Publications by authors named "Minkyo Song"

47 Publications

Circulating immune- and inflammation-related biomarkers and early-stage noncardia gastric cancer risk.

Eur J Cancer Prev 2021 Jul 8. Epub 2021 Jul 8.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA Division of Cancer Information and Control Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute Department of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: In Helicobacter pylori-driven gastric cancer, mucosal colonization induces chronic inflammation that may variably progress to cancer. Prospective studies of circulating inflammation-related proteins have suggested weak associations with gastric cancer risk. To assess potential utility as a screening tool in clinical settings, we examined circulating levels of a wide range of key inflammation molecules for associations with early-stage gastric cancer.

Methods: We used pretreatment EDTA plasma from 239 individuals with early-stage noncardia gastric cancer (203 stage I and 36 stage II) and 256 age-frequency-matched H. pylori-seropositive cancer-free controls within the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Levels of 92 biomarkers were measured by proximity extension assays using Olink's Proseek Immuno-oncology Panel. Odds ratios (ORs) for association with gastric cancer risk were calculated for quantiles (two to four categories) of each biomarker from unconditional logistic regression models, adjusted for age, sex, smoking and alcohol consumption. Two-sided P values <0.05 were considered as significant. The false discovery rate (FDR) was used to correct for multiple comparisons.

Results: Of 83 evaluable biomarkers, lower levels of TNFRSF12A (per quartile OR, 0.82; nominal P-trend = 0.02) and ADGRG1 (per quartile OR, 0.84; nominal P-trend = 0.03) were associated with early-stage gastric cancer but were not statistically significant after FDR correction.

Conclusion: Our study did not identify any inflammation-related biomarkers that may be useful for early disease detection. To date, this is the first assessment of circulating inflammation-related proteins in early-stage gastric cancer. Given the complex inflammation processes preceding malignant transformation, further investigation of other biomarkers is warranted.
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http://dx.doi.org/10.1097/CEJ.0000000000000706DOI Listing
July 2021

Associations of circulating mediators of inflammation, cell regulation and immune response with esophageal squamous cell carcinoma.

J Cancer Res Clin Oncol 2021 Jun 14. Epub 2021 Jun 14.

Division of Cancer Epidemiology and Prevention, Department of Preventive Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.

Background: Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer globally. The development of squamous cell carcinoma has important inflammatory influences and effects. We, therefore, examined circulating levels of inflammation- and immune-related proteins for associations with ESCC.

Methods: We used pre-treatment EDTA plasma from 80 ESCC patients (44% clinical stages I and II) and 80 cancer-free control individuals within the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Levels of 184 biomarkers were measured by high-throughput multiplexed proximity extension assays using Olink's Proseek Cell Regulation and Immuno-Oncology Panels. ESCC odds ratios (OR) per quantile (based on two to four categories) of each biomarker were calculated by unconditional logistic regression models, adjusted for age, sex, cigarette smoking and alcohol consumption. Correlations among continuous biomarker levels were assessed by Spearman's rank correlation. All statistical tests were two-sided with p values < 0.05 considered as significant. Given the exploratory nature of the study, we did not adjust for multiple comparisons.

Results: Seven proteins were undetectable in nearly all samples. Of the remaining 177 evaluable biomarkers, levels of cluster of differentiation 40 (CD40, per quartile OR 1.64; p trend = 0.018), syntaxin 16 (STX16, per quartile OR 1.63; p trend = 0.008), heme oxygenase 1 (per quartile OR 1.59; p trend = 0.014), and γ-secretase activating protein (GSAP, per quartile OR 1.47; p trend = 0.036) were significantly associated with ESCC. Amongst these significant markers, levels of CD40, STX16, and GSPA were moderately correlated (Rho coefficients 0.46-0.55; p < 0.05).

Conclusion: Our case-control study expands the range of inflammation and immune molecules associated with ESCC. These novel findings warrant replication and functional characterization.
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http://dx.doi.org/10.1007/s00432-021-03687-3DOI Listing
June 2021

Prediagnostic circulating inflammation-related biomarkers and gastric cancer: A case-cohort study in Japan.

Cytokine 2021 Aug 10;144:155558. Epub 2021 May 10.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Gastric cancer is preceded by a chronic inflammatory process. Circulating levels of inflammation-related markers may reveal molecular pathways contributing to cancer development. Our study evaluated risk associations of gastric cancer with a wide range of systemic soluble inflammation and immune-response proteins. We performed a case-cohort analysis within the JPHC Study II, including a subcohort of 410 participants selected randomly within defined age and sex groups, and 414 individuals with incident gastric cancer. Ninety-two biomarkers were measured in baseline plasma using proximity extension assays. Gastric cancer multivariable hazard ratios were calculated for two to four quantiles used as ordinal variables of each biomarker by Cox proportional hazards regression models with age as the time metric. Of 73 evaluable biomarkers, three (CCL11, CCL20 and IL17C) were associated with increased gastric cancer risk and two (CCL23 and MMP1) with reduced cancer risk (P < 0.05). However, no association was statistically significant after a false discovery rate correction. This study largely expands the range of inflammation molecules evaluated for gastric cancer risk but failed to identify novel associations with this neoplasia.
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http://dx.doi.org/10.1016/j.cyto.2021.155558DOI Listing
August 2021

Circulating Levels of Sex Steroid Hormones and Gastric Cancer.

Arch Med Res 2021 Mar 26. Epub 2021 Mar 26.

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

Background And Aims: Men develop gastric cancer more frequently than women, yet little is known about the mechanisms underlying this sex difference. Sex steroid hormones may influence gastric cancer risk. We therefore assessed whether major circulating adrenal precursors, androgens and estrogens were associated with gastric cancer in a high-risk Mexican population.

Methods: Blood samples were collected at time of diagnosis from 50 noncardia gastric cancer patients and 50 histologically confirmed non-atrophic gastritis controls. Serum levels of estradiol, testosterone and dehydroepiandrosterone (DHEA) measured with a validated mass spectrometry method were categorized in tertiles as low (T1), middle (T2), and high (T3). Unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI), adjusting for age, sex, and education.

Results: Levels of DHEA were inversely associated with gastric cancer (p-trend per tertile increase: <0.0001), with adjusted ORs (95% CI) of T2 and T3 (vs. T1) of 0.25 (0.09-0.70) and 0.10 (0.03-0.34), respectively. Levels of estradiol and testosterone were not significantly associated with gastric cancer.

