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Flap endonuclease 1 (FEN1) is a critical protein in DNA repair, genomic stability, and carcinogenesis. Functional polymorphisms in FEN1 promoter -69GA (rs174538) and 3'UTR 4150GT (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.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).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).FEN1 may contribute to oral cancer risk determination via protein expression and/or post-transcription modification, but may not be a practical genetic marker.

The elevated expression of interleukin-18 (IL-18) among lung cancer patients raised our curiosity to examine the role of IL-18 genotypes in lung cancer.IL-18 -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 358 lung cancer cases and 716 controls were determined via the PCR-RFLP methodology.The distributions of genotypic and allelic frequencies of IL-18 -607, but not those of -656 or -137, were differentially distributed between cases and controls. IL-18 -607 AC and CC genotypes were both lower (45.8% and 16.2%) in lung cancer patients compared to controls (51.4% and 24.7%). In addition, IL-18 -607 AC and CC genotypes were of significantly lower percentages both among non-smokers and smokers. Otherwise, no differential distribution was found regarding IL-18 -656 or -137.IL-18 -607 C allele can serve as a protective predictor for lung cancer risk in Taiwanese.

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.

This cross-sectional study assessed the moderating effects of self-esteem and perceived support from friends on the association between self-stigma and suicide risk in individuals with schizophrenia. We included 300 participants (267 with schizophrenia and 33 with schizoaffective disorder). Suicide risk was assessed using items adopted from the suicide module of the Mini-International Neuropsychiatric Interview; self-stigma was assessed using the Self-Stigma Scale–Short; perceived support from friends was assessed using the Friend Adaptation, Partnership, Growth, Affection, and Resolve Index; and self-esteem was assessed using the Rosenberg Self-Esteem Scale. A moderation analysis was performed to examine the moderating effects of self-esteem and perceived support from friends on the association between self-stigma and suicide risk. The results indicated that self-stigma was positively associated with suicide risk after the effects of other factors were controlled for. Both perceived support from friends and self-esteem significantly reduced the magnitude of suicide risk in participants with self-stigma. Our findings highlight the value of interventions geared toward ameliorating self-stigma and enhancing self-esteem in order to reduce suicide risk in individuals with schizophrenia.

Asthma is a chronic airway inflammation disease and the diagnosis and treatment strategies remain difficult. MicroRNAs play important roles in many biological and pathological processes including asthma development. There is no study confirming the contribution of genetic variants in miR-145 to asthma etiology. We hypothesize that single nucleotide polymorphisms (SNPs) in the promoter region of miR-145 may be associated with the risk of asthma in Taiwanese. We used a case–control study to test this hypothesis. In 198 asthma patients and 453 healthy controls, the genotypes of miR-145 rs4705342 and rs4705343 were determined, and the associations of miR-145 genotypes with asthma risk and severity were evaluated. The distribution of miR-145 rs4705342 genotypes between asthma patients and non-asthmatic control groups were significantly different (p = 0.0187). In multivariable logistic regression analysis, compared with the wild-type TT genotype, individuals carrying the variant genotypes had progressively decreased risks of asthma: the odds ratio (OR) for the heterogeneous variant genotype (CT) and homozygous variant genotype (CC) was 0.77 (95% CI 0.55–1.10, p = 0.1788) and 0.41 (95% CI 0.21–0.79, p = 0.0102), respectively (p for trend = 0.0187). In allelic test, the C allele was associated with a 31% reduced risk of asthma (OR = 0.69, 95% CI 0.53–0.90, p = 0.0070). In addition, the rs4705342 variant genotypes were correlated with the symptom severity (p = 3 × 10–5). Furthermore, the variant genotypes correlated with lower miR-145-5p expression level in serum (p = 0.0001). As for rs4705343, there was no differential distribution of genotypes between cases and controls. Our data provide evidence for miR-145 rs4705342 to serve as a novel biomarker for asthma risk prediction.

Background: The role of epigenetic alterations in the pathogenesis of retinal degenerative diseases, such as macular degeneration is not well established. This study aimed to evaluate whether treatments with gamma-mangostin can rescue the hydrogen peroxide (H(2)O(2))-induced cytotoxicity in human retinal pigment epithelial (ARPE-19) cells. Materials and Methods: ARPE-19 cells were treated with H(2)O(2) alone or with gamma-mangostin plus H(2)O(2) to investigate changes relating to cell viability, appearance of sub-G1 cells, antioxidant enzymes, and apoptotic-related proteins. Results: The data showed that under H(2)O(2) treatment of 400 μM, there was a significant decrease in cell viability and enhanced apoptosis, together with an increased expression of Bax, Bad, cleaved-caspase-3, -8, and -9 at the protein level. On the contrary, the protein expression levels of Bcl2 and Bcl-xl were decreased. Gamma-mangostin pre-treatments (2-16 μM) could effectively prevent all alterations. Conclusion: Gamma-mangostin may conduct its eye-protective effects against H(2)O(2)-induced oxidative damage via anti-apoptotic and antioxidant mechanisms in ARPE-19 cells.

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.

