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In order to improve the hardness and tribological performance of Ti6Al4V alloy, NiCoCrAlY–B4C composite coatings with B4C of 5%, 10% and 15% (mass fraction) were fabricated on its surface by laser cladding (LC). The morphologies, chemical compositions and phases of obtained coatings were analyzed using scanning electronic microscope (SEM), energy dispersive spectrometer (EDS), and X-ray diffraction (XRD), respectively. The effects of B4C mass fraction on the coefficient of friction (COF) and wear rate of NiCoCrAlY–B4C coatings were investigated using a ball-on-disc wear tester. The results show that the NiCoCrAlY–B4C coatings with different B4C mass fractions are mainly composed of NiTi, NiTi2, α-Ti, CoO, AlB2, TiC, TiB and TiB2 phases. The COFs and wear rates of NiCoCrAlY–B4C coatings decrease with the increase of B4C content, which are contributed to the improvement of coating hardness by the B4C addition. The wear mechanisms of NiCoCrAlY–B4C coatings are changed from adhesive wear and oxidation wear to fatigue wear with the increase of B4C content.

An elevated fasting glucose level in non-diabetic individuals is a key predictor of type 2 diabetes. Genome-wide association studies (GWAS) have identified hundreds of SNPs for fasting glucose but most of their functional roles in influencing the trait are unclear. This study aimed to identify the mediation effects of DNA methylation between SNPs identified as significant from GWAS and fasting glucose using Mendelian randomisation (MR) analyses. We first performed GWAS analyses for three cohorts (Taiwan Biobank with 18,122 individuals, the Healthy Aging Longitudinal Study in Taiwan with 1989 individuals and the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance with 416 individuals) with individuals of Han Chinese ancestry in Taiwan, followed by a meta-analysis for combining the three GWAS analysis results to identify significant and independent SNPs for fasting glucose. We determined whether these SNPs were methylation quantitative trait loci (meQTLs) by testing their associations with DNA methylation levels at nearby CpG sites using a subsample of 1775 individuals from the Taiwan Biobank. The MR analysis was performed to identify DNA methylation with causal effects on fasting glucose using meQTLs as instrumental variables based on the 1775 individuals. We also used a two-sample MR strategy to perform replication analysis for CpG sites with significant MR effects based on literature data. Our meta-analysis identified 18 significant (p

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

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.

Background: High disease burden suggests the desirability to identify high-risk Asian never-smoking females (NSF) who may benefit from low-dose CT (LDCT) screening. In North America, one is eligible for LDCT screening if one satisfies the U.S. Preventive Services Task Force (USPSTF) criteria or has model-estimated 6-year risk greater than 0.0151. According to two U.S. reports, only 36.6% female patients with lung cancer met the USPSTF criteria, while 38% of the ever-smokers ages 55 to 74 years met the USPSTF criteria. Methods: Using data on NSFs in the Taiwan Genetic Epidemiology Study of Lung Adenocarcinoma and the Taiwan Biobank before August 2016, we formed an age-matched case–control study consisting of 1,748 patients with lung cancer and 6,535 controls. Using these and an estimated age-specific lung cancer 6-year incidence rate among Taiwanese NSFs, we developed the Taiwanese NSF Lung Cancer Risk Models using genetic information and simplified questionnaire (TNSF-SQ). Performance evaluation was based on the newer independent datasets: Taiwan Lung Cancer Pharmacogenomics Study (LCPG) and Taiwan Biobank data after August 2016 (TWB2). Results: The AUC based on the NSFs ages 55 to 70 years in LCPG and TWB2 was 0.714 [95% confidence intervals (CI), 0.660–0.768]. For women in TWB2 ages 55 to 70 years, 3.94% (95% CI, 2.95–5.13) had risk higher than 0.0151. For women in LCPG ages 55 to 74 years, 27.03% (95% CI, 19.04–36.28) had risk higher than 0.0151. Conclusions: TNSF-SQ demonstrated good discriminative power. The ability to identify 27.03% of high-risk Asian NSFs ages 55 to 74 years deserves attention. Impact: TNSF-SQ seems potentially useful in selecting Asian NSFs for LDCT screening.

Patients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%–89.9%) and 76.7% (95% CI = 37.2%–99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%–57.7%) and 49.3% (95% CI = 21.9%–84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.

