Publications by authors named "Chien-Jen Chen"

473 Publications

Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers.

Front Oncol 2021 24;11:753788. Epub 2021 Sep 24.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.

Objectives: Lung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by ) and its ligands, programmed death ligand 1 () and 2 (), associated with lung cancer risk in never-smoking women.

Materials And Methods: During September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan. SNP data were obtained and analyzed from the genome-wide association study dataset and through an imputation method. The expression quantitative trait loci (eQTL) analysis was performed in both tumor and non-tumor tissues for the correlation between genetic expression and identified SNPs.

Results: A total of 12 SNPs related to LUAD risk were identified in never-smoking women, including rs2381282, rs4742103, rs4237162, rs4742104, rs12237624, rs78096119, rs6476988, rs7857315, rs10975178, rs7854413, rs56001683, and rs7858319. Among them, six tagged SNPs rs2381282, rs4742103, rs4237162, rs4742104, rs78096119, and rs56001683 were significantly associated with LUAD risk. Specifically, two SNPs, rs12237624 and rs78096119, were associated with previous pulmonary tuberculosis infection in relation to LUAD susceptibility. Through an eQTL assay, we found that rs2381282 ( < 0.001), rs12237624 ( = 0.019), and rs78096119 ( = 0.019) were associated with the expression levels of programed death ligand 2.

Conclusions: Novel SNPs of programed death ligand 2 associated with lung adenocarcinoma risk were identified. Among them, two SNPs were associated with pulmonary tuberculosis infection in relation to lung adenocarcinoma susceptibility. These SNPs may help to stratify high-risk populations of never-smokers during lung cancer screening.
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http://dx.doi.org/10.3389/fonc.2021.753788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497977PMC
September 2021

Reproductive and environmental exposures and the breast cancer risk in Taiwanese women.

Sci Rep 2021 08 2;11(1):15656. Epub 2021 Aug 2.

Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.

Breast cancer (BC) incidence is increasing around the globe, including in Taiwan, though the cause of the increasing incidence is less clear. We followed up 11,296 Taiwanese females who did not have BC at baseline, and ascertained new invasive BC (N = 351) through data linkage to the National Cancer Registry from 1991 to 2018 to examine whether reproductive, lifestyle and environmental risk factors including polycyclic aromatic hydrocarbons (PAH) were associated with BC risk. We conducted a nested case-control study using baseline blood available from a total of 305 women with BC and 598 women without BC matched on time in cohort. We examined the association of PAH-albumin adducts and BC risk using conditional logistic regression models. Age at menarche (HR 0.6 (95% CI 0.5-0.9) for ≥ 15 vs. < 13 years) and multiparity were associated with BC risk (HR 2.0 (95% CI 1.4-2.8), 2.8 (1.9-4.2), and 2.4 (1.0-5.0) for 3-4, 1-2 and 0 live birth, compared with women ≥ 5 births). PAH-albumin adducts were not associated with BC risk. Given the increasing BC incidence in Taiwan, there is a need to identify environmental factors that are important to this population.
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http://dx.doi.org/10.1038/s41598-021-95290-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329069PMC
August 2021

Cancer patterns in nasopharyngeal carcinoma multiplex families over 15 years.

Cancer 2021 Jul 29. Epub 2021 Jul 29.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.

Background: Genetic and environmental factors are important determinants of nasopharyngeal carcinoma (NPC). NPC is associated with Epstein-Barr virus (EBV) infection. Studies have reported familial aggregation of NPC, but evidence has been mixed for elevated rates of cancers other than NPC.

Methods: The authors reassessed their previous evaluation of familial aggregation of cancer in 348 high-risk Taiwanese multiplex families with 2 or more NPC cases enrolled between 1980 and 2003. Participants were linked to the Taiwan National Cancer Registry and National Death Registry to identify cancers.

Results: In all, 2590 individuals contributed 37,959 person-years over an average of 15 years of follow-up; 314 incident cancers were identified. The authors computed multiple primary standardized incidence ratios (MP-SIRs) to evaluate the overall risk and the risk of infection-associated, EBV-associated, and individual cancers. The overall MP-SIR was 1.24 (95% confidence interval [CI], 1.10-1.38). The exclusion of excess NPC risk led to an overall MP-SIR of 1.11 (95% CI, 0.98-1.25). Similarly, the risk of cancers associated with infectious agents was driven by the excess in NPC, and its exclusion led to an MP-SIR of 1.22 (95% CI, 0.99-1.48) for infection-associated cancers and to an MP-SIR of 1.18 (95% CI, 0.72-1.82) for EBV-associated cancers. The authors observed a significant excess of second cancers among NPC cases (oral cancer, mouth cancer, tongue cancer, gum cancer, nasal cavity cancer, bone cancer, and non-Hodgkin lymphoma).

Conclusions: This reassessment of the largest NPC multiplex family study confirms the presence of NPC coaggregation within families in Taiwan but does not provide evidence for a broader familial syndrome involving NPC and other tumors. Among NPC cases, elevated rates of secondary cancers, mostly at the, head and neck and hematopoietic cancers suggest radiation treatment effects on subsequent cancer risk.
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http://dx.doi.org/10.1002/cncr.33799DOI Listing
July 2021

Immunologic markers and risk of hepatocellular carcinoma in hepatitis B virus- and hepatitis C virus-infected individuals.

Aliment Pharmacol Ther 2021 09 19;54(6):833-842. Epub 2021 Jul 19.

Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Background: Clinical and experimental studies suggest immunologic proteins contribute to hepatocellular carcinoma (HCC) development.