Background/aim Xeroderma pigmentosum complementation group C (XPC) is reported to play important roles in DNA integrity and genomic instability, however, the contribution of XPC to oral carcinogenesis is largely uncertain. Therefore, we aimed at examining the contribution of XPC genotypes to oral cancer. Materials and methods The genotypes of XPC rs2228001 and rs2228000 were examined among 958 oral cancer patients and 958 control subjects by polymerase chain reaction-restriction fragment length polymorphism methodology and corresponding DNA repair capacity was checked. Results First, the percentages of XPC rs2228001 AC and CC were higher among oral cancer patients than controls. Second, no significant association was observed regarding XPC rs2228000. Third, there was a synergistic influence of smoking and betel quid chewing behaviors and XPC rs2228001 genotype on oral cancer risk. Last, functional experiments showed DNA repair capacity was lower for AC/CC carriers than AA carriers. Conclusion XPC rs2228001 C allele, which was associated with decreased DNA repair capacity, may interact with smoking and betel quid chewing behaviors on oral cancer risk.

Triple negative breast cancer (TNBC) is one of the most challenging breast cancer types. Interleukin-8 (IL-8) is a pro-tumorigenic cytokine, promoting tumor proliferation and migration. This study aimed to examine the contribution of IL-8 rs4073 genotypes to breast cancer risk and provide a summary of related literature.IL-8 genotypic profiles were determined among 1,232 breast cancer cases and 1,232 controls via polymerase chain reaction-restriction fragment length polymorphism methodology.The IL-8 rs4073 AT and AA genotypes had significantly lower prevalence in the case group compared to control group. Allelic frequency analysis showed that individuals carrying the A allele have relatively decreased risk for breast cancer. The stratification analysis showed that IL-8 rs4073 genotypes were protective markers for those with younger (≤55) age.IL-8 rs4073 A allele is a novel predictor for breast cancer, especially TNBC.

BACKGROUND/AIM Oral cancer incidence is highest worldwide in Taiwan, and practical markers for personalized therapeutic strategies such as immunotherapies, is lacking. Interleukin-12 (IL12) is a cytokine that is reported to exhibit potent tumoricidal effects, however, its genotypic contribution to oral cancer is still largely unknown. We aimed to examine whether IL12A rs568408 and rs2243115 genotypes are associated with oral cancer risk in Taiwan. MATERIALS AND METHODS Genotypic characteristics of IL12A were determined among 958 oral cancer cases and age- and gender-matched individuals via typical polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS The variant genotypes of IL12A rs568408 and rs2243115 were not found to be significantly associated with elevated oral cancer risk (all p>0.05). Moreover, there was no interaction between IL12A genotypes and personal smoking, alcohol drinking and betel quid chewing behaviors (all p>0.05). CONCLUSION IL12A rs568408 and rs2243115 genotypes may not serve as good predictors for oral cancer risk.

Background/aim We aimed to examine the association of the genotypes of Nijmegen breakage syndrome 1 (NBS1), a critical gene in DNA double strand break repair machinery, with bladder cancer risk in Taiwan. Materials and methods NBS1 rs1805794 genotypes among 375 bladder cancer patients and 375 non-cancer healthy controls were determined via the polymerase chain reaction-restriction fragment length polymorphism methodology and their association with bladder cancer risk were evaluated. Results The results showed that the percentages of GG, CG and CC of NBS1 rs1805794 genotypes were 45.4%, 43.7% and 10.9% in the bladder cancer patient group and 47.2%, 43.2% and 9.6% in the non-cancer control group, respectively (p for trend=0.7873). The analysis of allelic frequency distributions showed that the variant C allele of NBS1 rs1805794 does not contribute to an increased bladder cancer susceptibility (p=0.5066). Conclusion The genotypes of NBS1 rs1805794 are not closely associated with personal susceptibility to bladder cancer.

Background/aim The present study aimed at evaluating the contribution of IL-4 promoter T-1099G (rs2243248), C-589T (rs2243250), C-33T (rs2070874) genotypes to the risk of breast cancer in Taiwanese. Materials and methods A total of 1232 breast cancer patients and 1232 age-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Results Genotypic frequencies of IL-4 rs2243248, rs2243250 and rs2070874 were not differentially distributed between case and control groups. Consistently, there was no difference in the distribution of allelic frequencies among patients and controls. Conclusion IL-4 rs2243248, rs2243250 and rs2070874 do not confer breast cancer susceptibility in Taiwanese.

Background/Aim: In literature, few studies have examined the diagnostic or prognostic potential of matrix metalloproteinases (MMP) in pterygium, whose formation and progression are closely related to imbalance in the extracellular microenvironment. In this study, we investigated the contribution of MMP7 promoter (A-181G and C-153T) polymorphic genotypes to pterygium risk. Materials and Methods: A total of 134 cases and 268 controls were collected and their MMP7 genotypes at A-181G and C-153T were examined by polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The AA, AG and GG genotypes at MMP7 promoter A-181G were non-significantly differentially distributed between the two groups at 85.8, 11.2 and 3.0%, respectively, in pterygium cases and 88.4, 9.7 and 1.9% in controls, respectively (p for trend=0.6822). There was no polymorphic genotype for MMP7 C-153T among our Taiwanese cohort. Conclusion: A-181G and C-153T genotypes at MMP7 do not have a direct role in determining Taiwanese susceptibility to pterygium.