An elevated fasting glucose level in non-diabetic individuals is a key predictor of type 2 diabetes. Genome-wide association studies (GWAS) have identified hundreds of SNPs for fasting glucose but most of their functional roles in influencing the trait are unclear. This study aimed to identify the mediation effects of DNA methylation between SNPs identified as significant from GWAS and fasting glucose using Mendelian randomisation (MR) analyses.We first performed GWAS analyses for three cohorts (Taiwan Biobank with 18,122 individuals, the Healthy Aging Longitudinal Study in Taiwan with 1989 individuals and the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance with 416 individuals) with individuals of Han Chinese ancestry in Taiwan, followed by a meta-analysis for combining the three GWAS analysis results to identify significant and independent SNPs for fasting glucose. We determined whether these SNPs were methylation quantitative trait loci (meQTLs) by testing their associations with DNA methylation levels at nearby CpG sites using a subsample of 1775 individuals from the Taiwan Biobank. The MR analysis was performed to identify DNA methylation with causal effects on fasting glucose using meQTLs as instrumental variables based on the 1775 individuals. We also used a two-sample MR strategy to perform replication analysis for CpG sites with significant MR effects based on literature data.Our meta-analysis identified 18 significant (p 5 × 10Our analysis results suggest that rs2232326 and rs2232328 in G6PC2 may affect DNA methylation at CpGs near the gene and that the methylation may have downstream effects on fasting glucose. Therefore, SNPs in G6PC2 and CpGs near G6PC2 may reside along the pathway that influences fasting glucose levels. This is the first study to report CpGs near G6PC2, an important gene for regulating insulin secretion, mediating the effects of GWAS-significant SNPs on fasting glucose.

This article comprehensively considers timeliness of emergency rescue and cost constraints. Based on the transportation costs from the rescue center to the disaster site and the cost of setting up the rescue center, golden rescue timeis taken into account. The penalty cost caused by losing the golden rescue time is considered, thereby quantifying timeliness as another dimension of cost. The problem is solved using K-means clustering algorithm and fruit fly algorithm (FOA). With the purpose of minimizing the weighted sum of construction costs, transportation costs and penalty costs of emergency rescue centers, suitable location is selected for establishment of emergency rescue center. Finally, modified two algorithms (RWFOA and MFOA) are compared in optimization performance. The K-means clustering analysis and FOA are used to simplify and solve the original model, which can solve complex problems. In comparison between RWFOA and MFOA, the optimal value of MFOA is lower.

Salinity is one of the most important abiotic stresses, which affects the yield and quality of banana (Musa paradisiaca). To understand the salinity tolerance mechanisms of banana, the iTRAQ technique is employed to reveal the proteomic response of Brazil banana under different durations of 60 mmol/L NaCl stress. We have identified 77 DEPs and classified them into nine functional categories, compared with control (0 mmol/L NaCl treatment). The four major categories involve protein synthesis and degradation, photosynthesis, defense response, and energy and carbohydrate metabolism. The results indicate that photosynthesis, protein synthesis and degradation, lipid metabolism and secondary metabolism are promoted to limit damage to a repairable level. The accumulation of ROS under salt stress is harmful to cells and causes up-regulation of antioxidant systems. Furthermore, to cope with cells injured by salt stress, PCD is used to remove the damaged. Additionally, the cytoskeleton can play an important role in maintaining cellular and redox homeostasis. Different categories of functional proteins by changing the abundance ratio shows that plants have different mechanisms of response to salinity. Conclusively, Function of the observed changes in protein expression objective is to establish a new metabolic process of steady-state balance. To my knowledge, this is the first report that investigates responses of M. paradisiaca to salt stress by proteomic analysis.

BACKGROUND/AIM Epidermal growth factor receptor (EGFR), mothers against decapentaplegic homolog 7 (SMAD7) and transforming growth factor betta (TGFB) are crucial for colorectal cancer (CRC) tumorigenesis. This study investigated whether polymorphisms in EGFR, SMAD7, and TGFB are associated with CRC risk in patients with Lynch syndrome. MATERIALS AND METHODS Genotyping was performed using Sequenom iPLEX MassArray. Association between genetic polymorphisms and CRC was assessed using a weighted Cox proportional hazard model. RESULTS Patients carrying the AA genotype of EGFR rs2227983 had a significantly higher CRC risk than those carrying the G allele (HR=2.55, 95% CI=1.25-5.17). The dominant model of SMAD7 rs12953717 (CT + TT genotypes) significantly increased CRC risk (HR=2.17, 95% CI=1.12-4.16) when compared to the wild-type CC genotype. Similarly, the GG genotype of TGFBR2 rs6785358 significantly increased the risk of CRC (HR=21.1, 95% CI=5.06-88.1) compared to the AA genotype. CONCLUSION EGFR, SMAD7, and TGFBR2 are associated with CRC risk in patients with Lynch syndrome.

