, production of reactive oxygen species (ROS) and DNA adducts. In addition, the impact of crocetin on As 2 O 3induced cardiotoxicity was evaluated. Results: As 2 O 3 decreased the viability of HUVEC cells and led to apoptosis. Additionally, As 2 O 3 elevated NADPH oxidase activity, and the levels of intracellular ROS. Furthermore, the formamidopyrimidine DNA-glycosylase-and endonuclease III-digestible adducts were induced by As 2 O 3 . Crocetin treatment reversed the As 2 O 3induced reduction in cell viability, the induction of apoptosis, the activation of NADPH oxidase activity, ROS levels and DNA adducts. Conclusion: Crocetin protects from As 2 O 3 -induced cardio-toxicity.Arsenic trioxide (As 2 O 3 ) is a very toxic agent used in Chinese medicine, which has been used to successfully treat refractory acute promyelocytic leukemia (1). The efficacy of As 2 O 3 has been reported for its capacity to induce acute promyelocytic leukemia cells to undergo apoptosis, however, its cardio-toxicity has hindered its therapeutic application (2, 3). In addition, accumulated literature has pointed that chronic exposure to As 2 O 3 from drinking water is closely associated with various human diseases, including atherosclerosis (4), diabetes mellitus (5), hypertension (6), ischemic heart disease (7, 8), peripheral vascular disease (9), and cancer (10,11). Up to date, relatively few published articles are available on the influence of acute or chronic As 2 O 3 exposure on the vascular endothelial system. At the same time, the identification of potential traditional Chinese medicine for the prevention of the diseases associated with chronic exposure to As 2 O 3 is of great interest. Εndothelial cells, human umbilical vein endothelial cells (HUVEC) are frequently used as the cell model, are the main targets of vasculopathy caused by As 2 O 3 exposure. As 2 O 3 has been reported to cause oxidative stress, and induce endothelial cells to undergo programmed cell death (12). Oxidative stress and its intracellular consequences are believed to be the major cause of As 2 O 3 cytotoxicity (13).Crocetin (C 20 H 24 O 4 ; molecular weight 328.4g/mol) is a primary constituent of saffron (Crocus sativus L), which has been known to possess lots of beneficial pharmacological effects, such as anti-inflammatory ( 14) and anti-apoptotic (15, 16). Crocetin has also been reported to effectively eliminate ischemia-reperfusion-induced oxidative damage in rats and scavenge free radicals (17). More interesting, crocetin has beneficial cardiovascular effects, su...

Background/Aim: The over-expression of enhancer of zeste homolog 2 (EZH2) protein is found in oral cancer tissues. However, the genetic role of the enhancer of EZH2 in the etiology of oral cancer is unknown. The aim of this study was to evaluate the association of EZH2 genotypes with oral cancer risk among Taiwanese. Materials and Methods: Three polymorphic variants of EZH2, rs887569 (C to T), rs41277434 (A to C), and rs3757441 (T to C), were analyzed regarding their association with oral cancer risk among 958 oral cancer patients and the same number of healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, the interaction of EZH2 rs887569, rs41277434, and rs3757441 genotypes with personal behaviors such as smoking, alcohol drinking, and betel quid chewing were also examined.Results: The EZH2 genotypes rs887569, rs41277434, and rs3757441, were not significantly associated with oral cancer risk (p for trend=0. 1735, 0.5658, and 0.4606, respectively). The analysis of allelic frequency distribution also supported the findings that the variant alleles at EZH2 rs887569, rs41277434, and rs3757441 may not serve as determinants of oral cancer risk (all p>0.05). There was no interaction between EZH2 rs887569, rs41277434, or rs3757441 genotypes with personal smoking, alcohol drinking or betel quid chewing behaviors. Conclusion: EZH2 genotypes cannot predict oral cancer risk in Taiwan.Worldwide, oral cancer is ranked sixth among common cancers and has the incidence in Taiwan (1, 2). It has been reported that cancer of the oral cavity and oropharynx represented more than 475,000 newly diagnosed cases all of the world in 2020 (3, 4). In addition to environmental factors, such as tobacco smoking, alcohol drinking, betel quid chewing, and virus infection (5), genetic factors have been suggested to affect an individual's risk for oral cancer (6-13). Although the development of modern facilities is rapid and health care of cancer has been greatly improved in recent years, more than 450,000 patients worldwide are diagnosed with oral cancer annually, and oral cancer maintains a fiveyear survival rate of under 50% (14, 15). The fact that the newly diagnosed cases of oral cancer have been increasing for at least three decades has urged genomic scientists to find more practical and feasible markers for early detection of oral cancer to help decrease its incidence (16).Human enhancer of zeste homolog 2 (EZH2) gene is located on the long arm of chromosome 7 at 7q35, contains 2669