Background/aim Oral cancer is of the highest incidence worldwide in Taiwan, and a better marker for personalized therapeutic strategies such as immunotherapies is urgently needed. Interleukin-12 (IL12) is a cytokine that has been reported to exhibit potent tumoricidal effects, however, its genotypic contribution to oral cancer is still largely unknown. The current study aimed at investigating whether IL12B rs3212227 genotype is associated with oral cancer in Taiwan. Materials and methods Genotypic characteristics of IL12B rs3212227 were determined among 958 oral cancer cases and age- and gender-matched individuals via typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Results The AA, AC and CC genotypes of IL12B rs3212227 were 38.2, 38.9 and 22.9% in the case group and 36.2, 41.5 and 22.3% in the control group (p=0.5189), respectively. Conclusion IL12B rs3212227 genotype was associated with oral cancer risk only in betel quid chewers.

BACKGROUND/AIM Matrix metalloproteinase-9 (MMP-9) is responsible for modifying extracellular components and plays a crucial role in the metastatic behavior of cancer. This study aimed at examining the role of MMP-9 rs3918242 genotypes on colorectal cancer (CRC) risk. MATERIALS AND METHODS A total of 362 CRC patients and 362 healthy subjects in Taiwan, were examined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS The MMP-9 rs3918242 TT genotype carriers had a slightly increased risk of CRC compared to CC carriers (p=0.1642, OR=1.88, 95% CI=0.84-4.16). Patients of CT/TT genotypes were on significantly higher risk of metastasis (p=0.0027) than those of CC genotype. No obvious association was found between MMP-9 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No significant correlation was observed between MMP-9 genotypic distributions with age, gender, tumor size or location. CONCLUSION MMP-9 rs3918242 genotypes may interact with BMI to serve as a predictor for higher CRC risk, and independently as a predictor for metastasis.

Background/Aim: Acute lymphoblastic leukemia (ALL) is frequent among children. Few studies have researched the relationship between maternally expressed gene 3 (MEG3) and cancer risk. We hypothesized long non-coding RNA MEG3 polymorphisms might influence the risk of childhood ALL. Materials and Methods: In a total of 266 patients with childhood ALL and 266 healthy controls, genotypes of MEG3 rs7158663, rs3087918, rs11160608 and rs4081134 single nucleotide polymorphisms were investigated for their associations with childhood ALL. Results: MEG3 rs7158663 AG and AA genotypes were significantly associated with ALL [odds ratio=1.61 (95% confidence interval=1.12-2.31) and 2.21 (1.16-4.22), respectively]. The A allele also exhibited a statistical association with higher risk of ALL (p=0.0015). There was no positive association as for rs3087918, rs11160608 or rs4081134. Interestingly, a significant interaction between MEG3 rs7158663 and age (≥3.5 years) and gender (male) was found. Conclusion: MEG3 rs7158663 AG/AA genotypes were associated with higher susceptibility to childhood ALL. These novel findings should be validated in larger populations and different ethnicities.

This study investigated whether genetic variations in cyclin D1 (CCND1) are associated with susceptibility to childhood acute lymphoblastic leukemia (ALL).A total of 266 childhood ALL cases and 266 healthy controls were genotyped for CCND1 rs9344 and rs678653.There was a significant difference in the genotypic distribution of rs9344 between childhood ALL patients and healthy controls (p=0.0077). Compared to the AA genotype, AG and GG genotypes were associated with significantly decreased risks of childhood ALL with odds ratio (OR) of 0.65 [95% confidence interval (CI)=0.44-0.94, p=0.0234] and 0.45 (95%CI=0.26-0.78, p=0.0040), respectively. Supporting this, allelic frequency distributions between childhood ALL patients and controls was significantly different (OR=0.68, 95%CI=0.53-0.88, p=0.0025). There was no significant difference in the genotypic and allelic distributions of rs678653 between cases and controls.CCND1 rs9344, but not rs678653, may serve as a predictive marker of susceptibility for childhood ALL.

BACKGROUND/AIM Breast cancer incidence is highest among women worldwide, and practical markers for personalized therapeutic strategies are few. Interleukin-12 (IL-12) is a cytokine that is reported to be significantly lower in healthy controls than breast cancer cases, however, its genotypic contribution to carcinogenesis has never been revealed in breast cancer. We examined whether IL-12A rs568408 and rs2243115 genotypes contribute to elevated breast cancer risk and summarized related literature among other cancers. MATERIALS AND METHODS IL-12A genotypic profiles were determined among 1,232 breast cancer cases and 1,232 healthy controls via polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS The variant genotypes of IL-12A rs568408 and rs2243115 were not found to be significantly associated with elevated breast cancer risk (both p>0.05). CONCLUSION IL-12A rs568408 and rs2243115 genotypes may not serve as good predictors of breast cancer risk.