Aim: To evaluate circulating immunologic markers and HCC risk.

Methods: From a Taiwanese cohort of chronically hepatitis B virus (HBV)-infected individuals followed over time (REVEAL-HBV), we sampled 175 who developed HCC, 117 cirrhosis only, and 165 non-cirrhotic controls. From a similar Taiwanese cohort of chronically hepatitis C virus (HCV)-infected individuals (REVEAL-HCV), we included 94 individuals who developed HCC, 68 cirrhosis only and 100 non-cirrhotic controls. We compared pre-diagnostic plasma levels of 102 markers in HCC cases to non-cirrhotic and cirrhotic controls using polytomous logistic regression. A priori markers included insulin-like growth factor binding protein-3 (IGFBP-3), intercellular adhesion molecule 1 (ICAM-1) and interleukin 6 (IL-6). P-values for other markers were corrected for multiple testing (false discovery rate = 10%).

Results: In both REVEAL-HBV and REVEAL-HCV, increasing levels of ICAM-1 were associated with increased risk of HCC compared to non-cirrhotic controls (P-trend 0.02 and 0.001, respectively). In both REVEAL-HBV and REVEAL-HCV, two novel markers [C-X-C motif chemokine 11 (CXCL11) and hepatocyte growth factor (HGF)] were positively associated [strongest odds ratio (OR) 4.55 for HGF in HCV], while two [complement factor H related 5 (CFHR5) and stem cell factor (SCF)] were negatively associated (strongest OR 0.14 for SCF in HCV) with development of HCC compared to non-cirrhotic controls.

Conclusions: We confirmed the association for ICAM-1 and identified 4 additional proteins associated with HBV- and HCV-related HCC. These findings highlight the importance of immunologic processes in HBV- and HCV-related HCC.
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http://dx.doi.org/10.1111/apt.16524DOI Listing
September 2021

Feasibility and Safety of Chronic Total Occlusion Percutaneous Coronary Intervention via Distal Transradial Access.

Front Cardiovasc Med 2021 10;8:673858. Epub 2021 May 10.

Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.

The current study aims to verify the feasibility and safety of chronic total occlusion (CTO)-percutaneous coronary intervention (PCI) via the distal transradial access (dTRA). Between April 2017 and December 2019, 298 patients who underwent CTO PCI via dTRA were enrolled in this study. The baseline demographic and procedural characteristics were listed and compared between groups. The incidences of access-site vascular complications and procedural complications and mortality were recorded. The mean J-CTO (Japanese chronic total occlusion) score was 2.6 ± 0.9 points. The mean access time was 4.6 ± 2.9 min, and the mean procedure time was 115.9 ± 55.6 min. Left radial snuffbox access was performed successfully in 286 patients (96.5%), and right radial snuffbox access was performed successfully in 133 patients (97.7%). Bilateral radial snuffbox access was performed in 107 patients (35.9%). 400 dTRA (95.5%) received glidesheath for CTO intervention. Two patients (0.7%) developed severe access-site vascular complications. None of the patients experienced severe radial artery spasm and only 2 patients (0.5%) developed radial artery occlusion during the follow-up period. The overall procedural success rate was 93.5%. The procedural success rate was 96.5% in patients with antegrade approach and 87.7% in patients with retrograde approach. It is both safe and feasible to use dTRA plus Glidesheath for complex CTO intervention. The incidences of procedure-related complications and severe access-site vascular complications, and distal radial artery occlusion were low.
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http://dx.doi.org/10.3389/fcvm.2021.673858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141614PMC
May 2021

Genetic variants associated with serum alanine aminotransferase levels among patients with hepatitis C virus infection: A genome-wide association study.

J Viral Hepat 2021 09 3;28(9):1265-1273. Epub 2021 Jun 3.

Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Information on genetic variants associated with elevated serum alanine aminotransferase (ALT) levels remains limited. A genome-wide association study was performed to identify single-nucleotide polymorphisms (SNPs) associated with ALT levels. The ALT-associated SNP was further evaluated for hepatocellular carcinoma (HCC) risk. A cohort of 892 anti-HCV seropositive patients was used for genome-wide SNP array to examine the associations with baseline ALT levels. SNPs <10 were further tested for associations with serial ALT levels then validated in 486 anti-HCV seropositives. Multinomial logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals of SNPs associated with ALT. The SNP was evaluated for HCC risk by using Cox's proportional hazards models. After quality control, 803 participants with 564,464 SNPs were included in the analysis. Of these, 12 SNPs were associated with ALT (p < 10 ). Among the participants, 158 (19.7%) had ALT persistently ≤15 U/L, 327 (40.7%) ever >15 U/L but never >45 U/L, and 318 (39.6%) ever >45 U/L during follow-up. The rs568800 was associated with serial ALT levels, and this was replicated in the external population significantly (p < .05). The A allele (vs C) of rs568800 was associated with ALT >15 U/L but ≤45 U/L and ALT >45 U/L, with the adjusted ORs of 1.41 (1.11-1.78) and 1.86 (1.34-2.60), respectively. The adjusted HRs for HCC were 2.09 (0.90-4.89) for AC and 2.64 (1.13-6.17) for AA (CC as a reference). In conclusion, the rs568800 was associated with serum ALT levels and HCC risk. Clinical utility should be evaluated among patients who have received antivirals.
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http://dx.doi.org/10.1111/jvh.13550DOI Listing
September 2021

Postdiagnosis Aspirin Use Associated With Decreased Biliary Tract Cancer-Specific Mortality in a Large Nationwide Cohort.