Conclusions: Our study provides evidence that higher concentration of circulating DHEA may be associated with lower risk of noncardia gastric cancer. Longitudinal studies are needed to evaluate the temporality of this association and investigate mechanisms of disease pathogenesis.
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http://dx.doi.org/10.1016/j.arcmed.2021.03.001DOI Listing
March 2021

Identification of anti-Epstein-Barr virus (EBV) antibody signature in EBV-associated gastric carcinoma.

Gastric Cancer 2021 Jul 4;24(4):858-867. Epub 2021 Mar 4.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr., Bethesda, MD, 20892, USA.

Background: Around 10% of gastric carcinomas (GC) contain Epstein-Barr virus (EBV) DNA. We characterized the GC-specific antibody response to this common infection, which may provide a noninvasive method to detect EBV-positive GC and elucidate its contribution to carcinogenesis.

Methods: Plasma samples from EBV-positive (n = 28) and EBV-negative (n = 34) Latvian GC patients were immune-profiled against 85 EBV proteins on a multi-microbial Nucleic Acid Programmable Protein Array (EBV-NAPPA). Antibody responses were normalized for each sample as ratios to the median signal intensity (MNI) across all antigens, with seropositivity defined as MNI ≥ 2. Antibodies with ≥ 20% sensitivity at 95% specificity for tumor EBV status were verified by enzyme-linked immunosorbent assay (ELISA) and validated in independent samples from Korea and Poland (n = 24 EBV-positive, n = 65 EBV-negative).

Results: Forty anti-EBV IgG and eight IgA antibodies were detected by EBV-NAPPA in ≥ 10% of EBV-positive or EBV-negative GC patients, of which nine IgG antibodies were discriminative for tumor EBV status. Eight of these nine were verified and seven were validated by ELISA: anti-LF2 (odds ratio = 110.0), anti-BORF2 (54.2), anti-BALF2 (44.1), anti-BaRF1 (26.7), anti-BXLF1 (12.8), anti-BRLF1 (8.3), and anti-BLLF3 (5.4). The top three had areas under receiver operating characteristics curves of 0.81-0.85 for distinguishing tumor EBV status.

Conclusions: The EBV-associated GC-specific humoral response was exclusively directed against lytic cycle immediate-early and early antigens, unlike other EBV-associated malignancies such as nasopharyngeal carcinoma and lymphoma where humoral response is primarily directed against late lytic antigens. Specific anti-EBV antibodies could have utility for clinical diagnosis, epidemiologic studies, and immune-based precision treatment of EBV-positive GC.
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http://dx.doi.org/10.1007/s10120-021-01170-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206016PMC
July 2021

Sonoelastography for pelvic metastatic malignant pheochromocytoma: A case report.

Curr Med Imaging 2021 Jan 21. Epub 2021 Jan 21.

Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102, Heukseok-ro, Dongjak-gu, Seoul, 06973. Korea.

Pheochromocytoma are tumors arising from the chromaffin tissue located in the adrenal medulla and are associated with typical symptoms and signs. Occasionally, metastasis, defined as the presence of tumor cells at sites other than the original site, secondary to pheochromocytoma have been reported. Pelvic metastatic malignant pheochromocytoma has rarely been reported in the English literature. Here, we have reported a very rare case of pelvic metastatic malignant pheochromocytoma, with particular focus on sonoelastographic features.
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http://dx.doi.org/10.2174/1573405617666210122085839DOI Listing
January 2021

Neutrophil-to-lymphocyte ratio and mortality in the United States general population.

Sci Rep 2021 01 11;11(1):464. Epub 2021 Jan 11.

Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, MD, 6E204, USA.

The neutrophil-to-lymphocyte ratio (NLR) in peripheral blood reflects the balance between systemic inflammation and immunity and is emerging as a prognostic biomarker in many diseases, but its predictive role for mortality in the general population has not been investigated. We analyzed 1999-2014 National Health and Nutrition Examination Survey mortality-linked data, followed up until 2015. In participants aged > 30 with measurements of differential white blood cell counts, NLR was calculated and categorized into quartiles. Associations of increased NLR with overall or cause-specific mortality were assessed with Cox proportional hazard regression models, adjusted for potential confounders. Increased NLR was associated with overall mortality (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.10-1.17, per quartile NLR) and mortality due to heart disease (1.17, 1.06-1.29), chronic lower respiratory disease (1.24, 1.04-1.47), influenza/pneumonia (1.26, 1.03-1.54) and kidney disease (1.26, 1.03-1.54). NLR was associated with cancer mortality only in the first follow-up year (HR 1.48, 95% CI 1.11-1.98). The association with chronic lower respiratory disease mortality was stronger in individuals with prevalent lung diseases (HR 1.46, 95% CI 1.14-1.88, P = 0.01), while NLR showed positive associations with mortality from heart disease (1.21, 1.07-1.38) and cerebrovascular disease (1.30, 1.04-1.63) only among individuals without these conditions at baseline. NLR is associated with mortality overall and due to certain causes in the general population. Associations over short follow-up intervals and among individuals with conditions at baseline suggest effects of disordered inflammation and immunity on progression of those conditions, while other associations may reflect contributions to disease etiology.
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http://dx.doi.org/10.1038/s41598-020-79431-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801737PMC
January 2021

Premature Years of Life Lost Due to Cancer in the United States in 2017.

Cancer Epidemiol Biomarkers Prev 2020 12 13;29(12):2591-2598. Epub 2020 Nov 13.

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

Background: Burden of cancer mortality is often measured by death counts or mortality rates, but potential years of life lost (PYLL) and PYLL per death may be more useful to estimate the impact of cancer-related deaths occurring at younger ages.

Methods: We used U.S. national death certificate data. A total of 45 categories of common cancers were grouped for cancer-specific calculations of PYLL and PYLL per death. PYLL was defined as the sum of the total years of life lost prior to age 75 years.

Results: The largest number of PYLL in 2017 was due to deaths from cancers of the lung/bronchus (891,313; 20.8%), colon/rectum (409,538; 9.6%), and breast (400,643; 9.4%). Cancers with the highest PYLLs generally also caused the largest number of deaths and had the highest mortality rates, with the exception of prostate cancer (5.1% of deaths, 2.0% of PYLL). In contrast, PYLLs per death were greatest for deaths due to cancers of testis (mean = 34.0 years), bones/joints (26.4), and other endocrine sites including thymus (25.2).

Conclusions: Although PYLLs generally reflect mortality rates, they more heavily weigh cancers that occur at younger ages. In contrast, PYLL per death, which is an average quantification of life years lost for individual patients with cancer, shows a different pattern.