The SORBS1 gene plays an important role in insulin signaling. We aimed to examine whether common single-nucleotide polymorphisms (SNPs) of SORBS1 are associated with prevalence and incidence of diabetes, age at onset of diabetes, and the related traits of glucose homeostasis. A total of 1135 siblings from 492 ethnic Chinese families were recruited at baseline, and 630 were followed up for 5.19 ± 0.96 years. Nine SNPs including rs7081076, rs2281939, rs3818540, rs2274490, rs61739184, rs726176, rs2296966, rs17849148, and rs3193970 were genotyped and examined. To deal with correlated data of subjects within the same families, the generalized estimating equations approach was applied throughout all association analyses. The GG genotype of rs2281939 was associated with a higher risk of diabetes at baseline, an earlier onset of diabetes, and higher steady-state plasma glucose levels in the modified insulin suppression test. The minor allele T of rs2296966 was associated with higher prevalence and incidence of diabetes, an earlier onset of diabetes, and higher 2-h glucose during oral glucose tolerance test. These two SNPs revealed independent associations with age of diabetes onset as well as risk of diabetes at baseline. These findings supported that SORBS1 gene participates in the pathogenesis of diabetes.

Background DNA repair genes are crucial for maintaining genomic stability by preventing mutagenesis and carcinogenesis. The present retrospective cohort study aimed at investigating whether MLH1, APEX1, MUTYH, OGG1, NUDT1, XRCC5, XPA, and ERCC2 single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in Chinese population with Lynch syndrome. Methods From Amsterdam criteria family registry, we identified 270 patients with Lynch syndrome. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between DNA repair SNPs and CRC were calculated using a weighted Cox proportional hazard regression model. Results Heterozygous variants of rs1799832 in NUDT1 (HR = 2.97, 95% CI = 1.51-5.83) and rs13181 in ERCC2 (HR = 2.69, 95% CI = 1.10-6.55) were significantly associated with an increased risk of CRC compared with wild-type homozygous CC and TT genotypes, respectively. However, the variant CG+GG genotype of MUTYH rs3219489 was associated with a decreased risk of CRC (HR = 0.49, 95% CI = 0.26-0.91) compared with the homozygous CC wild-type counterparts. Conclusion Our findings revealed that polymorphisms of DNA repair genes that include NUDT1, ERCC2, and MUTYH are associated with CRC in patients with Lynch syndrome in Chinese population. Further studies with large sample size are needed to confirm our findings.

Background Oral verrucous hyperplasia is commonly observed in the oral cavity of betel quid chewers and is a potential malignant disorder. However, the prognostic factors and genetic alterations of oral verrucous hyperplasia are unclear. Methods We calculate the survival rate and prognostic factors using a Kaplan-Meier analysis and Cox proportional hazards regression model. Copy number variations were analyzed using a single-nucleotide polymorphism (SNP) array. Results The 5-year disease-free and cancer-free survival rates of patients with oral verrucous hyperplasia were approximately 40% and 70%, respectively. Heavy betel quid chewing, advanced oral submucous fibrosis, and nonbuccal and nontongue lesions were risk factors for malignant transformation, whereas dysplasia did not affect outcomes. The gene amplification of CTTN, FOLR3, ORAOV1, PPFIA1, and RNF121 were associated with the poor prognosis of oral verrucous hyperplasia. Conclusion Heavy betel quid chewing, advanced oral submucous fibrosis, and nonbuccal and nontongue lesions are high-risk factors of patients with oral verrucous hyperplasia. The 5-copy number variation-associated genes could be used for early diagnosis and predicting the prognosis.