Hepatology 2021 Oct 20;74(4):1994-2006. Epub 2021 Jul 20.

Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Background And Aims: Biliary tract cancer (BTC) is rare and has limited treatment options. We aimed to examine aspirin use on cancer-specific survival in various BTC subtypes, including gallbladder cancer, ampulla of Vater cancer, and cholangiocarcinoma.

Approach And Results: Nationwide prospective cohort of newly diagnosed BTC between 2007 and 2015 were included and followed until December 31, 2017. Three nationwide databases, namely the Cancer Registration, National Health Insurance, and Death Certification System, were used for computerized data linkage. Aspirin use was defined as one or more prescriptions, and the maximum defined daily dose was used to evaluate the dose-response relationship. Cox's proportional hazards models were applied for estimating HRs and 95% CIs. Analyses accounted for competing risk of cardiovascular deaths, and landmark analyses to avoid immortal time bias were performed. In total, 2,519 of patients with BTC were exposed to aspirin after their diagnosis (15.7%). After a mean follow-up of 1.59 years, the 5-year survival rate was 27.4%. The multivariate-adjusted HR for postdiagnosis aspirin users, as compared with nonusers, was 0.55 (95% CI: 0.51 to 0.58) for BTC-specific death. Adjusted HRs for BTC-specific death were 0.53 (95% CI: 0.48 to 0.59) and 0.42 (95% CI: 0.31 to 0.58) for ≤ 1 and > 1 maximum defined daily dose, respectively, and showed a dose-response trend (P < 0.001; nonusers as a reference). Cancer-specific mortality was lower with postdiagnosis aspirin use in patients with all major BTC subtypes.

Conclusions: The nationwide study revealed that postdiagnosis aspirin use was associated with improved BTC-specific mortality of various subtypes. The findings suggest that additional randomized trials are required to investigate aspirin's efficacy in BTC.
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http://dx.doi.org/10.1002/hep.31879DOI Listing
October 2021

GT-Repeat Polymorphism in the HO-1 Gene Promoter Is Associated with Risk of Liver Cancer: A Follow-Up Study from Arseniasis-Endemic Areas in Taiwan.

J Clin Med 2021 Apr 3;10(7). Epub 2021 Apr 3.

Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.

The induction of heme oxygenase-1 (HO-1) has been shown to have therapeutic potential in experimental models of hepatitis and liver fibrosis, which are closely related to liver cancer. In humans, HO-1 induction is transcriptionally modulated by the length of a GT-repeat [(GT)n] in the promoter region. We aimed to investigate the effect of HO-1 (GT)n variants on liver cancer in a human population. We determined the HO-1 genotype in 1153 study subjects and examined their association with liver cancer risk during a 15.9-year follow-up. Allelic polymorphisms were classified as short [S, <27 (GT)n] or long [L, ≥27 (GT)n]. Newly developed cancer cases were identified through linkage to the National Cancer Registry of Taiwan. Multivariate Cox regression analysis was used to evaluate the effect of the HO-1 (GT)n variants. Alpha-fetoprotein (AFP) and cirrhosis history were also examined. The S/S genotype was found to be significantly associated with liver cancer risk, compared to the L/S and L/L genotypes. The S/S genotype group also had a higher percentage of subjects with abnormal AFP levels than other groups. There were significant percentages of cirrhosis among groups who carried S-alleles. Our findings indicate that short (GT)n variants in the HO-1 gene may confer susceptibility to rather than protection from liver cirrhosis/cancer.
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http://dx.doi.org/10.3390/jcm10071489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038349PMC
April 2021

HLA zygosity increases risk of hepatitis B virus-associated hepatocellular carcinoma.

J Infect Dis 2021 Apr 14. Epub 2021 Apr 14.

Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Background: Diversity in the human leukocyte antigen (HLA) genes might be associated with disease outcomes - the heterozygote advantage hypothesis. We tested this hypothesis in relation to hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).

Methods: We utilized DNA from >10,000 Taiwanese individuals with current or past HBV infection to examine the association between HLA diversity and critical natural history steps in the progression from HBV infection to HCC. Individuals were classified as homozygotes at a given locus when imputed to carry the same 4-digit allele for the two HLA alleles at that locus.

Results: Increase in number of homozygous HLA class II loci was associated with an increased risk of chronic HBV infection (Ptrend=1.18×10 -7). Among chronic HBV carriers, increase in number of homozygous HLA class II loci was also associated with an increased risk of HBV-associated HCC (Ptrend=0.031). For individual HLA loci, HLA-DQB1 homozygosity was significantly associated with HCC risk (adjusted hazard ratio=1.40, 95% confidence interval=1.06-1.84). We also found that zygosity affects risk of HCC through its ability to affect viral control.

Conclusions: Homozygosity at HLA class II loci, particularly HLA-DQB1, is associated with a higher risk of HBV-associated HCC.
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http://dx.doi.org/10.1093/infdis/jiab207DOI Listing
April 2021

Smoking and nasopharyngeal cancer: individual data meta-analysis of six prospective studies on 334 935 men.

Int J Epidemiol 2021 07;50(3):975-986

School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.

Background: The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC.

Methods: We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status.

Results: During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26).

Conclusions: This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12-16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions.
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http://dx.doi.org/10.1093/ije/dyab060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271191PMC
July 2021

Sub-multiplicative interaction between polygenic risk score and household coal use in relation to lung adenocarcinoma among never-smoking women in Asia.

Environ Int 2021 02 29;147:105975. Epub 2020 Dec 29.

Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.
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http://dx.doi.org/10.1016/j.envint.2020.105975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378844PMC
February 2021

Association between arsenic exposure, DNA damage, and urological cancers incidence: A long-term follow-up study of residents in an arseniasis endemic area of northeastern Taiwan.

Chemosphere 2021 Mar 30;266:129094. Epub 2020 Nov 30.

National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan; Graduate Institute of Life Sciences, National Defence Medical Center, Taipei, Taiwan; Department of Safety, Health and Environmental Engineering, National United University, Miaoli, Taiwan. Electronic address:

Arsenic is a well-established human carcinogen and is considered a health risk worldwide, especially where groundwater is consumed as drinking water. In 2018, bladder and kidney cancers were the 14th and 17th leading causes of global cancer mortality, respectively. Our aim was to investigate the association between arsenic exposure, DNA damage, and the incidence of bladder and kidney cancers. A total of 788 participants aged ≥40 years were enrolled in a prospective cohort study in Taiwan between 1991 and 1994, with follow-up between 2011 and 2014. Well-water and first-morning spot urine samples were collected between 1991 and 1994 to estimate arsenic exposure, and the baseline urinary levels of 8-Oxo-2'-deoxyguanosine (8-OHdG) and N7-methylguanine (N7-MeG) were quantified to assess DNA lesions. The Cox proportional hazard model was used to estimate the effects of arsenic exposure and DNA adduct levels on the risk of bladder or kidney cancer. Urinary arsenic species were associated with significantly increased 8-OHdG and N7-MeG after adjusting for age, sex, and cigarette smoking. Only non-statistically significant mediation effects of 8-OHdG were observed. In a fully adjusted Cox model, participants with arsenic exposure and urinary 8-OHdG levels higher than the median had a higher risk of bladder cancer (HR = 4.60, confidence interval: 1.43-14.85). Overall, the combined effects of high cumulative arsenic exposure from artesian well-water and advanced DNA damage predicted the risk of bladder cancer.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129094DOI Listing
March 2021

Characteristics of Patients With Chronic Hepatitis B Virus Infection With Genotype E Predominance in Burkina Faso.

Hepatol Commun 2020 Dec 15;4(12):1781-1792. Epub 2020 Sep 15.

Division of Gastroenterology and Hepatology Mayo Clinic Rochester MN.

Hepatitis B virus (HBV) genotype E (HBV-E) accounts for the majority of chronic hepatitis B (CHB) infections in West Africa. We aimed to determine factors associated with HBV-E-induced hepatocellular carcinoma (HCC) in West Africa. Data on patients from Burkina Faso who were hepatitis B surface antigen positive (HBsAg+) and had CHB were analyzed. HBV viral load and hepatitis B e antigen (HBeAg) status were measured in 3,885 individuals with CHB without HCC (CHB HCC-) and 59 individuals with CHB with HCC (CHB HCC+). HBV genotyping was performed for 364 subjects with CHB HCC- and 41 subjects with CHB HCC+. Overall, 2.5% of the CHB HCC- group was HBeAg+ compared with 0% of the CHB HCC+ group. Of the 364 patients who were CHB HCC- with available genotyping, the frequencies of HBV genotypes E and C/E were 70.3% and 12.9%, respectively. Age (odds ratio [OR] for older age, 1.08; 95% confidence interval [CI], 1.06-1.10 per 1-year increase in age), male sex (OR, 2.03; 95% CI, 1.11-3.69), and HBV viremia (OR, 1.48; 95% CI, 1.31-1.67 per 1 log10 IU/mL) were each associated with HCC diagnosis. Patients with genotype E had a lower HBeAg prevalence (6.3% vs. 14.9%), lower HBV viral load, and higher prevalence of cirrhosis (14.5% vs. 4.8%) than patients with genotype C/E. HBV-E is the most common circulating strain (70.3%) in West African patients. HCC was associated with older age, male sex, and high HBV viral load. It is expected that these results will further inform guidance on clinical management of HBV infection in West Africa.
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http://dx.doi.org/10.1002/hep4.1595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706297PMC
December 2020

Patterns of Human Leukocyte Antigen Class I and Class II Associations and Cancer.

Cancer Res 2021 02 3;81(4):1148-1152. Epub 2020 Dec 3.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.

Human leukocyte antigen (HLA) gene variation is associated with risk of cancers, particularly those with infectious etiology or hematopoietic origin, given its role in immune presentation. Previous studies focused primarily on HLA allele/haplotype-specific associations. To answer whether associations are driven by HLA class I (essential for T-cell cytotoxicity) or class II (important for T-cell helper responses) genes, we analyzed GWAS from 24 case-control studies and consortia comprising 27 cancers (totaling >71,000 individuals). Associations for most cancers with infectious etiology or of hematopoietic origin were driven by multiple HLA regions, suggesting that both cytotoxic and helper T-cell responses are important. Notable exceptions were observed for nasopharyngeal carcinoma, an EBV-associated cancer, and CLL/SLL forms of non-Hodgkin lymphomas; these cancers were associated with HLA class I region only and HLA class II region only, implying the importance of cytotoxic T-cell responses for the former and CD4 T-cell helper responses for the latter. Our findings suggest that increased understanding of the pattern of HLA associations for individual cancers could lead to better insights into specific mechanisms involved in cancer pathogenesis. SIGNIFICANCE: GWAS of >71,000 individuals across 27 cancer types suggest that patterns of HLA Class I and Class II associations may provide etiologic insights for cancer.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-2292DOI Listing
February 2021

Epidemiology of Virus Infection and Human Cancer.

