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This study assessed the interactions among IGF-1, AKT2, FOXO1, and FOXO3 variations and the interactions of gene and physical activity on handgrip strength, arm muscle mass-adjusted handgrip (armGrip), gait speed (GS), timed up and go (TUG), and leg press strength (LPS). Nine single nucleotide polymorphisms (SNPs) containing three IGF-1 SNPs (rs6214, rs5742692, and rs35767), two AKT2 SNPs (rs892119 and rs35817154), two FOXO1 SNPs (rs17446593 and rs10507486), and two FOXO3 SNPs (rs9480865 and rs2153960) were genotyped in 472 unrelated elders with a mean age of 73.8 years. We observed significant interactions of IGF-1 SNP rs6214 and rs35767 with regular physical activity on TUG and GS; and AKT2 SNP rs892119 and FOXO3 SNP rs9480865 with regular physical activity on armGrip. Genotype GG of IGF-1 rs6214 and rs35767 in individuals without regular physical activity had poor performance in TUG and GS, as well as GG of AKT2 rs892119 decreased armGrip in individuals without regular physical activity. After FDR adjustment, no significant gene-gene interactions were found. A sedentary lifestyle may increase the risk of impairing physical performance and regular physical activity is a remedy for sarcopenia, even a little regular physical activity can overcome carrying some risk alleles in this pathway.

Chemical vapor deposition (CVD) was applied to the synthesis of carbon nanotubes with acetylene as the carbon source at 600–800 °C in a nitrogen atmosphere. The mesoporous material MCM-41 was selected as the template, and Ni and Fe were selected as the catalysts. MCM-41 was synthesized for the templates and used for acetylene decomposition to form carbon nanotubes at various temperatures. In Raman spectrometry analysis, the synthesized carbon nanomaterials exhibited an insignificant difference in the degree of graphitization under various pyrolysis temperatures. Results indicated that the liquid products (tar and residues) were the main fraction during acetylene decomposition. For exhaust gas, the concentration of hydrocarbons increased with an increase in temperature. NO concentrations decreased with an increase in temperature. The constituents of exhaust gases (CO, CO2, hydrocarbon and NO) were similar during the synthesis of carbon nanomaterials with various catalysts on templates. The sequence of the abundance of polycyclic aromatic hydrocarbons (PAHs) was C-Ni-MCM-41 > C-Fe-MCM-41 > C-MCM-41 system at the same pyrolysis temperature, and high PAH levels presented for high pyrolysis temperatures. For 52 volatile organic compounds (VOCs), the concentrations were C-MCM-41 > C-Fe-MCM-41 > C-Ni-MCM-41, and low concentration was determined for acetylene pyrolysis at high temperatures.

We assessed gene–gene and gene-physical activity interactions of polymorphisms in C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and lymphotoxin α (LTA) genes on lower extremity performance in community-dwelling elders in Taiwan. Five SNPs (rs1205, rs1130864, rs1800947, rs2794520, and rs3093059) of CRP gene, three SNPs (rs909253, rs1041981, and rs2239704) of LTA gene, and three SNPs (rs3093662, rs1800629, and rs1799964) of TNF-α gene of 472 unrelated elders were genotyped. Lower extremity performance included timed up-and-go test (TUG), walking speed, weight-adjusted leg press (waLP), and timed chair stand (TCS). We detected significant interactions between physical activity with CRP rs2794520, rs1205, and rs3093059; LTA rs909253 and rs1041981; and TNF-α rs1799964 for TCS in women after covariate adjustment (all P

Gene effects on osteoporosis have been studied separately and may have been masked by gene-gene and gene-environment interactions. We evaluated gene-gene and gene-physical activity interactions of the variants of tumor necrosis factor-α (TNF-α) and vitamin D receptor (VDR) genes on osteoporosis. A total of 472 elders were included. Seven variants (TNF-α: rs1799964, rs1800629, rs3093662; VDR: rs7975232, rs1544410, rs2239185, rs3782905) were genotyped. Bone mineral densities of the lumbar spine, femoral neck, and total hip were measured by dual-energy X-ray absorptiometry. Predictive models' ability to discriminate osteoporosis status was evaluated by areas under the receiver operating characteristics (AUROC) curve. After multivariable adjustment, significant interactions of TNF-α rs1800629 and VDR rs3782905 were observed on overall and lumbar spine osteoporosis. In elderly women, we found that those carrying the CG/CC genotype of VDR rs3782905 were significantly associated with increased odds of overall osteoporosis compared with those carrying the GG genotype of VDR rs3782905 among those carrying TNF-α rs1800629 GG genotype. The adjusted odds ratios (ORs) for VDR rs3782905 CG/CC genotype in elderly women carrying TNF-α rs1800629 AG/AA and GG genotypes were 0.1 (0.01, 0.98) and 3.54 (1.51, 8.30), respectively. We observed significant differences in AUROCs between the model with traditional covariates plus variants and their interaction term and the model with traditional covariates only (AUROCs: 0.77 and 0.81; p = 0.028). Although the sample size of this study may have been relatively small, our results suggest that the interaction of the CG/CC genotype of VDR rs3782905 with TNF-α rs1800629 GG genotype was associated with increased odds of overall and lumbar spine osteoporosis in elderly women.