Background/aim Rs3824129 is a functional six-nucleotide insertion(I)/deletion(D) polymorphism in the promoter region of caspase 8, an essential apoptosis gene. We aimed to examine the association of this polymorphism with the risk of bladder cancer in the Taiwanese population. Materials and methods Caspase-8 rs3834129 genotypes were determined and their associations with bladder cancer risk were evaluated among 375 patients and 375 controls by the PCR-RFLP methodology. In addition, the interaction of caspase-8 rs3834129 genotypes with personal behaviors and clinicopathological features were examined. Results The frequencies of II, ID and DD genotypes for caspase-8 rs3834129 were non-differentially distributed between the two groups (p for trend=0.7187). Analysis of allelic frequency distribution also indicated that the D variant allele was not associated with a risk of bladder cancer. There was no obvious joint interaction between caspase-8 rs3834129 genotypes and smoking, alcohol consumption, and clinical stage and grade. Conclusion Caspase-8 rs3834129 genotypes play a minor role in the personal susceptibility to bladder cancer in Taiwan.

BACKGROUND/AIM The aim of this study was to examine the role of caspase-8 rs3834129 polymorphism on colorectal cancer (CRC) risk in Taiwanese CRC patients and healthy controls. MATERIALS AND METHODS The caspase-8 rs3834129 (-652 6N insertion/deletion) polymorphic genotypes were analyzed in 362 patients with CRC and the same number of age- and gender-matched healthy subjects. The interaction of caspase-8 rs3834129 genotypes with personal behaviors and clinicopathological features were also examined. RESULTS The percentage of variants ID and DD for caspase-8 rs3834129 genotype were 37.6 and 5.8% in CRC group and 39.0 and 6.6% in the control group, respectively (p for trend=0.7987). The allelic frequency distribution analysis showed that caspase-8 rs3834129 D allele conferred a non-significant lower susceptibility for CRC compared with I allele (OR=0.92, 95%CI=0.74-1.20, p=0.5063). There was no obvious link between caspase-8 rs3834129 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No statistically significant correlation was observed between caspase-8 rs3834129 genotypic distribution and age, gender, tumor size, location or metastasis status. CONCLUSION Overall, caspase-8 rs3834129 genotypes may not serve as predictors for CRC risk or prognosis.

The UCLA Loneliness Scale (Version 3; UCLA-LSV3) is widely used for assessing loneliness. Nevertheless, the validity of this scale for assessing loneliness in individuals with schizophrenia or schizoaffective disorder has not been determined. Additionally, studies validating the eight-item and three-item versions of UCLA-LSV3 have not included individuals with severe mental illness; therefore, whether the short versions are comparable to the full 20-item version of UCLA-LSV3 for this population is unclear. The present study examined the unidimensional structure, internal consistency, concurrent validity, and test–retest reliability of the Chinese versions of UCLA-LSV3 (i.e., 20-item, 8-item, and 3-item versions) to determine which version is most appropriate for assessing loneliness in individuals with schizophrenia or schizoaffective disorder in Taiwan. A total of 300 participants (267 with schizophrenia and 33 with schizoaffective disorder) completed the scales, comprising UCLA-LSV3, the Center for Epidemiological Studies Depression Scale (CES-D), the suicidality module of the Kiddie Schedule for Affective Disorders and Schizophrenia–Epidemiological Version (K-SADS-E), and the family and peer Adaptation, Partnership, Growth, Affection, and Resolve (APGAR) index. Construct validity was evaluated through confirmatory factor analysis. The three versions of UCLA-LSV3 were compared with the CES-D, the suicidality module of the K-SADS-E, and the family and peer APGAR index to establish concurrent validity. The results indicated that all three versions of UCLA-LSV3 exhibited acceptable to satisfactory psychometric properties in terms of unidimensional constructs, concurrent validity, and test–retest reliability. The full version of UCLA-LSV3 had the best performance, followed by the eight-item version and the three-item version. Moreover, the three versions had relatively strong associations with each other. Therefore, when deliberating which version of UCLA-LSV3 is the best choice for assessing loneliness in individuals with schizophrenia or schizoaffective disorder, healthcare providers and therapists should consider time availability and practicality.

6-hydroxydopamine (6-OHDA) is used to induce oxidative damage in neuronal cells, which can serve as an experimental model of Parkinson’s disease (PD). Jujuboside A and B confer free radical scavenging effects but have never been examined for their neuroprotective effects, especially in PD; therefore, in this study, we aimed to investigate the feasibility of jujubosides as protectors of neurons against 6-OHDA and the underlying mechanisms. 6-OHDA-induced neurotoxicity in the human neuronal cell lines SH-SY5Y and SK-N-SH, was used to evaluate the protective effects of jujubosides. These findings indicated that jujuboside A and B were both capable of rescuing the 6-OHDA-induced loss of cell viability, activation of apoptosis, elevation of reactive oxygen species, and downregulation of the expression levels of superoxide dismutase, catalase, and glutathione peroxidase. In addition, jujuboside A and B can reverse a 6-OHDA-elevated Bax/Bcl-2 ratio, downregulate phosphorylated PI3K and AKT, and activate caspase-3, -7, and -9. These findings showed that jujubosides were capable of protecting both SH-SY5Y and SK-N-SH neuronal cells from 6-OHDA-induced toxicity via the rebalancing of the redox system, together with the resetting of the PI3K/AKT apoptotic signaling cascade. In conclusion, jujuboside may be a potential drug for PD prevention.

