Significant Contribution of Interleukin-18 Genotypes to Childhood Acute Lymphocytic Leukemia Risk in Taiwanese.

BACKGROUND/AIM: Evidence has shown that interleukin-18 (IL-18) has both antitumor and pro-tumor effects in various types of leukemia. The current study aimed at investigating the contribution of IL-18 polymorphisms to the risk of childhood acute lymphocytic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: IL-18 promoter -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 266 childhood ALL cases and 266 controls were determined by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The distributions of genotypic and allelic frequencies of IL-18 rs1946519, rs1946518 or rs187238, were not significantly different between childhood ALL cases and controls (all p>0.05). However, in the stratification analysis among the cases, IL-18 rs187238 GC and CC genotypes were associated with increased childhood ALL risk and shorter survival (OR=4.19 and 2.93, 95%CI=2.04-8.64 and 1.19-7.23, p=0.0001 and 0.0250, respectively). No association was found with rs1946519 and rs1946518 (all p>0.05). CONCLUSION: IL-18 rs187238 GC and CC genotypes can serve as predictors for childhood ALL prognosis among Taiwanese. Validation in larger and various populations can greatly extend the feasibility of this novel predictor.

Contribution of Cyclin-dependent Kinase Inhibitor 1B Genotypes to Childhood Leukemia Risk.

BACKGROUND/AIM: Although genetic differences in cell-cycle control genes have been associated with cancer risk, to our knowledge, no report has specifically examined the role of gene variants in childhood acute lymphoblastic leukemia (ALL). Cyclin-dependent kinase inhibitor 1B (CDKN1B; also known as p27/KIP1) is a cell-cycle regulating gene. This study aimed at investigating the association between CDKN1B genotypes and childhood ALL risk. MATERIALS AND METHODS: In 266 childhood ALL cases and 266 healthy controls, the CDKN1B rs34330 and 2066827 polymorphisms were genotyped, and the association of CDKN1B genotypes with childhood ALL risk were analyzed. RESULTS: The genotypes of CDKN1B rs34330 and 2066827 were similarly distributed between the control and case groups (p for trend=0.8718 and 0.4030, respectively). The allelic frequency also exhibited no statistical difference (p=1.0000 and 0.6666, respectively). There was no significant interaction between CDKN1B genotypes and age or sex. CONCLUSION: CDKN1B genotypes were not found to be minor contributors to childhood ALL susceptibility in Taiwan.

Novel Contribution of Long Non-coding RNA MEG3 Genotype to Prediction of Childhood Leukemia Risk.

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.

Significant Association of CCND1 Genotypes With Susceptibility to Childhood Acute Lymphoblastic Leukemia.

BACKGROUND/AIM: This study investigated whether genetic variations in cyclin D1 (CCND1) are associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A total of 266 childhood ALL cases and 266 healthy controls were genotyped for CCND1 rs9344 and rs678653. RESULTS: 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. CONCLUSION: CCND1 rs9344, but not rs678653, may serve as a predictive marker of susceptibility for childhood ALL.

Significant Associations of lncRNA H19 Genotypes with Susceptibility to Childhood Leukemia in Taiwan.

The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08-2.14, p = 0.0429) and 1.94 (95%CI, 1.15-3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13-1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.

MiR-196a-2 Genotypes Determine the Susceptibility and Early Onset of Childhood Acute Lymphoblastic Leukemia.

BACKGROUND/AIM: The roles of microRNAs (miRNAs) in tumorigenesis have attracted a lot of attention. The current study aimed at examining the association of the miR-196a-2 rs11614913 genotypes with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: This case-control investigation recruited 266 patients with childhood ALL and 266 healthy controls, and the miR-196a-2 rs11614913 genotypes of each participant were examined via the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The frequency of miR-196a-2 C allele in controls was 0.440 compared with 0.423 in ALL patients. In addition, there was no significant association between CT or CC genotypes with susceptibility to childhood ALL (OR=0.89 and 0.89, 95%CI=0.60-1.30 and 0.54-1.45, p=0.5427 and 0.6302). Furthermore, the frequencies of miR-196a-2 polymorphisms were not associated with age, gender and clinical outcomes in ALL cases. CONCLUSION: The miR-19a-2 genotypes are not associated with susceptibility to childhood ALL in Taiwan.

First case of Coronavirus Disease 2019 (COVID-19) pneumonia in Taiwan.

An outbreak of respiratory illness proved to be infected by a 2019 novel coronavirus, officially named Coronavirus Disease 2019 (COVID-19), was notified first in Wuhan, China, and has spread rapidly in China and to other parts of the world. Herein, we reported the first confirmed case of novel coronavirus pneumonia (NCP) imported from China in Taiwan. This case report revealed a natural course of NCP with self-recovery, which may be a good example in comparison with medical treatments.