We studied 472 elders to assess joint association of vitamin D receptor (VDR) variability and physical activity on low handgrip strength (LHS) and osteoporosis (OST). Our findings showed that higher risks of OST were associated with physically inactive elders with some specific VDR variations, highlighting the importance of promotion program for physical activity. The aim of this study was to determine the joint association between VDR variability and physical activity on LHS and OST in community-dwelling elders. Bone mineral density of the lumbar spine (LS), the femoral neck (FN), and the total hip were measured by dual-energy X-ray absorptiometry. Four single-nucleotide polymorphisms (SNPs) (rs7975232, rs1544410, rs2239185, and rs3782905) of the VDR gene were examined in 472 participants. Physical inactivity and each of the four SNPs were jointly associated with a significantly greater risk of LHS in people than that associated with each of the VDR SNPs or low physical activity alone. Physically inactive men with the AG or AA genotype of rs2239185 had a significantly greater risk of overall, LS, and FN OST than those of physically active men with the GG genotype [odds ratio (OR) 3.57, 95 % confidence interval (CI) 1.10–11.65; OR 4.74, 95 % CI 1.43–15.70; and OR 5.06, 95 % CI 1.08–23.71, respectively]. Similarly, physically inactive women with the CG or CC genotype of rs3782905 and the AG or AA genotype of rs1544410 had a significantly greater risk of FN OST than physically active women with the GG genotype (OR 5.33, 95 % CI 1.23–23.06 and OR 5.36, 95 % CI 1.11–25.94, respectively). VDR polymorphisms and physical activity are jointly associated with LHS and OST in elders. Health care programs should promote physical activity among elders as a cost-effective way to prevent LHS and OST, especially in those who may be genetically predisposed.

This retrospective cohort study investigated the association between epidermal growth factor receptor (EGFR) polymorphisms and clinical outcomes in colorectal cancer (CRC) patients treated with 5-fluorouracil (5-FU)-based chemotherapy. We genotyped 3 EGFR polymorphisms including R497K, G-216T, and the (CA)n repeat, among 499 histologically confirmed CRC patients who had received 5-FU-based chemotherapy after surgery between 1995 and 2001. Survival analyses of EGFR polymorphisms were performed by the log rank test and Kaplan–Meier curves. We used the Cox proportional hazard model to evaluate the association between EGFR genotypes and clinical outcomes. Stratification analysis by gender, tumor stage, and subsite were also carried out. CRC patients with the EGFR (CA)n L/L genotype compared to those with the S/S+S/L genotype had a significantly better overall survival (L, ≥20 repeats; S

Supplemental Digital Content is available in the text, Pulmonary tuberculosis (PTb) and pneumonia are diseases that may exist concomitantly. Population study investigating the subsequent pneumonia development in PTb patients is limited. This study compares the risk of pneumonia between cohorts with and without PTb. We used the claims data of the Taiwan National Health Insurance to identify a cohort with PTb (N = 3417) newly diagnosed in 2000–2006 without pneumonia history, and a randomly selected comparison cohort (N = 6834) free of PTb and pneumonia, frequency matched by propensity score. Incidence rates and hazard ratios of pneumonia were calculated by sex, age, and comorbidity starting in the 7th month after the cohorts being established until the end of 2011. We found the incidence of pneumonia to be 1.9-fold higher in the PTb cohort than in the PTb free cohort (51.6 vs 27.0 per 1000 person-years). The PTb cohort had a Cox method estimated adjusted hazard ratio of 2.14 (95% confidence interval = 1.96–2.32). We also found that the risk was greater for men than for women, but lower for young adults aged 20–39 years. Comorbidity interacted with PTb by aggravating the pneumonia risk, particularly for those with asthma. For PTb patients comorbid with asthma, the pneumonia incidence was 2.5-fold higher than for PTb patients free of comorbidities (75.9 vs 29.3 per 1000 person-years). Our results display that PTb patients have an elevated risk of developing pneumonia. Adequate follow-up should be provided to the PTb patients, especially those with comorbidity.