Matrix metalloproteinase 9 (MMP9) is highly expressed in gastric cancer but the role of MMP9 is unclear. This study aimed at revealing the association of MMP9 promoter rs3918242 genotypes with gastric cancer risk.MMP9 rs3918242 genotypes of 121 patients with gastric cancer and 363 healthy individuals were examined by polymerase chain reaction-restriction fragment length polymorphism methodology using serum samples.MMP9 rs3918242 TT genotype carriers had an elevated gastric cancer risk compared to wild-type CC carriers (odds ratio=3.92, 95% confidence interval=1.28-11.99; p=0.0103). Patients with CT/TT genotypes were at higher risk of metastasis (p=0.0178) than those with CC. No correlation was found between MMP9 rs3918242 genotype and gastric cancer risk with smoking or alcohol behavior, nor Helicobacter pylori infection. No correlation was observed for MMP9 rs3918242 genotypic distributions with age, gender, or body mass index.Carrying a T allele for MMP9 rs3918242 may be predictive for higher gastric cancer risk, and as a predictor for higher risk of metastasis.

Background/aim The current study aimed at evaluating the contribution of IL-13 promoter rs1881457 and rs1800925 genotypes to the risk of breast cancer in Taiwan. Materials and methods A total of 1,232 breast cancer cases and 1,232 age-matched controls were genotyped by typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Results As for IL-13 rs1881457, the rates of AA, AC and CC genotypes were 54.8, 37.9 and 7.3% among the cases, and 53.8, 38.7 and 7.5% among the healthy controls, respectively; there were no statistically significant differences between the two groups (p for trend=0.8889). Also, regarding IL-13 rs1800925, there were no statistically significant differences between the two groups either (p for trend=0.6803). Furthermore, the allelic frequencies for IL-13 rs1881457 and rs1800925 were not differentially distributed between the case and control groups (p=0.6515 and 0.8753, respectively). Conclusion The rs1881457 and rs1800925 IL-13 promoter polymorphisms may not serve as breast cancer susceptibility determinants for Taiwanese.

Background The study aims to evaluate the contribution of excision repair cross-complementing group 1 (ERCC1), which plays an important role in genome integrity maintenance, to lung cancer risk. Materials and methods ERCC1 rs11615 and rs3212986 genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism analysis and their association with lung cancer risk was examined among 358 lung cancer patients and 716 controls. Results The proportions of CC, CT and TT for the rs11615 genotype were 43.6%, 41.6% and 14.8% in the case group and 50.0%, 41.1% and 8.9% in the control group, respectively (p for trend=0.0082). Allelic analysis showed that ERCC1 rs11615 T-allele carriers have a 1.32-fold higher risk of lung cancer than wild-type C-allele carriers [95%confidence interval (CI)=1.09-1.60, p=0.0039]. In addition, a significant interaction between the rs11615 genotype and smoking status was observed. Conclusion The T allele of ERCC1 rs11615 jointly with smoking habits may contribute to a higher lung cancer risk in Taiwan.

Background/aim A single study has shown positive association and genotype-phenotype correlation between metalloproteinase-9 (MMP-9) promoter genotypes and adult acute lymphocytic leukemia (ALL). However, there is no report about childhood ALL. Thus, this study aimed at examining the role of MMP-9 rs3918242 genotypes in childhood ALL risk. Patients and methods A total of 266 childhood ALL cases and 266 healthy controls in Taiwan were examined for their MMP-9 rs3918242 genotypes via polymerase chain reaction-restriction fragment length polymorphism methodology. Results The MMP-9 rs3918242 CT or TT genotype carriers only had a slightly increased risk compared with CC carriers (p=0.6386 and 0.6005, respectively). The allelic frequency analysis also supported the idea that the variant T allele at MMP-9 rs3918242 is not differentially distributed between the case and control groups (p=0.4834). Conclusion MMP-9 rs3918242 genotypes may indirectly influence the risk of childhood ALL. Further validations in other populations and analysis of the detail mechanisms are needed.

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.

The studies about the roles of matrix metalloproteinases (MMPs) in pterygium diagnosis and/or prognosis are mainly based on their mRNA and protein levels, while the genomic roles of MMPs are seldom examined. The aim of this study was to investigate the contribution of MMP-9 genotypes to pterygium risk.MMP-9 rs3918242 was genotyped in 134 pterygium cases and 268 controls via polymerase chain reaction-restriction fragment length polymorphism.The rs3918242 genotype percentages of CC, CT, and TT were 73.1, 25.4 and 1.5% among cases and 74.6, 23.1 and 2.3% among controls (p trend=0.7928). The odds ratios after adjusting for age and gender for CT and TT genotypes at rs3918242 were 1.08 and 0.92 (95%CI=0.66-1.73 and 0.45-2.89, p=0.6478 and 0.6389), respectively. In addition, allelic frequency analysis showed no significant difference in the distribution of allelic frequencies between the pterygium and control groups.The genotypes at MMP-9 rs3918242 play a minor role in determining personal susceptibility to pterygium.