Significant Association Between the MiR146a Genotypes and Susceptibility to Childhood Acute Lymphoblastic Leukemia in Taiwan.

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.

HOGG1 rs1052133 Genotypes and Risk of Childhood Acute Lymphoblastic Leukemia in a Taiwanese Population.

BACKGROUND/AIM: Cells suffer from oxidative DNA damage which leads to the accumulation of 8-oxoguanine (8-oxoG) adducts in our genome that can become carcinogenic. The human 8-oxoG DNA glycosylase 1 (hOGG1) plays a central role in repairing these 8-oxoGs via the base excision repair pathway. Mounting evidence has suggested that hOGG1 polymorphisms may affect the activity of hOGG1 and serve as genomic markers for the prediction of personal susceptibility to several cancers. To determine whether the commonly examined hOGG1 rs1052133 (Ser326Cys) polymorphism is associated with the risk of childhood acute lymphoblastic leukemia (ALL) among Taiwanese children, we genotyped the hOGG1 rs1052133 (Ser326Cys) in 266 cases and 266 controls. RESULTS: The distributions of the GG, CG and CC genotypes at the hOGG1 rs1052133 were 49.2, 39.1 and 11.7% in the control group and 48.1, 36.1 and 15.8% in the case group (p=0.3656). The combined genotypes CG+CC were not associated with increased risk of childhood ALL (odds ratio [OR]=1.05, 95% confidence interval [CI]=0.74-1.47, p=0.7947). CONCLUSION: The hOGG1 rs1052133 polymorphism is not associated with susceptibility to childhood ALL in the Taiwanese population.

Matrix Metalloproteinase-1 Genotype Contributes to the Risk of Non-solid Tumor in Childhood Leukemia.

AIM: Up-regulation of metalloproteinase (MMPs) proteins have been shown in various types of solid cancers and the genotype of MMP1 has been associated with the risk of solid cancers. However, the contribution of MMP1 genotype to leukemia has never been investigated to our knowledge. Therefore, in this study we aimed to evaluate the contribution of the genotypic variants in the promoter region of MMP1 to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan. MATERIALS AND METHODS: In this case-control study, 266 patients with childhood ALL and 266 non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The distribution of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter rs1799750 genotype was 49.2%, 39.5% and 11.3% in the childhood ALL group and 36.8%, 43.6% and 19.5% in the non-cancer control group, respectively (p for trend=0.0046), significantly differentially distributed between childhood ALL and control groups. The carrier comparisons in dominant and recessive models also support the findings that 1G appears to be the protective allele in childhood ALL. In genotype and gender interaction analysis, it was found that boys carrying the MMP1 rs1799750 1G/2G or 1G/1G genotypes had lower odds ratios(ORs) of 0.68 and 0.43 [95% confidence intervals (CI)=0.47-0.98 and 0.26-0.73, p=0.0395 and 0.0013, respectively] for childhood ALL than those carrying the 2G/2G genotype. Analysis of genotype inaction with age of onset age showed those aged less than 3.5 years at onset carrying the 1G/2G or 1G/1G genotypes had lower ORs (0.0183 and 0.0004, respectively) for childhood ALL, but there was no such difference for those having an age at onset of 3.5 years or more. CONCLUSION: Our results indicate that the MMP1 rs1799750 1G allele is a protective biomarker for childhood ALL.

The Association of Flap Endonuclease 1 Genotypes with the Risk of Childhood Leukemia.

AIM: Flap endonuclease 1 (FEN1) is one of the most important proteins in maintaining genome stability and preventing carcinogenesis. In recent years, the contribution of two variants of FEN1, rs174538 and rs4246215, regarding cancer risk have been investigated in lung, breast, liver, esophageal, gastric, colorectal cancer and glioma. However, it has not been revealed whether rs174538 and rs4246215 are associated with leukemia. Therefore, in the present study we aimed to evaluate the contribution of these genotypic polymorphisms in FEN1 to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan. MATERIALS AND METHODS: In total, 266 patients with childhood ALL and an equal number of recruited non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The FEN1 rs174538 genotype, but not rs4246215, was differently distributed between childhood ALL and control groups. The AG and AA of FEN1 rs174538 genotypes were significantly less frequently found in childhood ALL patients than in controls (odds ratio [OR]=0.68 and 0.48, 95%confidence intervals [CI]=0.47-0.98 and 0.24-0.82, respectively). As for gender, boys carrying the FEN1 rs174538 AG or AA genotype conferred lower ORs of 0.55 and 0.36 (95%CI=0.33-0.91 and 0.18-0.73, p=0.0053) for childhood ALL. Regarding age, those equal to or greater than 3.5 years of age at onset carrying the FEN1 rs174538 AG or AA genotype were of lower risk (ORs=0.53 and 0.32, 95%CI=0.31-0.90 and 0.15-0.70, p=0.0042). CONCLUSION: The FEN1 rs174538 A allele is a protective biomarker for childhood ALL and this association is more significant in males and in patients at onset age of 3.5 years or older.