Human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV), is not routinely isolated in cell cultures, and thus detection of HHV-8-specific antibodies is usually performed. In this study, we performed recombinant antigens ORF66- and ORFK12-based Western blot strip assays and ELISA, and surveyed the seroprevalence of HHV-8 antibodies in HIV-positive and -negative patients. In serum samples from patients with positive plasma HHV-8 DNA, the sensitivity of the Western blot strip assay was 100% for the anti-ORF66 antibodies and 83.3% for the anti-ORFK12 antibodies. In addition, ORF66-based ELISA showed higher levels of specificity (87.3%) and sensitivity (84.8%) than ORFK12-based ELISA. Moreover, the area under the receiver-operating characteristics curves (AUROC) was 0.76 for ORF66-based ELISA and 0.66 for ORFK12-based ELISA. The seroprevalence of HHV-8 antibodies to ORF66 and/or ORFK12 in the HIV-infected patients (55%, 97/176) was significantly higher than in the DM patients (45%, 135/301) (P = 0.03) and the HIV-/DM-negative group (11%, 11/100) (P < 0.01). In the HIV-infected patients, the seropositivity of the HHV-8-specific antibody was 30% to both antigens, 19% to ORFK12 and 5.7% to ORF66. Importantly, HHV-8 seropositivity in the HIV-infected patients was significantly associated with the transmission method of intravenous injection and high levels of HIV RNA loading (P < 0.01), but not with gender, CD4 cell numbers or AIDS symptoms. This study assessed the sensitivity and specificity of ORF66 and ORFK12 for the detection of HHV-8 antibodies, providing novel antigens for the diagnosis of HHV-8 infection and epidemiology of HHV-8 seroprevalence.

The objective of this study was to assess the correlation between blood lead levels (BLL) with both renal dysfunction and hyperuricemia among aboriginals and non-aboriginals in Taiwan. 1318 aboriginals and 1247 non-aboriginals over 40 years of age volunteered for this study. During routine health examinations at a clinic, blood samples were taken and a questionnaire was administered. Male uric acid (BUA) concentration (7.2 mg/dL) in serum was higher than for females (5.9 mg/dL). BUA concentration among aboriginals was higher (6.9 mg/dL) than among non-aboriginals (5.9 mg/dL). A test for trend of odds ratio (OR) for renal dysfunction and hyperuricemia indicated a significant correlation with BLL for both ethnic groups. Multiple logistic regression showed people who had BLLs exceeding 7.5 microg/dL were at a higher risk for renal dysfunction (OR=1.92, 95% CI: 1.18-3.10) and hyperuricemia (OR=2.72, 95% CI: 1.64-4.52). We concluded that BLL was significantly correlated with renal dysfunction and hyperuricemia in both ethnic groups. Further research is needed to investigate the exact mechanism causing a higher incidence of related disease among aboriginal Taiwanese.

Humic acid (HA) in well water used by the inhabitants for drinking is one of the possible etiological factors for blackfoot disease (BFD). Moreover, within BFD endemic areas cancers occur at significantly higher rates than in areas free of BFD. In this study, the genotoxic potential of HA is assessed using human peripheral blood lymphocytes. The cells were exposed to HA (0–200 μg/mL for 2 h), and the induction of DNA primary damage in cellular DNA was evaluated by single-cell gel electrophoresis (comet assay). HA-induced DNA damage was decreased by superoxide (O 2 − ), hydrogen peroxide (H 2 O 2 ), and reactive oxygen species (ROS) scavengers (superoxide dismutase, catalase, and Trolox), and nitric oxide (NO) synthase inhibitors ( N G -nitro- l -arginine methyl ester and N G -methyl- l -arginine). Moreover, formamidopyrimidine-DNA glycosylase (Fpg) and endonuclease III (Endo III), known to catalyze the excision of oxidized bases, increase the amount of DNA migration in HA-treated cells. Pretreatment of the cells with both the Ca 2+ -chelator BAPTA and EGTA completely inhibited HA-induced DNA damage, indicating that HA-induced changes in Ca 2+ -homeostasis are the predominant pathways for the HA induction of genotoxicity. Furthermore, sister chromatid exchange was found in the HA-treated lymphocytes. Our findings suggest that HA can induce oxidative DNA damage and genotoxicity in human lymphocytes.

Osteoporosis (OST) is a complex multifactorial disease considered to result from interactions of multiple gene and environmental factors. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 are pleiotropic cytokines essential for bone remodeling; and hormone leptin has immunomodulatory effects that stimulate the synthesis of IL-6 and TNF-α. Leptin is involved in the modulation of bone growth and turnover; and its actions are bound by leptin receptor (LEPR). Prior studies evaluated the effects of TNF-α, IL-6, and LEPR gene polymorphisms separately on bone mineral densities (BMD) or OST. In this study, we assessed the roles of TNF-α and IL-6 gene polymorphisms in OST through joint effects and interactions with LEPR gene. We also evaluated possible joint effects and interactions between these polymorphisms and physical activity. Ten tag-SNPs (rs1799964, rs1800629, rs3093662 in TNF-α; rs1880243, rs1800796, rs1554606 in IL-6; and rs1751492, rs8179183, rs1805096, rs1892534 in LEPR) were used to genotype 103 OST cases and 369 controls. BMD of lumbar spine (LS), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry. Our data showed that TNF-α and IL-6 polymorphisms were associated with overall and site-specific OST in both sexes, and that these associations were dependent on rs1805096 and rs1892534 genotypes of LEPR. In men, LEPR A-G-G-G haplotype was associated with FN OST (OR 4.65, 95 % CI 1.61–13.40, p = 0.004). Genotype AA/AG of LEPR rs1751492 was associated with overall and FN OST in women without physical activity, but not in women with physical activity (p