Background/Aim: Interleukin-16 has been reported to exhibit tumoricidal effects, however, the contribution of IL-16 genotypes to lung cancer is still largely unrevealed. This study aimed at investigating whether IL-16 genotypes contribute to lung cancer susceptibility. Materials and Methods: IL-16 rs4778889, rs11556218, and rs4072111 genotypic characteristics were determined among 358 lung cancer patients and 716 controls via the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methodology. Results: The highlight finding is that the distributions of genotypic (p=8.6E-10) and allelic (p=0.0001) frequencies of IL-16 rs11556218 was significantly different between cases and controls. In detail, the frequencies of IL-16 rs11556218 heterozygous variant TG and homozygous variant GG were 36.6 and 7.3% among the lung cancer patients, significantly higher than those among the controls (22.5% and 2.6%). On the other way, no difference was observed regarding IL-16 rs4778889 or IL-16 rs4072111. Conclusion: The present study indicates IL-16 rs11556218 G allele is significantly associated with increased Taiwan lung cancer risk.

Background/Aim: Mounting evidence has shown that miRNAs play a critical role in the regulation of hematopoiesis of cell proliferation and apoptosis as well as in tumorigenesis. The miR146a rs2910164 polymorphism, which is closely responsive for its expression, has been reported to associate with the risk of several solid cancers. The study aimed at examining the association of the it with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. Materials and Methods: We recruited 266 patients with childhood ALL and 266 healthy controls, and rs2910164 genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The allele G was associated with decreased childhood ALL risk (OR=0.66, 95%CI=0.52-0.85, p=0.0011). Consistently, the GG genotype was associated with a decreased susceptibility (OR=0.40, 95%CI=0.23-0.67, p=0.0004). Patients with CG and GG genotypes were of earlier onset than those with CC genotype (p=0.0255 and p=0.0001). Conclusion: MiR146a rs2910164 G allele serves as a protective marker for childhood ALL in Taiwan.

To investigate the association between adiponectin (ADIPOQ) genotypes and colorectal cancer (CRC) risk among Taiwanese.Polymerase chain reaction-restriction fragment length polymorphism was adopted to identify ADIPOQ rs266729, rs2241766 and rs1501299 genotypes among 362 CRC patients and 362 healthy controls.ADIPOQ rs266729 GG genotype (p=0.0075) and G allele (p=0.0061) are associated with a significantly increased CRC risk. There is no differential distribution of rs2241766 and rs1501299 genotypes. As for the gene-lifestyle interaction, there are obvious joint effects of rs266729 genotype on the CRC risk among non-smoker, non-alcohol drinker, while not on smoker or non-drinker subgroups. No significant correlation was observed between rs266729 genotypic distributions and age, gender, tumor size, location or metastasis status. Interestingly, a correlation of rs266729 genotype and larger BMI on CRC risk was found.G allele at ADIPOQ rs266729 may serve as a determiner for CRC risk, especially for those with BMI ≥24.

Aim The aim of this study was to evaluate the contribution of human mouse double minute 2 (MDM2) gene polymorphisms to the risk of Taiwan lung cancer. Materials and methods In this case-control study, the association of MDM2 rs2279744 genotypes with lung cancer risk was investigated among 358 lung cancer patients and 716 age-, gender- and smoking status-matched controls in Taiwan. Results The percentages of MDM2 rs2279744 GT and GG genotypes were 50.0% and 27.4% in lung cancer group and 50.0% and 26.5% in control group, respectively [odds ratio (OR)=1.03 and 1.07, 95% confidence interval (CI)=0.75-1.43 and 0.75-1.53, respectively]. The analysis about allelic frequency showed that G allele at MDM2 rs2279744 conferred a non-significant increased cancer risk (OR=1.03, 95%CI=0.86-1.24). Conclusion Polymorphisms of MDM2 rs2279744 may play a role in lung carcinogenesis. However, the studied genotypes were not shown as predictors of lung cancer susceptibility.

Few studies have examined the contribution of matrix metalloproteinases (MMP) to either diagnosis or prognosis of pterygium. The aim of this study was to investigate the contribution of MMP-1 genotypes to pterygium risk.A total of 134 cases and 268 controls were included and their MMP-1 -1607 (rs1799705) genotypes were examined by polymerase chain reaction-restriction fragment length polymorphism.The percentages of 2G/2G, 1G/2G, and 1G/1G for rs1799705 genotypes were 48.5, 36.6 and 14.9% among patients and 33.9, 44.8, and 21.3% among controls (p trend=0.0167). The odds ratios (ORs) after adjusting for age and gender for 1G/2G and 1G/1G genotypes at rs1799705 were 0.54 (95%CI=0.33-0.89, p=0.0168) and 0.46 (95%CI=0.27-0.88, p=0.0192), respectively. Consistently, the adjusted OR for those carrying the 1G allele at MMP-1 -1607 was 0.61 (95%CI=0.41-0.78, p=0.0167), compared with the wild-type 2G allele.The genotypes at rs1799705 play a role in determining personal susceptibility to pterygium.