Impact: Mortality rates, PYLL, and PYLL per death are complementary measures of the burden of deaths due to cancer that should be considered in tandem to prioritize public health interventions focused on preventing premature mortality.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710589PMC
December 2020

Immunoproteomic Profiles in Gastric Cancer.

J Proteome Res 2021 01 27;20(1):409-419. Epub 2020 Oct 27.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20892-2590, United States.

Chronic infection is the major risk factor for gastric cancer (GC). However, only some infected individuals develop this neoplasia. Previous serology studies have been limited by investigating small numbers of candidate antigens. Therefore, we evaluated humoral responses to a nearly complete immunoproteome (1527 proteins) among 50 GC cases and 50 controls using Nucleic Acid Programmable Protein Array (NAPPA). Seropositivity was defined as median normalized intensity ≥2 on NAPPA, and 53 anti- antibodies had >10% seroprevalence. Anti-GroEL exhibited the greatest seroprevalence (77% overall), which agreed well with ELISA using whole-cell lysates of cells. After an initial screen by -NAPPA, we discovered and verified that 12 antibodies by ELISA in controls had ≥15% of samples with an optical reading value exceeding the 95th percentile of the GC group. ELISA-verified antibodies were validated blindly in an independent set of 100 case-control pairs. As expected, anti-CagA seropositivity was positively associated with GC (odds ratio, OR = 5.5; < 0.05). After validation, six anti- antibodies showed lower seropositivity in GC, with ORs ranging from 0.44 to 0.12 ( < 0.05): anti-HP1118/Ggt, anti-HP0516/HsIU, anti-HP0243/NapA, anti-HP1293/RpoA, anti-HP0371/FabE, and anti-HP0875/KatA. Among all combinations, a model with anti-Ggt, anti-HslU, anti-NapA, and anti-CagA had an area under the curve of 0.73 for discriminating GC . controls. This study represents the first comprehensive assessment of anti- humoral profiles in GC. Decreased responses to multiple proteins in GC may reflect mucosal damage and decreased bacterial burden. The higher prevalence of specific anti- antibodies in controls may suggest immune protection against GC development.
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http://dx.doi.org/10.1021/acs.jproteome.0c00466DOI Listing
January 2021

Association of sleep duration and quality with elevated hs-CRP among healthy Korean adults.

PLoS One 2020 25;15(8):e0238053. Epub 2020 Aug 25.

Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.

This study aimed to investigate the association of sleep duration and quality with high-sensitivity C-reactive protein (hs-CRP) among middle-aged and elderly Koreans. Among a total of 74,867 participants (25,069 men and 49,798 women) recruited for the Health Examinees (HEXA) study, adjusted geometric means of hs-CRP level were compared across categories of sleep duration (<6, 6-7, 8-9, and ≥10 hours) and sleep quality (difficulty in initiating sleep and maintaining sleep) using ANCOVA models. Odds ratios (ORs) and 95% confidence intervals (CIs) for elevated hs-CRP (>3 mg/L) associated with sleep characteristics were estimated using multivariable-adjusted logistic regression models. Men who slept ≥10 hours per day were significantly associated with elevated hs-CRP (OR = 1.47, 95% CI 1.11-1.95). Whereas in women, difficulty in initiating sleep (OR = 1.28, 95% CI 1.04-1.57 for "Always"), and maintaining sleep was significantly associated with elevated hs-CRP levels (OR = 1.13, 95% CI 1.02-1.26 for "Often"; OR = 1.11, 95% CI 0.97-1.28 for "Always"). Additionally, women who experienced poor sleep quality presented an elevated level of hs-CRP (OR = 1.13, 95% CI 1.03-1.23). Our findings suggest that excessive sleep duration and poor sleep quality are significantly associated with the elevated inflammatory marker, specifically hs-CRP. Further research is needed to examine the effect of sleep interventions focused on these factors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238053PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446961PMC
October 2020

Metabolic Syndrome, Physical Activity, and Inflammation: A Cross-Sectional Analysis of 110 Circulating Biomarkers in Japanese Adults.

Cancer Epidemiol Biomarkers Prev 2020 08 28;29(8):1639-1646. Epub 2020 May 28.

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

Background: Metabolic syndrome (MetS) is a systemic inflammatory state. Low physical activity (PA) could modify this patho-physiology or act as an independent contributor to inflammation. Previous studies of both conditions have identified altered levels of inflammation- and immune-related proteins based on limited sets of candidate markers.

Methods: We investigated associations of MetS and low PA with circulating inflammation markers in a stratified random sample of Japanese adults ( = 774, mean age 60.7 years) within the Japan Public Health Center-based Prospective Study (JPHC) Cohort II. AHA/NHLBI criteria were used to define MetS (19%) and the bottom quartile of PA was considered low. 110 circulating biomarkers, including cytokines, chemokines, and soluble receptors were measured by multiplex bead-based and proximity-extension assays. Associations of MetS and low PA with marker quantiles were adjusted for each other and for age, sex, study site, cigarette smoking, alcohol consumption, and blood sample fasting state by ordinal logistic regression. values were corrected for FDR.

Results: MetS was significantly associated with levels of six markers: IL18R1 [odds ratio 2.37; 95% confidence interval (CI), 1.45-3.87], CRP (2.07; 95% CI, 1.48-2.90), SAP (2.08; 95% CI, 1.47-2.95), CCL19/MIP3β (2.06; 95% CI, 1.48-2.88), CXCL12/SDF1α+β (0.48; 95% CI, 0.32-0.65), and CCL28 (0.44; 95% CI, 0.27-0.71). Low PA had no significant marker associations.

Conclusions: Positively associated markers with MetS are mostly Th1 immune response-related and acute phase proteins, whereas negatively associated markers are generally Th2-related.

Impact: MetS is associated with a broad range of alterations in immune and inflammatory biomarkers that may contribute to risks of various chronic diseases, independent of low PA.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-1513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528457PMC
August 2020

Low Epstein-Barr Virus Prevalence in Cardia Gastric Cancer Among a High-Incidence Chinese Population.

Dig Dis Sci 2021 Apr 4;66(4):1220-1226. Epub 2020 May 4.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Room 6E110, 9609 Medical Center Drive, Rockville, MD, 20892-9776, USA.

Background: Epstein-Barr virus (EBV) positivity is associated with better gastric cancer prognosis and is found in a relatively fixed 9% of tumors worldwide.