This study assesses interactions of tumor necrosis factor α (TNF-α) gene polymorphisms with C-reactive protein (CRP) or lymphotoxin α (LTA) gene on serum CRP and TNF-α levels and handgrip strength. Eleven single nucleotide polymorphisms (SNPs), including rs2794520, rs1205, rs1130864, rs1800947, and rs3093059 in CRP; rs1799964, rs1800629, and rs3093662 in TNF-α; and rs2239704, rs909253, and rs1041981 in LTA, were genotyped in 472 unrelated elders (mean age 73.8 years). Among elders with TNF-α rs1799964 AA genotype, adjusted mean difference for handgrip strength decreased by −2.60 (−4.82, −0.38) and −2.51 kg (−4.75, −0.28) for LTA rs909253 and rs1041981 in women and by −2.39 kg (−3.98, −0.81) for CRP rs3093059 in men. Among elders with TNF-α rs1799964 AA genotype, adjusted mean ratios for hs-CRP levels increased by 2.32 (1.38, 3.90) and 2.27 (1.35, 3.84) for both CRP rs909253 and rs1041981 in women. The A-A-C LTA haplotype was associated with TNF-α levels that were 1.55 times higher than those of the C-G-A haplotype (P = 0.005). The joint effects of SNPs (the rs1800947 or rs3093059 of CRP, rs1799964 or rs1800629 of TNF-α, and rs909253 or rs1041981 of LTA) and physical inactivity appeared to have greater magnitude of decreased handgrip strength than main effects of these SNPs and physical inactivity. Our data showed that significant interactions of TNF-αrs1799964 and LTA rs909253 were observed. Moreover, joint effects of these CRP, TNF-α, and LTA risk alleles with physical inactivity in elders were observed, suggesting that physical activity may modulate effects of genotypes on handgrip strength.

The aim of this study was to evaluate the interacted association between EDNRA and EDN1 polymorphisms and gender, regular exercise, and obesity status on carotid intima media thickness (IMT) in community- dwelling subjects of the Taichung Community Health Study. Five single-nucleotide polymorphisms (SNPs rs1395821, rs1878406, rs5333, rs1800541, and rs5370) of the EDNRA and EDN1 gene were examined in 480 participants from 160 families. The IMT protocol involves scanning the common carotid arteries (CCAs), the carotid bifurcations (bulb), and the origins (first 1 cm) of the internal carotid arteries (ICAs). Generalized linear models with a generalized estimating equation were employed to consider the dependence among family members. After multivariate adjustment, the effects of interactions between EDNRA and EDN1 gene with gender, obesity, and exercise were observed. For gene-gender interaction on CCA IMT, the adjusted mean for men carrying the GA/GG genotype of EDNRASNP rs1878406 was 1.18 times higher than that for men carrying the AA genotype (95% CI: 1.01, 1.37). As for bulb and ICA IMT, the adjusted mean values for women carrying the AC/AA genotype of EDN1 rs5370 was lower than those carrying the CC genotype: 0.89, [0.82, 0.98]; and 0.90 [0.83, 0.99], respectively. We did observe significant effects of EDNRA SNPs rs1395821 and rs5333 in individuals who regularly exercised. A significantly lower adjusted mean in CCA IMT for non-obese individuals carrying EDNRA SNP rs5333 was observed (0.92 [0.86, 0.99]) compared with non-obese individuals carrying the AA genotype. This study first reported significant interactions of EDNRA and EDN1 polymorphisms with gender, regular exercise, and obesity on carotid IMT in Han Chinese participants.

To investigate the relationship between the blood lead level (BLL) and blood pressure among aborigines and non-aborigines in central Taiwan, a community-based survey that included demographic data, medical history, and blood chemistry analyses was conducted among 2,565 adults during an annual health examination. BLLs were analyzed using a graphite furnace atomic absorption spectrometer (AAS). There was a dose response among the non-aborigines (high BLL odds ratio = 2.97, compared with low BLL) but not among aborigines. Based on multiple linear regression models, BLLs were positively correlated with both systolic (an increase of 0.85 mm Hg/microg/dL) and diastolic (an increase of 0.48 mm Hg/microg/dL) blood pressures after adjusting for age, gender, ethnic group, alcohol consumption, and body mass index. BLLs were higher among aborigines than non-aborigines and were significantly correlated with blood pressure, particularly systolic pressure. The association should be considered causal.