Recent Results Cancer Res 2021 ;217:13-45

Genomics Research Center, Academia Sinica, 128 Academia Road, Sect. 2, Taipei, 115, Taiwan.

Seven viruses including the Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Kaposi's sarcoma herpes virus (KSHV), human immunodeficiency virus, type-1 (HIV-1), human T cell lymphotrophic virus, type-1 (HTLV-1), and human papillomavirus (HPV) have been classified as Group 1 human carcinogens by the International Agency for Research on Cancer (IARC). The conclusions are based on the findings of epidemiological and mechanistic studies. EBV, HPV, HTLV-1, and KSHV are direct carcinogens; HBV and HCV are indirect carcinogens through chronic inflammation; and HIV-1 is an indirect carcinogen through immune suppression. Some viruses may cause more than one cancer, while some cancers may be caused by more than one virus. However, only a proportion of persons infected by these oncogenic viruses will develop specific cancers. A series of studies have been carried out to assess the viral, host, and environmental cofactors of EBV-associated nasopharyngeal carcinoma, HBV/HCV-associated hepatocellular carcinoma, and HPV-associated cervical carcinoma. Persistent infection, high viral load, and viral genotype are important risk predictors of these virus-caused cancers. Risk calculators incorporating host and viral risk predictors have been developed for the prediction of long-term risk of hepatocellular carcinoma, nasopharyngeal carcinoma and cervical cancer. These risk calculators are useful for the triage and clinical management of infected patients. Both clinical trials and national programs of immunization, antiviral therapy and screening have demonstrated a significant reduction in the incidence of cancers caused by HBV, HCV, and HPV. Future research on gene-gene and gene-environment interactions of oncogenic viruses and the human host using large-scale longitudinal studies with serial measurements of biosignatures are in urgent need.
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http://dx.doi.org/10.1007/978-3-030-57362-1_2DOI Listing
January 2021

Impact of high triglyceride/high-density lipoprotein cholesterol ratio (insulin resistance) in ST-segment elevation myocardial infarction.

Medicine (Baltimore) 2020 Oct;99(43):e22848

Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung.

The ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) has been proposed as an easily obtainable atherogenic marker and high TG/HDL-C ratio is associated with insulin resistance. This study investigated the associated between a high TG/HDL-C ratio and cardiovascular mortality in patients with ST-segment elevation myocardial infarction (STEMI), with or without diabetes mellitus (DM).Between January 2005 and December 2014, 1661 patients with STEMI underwent primary percutaneous coronary intervention in our hospital. Of these, 289 were classified into group 1 (with both DM and a high TG/HDL-C ratio), 295 into group 2 (with DM, but without a high TG/HDL-C ratio), 501 into group 3 (without DM, but a high TG/HDL-C ratio), and 576 into group 4 (without DM or a high TG/HDL-C ratio).Older age, longer chest pain to reperfusion time, poor hemodynamic condition, and higher prevalence of multiple vessel coronary artery disease were noted in those with DM. Poor outcomes including higher 30-day and 1-year cardiovascular mortality and all-cause mortality rates were noted in those with DM but without a high TG/HDL-C ratio. Patients with DM but without a high TG/HDL-C ratio had a Hazard ratio of 3.637 for cardiovascular mortality relative to those without DM, but without a high TG/HDL-C ratio.Even though a high TG/HDL-C ratio is associated with insulin resistance, patients with or without DM, but with a high TG/HDL-C ratio had better 30-day and 1-year outcomes.
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http://dx.doi.org/10.1097/MD.0000000000022848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581178PMC
October 2020

Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients.

Cancers (Basel) 2020 Jul 28;12(8). Epub 2020 Jul 28.

Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.

Early onset breast cancer (EOBC), diagnosed at age ~40 or younger, is associated with a poorer prognosis and higher mortality rate compared to breast cancer diagnosed at age 50 or older. EOBC poses a serious threat to public health and requires in-depth investigation. We studied a cohort comprising 90 Taiwanese female patients, aiming to unravel the underlying mechanisms of EOBC etiopathogenesis. Sequence data generated by whole-exome sequencing (WES) and whole-genome sequencing (WGS) from white blood cell (WBC)-tumor pairs were analyzed to identify somatic missense mutations, copy number variations (CNVs) and germline missense mutations. Similar to regular breast cancer, the key somatic mutation-susceptibility genes of EOBC include (40% prevalence), (37%), (17%) and (17%), which are frequently reported in breast cancer; however, the structural protein-coding genes (19%), (16%) and (11%) show a significantly higher prevalence in EOBC. Furthermore, the top 2 genes harboring EOBC germline mutations, (19%) and (19%), encode structural proteins. Compared to conventional breast cancer, an unexpectedly higher number of EOBC susceptibility genes encode structural proteins. We suspect that mutations in structural proteins may increase physical permeability to environmental hormones and carcinogens and cause breast cancer to occur at a young age.
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http://dx.doi.org/10.3390/cancers12082089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464007PMC
July 2020

Epstein-Barr Virus-Based Nasopharyngeal Carcinoma (NPC) Risk Prediction Scores Are Elevated in NPC Multiplex Family Members in Taiwan.