Aim: We aimed to examine the EBV status of gastric adenocarcinomas in a very high-incidence population and to compare prevalence between cardia and non-cardia anatomic subsites.

Methods: We evaluated 1035 adult gastric adenocarcinoma cases presenting during 1997-2005 to the Shanxi Cancer Hospital in Taiyuan, Shanxi Province, China. EBV-encoded RNA was detected in alcohol-fixed paraffin-embedded tumor specimens by in situ hybridization. Associations were assessed in case-case comparisons using the Chi-squared test for categorical variables and the Mann-Whitney U test for continuous variables, with p values < 0.05 considered statistically significant. Adjusted odds ratios were calculated using logistic regression, and mortality hazard ratios (HRs) were estimated by Cox proportional hazards regression.

Results: Sixty-four percent of the evaluated cancers were found in the cardia. Cardia tumor localization was associated with male sex, advanced primary tumor stage, better differentiated histology, and intestinal-type Lauren classification. Four percent of the non-cardia and only 0.9% of cardia cancers were EBV-positive. EBV positivity was associated with better overall survival (adjusted HR 0.30, 95% CI 0.14-0.63).

Conclusions: Our study highlights unusually low EBV prevalence in gastric adenocarcinoma among a high-incidence population, particularly for cardia cancers. These findings suggest a unique risk factor profile for the high incidence of gastric cancer in this population.
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http://dx.doi.org/10.1007/s10620-020-06288-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685001PMC
April 2021

HTLV-1 infection and health outcomes.

Lancet Infect Dis 2020 04;20(4):406-407

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(20)30043-8DOI Listing
April 2020

Associations of Viral Seroreactivity with AIDS-Related Non-Hodgkin Lymphoma.

AIDS Res Hum Retroviruses 2020 05 2;36(5):381-388. Epub 2020 Mar 2.

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

Infection with human immunodeficiency virus (HIV) is associated with substantially increased incidence of non-Hodgkin lymphoma (NHL). This risk may be driven, in part, by reduced immune control over viral infections in the setting of acquired immunodeficiency syndrome (AIDS), although the lymphomagenic mechanisms are not yet established. We used bead-based multiplex assays to measure antibody seroreactivity to 32 viral antigens representing 22 different viral infections (human herpesviruses 1-8, hepatitis B and C virus, human T-lymphotropic virus type-1, and human polyomaviruses) in two prospective HIV cohorts. Incident ( = 28) and prevalent ( = 38) AIDS-related NHL cases were matched by age, sex, race, and CD4 count to 67 HIV-positive control individuals without AIDS-NHL. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of AIDS-NHL with the number of different viruses to which an individual was seropositive and seroreactivity to individual antigens. Seropositivity to an increasing number of viruses was inversely associated with AIDS-NHL (OR per virus = 0.84, 95% CI = 0.72-0.98). Seroreactivity to herpes simplex virus 2 2mgG unique antigen (OR = 0.47; 95% CI = 0.23-0.97) and to WU polyomavirus viral capsid protein (OR = 0.26, 95% CI = 0.10-0.65) was significantly lower in AIDS-NHL cases compared to controls. In this evaluation of antibodies to multiple viruses, we observed an inverse association between seropositivity to a larger number of viruses and AIDS-NHL. While in need of further evaluation, our data raise the novel hypothesis that insufficient exposures or impaired humoral immune responses to viral infections may be associated with AIDS-related lymphomagenesis.
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http://dx.doi.org/10.1089/AID.2019.0208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232664PMC
May 2020

Circulating Antibodies against Epstein-Barr Virus (EBV) and p53 in EBV-Positive and -Negative Gastric Cancer.

Cancer Epidemiol Biomarkers Prev 2020 02 12;29(2):414-419. Epub 2019 Nov 12.

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

Background: Epstein-Barr virus (EBV)-positive gastric cancers have clinicopathologic differences from EBV-negative tumors and lack mutation. Serologic profiles may inform viral contribution to carcinogenesis.

Methods: We compared humoral responses of EBV-positive ( = 67) and EBV-negative ( = 137) patients with gastric cancer from the International EBV-Gastric Cancer Consortium. Serum antibodies against four EBV proteins, nuclear (EBNA), viral capsid (VCA), early-diffuse (EA-D), and Zta replication activator (ZEBRA), and to p53 were assessed by multiplex assays. OR of antibody level tertiles (T1-T3) were adjusted by logistic regression. We also conducted a meta-analysis of reported anti-p53 seropositivity in gastric cancer.

Results: Consistent with EBV's ubiquity, 99% of patients were seropositive for anti-EBNA and 98% for anti-VCA, without difference by tumor EBV status. Seropositivity varied between patients with EBV-positive and EBV-negative tumors for anti-EA-D (97% vs. 67%, respectively, < 0.001) and anti-ZEBRA (97% vs. 85%, respectively, = 0.009). Adjusted ORs (vs. T1) for patients with EBV-positive versus EBV-negative tumors were significantly elevated for higher antibodies against EBNA (2.6 for T2 and 13 for T3), VCA (1.8 for T2 and 2.4 for T3), EA-D (6.0 for T2 and 44 for T3), and ZEBRA (4.6 for T2 and 12 for T3). Antibodies to p53 were inversely associated with EBV positivity (3% vs. 15%; adjusted OR = 0.16, = 0.021). Anti-p53 prevalence from the literature was 15%.

Conclusions: These serologic patterns suggest viral reactivation in EBV-positive cancers and identify variation of p53 seropositivity by subtype.

Impact: Anti-EBV and anti-p53 antibodies are differentially associated with tumor EBV positivity. Serology may identify EBV-positive gastric cancer for targeted therapies.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272980PMC
February 2020

Prediagnostic circulating inflammation biomarkers and esophageal squamous cell carcinoma: A case-cohort study in Japan.