This study examined the possible effect of cytochrome P450 (CYP1A1), glutathione S-transferase (GSTM1 and T1) and N-acetyltransferases 2 (NAT2) polymorphisms on DNA-protein crosslinks (DPC) formation in the white blood cells of breast cancer patients, and assessed the levels of DPC detected. Sixty cases of breast cancer were examined, all involving women diagnosed with primary, histopathologically confirmed breast cancer at the Chinese Medical College Hospital in central Taiwan. Additionally, 60 healthy women without breast cancer were selected as a control group, matched by age, cigarette smoking habits, and history of breast cancer among first-degree relatives. Known risk factors for breast cancer, including menarche before 13 years of age (OR=3.2; CI, 1.1-9.5), no history of breast-feeding (OR=4.7; CI, 1.5-14.4) and use of oral contraceptives (OR=9.1; CI, 2.8-29.8), were found to be significantly associated with breast cancer. For the CYP1A1 MspI polymorphism, 16.7 and 18.3% of cases and controls, respectively contained both alleles with the MspI restriction fragment length polymorphism (RFLP). Regarding the NAT2 allele, 25.0 and 21.7% of cases and controls carried slow genotypes. For GSTM1 and GSTT1, 56.7 and 45.0% of cases, as well as 58.3 and 43.3% of controls, contained the null genotype. Meanwhile, chi(2)-tests found no significant differences between the groups. After controlling for confounders such as cigarette smoking and family history of breast cancer, the DPC value of the case group significantly exceeded that of the control group (1.62% versus 0.98%, P0.001). In conclusion, our findings were inconsistent with those of previous studies that showed polymorphism genes (CYP1A1, NAT2, GSTM1 and GSTT1) were associated with cancer risk. However, this study indicated that genotypic variants of these polymorphisms did not elevate the risk for breast cancer, individually or interactively. Additionally, this investigation represents the first description of the use of DPC as a biomarker to assess the level of DNA damage of breast cancer patients. Our data suggest that the DPC method is a useful tool for detecting DNA damage, and DPC formation may be associated with the induction of breast cancer.

Background Diabetic nephropathy (DN) has become one of the most common causes of end-stage renal disease (ESRD) in many countries, such as 44.5% in Taiwan. Previous studies have shown that there is a genetic component to ESRD. Studies attempting to determine which genetic variants are related to DN in Han Chinese are limited. A case–control study was conducted to identify DN susceptibility variants in Han Chinese patients with type 2 diabetes. Results We included 574 unrelated type 2 diabetes patients (217 DN cases and 357 controls), who were genotyped using Illumina HumanHap550-Duo BeadChip. In single-SNP association tests, the SNPs rs11647932, rs11645214, and rs6499323 located at 16q22.1 under the additive-effect disease model were significantly associated with an approximately 2-fold increased risk of DN. In haplotype association tests, identified haplotypes located in the chromosome 16q22.1 region (containing ST3GAL2, COG4, SF3B3, and IL34 genes) raised DN risk. The strongest association was found with haplotype rs2288491-rs4985534-rs11645214 (C-C-G) (adjusted odds ratio [AOR] 1.93, 95% confidence interval [CI] 1.83-2.03, p = 6.25 × 10−7), followed by haplotype rs8052125-rs2288491-rs4985534-rs11645214 (G-C-C-G) (AOR 1.92, 95% CI 1.82-2.02, p = 6.56 × 10−7), and haplotype rs2303792-rs8052125-rs2288491-rs4985534-rs11645214 (A-G-C-C-G) (AOR 1.91, 95% CI 1.81-2.01, p = 1.15 × 10−6). Conclusions Our results demonstrate that the novel SNPs and haplotypes located at the 16q22.1 region may involve in the biological pathways of DN in Han Chinese patients with type 2 diabetes. This study can provide new insights into the etiology of DN. Electronic supplementary material The online version of this article (doi:10.1186/s12863-014-0113-8) contains supplementary material, which is available to authorized users.

The objective of this study was to investigate the association between chromium (Cr) concentrations and sister chromatid exchanges (SCE) formation in Cr workers and to assess the effects of susceptible genes (glutathione S-transferase M1 and T1) on the frequency of deletion and SCE/cell. Urinary Cr concentration was significantly elevated in Cr workers (3.67 +/- 3.89 microg/g creatinine) compared to control group (1.21 +/- 1.16 microg/g creatinine, P0.01). There was also a significant difference of superoxide dismutase (SOD) levels between Cr workers (6.86 +/- 0.80 U/mg Hb) and controls (7.16 +/- 0.53 U/mg Hb, P0.01). The frequencies of SCE and high frequency cells (HFC) were significantly correlated with smoking habits and with duration of exposure to Cr. A significantly higher percentage (50%) of Cr workers had both the null GSTM1 and GSTT1 genotype as compared to 10% of the controls (P0.01). However, the chromosomal DNA damage effect of GSTM1 and GSTT1 genotypes, individually or in combination, was not revealed in Cr exposed workers.