Few studies have examined the genetic role of matrix metalloproteinases (MMPs) to early detection or prediction in gastric cancer development. In this study, the contribution of MMP7 promoter (A-181G and C-153T) polymorphic genotypes to gastric cancer risk in Taiwanese was investigated for the first time.A total of 121 cases and 363 controls were enrolled and their MMP7 genotypes at A-181G and C-153T were examined by polymerase chain reaction-restriction fragment length polymorphism methodology using genomic DNA from serum.The GG genotype at MMP7 A-181G was found to represent a risk factor for gastric cancer, especially among smokers. No individual with variant genotype carrier at MMP7 C-153T was found among this Taiwanese population.The G allele of MMP7 A-181G may serve as an early predictor for gastric cancer risk in Taiwanese; other gastric cancer markers are still urgently needed.

Oxidative stress may play critically important roles in the etiology of Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is a physiological neurotoxin reported to induce oxidative-induced apoptosis of dopaminergic neurons in PD mice models. Valproic acid (VPA), a clinical mood stabilizer, is a HDAC inhibitor with neuroprotective capacities. In the study, we aim at examining the feasibility of VPA as a protector for dopaminergic neurons against damage from 6-OHDA, and the intracellular mechanisms. The 6-OHDA-induced neurotoxicity to the human dopaminergic cell line SH-SY5Y was applied for examining VPA protective effects. Pretreatment with VPA was able to improve cell viability and reduce 6-OHDA-induced reactive oxygen species. Furthermore, a significant suppression of apoptotic caspases including cleaved caspase-3, caspase-7, and caspase-9 was observed. The results also revealed VPA decreased the 6-OHDA-induced Bax/Bcl2 ratio, as measured at protein level. These novel findings indicate that VPA may be capable of protecting the SH-SY5Y dopaminergic neuronal cells from 6-OHDA-induced toxicity via the deceasing of apoptotic caspases (cleaved caspase-3, caspase-7, and caspase-9) and reducing of the Bax/Bcl2 ratio. Very possibly, VPA could serve as not only a mood stabilizer but also a potential antidote for PD prevention.

Background/Aim: Recently, mounting evidence has shown that caspase-8 (CASP8) rs3834129 (-652, 6N insertion/deletion) polymorphism may serve as a genetic biomarker for personal risk of various cancer types. The contribution of CASP8 rs3834129 polymorphism has been investigated in several oral cancer populations, but not in Taiwan. This study investigated the role of CASP8 rs3834129 polymorphism on oral risk in Taiwan. Materials and Methods: CASP8 rs3834129 polymorphic genotypes were determined and their associations with oral cancer risk were investigated among 788 patients with oral cancer and 956 age- and gender-matched healthy controls via polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) methodology. In addition, the interaction of CASP8 rs3834129 genotype with personal behavior and clinicopathological features were also examined. Results: The frequencies of II, ID and DD genotypes for CASP8 rs3834129 were 57.5, 36.5 and 6.0% in the patient group and 54.0, 39.0 and 7.0% in the healthy control group, respectively (p for trend=0.3052), genotypes were not significantly differentially distributed between the two groups. The comparisons in allelic frequency distribution also supported the findings that the D variant allele may not serve as a determinant of risk for oral cancer. There was no interaction of CASP8 rs3834129 genotype with age, gender, smoking, alcohol or betel quid consumption in regard to oral cancer risk. Conclusion: Our results indicate that the caspase-8 genotype does not appear to play a direct role in personal susceptibility to oral cancer in Taiwan.

Background/Aim: Matrix metalloproteinase 2 (MMP2) is up-regulated in many cancers. However, the association of MMP2 genotype to nasopharyngeal cancer (NPC) susceptibility in Taiwan remains elusive. Materials and Methods: In this study, the role of MMP2 promoter C-1306T (rs243865) and C-735T (rs2285053) genotypes were investigated among 208 NPC patients and 416 healthy controls, and their role in NPC staging and TNM classifications were examined. Results: There was no differential distribution as for the genotypic or allelic frequencies at MMP2 promoter C-1306T or C-735T between the control and case groups. Noticeably, those with MMP2 C-1306T CT+TT genotypes had a lower metastatic risk than those with CC (p=0.0295). As for staging, T and N classifications, there was no differential distribution in C-1306T genotypes (p>0.05). Also, there was no differential distribution of C-735T genotypes according to different behavioral/clinicopathological characteristics. Conclusion: CT and TT genotypes at MMP2 C-1306T were associated with a significantly decreased risk of NPC metastasis.