Int J Cancer 2020 08 3;147(3):686-691. Epub 2019 Dec 3.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Esophageal squamous cell carcinoma (ESCC) is the predominant histologic subtype of esophageal cancer worldwide. Measurements of circulating inflammation-related biomarkers may inform etiology or provide noninvasive signatures for early diagnosis. We therefore examined levels of inflammation molecules for associations with ESCC risk. Using a case-cohort study designed within the Japan Public Health Center-based Prospective Study, we measured baseline plasma levels of 92 biomarkers using a multiplex assay in a subcohort of 410 randomly selected participants and 66 participants with incident ESCC (including four cases that occurred in the subcohort). ESCC hazard ratios (HRs) were calculated for 2-4 quantiles of each biomarker by Cox proportional hazards regression models with age as the time metric, adjusted for sex, smoking and alcohol use. Twenty analytes were undetectable in nearly all samples. Of the remaining 72, 12 biomarkers (FGF19, ST1A1, STAMBP, AXIN1, CASP8, NT3, CD6, CDCP1, CD5, SLAMF1, OPG and CSF1) were associated with increased ESCC risk (p  < 0.05) with HRs per quantile 1.28-1.65. Seven biomarkers (CXCL6, CCL23, CXCL5, TGFA, CXCL1, OSM and CCL4) were inversely associated with HRs 0.57-0.72. FGF19, CASP8, STAMBP, ST1A1 and CCL-4 met statistical significance with false discovery rate correction. Associations did not differ <5 vs. ≥5 years between blood collection and ESCC diagnosis. CASP8, STAMBP and ST1A1 were strongly correlated (p < 0.05). Our study expands the range of inflammation molecules associated with the development of this highly lethal neoplasia. Correlations among these novel biomarkers suggest a possible shared pathway. These findings need replication and could further delineate ESCCs molecular mechanisms of carcinogenesis.
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http://dx.doi.org/10.1002/ijc.32763DOI Listing
August 2020

Association between family history of diabetes and clusters of adherence to healthy behaviors: cross-sectional results from the Health Examinees-Gem (HEXA-G) study.

BMJ Open 2019 06 16;9(6):e025477. Epub 2019 Jun 16.

Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.

Objectives: This study evaluated whether individuals with affected family member adhered to healthy behaviours.

Design And Setting: This was a cross-sectional study of participants selected from health examinees who underwent the national health check-up programme of Korea in 39 centres between 2004 and 2013.

Participants: The baseline data of 128 520 participants enrolled in the Health Examinees-Gem study were used for analysis.

Main Outcomes And Measures: Associations of family history of diabetes with adherence to regular exercise, healthy diet and body composition, and clusters of healthy behaviours were evaluated while adjusting for potential confounders selected by a directed acyclic graph.

Results: Participants with a family history of diabetes were more likely to adhere to a regular exercise regimen (OR=1.12, 95% CI 1.06 to 1.18 for men and OR=1.10, 95% CI 1.07 to 1.14 for women) and healthy diet (OR=1.06, 95% CI 1.01 to 1.12 for men and OR=1.06, 95% CI 1.01 to 1.12 for women) but were less likely to have a normal body composition (OR=0.83, 95% CI 0.78 to 0.87 for men and OR=0.83, 95% CI 0.80 to 0.86 for women). These associations were strengthened when the affected family members were siblings, the number of affected members was increased or the age at diagnosis of the affected member was younger than 50 years. In men and women, having a normal body composition is important in determining the cluster of behaviours, and those with a family history of diabetes were less likely to adhere to the normal body composition cluster.

Conclusions: The group with high risk of diabetes showed healthy behaviors, but they did not have a normal body composition. Policies and campaigns targeting integrated health behaviors will be needed to reduce the burden of diseases and improve public health.
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http://dx.doi.org/10.1136/bmjopen-2018-025477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588964PMC
June 2019

Autoimmune Diseases and Gastric Cancer Risk: A Systematic Review and Meta-Analysis.

Cancer Res Treat 2019 Jul 3;51(3):841-850. Epub 2019 May 3.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.

Purpose: Autoimmunity is an alternative etiology of gastric inflammation, the initiating event in the gastric carcinogenic cascade. This mechanism may be an increasingly important cause of gastric cancer with the waning prevalence of its primary etiologic factor, chronic Helicobacter pylori infection.

Materials And Methods: PubMed and EMBASE were searched up to September 2018. Autoimmunity and 96 specific manifestations were considered for associations with gastric cancer risk. Random effects analysis was used to calculate pooled relative risk estimates (RR) and 95% confidence intervals (CI).

Results: We found a total of 52 observational studies representing 30 different autoimmune diseases. Overall, the presence of an autoimmune condition was associated with a gastric cancer pooled RR of 1.37 (95% CI, 1.24 to 1.52). Among the 24 autoimmune conditions with two or more independent reports, nine were significantly associated with increased gastric cancer risk: dermatomyositis (RR, 3.69; 95% CI, 1.74 to 7.79), pernicious anemia (RR, 2.84; 95% CI, 2.30 to 3.50), Addison disease (RR, 2.11; 95% CI, 1.26 to 3.53), dermatitis herpetiformis (RR, 1.74; 95% CI, 1.02 to 2.97; n=3), IgG4-related disease (RR, 1.69; 95% CI, 1.00 to 2.87), primary biliary cirrhosis (RR, 1.64; 95% CI, 1.13 to 2.37), diabetes mellitus type 1 (RR, 1.41; 95% CI, 1.20 to 1.67), systemic lupus erythematosus (RR, 1.37; 95% CI, 1.01 to 1.84), and Graves disease (RR, 1.27; 95% CI, 1.06 to 1.52).

Conclusion: Our analysis documents the wide range of autoimmune diseases associated with gastric cancer. These associations may reflect unreported links between these conditions and autoimmune gastritis. Further studies are warranted to investigate potential causal mechanisms.
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http://dx.doi.org/10.4143/crt.2019.151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639229PMC
July 2019

Circulating Inflammation Markers and Risk of Gastric and Esophageal Cancers: A Case-Cohort Study Within the Japan Public Health Center-Based Prospective Study.

Cancer Epidemiol Biomarkers Prev 2019 04 15;28(4):829-832. Epub 2019 Mar 15.

Division of Cancer Epidemiology and Genetics, NCI, Rockville, Maryland.

Background: Circulating inflammation proteins may be important mediators or markers of carcinogenic mechanisms. There have been few studies with limited numbers of analytes in patients with upper gastrointestinal (GI) tract tumors. We therefore evaluated risk associations of gastric and esophageal cancers with prediagnostic levels of a wide range of these molecules.

Methods: We performed a case-cohort analysis within the Japan Public Health Center-Based Prospective Study Cohort II, including incident cases of gastric ( = 446) and esophageal ( = 68) cancers and a random subcohort ( = 774). A total of 64 biomarkers were measured in baseline plasma using Luminex bead-based assays. The median time between blood collection and diagnosis was 8.1 years for gastric cancer and 9.4 years for esophageal cancer. HRs for association with each marker were adjusted for potential confounders using Cox regression.