The frequency of sister chromatid exchanges (SCEs), high SCE frequency cells (HFCs), and genetic polymorphism of genotypes glutathione S-transferase (GST) M1 and T1 were analyzed in peripheral lymphocytes of 35 workers occupationally exposed to chromium (Cr) and 35 matched control group. Results showed that workers exposed to Cr showed 6.07 SCE/cell, as compared to 4.76 SCE/cell for the control group (p

Detection of plasma human herpesvirus (HHV)-8 DNA correlates with antibodies to lytic HHV-8 antigens, being predictive of Kaposi's sarcoma in HIV-infected patients. We show that the prevalence of plasma HHV-8 DNA was 10.6% for HIV infection through sexual contact and 7.1% for HIV infection through intravenous injection. In addition, the prevalence of plasma HHV-8 DNA was significantly associated with male gender (9.4%) and HIV viral load below 1000 copies mL(-1) (12.1%), but not age or CD4 cell count in HIV-infected patients. The study suggested that detection of plasma HHV-8 DNA could be important for monitoring replicating HHV-8 in HIV-infected patients, and may have use as a marker for the diagnosis of HHV-8 infection in blood-borne transmission.

Low handgrip strength is one component of frailty, characterized by loss of reserves, including energy, physical ability, cognition and health. This study rated the effect of five single-nucleotide polymorphisms (SNPs) in C-reactive protein (CRP) gene on the serum CRP level and handgrip strength in elderly Taiwanese. Five SNPs (rs2794520, rs1205, rs1130864, rs1800947, and rs3093059) of CRP gene were utilized to genotype 472 unrelated elderly subjects (mean age 73.8years). Handgrip strength was measured by handgrip dynamometer (TTM Dynamometer, Tsutsumi, Tokyo). Our study demonstrated that minor alleles of rs2794520 and rs1205 were C, whereas they were T in most ethnic groups. There exist significant associations of three CRP polymorphisms (rs2794520, rs1205 and rs3093059) with serum CRP level and handgrip strength. All three had simultaneous influence on raising CRP levels and reducing handgrip strength. Genotype and sex interactions emerged for rs2794520 and rs1205 in relation to CRP levels (p0.05). In addition, haplotype C-C-C-C-C was associated with higher levels of CRP (exp(β)=1.45; p0.001) and lower handgrip strength (β=-1.00kg, p0.05). We conclude that SNPs rs2794520, rs1205, and rs3093059 of CRP gene, as well as haplotype C-C-C-C-C may be important biomarkers for susceptibility to low handgrip strength and high serum CRP level in elders; further studies are required.

This study determines whether irradiation by blue or green light has an adverse effect on the DNA of Down syndrome (DS) cells by examining the sister chromatid exchange (SCE) frequency of peripheral lymphocytes obtained from five neonates with DS and five karyotypically normal neonates (control). Lymphocytes in G 0 of the cell cycle were irradiated with blue or green fluorescent light for 1, 2, 4 or 6 h, and then cultured using a conventional method. Our results revealed that the induction of SCEs per cell in both groups increased in a dose-dependent manner, although more SCEs were respectively induced by the blue light. In addition, after 6 h of blue light irradiation, the net-induced SCEs in the DS groups were higher than those in the control groups.

Two feline malignant lymphoma cell lines, FT-1 and FT-G, established from cats naturally infected with the feline leukemia virus were analyzed for chromosomal aberrations. Both FT-1 and FT-G cells had a modal number of 38 which is the normal diploid (2n) chromosome number of the domestic cat. G-banding-analysis showed that FT-1 had a translocation involving the short arms of chromosome A2 and D3--t (A2;D3) (p-;p+), and FT-G had a translocation involving the short arms of chromosomes A2 and B2--t (A2;B2) (p-;p+). Our data suggest that the chromosomal translocations were closely associated with the tumorigenesis in malignant lymphoma in cats.