The significance of Cdk5 in cell-cycle control and cancer biology has gained increased attention. Here we report the inverse correlation between the protein levels of Cdk5 and p21CIP1 from cell-based and clinical analysis. Mechanistically, we identify that Cdk5 overexpression triggers the proteasome-dependent degradation of p21CIP1 through a S130 phosphorylation in a Cdk2-independent manner. Besides, the evidence from cell-based and clinical analysis shows that Cdk5 primarily regulates nuclear p21CIP1 protein degradation. S130A-p21CIP1 mutant enables to block either its protein degradation or the increase of cancer cell growth caused by Cdk5. Notably, Cdk5-triggered p21CIP1 targeting primarily appears in S-phase, while Cdk5 overexpression increases the activation of Cdk2 and its interaction with DNA polymerase δ. The in vivo results show that Cdk2 might play an important role in the downstream signaling to Cdk5. In summary, these findings suggest that Cdk5 in a high expression status promotes cancer growth by directly and rapidly releasing p21CIP1-dependent cell-cycle inhibition and subsequent Cdk2 activation, which illustrates an oncogenic role of Cdk5 potentially applied for future diagnosis and therapy. Cancer Res; 76(23); 6888–900. ©2016 AACR.

Metalloproteinase 2 (MMP2) is a multi-functional protein which has been shown to be up-regulated in patients with oral cancer, especially those with lymph node metastasis. However, the association of MMP2 genotype with oral cancer risk or metastatic behavior is unknown. This study aimed to evaluate the role of MMP2 promoter 1306 and -735 genotypes in the risk of oral cancer and metastasis.In this case-control study, MMP2 promoter 1306 (rs243865) and -735 (rs2285053) genotypes and their interaction with consumption of areca, cigarettes, and alcohol in determining oral cancer risk were investigated among 788 patients with oral cancer and 956 gender-matched healthy controls. In addition, their role in oral cancer metastasis were also examined.The distribution of CC, CT and TT for MMP2 promoter 1306 genotype was 79.0, 20.1 and 0.9% in the oral cancer group and 68.7, 29.2 and 2.1% in the non-cancer control group, respectively (p for trend=4.3E-6). The allelic frequency distributions showed that the variant T allele of MMP2 promoter 1306 conferred lower oral cancer susceptibility than the wild-type C allele (odds ratio=0.61, 95% confidence interval=0.50-0.75, p=1.1E-6). As for the MMP2 -735 genotypes, there was no differential distribution in genotypic or allelic frequencies. The variant CT and TT genotypes were also associated with lower metastasis rates within 5 years among the patients with oral cancer (odds ratio=0.34, 95% confidence interval=0.15-0.80, p=0.0102).The CT and TT genotypes of MMP2 promoter 1306 may have a protective effect on oral cancer susceptibility and metastasis risk within 5 years for Taiwanese. They may serve as predictive markers for oral cancer in precise medical practice.

Endometriosis is a major health issue among women of reproductive age. However, its etiology has not yet been completely understood. We investigated 10 single nucleotide polymorphisms from six novel nucleotide excision repair genes and the susceptibility to endometriosis. A total of 153 patients with endometriosis were recruited during 2000–2010 from central Taiwan. Pathological confirmation was necessary for all patients, and exclusion criteria included the presence of leiomyoma, adenomyosis, or cancer of the uterine, cervix, or ovary and a prescription of hormone therapy. Furthermore, a total of 636 age-matched individuals without endometriosis were recruited during the same time period from central Taiwan. The polymerase chain reaction coupled with restriction fragment length polymorphism methodology was applied for genotyping. The multivariate logistic regression analysis showed that subjects carrying the ERCC1 rs11615 TT (OR = 2.04, 95% CI = 1.36–3.41), ERCC2 rs1799793 AA (OR = 1.86, 95% CI = 1.14–3.11), and ERCC6 rs2228528 AA genotypes (OR = 1.79, 95% CI = 1.13–2.83) exhibited significantly increased risks of developing endometriosis compared with their counterparts carrying the wild-type genotypes. This study suggests that certain single nucleotide polymorphisms of nucleotide excision repair genes excision repair cross-complementation group 1 (ERCC1, ERCC2, and ERCC6) predispose women to the development of endometriosis.

Objectives This 1-year prospective study evaluated the implant success rate and marginal bone response of non-submerged implants with platform and non-platform switching abutments in posterior healed sites. Material and methods Nineteen patients (9 male, 10 female) with posterior partially edentulous spaces, between the ages of 23 and 76 (mean = 55.4 years), were included in this study. A total of 30 implants (15 implants restored with platform switching [PS] abutments [control] and 15 implants restored with non-platform switching [NPS] abutments [test]) were assigned between two groups using a randomization procedure. The definitive abutments with conical connections were placed at the time of surgery, and the definitive restorations were placed at 3 months. All patients were evaluated clinically and radiographically using standardized radiographs at time of implant placement (0), 3, 6 and 12 months after implant placement. Data were analyzed using Friedman test with post hoc pairwise comparisons, Mann–Whitney U-test, and Pearson's chi-square test at the significance level of α = 0.05. Results At 12 months, all 30 implants remained osseointegrated corresponding to a 100% success rate. The overall mean marginal bone level change at 12 months was −0.04 ± 0.08 mm for PS group and −0.19 ± 0.16 mm for NPS group. Statistically significant difference in the marginal bone level change was observed between groups at 0 to 12 months and 3 to 12 months (P