Chromosome 12q23-q24 has been linked to triglyceride (TG) levels by previous linkage studies, and it contains the Insulin-like growth factor 1 (IGF1) gene. We investigated the association between IGF1 and TG levels using two independent samples collected in Taiwan. First, based on 954 siblings in 397 families from the Stanford Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe), we found that rs978458 was associated with TG levels (β = -0.049, p = 0.0043) under a recessive genetic model. Specifically, subjects carrying the homozygous genotype of the minor allele had lower TG levels, compared with other subjects. Then, a series of stratification analyses in a large sample of 13,193 unrelated subjects from the Taiwan biobank (TWB) project showed that this association appeared in subjects with a family history (FH) of hypertension (β = -0.045, p = 0.0000034), but not in subjects without such an FH. A re-examination of the SAPPHIRe sample confirmed that this association appeared in subjects with an FH of hypertension (β = -0.068, p = 0.0025), but not in subjects without an FH. The successful replication in two independent samples indicated that IGF1 is associated with TG levels in subjects with an FH of hypertension in Taiwan.

// Wei-Chiao Chen 1, * , Wen-Chang Wang 2 , 3, * Hsing-Fang Lu 4 , Yukinori Okada 5 , Wei-Pin Chang 6 , Yii-Her Chou 7, 8 , Hui-Hua Chang 1, 9 , Jin-Ding Huang 1 , Der-Yuan Chen 10, 11, 12, 13 and Wei-Chiao Chang 2, 3, 4, 14, 15 1 Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan 2 The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan 3 Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan 4 Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan 5 Department of Statistical Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan 6 School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan 7 Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 8 Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 9 School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan 10 Department of Internal Medicine and Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan 11 Faculty of Medicine, National Yang Ming University, Taipei, Taiwan 12 Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan 13 Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan 14 Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan 15 Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Der-Yuan Chen, email: dychen@vghtc.gov.tw Wei-Chiao Chang, email: wcc@tmu.edu.tw Keywords: rheumatoid arthritis (RA), phospholipase D family, member 4 (PLD4), rs2841277, rs4672495 Received: May 01, 2017 Accepted: June 05, 2017 Published: July 18, 2017 ABSTRACT Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, can lead to long-term joint damage, chronic pain, and loss of motor function in the hands, and may share some common genetic factors with other autoimmune disorders, such as ankylosing spondylitis (AS). Many single-nucleotide polymorphisms (SNPs) were reported by genome-wide association studies (GWASs) of RA, but some of them have not been examined in the Taiwanese population. In this study, for 15 SNPs reported in previous RA and AS GWASs, we investigated their association with RA in a Taiwanese population. Based on 334 RA patients recruited from the Taichung Veterans General Hospital and 16,036 healthy subjects from the Taiwan Biobank (TWB) project, we observed that subjects having minor allele C at rs2841277 ( phospholipase D family, member 4 ( PLD4 )) have lower susceptibility of RA, compare to those having genotype TT (Odds ratio (OR) = 0.6, p = 3.0 x 10 -6 ). Among the RA patients, we observed that subjects having GG at rs4672495 have a lower proportion of severe RA, compare to other subjects (OR = 0.09, p = 5.6 x 10 -3 ). Results of a bioinformatics approach showed that rs2841277 is able to influence expression of LINC00638 and AHNAK2 and rs4672495 is able to influence the expression of B3GNT2 . In summary, this study replicated an association of rs2841277 with RA susceptibility and showed an AS-associated SNP, rs4672495, is associated with RA activity in the Taiwanese population.

Cytochrome P450 (CYP), glutathione-S-transferase (GST), and N-acetyltransferase (NAT) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP, GST, and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The interaction between these SNPs and cigarette smoking or meat consumption was also explored. We identified 270 patients with Lynch syndrome from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs). The GSTA1 rs3957356 TT (HR = 5.36, 95% CI = 2.39–12.0) and CYP1B1 rs1056836 CC (HR = 7.24, 95% CI = 3.51–14.9) were significantly associated with CRC risk when compared to wild-type CC and GG genotypes, respectively. However, the CYP1A1 rs4646903 CC genotype significantly reduced the risk of CRC (HR = 0.33, 95% CI = 0.12–0.89) when compared to TT genotype. Moreover, significant interactions were observed between NAT1 acetylation and CYP1B1 rs1056827 and meat consumption.Our results suggest that xenobiotic-metabolizing SNPs are not only associated with CRC risk in patients with Lynch syndrome in Taiwan but also interact with meat consumption to modify the disease risk. Environ. Mol. Mutagen., 2017. © 2017 Wiley Periodicals, Inc.