Oxidative stress has been associated with the carcinogenesis of colorectal cancer. Glutathione S-transferases (GSTs) modulate the elimination of free radical. We conducted a case―control study to examine the interaction between oxidative stress and GSTs polymorphisms on colorectal cancer risk. This study recruited 727 pathologically confirmed colorectal adenocarcinoma cases and 736 sex- and age-matched controls. Plasma protein carbonyls, as a parameter of oxidative stress, were measured using enzyme-linked immunosorbent assay. Genotypes of GSTMI, GSTTI and GSTPI genes were determined using polymerase chain reaction methods. The protein carbonyl levels were significantly higher in cases than in controls and exerted a dose-response relationship (P for trend < 0.001). Compared with the first carbonyl quartile subjects, those in the second, third and fourth quartiles had odds ratios (ORs) of 1.54 [95% confidence interval (CI) = 1.13―2.10], 1.52 (95% CI = 1.11―2.07) and 1.98 (95% CI = 1.46―2.67), respectively. This effect was significantly modified by GSTMI genotype (P for interaction = 0.037). The three-way interaction analysis revealed that interactions between GSTM1 genotype and cigarette smoking and between GSTTI genotype and alcohol drinking further modified the oxidative stress contribution for colorectal cancer (p for interaction were 0.067 and 0.054, respectively). The impact of oxidative stress was more prominent among ever-smokers with GSTMI-null genotype (OR = 3.45, 95% CI = 1.70― 6.97) and ever-drinkers with GSTT1-present genotype (OR = 3.87, 95% CI = 1.82―8.25). Our results indicate that interaction between oxidative stress and GSTs polymorphisms may play an important role in the pathogenesis of colorectal cancer.

This study investigated whether mothers with prenatal environmental tobacco smoke (ETS) exposure increased the newborn genetic damage and adverse birth outcomes. Study participants were women receiving prenatal care at three hospitals in Central Taiwan and their newborns. Participants were divided into two groups (nonsmokers and ETS-exposed non-smokers) based on maternal ETS-exposed status. Comet assay were performed for cord blood samples. Infants born to mothers with prenatal ETS exposure had the highest mean cord blood DNA damage score (69.7 +/- 42.3) and poorer birth outcomes. No negative fetal growth effects appeared among newborns with low DNA damage levels. Among newborns with high DNA damage levels (comet scores >50), those born to prenatal ETS exposure had an average reduction of 252.7 g in birth weight, 1.10 cm shorter in length and a 0.92-cm decrease in head circumference, compared to newborns with no smoking exposure. This study shows that the DNA damage scores can be used as an effect-modifier on the relationships between ETS exposure and adverse birth outcome. The association appears more apparent for the ETS exposure in relation with more severe DNA damage.

Reactive oxygen species (ROS) causes damage to DNA, but the role of ROS in breast carcinoma is still not clear. The objective of this study was to measure the urinary 8-OHdG levels of breast cancer patients at each stage of carcinogenesis and assess its association with the development of breast cancer. Sixty patients with malignant breast tumors were matched with 60 control subjects of the same ages in this case control study. Urinary 8-OHdG levels were significantly higher among breast cancer patients than among the control subjects, after making adjustments for confounders such as smoking, coffee consumption and use of oral contraceptives. The breast cancer patients were divided into three groups based on the stages of their cancer; urinary 8-OHdG levels decreased with each stage of breast carcinoma. Using multiple regression and logistic models adjusted for other covariates, urinary 8-OHdG levels significantly correlated with the development of breast cancer. However, it was found that breast cancer was not significantly influenced by CYP1A1, CYP1M1 or NAT2 polymorphisms. In conclusion, it was found that oxygen radical generation occurred within carcinoma cells, but the role of polymorphism of specific genes in the development of breast cancer should be evaluated.

Antrodia camphorata (A. camphorata), well known in Taiwan as a traditional Chinese medicine, has been shown to exhibit antioxidant and anticancer effects. In the present study, therefore, we have examined the effects of the fermented culture broth of A. camphorata (25-100 microg/ml) in terms of lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production, and inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression in RAW 264.7 macrophages. Our results indicate concentration-dependent A. camphorata inhibition of LPS-induced NO and PGE2 production, without appreciable cytotoxicity on the RAW 264.7 cells. A. camphorata also attenuates the production of LPS-induced tumor necrosis factor (TNF-alpha) and interleukin (IL)-1beta. Furthermore, A. camphorata blocks the IkappaB-alpha degradation induced by LPS. These results indicate that A. camphorata inhibits LPS induction of cytokine, iNOS and COX-2 expression by blocking NF-kappaB activation. Therefore, we report the first confirmation of the anti-inflammatory potential of this traditionally employed herbal medicine in vitro.

The objective of this study was to evaluate the correlations of genetic polymorphism of genotypes delta-aminolevulinic acid dehydratase (ALAD), blood lead levels (BLLs), zinc protoporphyrin (ZPP), sister chromatid exchanges (SCEs), and high SCE frequency cells (HFCs) in lead workers.Three groups of lead workers were included in the study: high lead exposure group (26 workers), low lead exposure group (31 workers) and control group (30 controls who lived in an area uncontaminated by lead). Blood samples were taken from all subjects and analyzed for lead levels, ALAD genotype and SCE levels.Occupationally exposed workers had significantly higher BLLs, ZPP and hemoglobin levels than the controls. There were no differences among the three groups regarding percentages of ALAD 1-1 and ALAD 1-2 genotypes, but the ALAD 2-2 genotype was not detected in any of the three groups. There were no significant differences among the three groups for BLLs, ZPP and hemoglobin levels based on ALAD 1-1 and ALAD 1-2. Average SCE values in the high lead exposure group were significantly greater than those in the control group (6.2 vs 5.2 SCEs/cell, P0.05). HFC analysis revealed a significantly higher HFC percentage (53.9%) in the high lead exposure group than in the low lead exposure group (16.1%) and the control group (10%). There appeared to be an interaction effect on HFC percentages between smoking and lead exposure. When multiple regression analysis was used, the factors that affected SCE levels were lead exposure and smoking, but ALAD genotypes did not have any significant effect.A significant association existed between both SCE and HFC levels and lead exposure. However, different ALAD genotypes were not found to be associated with levels of blood lead and ZPP in the three groups.