Results: In separate models, sEGFR and TSLP were nominally associated with gastric cancer risk, and CRP, CXCL11/ITAC, and CCL15/MIP1D were associated with esophageal cancer. However, no association satisfied statistical significance after FDR correction. Associations did not differ by time from blood collection to cancer (<5 vs. ≥5 years).

Conclusions: Our study failed to identify associations of circulating inflammation markers with risk of upper GI tract tumors.

Impact: To date, this is the largest assessment of inflammation-related proteins with gastric and esophageal cancer risks. However, the evaluated molecules may not fully represent the complex inflammation processes preceding malignant transformation. Further investigation of other markers in prospective studies is warranted, as demonstration of associations may have important implications for prevention and treatment of these cancers.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-1157DOI Listing
April 2019

Gastric Cancer: an Evolving Disease.

Curr Treat Options Gastroenterol 2018 Dec;16(4):561-569

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Dr., BG 9609/6E338, Rockville, MD, 20852, USA.

Purpose Of Review: Prevalence of Helicobacter pylori, the primary risk factor for gastric cancer, is declining globally. Paralleling this trend, gastric cancer incidence is also decreasing. Historically, the populations most affected by this neoplasia have been males, Asians, and groups with low socioeconomic status. This review provides an update on recently published literature regarding changes in gastric cancer epidemiology.

Recent Findings: Gastric cancer incidence trends vary by age, sex, race/ethnicity, and tumor anatomical location. Overall incidence appears to be leveling off among young birth cohorts in Western populations, where H. pylori has declined considerably. The changes are more prominent for females and for tumors arising beyond the esophageal-gastric junction. The classical incidence pattern of gastric cancer is evolving. While uncertain, several hypotheses may explain the changing burden of disease. The mix of gastric cancer risk factors appears to be shifting, with H. pylori no longer the sole etiological driver. These changes may eliminate the previous predilection of males and lead to increases in overall gastric cancer rates. Analytical studies addressing known and novel factors related to major societal transitions may provide clues to understanding re-emergence of this serious public health problem.
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http://dx.doi.org/10.1007/s11938-018-0203-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453722PMC
December 2018

Circulating inflammation-related markers and advanced gastric premalignant lesions.

J Gastroenterol Hepatol 2019 May 18;34(5):852-856. Epub 2018 Nov 18.

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

Background And Aim: Chronic Helicobacter pylori infection causes gastric mucosal inflammation as an important antecedent of gastric cancer. We aimed to evaluate associations of blood markers of inflammation with gastric intestinal metaplasia and dysplasia in H. pylori-infected individuals.

Methods: We compared pre-treatment serum levels of immune-related and inflammation-related markers between 99 individuals with intestinal metaplasia or dysplasia and 75 control individuals with non-atrophic gastritis within an H. pylori eradication trial in Mexico. Serum levels of 28 markers measured with Luminex bead-based assays were categorized in tertiles as low (T1), middle (T2), and high (T3). Logistic regression models were used to calculate age-adjusted and sex-adjusted odds ratios and 95% confidence intervals. All statistical tests were two-sided, and significance values were adjusted for multiple comparisons using false discovery rate methods.

Results: Five markers were nominally associated (P  < 0.05) with the presence of advanced premalignant gastric lesions. Adjusted odds ratios (95% confidence interval) of T2 and T3 versus T1 were 4.09 (1.65-10.17) and 3.08 (1.23-7.68) for CCL3/MIP1A, 3.21 (1.33-7.75) and 2.69 (1.10-6.57) for CCL20/MIP3A levels, 1.79 (0.77-4.18) and 2.39 (1.02-5.60) for IL-1β, 1.34 (0.56-3.19) and 3.02 (1.29-7.12) for IL-4, and 1.07 (0.44-2.59) and 3.07 (1.32-7.14) for IL-5, respectively. Two (IL-4 and IL-5) of the five markers had false discovery rate adjusted P  < 0.2.

Conclusions: Our results suggest that certain Th2 and other cytokines may have a role in promoting carcinogenesis in the setting of H. pylori infection. Additional research is needed to replicate these findings, extend to pre-diagnostic samples, and elucidate the underlying mechanisms.
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http://dx.doi.org/10.1111/jgh.14518DOI Listing
May 2019

Circulating inflammatory markers and colorectal cancer risk: A prospective case-cohort study in Japan.

Int J Cancer 2018 12 9;143(11):2767-2776. Epub 2018 Oct 9.

Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.

Blood levels of inflammation-related markers may reveal molecular pathways contributing to carcinogenesis. To date, prospective associations with colorectal cancer (CRC) risk have been based on few studies with limited sets of analytes. We conducted a case-cohort study within the Japan Public Health Center-based Prospective Study Cohort II, comparing 457 incident CRC cases during median 18 years follow-up with a random subcohort of 774 individuals. Baseline plasma levels of 62 cytokines, soluble receptors, acute-phase proteins, and growth factor markers were measured using Luminex bead-based assays. We estimated hazard ratios (HRs) associating each marker with CRC risk by Cox proportional hazards models adjusted for potential confounders. Subanalyses compared cases by years after blood draw (<5 vs. ≥5) and anatomical subsite (colon vs. rectum). Linear trends in quantiles of four C-C motif ligand (CCL) chemokines, one C-X-C motif ligand (CXCL) chemokine, and a soluble receptor were nominally associated with CRC risk based on p < 0.05, but none met false discovery rate corrected statistical significance. HRs for the 4th vs. 1st quartile were: 1.69 for CCL2/MCP1, 1.61 for soluble tumor necrosis factor receptor 2, 1.39 for CCL15/MIP1D, 1.35 for CCL27/CTACK, 0.70 for CXCL6/GCP2 and 0.61 for CCL3/MIP1A. Among cases diagnosed 5+ years after enrollment, CCL2/MCP1, CCL3/MIP1A and CXCL6/GCP2 retained nominal statistical significance. There were no significant differences in associations between colon and rectum. Our findings implicate chemokine alterations in colorectal carcinogenesis, but require replication for confirmation. Noninvasive chemokine assays may have potential application in colorectal cancer screening and etiologic research.
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http://dx.doi.org/10.1002/ijc.31821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235711PMC
December 2018

Prevalence of Participating in Physical Activity From 2 Korean Surveillance Systems: KNHANES and KCHS.

J Phys Act Health 2018 10 19;15(10):763-773. Epub 2018 Aug 19.

Background: This study aimed to estimate the prevalence and trends of participation in physical activity (PA) in Korean adults.