Long noncoding RNAs (lncRNAs) have been implicated in hypoxia/HIF-1-associated cancer progression through largely unknown mechanisms. Here we identify MIR31HG as a hypoxia-inducible lncRNA and therefore we name it LncHIFCAR (long noncoding HIF-1α co-activating RNA); we describe its oncogenic role as a HIF-1α co-activator that regulates the HIF-1 transcriptional network, crucial for cancer development. Extensive analyses of clinical data indicate LncHIFCAR level is substantially upregulated in oral carcinoma, significantly associated with poor clinical outcomes and representing an independent prognostic predictor. Overexpression of LncHIFCAR induces pseudo-hypoxic gene signature, whereas knockdown of LncHIFCAR impairs the hypoxia-induced HIF-1α transactivation, sphere-forming ability, metabolic shift and metastatic potential in vitro and in vivo. Mechanistically, LncHIFCAR forms a complex with HIF-1α via direct binding and facilitates the recruitment of HIF-1α and p300 cofactor to the target promoters. Our results uncover an lncRNA-mediated mechanism for HIF-1 activation and establish the clinical values of LncHIFCAR in prognosis and potential therapeutic strategy for oral carcinoma., Cancer cells adapt to the changing microenvironment by activating different pathways through multiple mechanisms. Here the authors identify long noncoding RNA MIR31HG as a HIF-1α co-activator required for the induction of the hypoxic response and show its oncogenic role in oral carcinogenesis.

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

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

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

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

PURPOSE To study the association between chronic hepatitis B virus (HBV) and age-related macular degeneration (AMD). METHODS Data used in this retrospective, frequency-matched cohort study were acquired from the Longitudinal Health Insurance Database 2000, which includes medical claims and registration files for 1 000 000 enrolees in the Taiwan National Health Insurance programme. The HBV cohort contained 17 796 patients who received a diagnosis of chronic HBV infection between January 1, 2000 and December 31, 2012. The non-HBV cohort contained 71 184 participants who were frequency-matched by age, sex and year of index date for comparison. Participants were followed until the end of 2013, and those who developed AMD during the study period were identified. A Cox proportional hazards regression model was used to compare the risk of AMD between cohorts. RESULTS The incidence of any type of AMD in all participants was 3.88 per 1000 person-years (PY; 2.27 per 1000 PY in the HBV cohort; 1.61 per 1000 PY in the non-HBV cohort). Compared with the non-HBV cohort, the adjusted hazard ratio (HR) for any type of AMD in the HBV cohort was 1.41 [95% confidence interval (CI) 1.23-1.63; p

BackgroundIn this study, the long-term efficacy of hepatitis B virus (HBV) vaccination was assessed using seroprevalence and an age–period–cohort (APC) model of HBV seromarkers among university entrants 30 years after the introduction of the national neonatal HBV vaccination program in Taiwan.MethodsIn total, data of 17,611 university entrants who underwent university entrance health examinations between 2005 and 2016 were included. The seroprevalence of the HBV surface antigen (HBsAg) and the levels of the antibody against the HBV surface antigen (anti-HBs) in each year group and sex were calculated. The levels of the antibody against the HBV core antigen were examined only for 2012 and 2016. The APC model was used to analyze the HBV carrier rates.ResultsThe chronic HBV infection (HBsAg positivity) rate decreased from 9.7% in university students born before June 1974 to P ConclusionsHBV vaccination is one of the most effective strategies for preventing HBV infection. However, for complete eradication of HBV infection, the development of strategies that detect vaccination failure more effectively than current strategies do and early implementation of appropriate treatments are both necessary.

Objective Both adenomyosis and endometriosis are characterized by the presence of ectopic endometrial glands and stroma and have been suggested to share some characteristics with malignant tumors. Although accumulating evidence indicates that endometriosis is associated with some cancer types, the cancer risks in patients with adenomyosis have been rarely examined. In this study, we investigated the relationship between adenomyosis and risks of common cancers. Methods This study included a cohort of 12,447 women with adenomyosis but not endometriosis, born in 1951-1984, and a cohort of 124,470 adenomyosis-free women matched by birth year. Their medical records (collected between 1996 and 2011) were obtained from the National Health Insurance Research Database of Taiwan. We first compared the distribution of cancer-free survival (CFS) between cohorts with and without adenomyosis. Subsequently, within the adenomyosis cohort, we examined whether time-to-onset of the identified cancer type was correlated with time-to-onset of adenomyosis. The Cox proportional hazards model was used to compare the distribution of CFS between the adenomyosis and adenomyosis-free cohorts and between the early- and late-diagnosed adenomyosis groups. For comparison, we further evaluated the cancer risks for a cohort of 10,962 women with endometriosis but not adenomyosis and a birth-year matched cohort of 109,620 endometriosis-free women. Results Compared with adenomyosis-free women, patients with adenomyosis had higher risks of endometrial and thyroid cancers, with estimated hazard ratios (HRs) (95% confidence interval) of 2.19 (1.51-3.16) and 1.70 (1.29-2.24), respectively. For both cancers, distributions of CFS were not significantly different between the early- and late-diagnosed adenomyosis groups. Furthermore, compared with endometriosis-free women, patients with endometriosis had higher risks of endometrial and ovarian cancers, with HRs of 1.89 (1.07-3.35) and 2.01 (1.27-3.16), respectively. Conclusions Women with adenomyosis are at higher risks of endometrial and thyroid cancers, while women with endometriosis are at higher risks of endometrial and ovarian cancers.