J Infect Dis 2021 02;223(3):441-444

Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

Nasopharyngeal carcinoma (NPC) is caused by Epstein-Barr virus (EBV) and is more likely to occur in susceptible families. Whether genetic susceptibility operates through altered EBV control is incompletely understood. We used a NPC risk prediction model based on 14 EBV markers to compare risk score distribution in unaffected members from multiplex families with that in population-based controls. Despite the absence of NPC at the time of antibody measurement, we observed an upward shift in risk score among multiplex family members compared to the general population, consistent with the possibility that genetic factors affect NPC risk through alterations in EBV control.
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http://dx.doi.org/10.1093/infdis/jiaa385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982447PMC
February 2021

Association Between Traffic Count and Cardiovascular Mortality: A Prospective Cohort Study in Taiwan.

J Epidemiol 2021 May 25;31(5):343-349. Epub 2020 Nov 25.

Genomics Research Center, Academia Sinica.

Background: Exposure to traffic-related pollution is positively associated with cardiovascular diseases (CVD), but little is known about how different sources of traffic pollution (eg, gasoline-powered cars, diesel-engine vehicles) contribute to CVD. Therefore, we evaluated the association between exposure to different types of engine exhaust and CVD mortality.

Methods: We recruited 12,098 participants from REVEAL-HBV cohort in Taiwan. The CVD mortality in 2000-2014 was ascertained by the Taiwan Death Certificates. Traffic pollution sources (2005-2013) were based on information provided by the Directorate General of Highway in 2005. Exposure to PM was based on a land-use regression model. We applied Cox proportional hazard models to assess the association of traffic vehicle exposure and CVD mortality. A causal mediation analysis was applied to evaluate the mediation effect of PM on the relationship between traffic and CVD mortality.

Results: A total of 382 CVD mortalities were identified from 2000 to 2014. We found participants exposed to higher volumes of small car and truck exhausts had an increased CVD mortality. The adjusted hazard ratio (HR) was 1.10 for small cars (95% confidence interval [CI], 0.94-1.27; P-value = 0.23) and 1.24 for truck (95% CI, 1.03-1.51; P-value = 0.03) per one unit increment of the logarithm scale. The findings were still robust with further adjustment for different types of vehicles. A causal mediation analysis revealed PM had an over 60% mediation effect on traffic-CVD association.

Conclusions: Exposure to exhaust from trucks or gasoline-powered cars is positively associated with CVD mortality, and air pollution may play a role in this association.
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http://dx.doi.org/10.2188/jea.JE20200082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021879PMC
May 2021

Impact of electrocardiographic morphology on clinical outcomes in patients with non-ST elevation myocardial infarction receiving coronary angiography and intervention: a retrospective study.

PeerJ 2020 7;8:e8796. Epub 2020 May 7.

Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

Background: The impact of electrocardiography (ECG) morphology on clinical outcomes in patients with non-ST segment elevation myocardial infarction (NSTEMI) receiving percutaneous coronary intervention (PCI) is unknown. This study investigated whether different ST morphologies had different clinical outcomes in patients with NSTEMI receiving PCI.

Methods: This retrospective study analyzed record-linked data of 362 patients who had received PCI for NSTEMI between January 2008 and December 2010. ECG revealed ST depression in 67 patients, inverted T wave in 91 patients, and no significant ST-T changes in 204 patients. The primary endpoint was long-term all-cause mortality. The secondary endpoint was long-term cardiac death and non-fatal major adverse cardiac events.

Results: Compared to those patients whose ECG showed an inverted T wave and non-specific ST-T changes, patients whose ECG showed ST depression had more diabetes mellitus, advanced chronic kidney disease (CKD) and left main artery disease, as well as more in-hospital mortality, cardiac death and pulmonary edema during hospitalization. Patients with ST depression had a significantly higher rate of long-term total mortality and cardiac death. Finally, multiple stepwise Cox regression analysis showed that an advanced Killip score, age, advanced CKD, prior percutaneous transluminal coronary angioplasty and ST depression were independent predictors of the primary endpoint.

Conclusions: Among NSTEMI patients undergoing coronary angiography, those with ST depression had more in-hospital mortality and cardiac death. Long-term follow-up of patients with ST depression consistently reveals poor outcomes.
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http://dx.doi.org/10.7717/peerj.8796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211404PMC
May 2020

Prediagnostic concentrations of circulating bile acids and hepatocellular carcinoma risk: REVEAL-HBV and HCV studies.

Int J Cancer 2020 11 8;147(10):2743-2753. Epub 2020 Jun 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.

Hepatocellular carcinoma (HCC) is the dominant histologic type of liver cancer, accounting for 75% of cases. Growing evidence suggests that the cross-talk between the gut microbiome and metabolome (ie, gut-liver axis) are related to the development of hepatic inflammation, and ultimately, HCC. Bile acids are metabolites, derived from cholesterol and synthesized in the liver, which may have a critical role in regulation of the gut-liver axis. We investigated whether prediagnostic circulating bile acids were associated with HCC risk, using the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer (REVEAL)-Hepatitis B Virus (HBV) and REVEAL-Hepatitis C Virus (HCV) cohorts from Taiwan. Fifteen bile acids were quantitated using liquid chromatography, from 185 cases and 161 matched controls in REVEAL-HBV and 96 cases and 96 matched controls in REVEAL-HCV. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between bile acid levels and HCC were calculated using multivariable-adjusted logistic regression. Higher levels of glycine and taurine conjugated primary bile acids were associated with a 2- to 8-fold increased risk of HBV- (eg, glycocholic acid OR = 3.38, 95% CI: 1.48-7.71, P < .003) and HCV-related HCC (eg, OR = 8.16, 95% CI: 2.21-30.18, P < .001). However, higher levels of the secondary bile acid deoxycholic acid were inversely associated with HBV-related HCC risk (OR = 0.41, 95% CI: 0.19-0.88, P = .02). Our study provides evidence that higher concentrations of bile acids-specifically, conjugated primary bile acids-are associated with increased HCC risk. However, our study does not support the hypothesis that higher levels of secondary bile acids increase liver cancer risk; indeed, deoxycholic acid may be associated with a decreased HCC risk.
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http://dx.doi.org/10.1002/ijc.33051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529994PMC
November 2020

Impact of cooking oil fume exposure and fume extractor use on lung cancer risk in non-smoking Han Chinese women.