Methods: The Korea National Health and Nutrition Examination Survey (KNHANES; 2009-2013) and the Korea Community Health Survey (KCHS; 2009-2013) were used to estimate the prevalence of PA. Age standardization was performed using population projections for Korea in 2005 as a standard population. Trends of the prevalence from 2009 to 2013 were assessed by joinpoint regression analysis.

Results: The age-standardized prevalence for achieving the recommended level of PA was 63.0% in KNHANES and 64.5% in KCHS for men, and 53.7% in KNHANES and 56.3% in KCHS for women. Decreasing trends were observed for the prevalence of achieving the recommended level of PA in the KNHANES and KCHS; however, only the trend for women in KNHANES was statistically significant.

Conclusions: Approximately, 60% of adults participate in the recommended level of PA in Korea. The survey design and characteristics should be considered when interpreting the prevalence of PA from different databases.
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http://dx.doi.org/10.1123/jpah.2017-0428DOI Listing
October 2018

Family history of cancer in first-degree relatives and risk of gastric cancer and its precursors in a Western population.

Gastric Cancer 2018 09 17;21(5):729-737. Epub 2018 Feb 17.

Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Bethesda, MD, 20892-9776, USA.

Background: Family history may inform risks of gastric cancer and preneoplastic lesions.

Methods: We examined associations with history of cancer in first-degree relatives for 307 incident gastric cancer cases among 20,720 male smokers in a prospective study in Finland. Cox regression was used to calculate gastric cancer hazard ratios (HR) and 95% confidence intervals (95% CI). Logistic regression was used to estimate odds ratios (OR) and 95% CIs for low serum pepsinogen, a marker of gastric atrophy.

Results: Gastric cancer risk was associated with gastric cancer history in first-degree relatives overall (HR 1.56, 95% CI 1.15-2.12), in fathers (HR 1.67, 95% CI 1.09-2.55) and in siblings (HR 2.05, 95% CI 1.25-3.38). Associations were significant for noncardia (HR 1.83, 95% CI 1.30-2.57) but not cardia (HR 0.93, 95% CI 0.46-1.87) cancers, and marginal for both intestinal-(HR 1.53, 95% CI 0.92-2.55) and diffuse-type (HR 1.47, 95% CI 0.72-3.03) histologies. Family history of other cancer types was not associated with gastric cancer risk. Family history of gastric cancer was associated with low pepsinogen (OR 1.29, 95% CI 1.11-1.50).

Conclusions: Family history of gastric cancer is strongly associated with specific subtypes of gastric cancer as well as with gastric atrophy, a risk factor for developing this malignancy.
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http://dx.doi.org/10.1007/s10120-018-0807-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380686PMC
September 2018

Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium.

Diabetologia 2017 06 7;60(6):1022-1032. Epub 2017 Mar 7.

Tohoku University Graduate School of Medicine, Miyagi Prefecture, Japan.

Aims/hypothesis: The aims of the study were to evaluate the association between type 2 diabetes and the risk of death from any cancer and specific cancers in East and South Asians.

Methods: Pooled analyses were conducted of 19 prospective population-based cohorts included in the Asia Cohort Consortium, comprising data from 658,611 East Asians and 112,686 South Asians. HRs were used to compare individuals with diabetes at baseline with those without diabetes for the risk of death from any cancer and from site-specific cancers, including cancers of the oesophagus, stomach, colorectum, colon, rectum, liver, bile duct, pancreas, lung, breast, endometrium, cervix, ovary, prostate, bladder, kidney and thyroid, as well as lymphoma and leukaemia.

Results: During a mean follow-up of 12.7 years, 37,343 cancer deaths (36,667 in East Asians and 676 in South Asians) were identified. Baseline diabetes status was statistically significantly associated with an increased risk of death from any cancer (HR 1.26; 95% CI 1.21, 1.31). Significant positive associations with diabetes were observed for cancers of the colorectum (HR 1.41; 95% CI 1.26, 1.57), liver (HR 2.05; 95% CI 1.77, 2.38), bile duct (HR 1.41; 95% CI 1.04, 1.92), gallbladder (HR 1.33; 95% CI 1.10, 1.61), pancreas (HR 1.53; 95% CI 1.32, 1.77), breast (HR 1.72; 95% CI 1.34, 2.19), endometrium (HR 2.73; 95% CI 1.53, 4.85), ovary (HR 1.60; 95% CI 1.06, 2.42), prostate (HR 1.41; 95% CI 1.09, 1.82), kidney (HR 1.84; 95% CI 1.28, 2.64) and thyroid (HR 1.99; 95% CI 1.03, 3.86), as well as lymphoma (HR 1.39; 95% CI 1.04, 1.86). Diabetes was not statistically significantly associated with the risk of death from leukaemia and cancers of the bladder, cervix, oesophagus, stomach and lung.

Conclusions/interpretation: Diabetes was associated with a 26% increased risk of death from any cancer in Asians. The pattern of associations with specific cancers suggests the need for better control (prevention, detection, management) of the growing epidemic of diabetes (as well as obesity), in order to reduce cancer mortality.
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http://dx.doi.org/10.1007/s00125-017-4229-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632944PMC
June 2017

Electronic Alerts with Automated Consultations Promote Appropriate Antimicrobial Prescriptions.

PLoS One 2016 17;11(8):e0160551. Epub 2016 Aug 17.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.

Background: To promote appropriate antimicrobial use in bloodstream infections (BSIs), we initiated an intervention program consisting of electronic alerts and automated infectious diseases consultations in which the identification and antimicrobial susceptibility test (ID/AST) results were reported.

Methods: We compared the appropriateness of antimicrobial prescriptions and clinical outcomes in BSIs before and after initiation of the program. Appropriateness was assessed in terms of effective therapy, optimal therapy, de-escalation therapy, and intravenous to oral switch therapy.

Results: There were 648 BSI episodes in the pre-program period and 678 in the program period. The proportion of effective, optimal, and de-escalation therapies assessed 24 hours after the reporting of the ID/AST results increased from 87.8% (95% confidence interval [CI] 85.5-90.5), 64.4% (95% CI 60.8-68.1), and 10.0% (95% CI 7.5-12.6) in the pre-program period, respectively, to 94.4% (95% CI 92.7-96.1), 81.4% (95% CI 78.4-84.3), and 18.6% (95% CI 15.3-21.9) in the program period, respectively. Kaplan-Meier analyses and log-rank tests revealed that the time to effective (p<0.001), optimal (p<0.001), and de-escalation (p = 0.017) therapies were significantly different in the two periods. Segmented linear regression analysis showed the increase in the proportion of effective (p = 0.015), optimal (p<0.001), and de-escalation (p = 0.010) therapies at 24 hours after reporting, immediately after program initiation. No significant baseline trends or changes in trends were identified. There were no significant differences in time to intravenous to oral switch therapy, length of stay, and 30-day mortality rate.