[A Community-Based Experience Model of Mental-Social Health Promotion for Older People in Taichung City].

Active ageing is one of the most important issues taken up by the WHO in regard to ageing societies. "Prolonging Healthy Life Expectance" and "Decreasing the Depression Rate Among Older People" are critical indicators for "2020 Healthy People in Taiwan". This paper conducts a trial run of the program planning and evaluation of mental-social health promotion using focus group research that surveys 29 administrative districts and a depression survey that randomly samples older individuals in Taichung City. We also introduce how we apply local characteristics to develop the 3-level and innovative-action plans to meet the needs of self-identity and social participation for older people. For example, the "Learning Mobile Classroom" program promotes health promotion using activities that are tailored to the lifestyle and culture characteristics of target individuals. Another example is the "Seniors Show", which uses community groups and annual active-ageing shows to promote a positive concept of aging and to promote social participation for older people. Finally, the "Navigator APP of Active Ageing", created using a geographic information system, addresses the resource information needs of older people. This experience in Taichung City uniquely empowers older people, allowing them to take the initiative to make a difference not only for mental-social wellness but also for the hope of life and for graceful ageing.

The association of methylenetetrahydrofolate reductase genotypes with the risk of childhood leukemia in Taiwan.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most prevalent type of pediatric cancer, the causes of which are likely to involve an interaction between genetic and environmental factors. To evaluate the effects of the genotypic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) on childhood ALL risk in Taiwan, two well-known polymorphic genotypes of MTHFR, C677T (rs1801133) and A1298C (rs1801131), were analyzed to examine the extent of their associations with childhood ALL susceptibility and to discuss the MTHFR genotypic contribution to childhood ALL risk among different populations. METHODOLOGY/PRINCIPAL FINDINGS: In total, 266 patients with childhood ALL and an equal number of non-cancer controls recruited were genotyped utilizing PCR-RFLP methodology. The MTHFR C677T genotype, but not the A1298C, was differently distributed between childhood ALL and control groups. The CT and TT of MTHFR C677T genotypes were significantly more frequently found in controls than in childhood ALL patients (odds ratios=0.60 and 0.48, 95% confidence intervals=0.42-0.87 and 0.24-0.97, respectively). As for gender, the boys carrying the MTHFR C677T CT or TT genotype conferred a lower odds ratio of 0.51 (95% confidence interval=0.32-0.81, P=0.0113) for childhood ALL. As for age, those equal to or greater than 3.5 years of age at onset of disease carrying the MTHFR C677T CT or TT genotype were of lower risk (odds ratio= 0.43 and 95% confidence interval=0.26-0.71, P=0.0016). CONCLUSIONS: Our results indicated that the MTHFR C677T T allele was a protective biomarker for childhood ALL in Taiwan, and the association was more significant in male patients and in patients 3.5 years of age or older at onset of disease.

Epidemiology of orthopedic fractures and other injuries among inpatients admitted due to traffic accidents: a 10-year nationwide survey in Taiwan.

To investigate the major injury patterns associated with traffic accidents and evaluate the risk factors of the main injury, a survey of Taiwan's national insurance admission data between 2002 and 2011 was performed. The incidence of traffic-accidents-related hospitalization was between 9.17% and 11.54% and the average mortality rate of the inpatients admitted due to traffic accidents was 0.68%. Of all inpatients due to road traffic accidents in Taiwan, orthopedic fractures were the most common injuries that accounted for 29.36% of them. There were a total of 391,197 cases of three orthopedic fracture groups that were divided into (1) fracture of upper limb, (2) fracture of lower limb, and (3) fracture of spine and trunk. An increase in national medical cost used for inpatients with orthopedic fractures was noted and ranged from US$ 45.6 million to US$ 86 million annually. These orthopedic fracture patterns were frequently associated with other injuries especially head injuries (ranged from 14% to 26%). A significant relation to male gender, older age, low income, and admission to high-level hospital to the observed fracture patterns was observed.