Background/Aim: Flap endonuclease 1 (FEN1) is a critical protein in DNA repair, genomic stability, and carcinogenesis. Functional polymorphisms in FEN1 promoter -69G>A (rs174538) and 3'UTR 4150G>T (rs4246215), have been associated with the susceptibility to several cancers, including lung, breast, esophageal, gastric, liver, colorectal, and gallbladder cancer, as well as glioma, endometriosis, and leukemia. However, the contribution of FEN1 variant genotypes to oral cancer has never been examined. Thus, we aimed to evaluate the contribution of FEN1 rs174538 and rs4246215 genotypes to oral cancer risk in Taiwan. Materials and Methods: The contribution of FEN1 genotypes to oral cancer risk was examined in 958 oral cancer patients and 958 age-and sex-matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The percentages of GG, AG, and AA genotypes at FEN1 rs174538 were 34.8%, 46.0%, and 19.2% among oral cancer patients and 37.8%, 45.2%, and 17.0% among healthy controls (p for trend=0.2788). The genotypic percentages of FEN1 rs4246215 were 35.9%, 45.9%, and 18.2% among oral cancer patients and 37.6%, 45.1%, and 17.3% among healthy controls (p for trend=0.7315). Overall, FEN1 rs174538 and rs4246215 were not differently distributed between the oral cancer patient and healthy control groups. The allele frequency analysis confirmed that FEN1 rs174538 and rs4246215 were non-differentially distributed among case and control groups (OR=1.11 and 1.05, 95%CI=0.98-1.27 and 0.93-1.20, p=0.1074 and 0.4491, respectively). Conclusion: FEN1 may contribute to oral cancer risk determination via protein expression and/or post-transcription modification, but may not be a practical genetic marker.Oral cancer is the fourth most prevalent and the fourth deathcausing cancer among males in Taiwan, where the incidence density of oral cancer is higher worldwide (1-3). In literature, several factors are revealed to contribute to the etiology of oral cancer in Taiwan, such as betel quid chewing, tobacco smoking, alcohol drinking, bad tooth brushing habits, and virus infection (4, 5). Interestingly, in recent years, specific inherited genotypes have been reported to contribute to personal oral cancer susceptibility (6-13). A better understanding of genomic, environmental and behavioral factors can contribute to precise and personalized oral cancer prediction and therapy.

Defects in the non-homologous end-joining (NHEJ) DNA repair pathway lead to genomic instability and carcinogenesis. However, the roles of individual NHEJ genes in nasopharyngeal carcinoma (NPC) etiology are not well-understood. The aim of this study was to assess the contribution of NHEJ genotypes, including XRCC4 (rs6869366, rs3734091, rs28360071, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and Ligase4 rs1805388, to NPC risk, with 208 NPC patients and 416 controls. Genotype–phenotype correlations were also investigated by measuring mRNA and protein expression in adjacent normal tissues and assessing the NHEJ repair capacity in blood lymphocytes from 43 NPC patients. The results showed significant differences in the distributions of variant genotypes at XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 between the cases and controls. The variant genotypes of these three polymorphisms were associated with significantly increased NPC risks. NPC patients with the risk genotypes at XRCC6 rs2267437 had significantly reduced expression levels of both mRNA and protein, as well as a lower NHEJ repair capacity, than those with the wild-type genotype. In conclusion, XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 in the NHEJ pathway were associated with NPC susceptibility. XRCC6 rs2267437 can modulate mRNA and protein expression and the NHEJ repair capacity.