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, can lead to long-term joint damage, chronic pain, and loss of motor function in the hands, and may share some common genetic factors with other autoimmune disorders, such as ankylosing spondylitis (AS). Many single-nucleotide polymorphisms (SNPs) were reported by genome-wide association studies (GWASs) of RA, but some of them have not been examined in the Taiwanese population. In this study, for 15 SNPs reported in previous RA and AS GWASs, we investigated their association with RA in a Taiwanese population. Based on 334 RA patients recruited from the Taichung Veterans General Hospital and 16,036 healthy subjects from the Taiwan Biobank (TWB) project, we observed that subjects having minor allele C at rs2841277 (phospholipase D family, member 4 (PLD4)) have lower susceptibility of RA, compare to those having genotype TT (Odds ratio (OR) = 0.6, p = 3.0 × 10−6). Among the RA patients, we observed that subjects having GG at rs4672495 have a lower proportion of severe RA, compare to other subjects (OR = 0.09, p = 5.6 × 10−3). Results of a bioinformatics approach showed that rs2841277 is able to influence expression of LINC00638 and AHNAK2 and rs4672495 is able to influence the expression of B3GNT2. In summary, this study replicated an association of rs2841277 with RA susceptibility and showed an AS-associated SNP, rs4672495, is associated with RA activity in the Taiwanese population.

Cytochrome P450 (CYP), glutathione-S-transferase (GST), and N-acetyltransferase (NAT) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP, GST, and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The interaction between these SNPs and cigarette smoking or meat consumption was also explored. We identified 270 patients with Lynch syndrome from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs). The GSTA1 rs3957356 TT (HR = 5.36, 95% CI = 2.39-12.0) and CYP1B1 rs1056836 CC (HR = 7.24, 95% CI = 3.51-14.9) were significantly associated with CRC risk when compared to wild-type CC and GG genotypes, respectively. However, the CYP1A1 rs4646903 CC genotype significantly reduced the risk of CRC (HR = 0.33, 95% CI = 0.12-0.89) when compared to TT genotype. Moreover, significant interactions were observed between NAT1 acetylation and CYP1B1 rs1056827 and meat consumption.Our results suggest that xenobiotic-metabolizing SNPs are not only associated with CRC risk in patients with Lynch syndrome in Taiwan but also interact with meat consumption to modify the disease risk. Environ. Mol. Mutagen. 59:69-78, 2018. © 2017 Wiley Periodicals, Inc.

C-reactive protein (CRP) encoded by CRP gene is a reflection of systemic inflammation. Many studies associated CRP level with diabetes and glucose levels, but the association of CRP gene with these traits is unclear. We conducted a cross-sectional study consisting of 945 siblings from 330 families collected by the Stanford Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe) to investigate associations between CRP polymorphisms, circulating CRP, diabetes, and glucose levels. Five single-nucleotide polymorphisms were analyzed: rs3093059, rs2794521, rs1417938, rs1800947, and rs1205. The generalized estimating equation approach was used to deal with correlated data within families. CRP level was positively correlated with diabetes prevalence and levels of fasting and 2-hour glucose (each P C at rs3093059 and G at rs1205 were associated with elevated CRP level (each P −6). Allele C at rs3093059 was associated with fasting glucose (β = 0.20, P = 0.045) and G at rs1205 was associated with 2-hour glucose (β = 0.46, P = 0.00090) post oral glucose tolerance test, but only the latter passed Bonferroni correction. No polymorphism was associated with diabetes. Since 2-hour glucose is an indicator of glucose tolerance, this study indicated CRP gene is associated with glucose intolerance.