Levels of sister chromatid exchanges (SCEs), high-SCE frequency cells (HFCs), DNA-protein cross-links (DPCs), blood lead (BLL), and zinc protoporphyrin (ZPP) were measured in peripheral blood from three groups. The lead workers were divided into two groups: a high BLL group (or =15 microg/dl) and a low BLL group (15 microg/dl). The control subjects were selected from an area that had not been contaminated with lead and had normal BLL and ZPP levels. In addition, exposure to airborne lead was measured for 11 lead workers, and the time-weighted average was shown to range from 0.19 to 10.32 mg/m(3). The BLL levels of 9 of 11 workers were15 microg/dl, of which, 3 exceeded current exposure limits (or =40 microg/dl). The BLL levels of all 11 controls were15 microg/dl. The average SCE and DPC values for the workers were 6.1 SCEs/cell and 1.9%, which were significantly higher (P0.01, Wilcoxon's test) than the value of 5.2 SCEs/cell and 1.1% for the control subjects. Lead workers had significantly higher BLL and ZPP levels than did the controls. Statistically significant increases in DPCs, SCEs, and HFCs were observed for the high-BLL group compared with the control group. The results of this study suggest that DPCs, SCEs, and HFCs are reliable biomarkers for monitoring workers exposed to lead and clearly indicate health effects from occupational exposure to lead.

Background: In Taiwan, 42% metastatic colorectal cancer (CRC) patients are frequently administered adjuvant chemotherapy in order to reduce the probability of tumor recurrence and prolong survival years after surgery. The treatment mainstay for CRC characterized with inter-individual variation in activities of drug metabolizing enzymes and DNA-repair capacity, may modulate the chemotherapeutic outcome in CRC patients. This retrospective cohort study investigated the association among drug metabolizing, DNA-repair enzymes genetic polymorphisms and overall survival in CRC patients treated with 5-fluorouracil (5-FU) based adjuvant hemotherapy. Method: To continue previous preliminary study, we recruited 2716 consecutive patients with newly diagnosed and histologically confirmed CRC from the Chang Gung Memorial Hospital between 1995 and 2001. We genotyped polymorphisms of 3 metabolizing genes (GSTM1, GSTT1, and GSTP1 Ile105Val) and 3 DNA-repair genes (XRCC1 Arg399Gln, XRCC3 Thr241Met,and XPD Lys751Gln) in 499 patients who had received postoperative chemotherapy. Cox proportional hazard models were used to calculate the Hazard ratios (HRs) and 95% confidence intervals (CIs). Survival analyses were performed using log-rank test and Kaplan-Meier curve. Results: In the study patients, mean age was 58 years (SD=12.4), 234 (47.1%) were women, and 211 (42.3%) had rectal cancer. Four hundred ninety-nine CRC patients were assessable for overall survival, the median follow-up period was 48.8 months (range 1.4 - 133.3 months). After adjusting for age and TNM stage, patients carrying the XPD Lys/Gln+Gln/Gln genotype had poorer survival than in patients with the XPD Lys/Lys genotype (HR=1.38, 95% CI=1.02-1.87). Furthermore, the XPD Lys/Gln genotype (HR=1.80, 95% CI=1.15-2.81) were also significantly associated with a short survival in rectal cancer patients. Combination analysis with the GSTT1, XPD, TNM stage, gender, and age in multivariable models revealed that the significant HRs for elder, TNM stage III, IV, XPD Lys/Gln, and GSTT1 null genotype were 1.02, 2.78, 17.0, 1.38, and 1.29, respectively Conclusion: The results suggest that polymorphisms of XPD Lys751Gln may be prognostic markers for predicting overall survival of CRC patients who receive 5-FU based adjuvant chemotherapy. Citation Format: Ching-Yu Lai, Fung-Chang Sung, Ling-Ling Hsieh, Reiping Tang, Fang-Yang Wu, Hung-Yi Chiou, Chih-Ching Yeh. Association between drug metabolizing and DNA-repair enzyme polymorphisms and overall survival of colorectal cancer patients treated with 5-FU based adjuvant chemotherapy in Taiwan. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-24. doi:10.1158/1538-7445.AM2013-LB-24