Association of X-ray repair cross-complementing-6 genotypes with childhood leukemia.

BACKGROUND: The Non-homologous end-joining repair gene XRCC6/Ku70 plays an important role in the repair of DNA double-strand breaks (DSBs), and has been found to be involved in the carcinogenesis of many types of cancers including oral, prostate, breast and bladder cancer. However, the contribution of XRCC6 to childhood leukemia has yet to be studied. In the present study, we investigated the association of XRCC6 genotypes with the risk of childhood leukemia. MATERIALS AND METHODS: Two hundred and sixty-six patients with childhood leukemia and an equal number of age-matched healthy controls recruited in Central Taiwan, were genotyped investigating these polymorphisms' association with childhood leukemia. RESULTS: As for XRCC6 promoter T-991C, patients carrying the TC genotype had a significantly increased risk of childhood leukemia compared with the TT wild-type genotype [odds ratio (OR)=2.30, 95% confidence interval (CI)=1.38-3.84, p=0.0047]. Meanwhile, the genotypes of XRCC6 promoter C-57G, A-31G and intron3 were not statistically associated with childhood leukemia risk. CONCLUSION: Our findings suggest that the XRCC6 genotype could serve as a predictor of childhood leukemia risk and XRCC6 could serve as a target for personalized medicine and therapy.

Invasively-treated incidence of lower extremity peripheral arterial disease and associated factors in Taiwan: 2000-2011 nationwide hospitalized data analysis.

BACKGROUND: Lower extremity (LE) peripheral artery disease (PAD), which is associated with a reduced quality of life and increased mortality from atherosclerotic cardio-/cerebro-vascular occlusion, is a significant public health problem, especial for an aging society such as that of Taiwan. METHODS: Specific datasets of the 2000-2011 nationwide inpatient databases were analyzed. Two inclusion criteria, including one of the major diagnosis codes of PAD and one of three categorical invasive treatments of LE PAD, were used consecutively to select cases diagnosed as LE PAD and receiving invasive treatment. The epidemiology of invasively-treated PAD in Taiwan was estimated, and the influences of potential confounders on these invasively-treated methods were evaluated. RESULTS: In general, the invasively-treated incidence of PAD in Taiwan doubled, from 3.73/10,000 (in 2000) to 7.48/10,000 (in 2011). On average, the total direct medical cost of one hospitalized and invasively-treated PAD case ranged from $US 4,600 to $US 5,900. The annual cases of bypass surgery for the PAD cases averaged 1,000 and the cases for limb amputation ranged from 4,100 to 5,100 annually. However, the number of percutaneous transluminal angioplasty (PTA) procedures remarkably increased by 15 times, from 600/year to 9,100/year, from 2000 to 2011. 51.3% of all the enrolled cases were treated with limb amputations, and female, young and middle-aged people (30-65 years of age), DM patients and those on a low income had a tendency to undergo amputation due to PAD. 37.6% of all the enrolled cases were treated with PTAs related to hypertension, cardiovascular disease, hyperlipidemia and catastrophic Illness. 2-year PTA failure rates of 22.13%, 11.91% and 10.61% were noted among the first (2000-2001), second (2004-2005) and the third (2008-2009) cohort groups, respectively. CONCLUSIONS: In Taiwan, a gender difference and age and period effects on the invasively-treated incidence of LE PAD were observed. Female, young and middle-aged people (30-50 and 50-65 years of age), DM patients and those on a low income had a tendency to undergo amputation. The number of PTA procedures remarkably increased, but the 2-year failure rate of PTAs reduced from 2000 to 2011.

Disulfide connectivity prediction based on structural information without a prior knowledge of the bonding state of cysteines.

Previous studies predicted the disulfide bonding patterns of cysteines using a prior knowledge of their bonding states. In this study, we propose a method that is based on the ensemble support vector machine (SVM), with the structural features of cysteines extracted without any prior knowledge of their bonding states. This method is useful for improving the predictive performance of disulfide bonding patterns. For comparison, the proposed method was tested with the same dataset SPX that was adopted in previous studies. The experimental results demonstrate that bridge classification and disulfide connectivity predictions achieve 96.5% and 89.2% accuracy, respectively, using the ensemble SVM model, which outperforms the traditional method (51.5% and 51.0%, respectively) and the model that is based on a single-kernel SVM classifier (94.6% and 84.4%, respectively). For protein chain and residue classifications, the sensitivity, specificity, and accuracy of ensemble and single-kernel SVM approaches are better than those of the traditional methods. The predictive performances of the ensemble SVM and single-kernel models are identical, indicating that the ensemble model can converge to the single-kernel model for some applications.