Sci Rep 2020 04 21;10(1):6774. Epub 2020 Apr 21.

Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.

Smoking tobacco is the major risk factor for developing lung cancer. However, most Han Chinese women with lung cancer are nonsmokers. Chinese cooking methods usually generate various carcinogens in fumes that may inevitably be inhaled by those who cook the food, most of whom are female. We investigated the associations of cooking habits and exposure to cooking fumes with lung cancer among non-smoking Han Chinese women. This study was conducted on 1,302 lung cancer cases and 1,302 matched healthy controls in Taiwan during 2002-2010. Two indices, "cooking time-years" and "fume extractor use ratio," were developed. The former was used to explore the relationship between cumulative exposure to cooking oil fumes and lung cancer; the latter was used to assess the impact of fume extractor use for different ratio-of-use groups. Using logistic models, we found a dose-response association between cooking fume exposure and lung cancer (odds ratios of 1, 1.63, 1.67, 2.14, and 3.17 across increasing levels of cooking time-years). However, long-term use of a fume extractor in cooking can reduce the risk of lung cancer by about 50%. Furthermore, we provide evidence that cooking habits, involving cooking methods and oil use, are associated with risk of lung cancer.
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http://dx.doi.org/10.1038/s41598-020-63656-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174336PMC
April 2020

Validation of an Epstein-Barr Virus Antibody Risk Stratification Signature for Nasopharyngeal Carcinoma by Use of Multiplex Serology.

J Clin Microbiol 2020 04 23;58(5). Epub 2020 Apr 23.

Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Serological testing for nasopharyngeal carcinoma (NPC) has recently been reinvigorated by the implementation of novel Epstein-Barr virus (EBV)-specific IgA and IgG antibodies from a proteome array. Although proteome arrays are well suited for comprehensive antigen selection, they are not applicable for large-scale studies. We adapted a 13-marker EBV antigen signature for NPC risk identified by proteome arrays to multiplex serology to establish an assay for large-scale studies. Taiwanese NPC cases ( = 175) and matched controls ( = 175) were used for assay validation. Spearman's correlation was calculated, and the diagnostic value of all multiplex markers was assessed independently using the area under the receiver operating characteristic curve (AUC). Two refined signatures were identified using stepwise logistic regression and internally validated with 10-fold cross validation. Array and multiplex serology showed strong correlation for each individual EBV marker, as well as for a 13-marker combined model on continuous data. Two refined signatures with either four (LF2 and BGLF2 IgG, LF2 and BMRF1 IgA) or two (LF2 and BGLF2 IgG) antibodies on dichotomous data were identified as the most parsimonious set of serological markers able to distinguish NPC cases from controls with AUCs of 0.992 (95% confidence interval [CI], 0.983 to 1.000) and 0.984 (95% CI, 0.971 to 0.997), respectively. Neither differed significantly from the 13-marker model (AUC, 0.992; 95% CI, 0.982 to 1.000). All models were internally validated. Multiplex serology successfully validated the original EBV proteome microarray data. Two refined signatures of four and two antibodies were capable of detecting NPC with 99.2% and 98.4% accuracy.
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http://dx.doi.org/10.1128/JCM.00077-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180240PMC
April 2020

Cigarette smoking increases the risk of nasopharyngeal carcinoma through the elevated level of IgA antibody against Epstein-Barr virus capsid antigen: A mediation analysis.

Cancer Med 2020 03 10;9(5):1867-1876. Epub 2020 Jan 10.

Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Background: The study aims are to evaluate the associations between nasopharyngeal carcinoma (NPC) risk and cigarette smoking and to explore the effects of cigarette smoking on Epstein-Barr virus (EBV) infection for NPC risk.

Methods: 1235 male NPC cases and 1262 hospital-based male controls matched to cases were recruited across six collaborative hospitals between 2010 and 2014. Using a standardized questionnaire, information on cigarette smoking and other potential risk factors for NPC was obtained. Blood was collected and used for anti-EBV VCA IgA and anti-EBV EA-EBNA1 IgA testing using standard methods. Unconditional logistic regression analysis was used to estimate odds ratio (OR) with 95% confidence interval (CI) for each risk factor after adjusting for confounders.

Results: 63.6% of cases and 44.0% of controls reported ever smoking cigarettes. After full adjustment, current smokers had a significant 1.60-fold (95% CI = 1.30-1.97) and former smokers a borderline significant 1.27-fold (95% CI = 1.00-1.60) increased NPC risk compared to never smokers. NPC risk increased with increasing duration, intensity, and pack-years of cigarette smoking but not with age at smoking initiation. Among controls, anti-EBV VCA IgA seropositivity rate was higher in current smokers than never smokers (14.0% vs 8.4%; OR = 1.82; 95% CI = 1.19-2.79). Mediation analyses showed that more than 90% of the cigarette smoking effect on NPC risk is mediated through anti-EBV VCA IgA.

Conclusion: This study confirms the association between long-term cigarette smoking and NPC and demonstrates that current smoking is associated with seropositivity of anti-EBV VCA IgA antibodies.
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http://dx.doi.org/10.1002/cam4.2832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050088PMC
March 2020

The Clinical Outcomes Based on the Achievement of Low-Density Lipoprotein Cholesterol Targets after ST Elevation Myocardial Infarction.

J Clin Med 2019 Dec 28;9(1). Epub 2019 Dec 28.

Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.

The clinical outcome of patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), with or without achievement of low-density lipoprotein cholesterol (LDL-C) targets, has rarely been investigated. This study was performed to investigate the comparison of clinical outcome in STEMI patients with or without achievement LDL-C targets (below 70 mg/dL and/or ≥50% reduction). Between November 2013 and December 2016, 689 STEMI patients underwent primary PCI in our hospital. Patients who were deceased, lost to follow-up, had no follow-up lipid profile, or had no side effects after statin use were excluded. A total of 343 patients were classified into group 1 (with LDL-C target achievement) and 172 patients were classified into group 2 (without LDL-C target achievement). Between the two groups, a higher prevalence of left main coronary artery disease, smaller pre-PCI stenosis, and a larger pre-PCI minimal luminal diameter were noted in group 2. The incidence of post-MI angina (8.7% vs. 6.4%; = 0.393), target vessel revascularization (2.3% vs. 3.5%; = 0.566), and recurrent MI (1.5% vs. 1.2%; = 1.000), showed similar results between the two groups during a one-year follow-up period. Initial LDL-C levels ≥130 mg/dL, left main coronary artery disease, and absence of diabetes mellitus were positively associated with non-achievement of LDL-C targets. After STEMI, 66.6% of patients could achieve LDL-C targets one year later. However, such patients did not show better clinical outcomes. Non-DM, initial LDL-C levels ≥130 mg/dL, and left main coronary artery disease were related to non-achievement of LDL-C targets.
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http://dx.doi.org/10.3390/jcm9010079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020017PMC
December 2019

Predicting Lung Cancer Occurrence in Never-Smoking Females in Asia: TNSF-SQ, a Prediction Model.

Cancer Epidemiol Biomarkers Prev 2020 02 17;29(2):452-459. Epub 2019 Dec 17.

Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.

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.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1221DOI Listing
February 2020

Phthalate exposure and prostate cancer in a population-based nested case-control study.

Environ Res 2020 02 8;181:108902. Epub 2019 Nov 8.

Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli, Taiwan. Electronic address:

Background: Phthalic acid esters are established as endocrine disruptors. The study aimed to evaluate the association between urinary phthalate metabolites and prostate cancer occurrence.

Methods: The study was based on the Taiwan Community-Based Cancer Screening Program, which was set up in 1991-1992 and followed periodically. By 2010, 80 incident prostate cancer cases were identified in the 12,020 men. For each case, 2 controls were randomly selected, matched by age (±3 years), urine collection date (±3 months), and residential township. Frequently used phthalate metabolites from the urine samples were quantified by liquid chromatography/electrospray ionization tandem mass spectrometry. Logistic regression was conducted to assess the association between the exposure levels and prostate cancer occurrence.

Results: Exposure to di (2-ethylhexyl), butyl-benzyl and di-isobutyl phthalates (DEHP, BBzP, DiBP) was positively associated with prostate cancer in men with waist circumference (WC) ≥90 cm but not in the leans. Odds ratio for the DEHP metabolite summary score (upper tertile compared to the rest) and prostate cancer were 7.76 (95% CI = 1.95-30.9) for WC ≥ 90 cm.

Conclusions: DEHP, BBzP, and DiBP exposure were associated with prostate cancer occurrence in abdominally obese men. The main limitation remains the lack of mechanistic experiments and comparable toxicological data.
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http://dx.doi.org/10.1016/j.envres.2019.108902DOI Listing
February 2020

The effect of complete revascularization in patients with ST-segment elevation myocardial infarction with Killip class ≥ III.

Coron Artery Dis 2020 01;31(1):13-19

Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung.

Background: The effect of complete revascularization (CR) on high-risk patients with ST-segment elevation myocardial infarction (STEMI) has remains a controversial issue, especially on patients in a critical condition. The aim of this study was to explore the effect of CR on patients with STEMI with Killip class ≥ III.

Methods: From January 2008 to December 2014, 185 patients diagnosed with STEMI with Killip class ≥ III and multiple vessel coronary artery disease received primary percutaneous coronary intervention (PCI). Eighty-nine patients underwent culprit-only PCI, and the remaining 96 patients underwent immediate or staged PCI for CR. Out of the 96 patients in the CR group, 51 patients underwent immediate CR, and 45 patients underwent CR during the same hospitalization. Thirty-day and 1-year clinical outcomes were compared between the culprit-only PCI group and the CR group as well as between the immediate CR group and staged CR group.

Results: There was a trend toward a lower incidence of post-PCI acute kidney injury in the culprit-only PCI group when compared with the CR group (14.8% vs. 26.0%; P = 0.069). Thirty-day and 1-year cardiovascular mortality and all-cause mortality were similar between the culprit-only PCI group and CR group. Decreased 1-year cardiovascular mortality and all-cause mortality were noted in the staged CR group compared with the immediate CR group.

Conclusion: was associated a higher possibility of post-PCI acute kidney injury and did not seem to improve 30-day or 1-year clinical outcomes. Patients undergoing staged CR during the same hospitalization had better clinical outcomes.
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http://dx.doi.org/10.1097/MCA.0000000000000815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903383PMC
January 2020
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