Conclusion: This novel form of stewardship program based on intervention by infectious disease specialists and information technology improved antimicrobial prescriptions in BSIs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160551PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988717PMC
July 2017

Determinants of Poor Self-rated Health in Korean Adults With Diabetes.

J Prev Med Public Health 2015 Nov 23;48(6):287-300. Epub 2015 Oct 23.

Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.

Objectives: Self-rated health is a measure of perceived health widely used in epidemiological studies. Our study investigated the determinants of poor self-rated health in middle-aged Korean adults with diabetes.

Methods: A cross-sectional study was conducted based on the Health Examinees Study. A total of 9759 adults aged 40 to 69 years who reported having physician-diagnosed diabetes were analyzed with regard to a range of health determinants, including sociodemographic, lifestyle, psychosocial, and physical variables, in association with self-rated health status using multivariate logistic regression models. A p-value <0.05 was considered to indicate statistical significance.

Results: We found that negative psychosocial conditions, including frequent stress events and severe distress according to the psychosocial well-being index, were most strongly associated with poor self-rated health (odds ratio [OR](Frequent stress events), 5.40; 95% confidence interval [CI], 4.63 to 6.29; OR(Severe distress), 11.08; 95% CI, 8.77 to 14.00). Moreover, younger age and being underweight or obese were shown to be associated with poor self-rated health. Physical factors relating to participants' medical history of diabetes, such as a younger age at diagnosis, a longer duration of diabetes, insulin therapy, hemoglobin A1clevels of 6.5% or more, and comorbidities, were other correlates of poor reported health.

Conclusions: Our findings suggest that, in addition to medical variables, unfavorable socioeconomic factors, and adverse lifestyle behaviors, younger age, being underweight or obese, and psychosocial stress could be distinc factors in predicting negative perceived health status in Korean adults with diabetes.
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http://dx.doi.org/10.3961/jpmph.15.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676642PMC
November 2015

What Are the Major Determinants in the Success of Smoking Cessation: Results from the Health Examinees Study.

PLoS One 2015 3;10(12):e0143303. Epub 2015 Dec 3.

Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.

Understanding mechanisms underlying smoking-related factors should be prioritized in establishing smoking prevention and cessation policy. The aim of this study was to identify factors significantly associated with smoking initiation and/or smoking cessation as well as the most important determinants of successful smoking cessation in a developed non-Western setting. Based on multiple logistic regression models, the odds ratios (ORs) for smoking initiation and cessation were estimated among males (N = 24,490) who had participated in the Health Examinees (HEXA) study. The Cox proportional hazards regression model was used to assess the association between selected predictors of smoking cessation and the likelihood of reaching this goal. Finally, Kaplan-Meier curves were constructed to illustrate the distribution of time from age at smoking initiation to age at smoking cessation. We found that the ORs for successfully quitting smoking increased with age, married status, educational achievement, having a non-manual job, drinking cessation and disease morbidity. Those exposed to secondhand smoking showed less likelihood of quitting smoking. A continual decrease in the ORs for successfully quitting smoking was observed according to increased smoking duration, smoking dose per day and lifetime tobacco exposure (ptrend <0.001). Among the selected predictors, lifetime tobacco exposure, educational attainment, alcohol drinking status and birth cohort were the major determinants in the success of smoking cessation. Our findings suggest that lifetime tobacco exposure, educational attainment, alcohol drinking status and birth cohort can determine success in smoking cessation. Public interventions promoting a smoke-free environment are needed to reinforce discouraging the initiation of, reducing, and quitting cigarette smoking.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143303PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669113PMC
June 2016

Short Sleep Duration and Its Correlates among Cancer Survivors in Korea: the Korea National Health and Nutrition Examination Surveys.

Asian Pac J Cancer Prev 2015 ;16(11):4705-10

Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea E-mail :

Background: Though a large proportion of cancer survivors are assumed to be commonly affected by sleep disturbance, few studies have focused on short sleep problems and its correlates among Korean cancer survivors. The purpose of this study was to evaluate the prevalence of short sleep in adult cancer survivors from a nationwide population-based sample and to identify risk factors for short sleep duration.

Materials And Methods: Based on the fourth and fifth Korea National Health and Nutrition Examination Surveys (2007-2012), 1,045 cancer survivors and 33,929 non-cancer controls were analyzed. The prevalence of short sleep was compared between these two groups. Associations between short sleep and its correlates were evaluated using multiple logistic regression among cancer survivors: odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated after adjusting for sociodemographic factors, lifestyle factors, psychological conditions, and cancer-related factors.

Results: About 8.1% of cancer survivors slept for less than 5 hours per day (6.2% men and 9.3% women), whereas this was the case for only 3.7% of non-cancer controls. Cancer survivors who had the lowest household income level showed a significantly higher likelihood for short sleep (adjusted OR 2.82, 95%CI 1.06-7.54). Self-reported poor health and depressive symptoms were found to be associated with significantly increased likelihood for short sleep in cancer survivors (adjusted OR 3.60, 95%CI 1.40-9.26 and adjusted OR 2.00, 95%CI 1.17-3.42). Gastric cancer survivors had a 3.97-fold increased risk for short sleep (95%CI 1.60-9.90).

Conclusions: The prevalence of short sleep occurs at a high rate among the Korean cancer survivors, which may indicate a poorer quality of life and a higher risk of future complications in survivorship. Targeted interventions that can assist cancer survivors to cope with sleep disturbances as well as ensuring psychological stability are warranted to reduce the latent disease burden.
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http://dx.doi.org/10.7314/apjcp.2015.16.11.4705DOI Listing
April 2016

Correlates of self-reported sleep duration in middle-aged and elderly Koreans: from the Health Examinees Study.

PLoS One 2015 1;10(5):e0123510. Epub 2015 May 1.

Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea; Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Korea; Cancer Research Institute, Seoul National University, Seoul, Korea.

Though various factors related to fluctuations in sleep duration have been identified, information remains limited regarding the correlates of short and long sleep duration among the Korean population. Thus, we investigated characteristics that could be associated with short and/or long sleep duration among middle-aged and elderly Koreans. A total of 84,094 subjects (27,717 men and 56,377 women) who participated in the Health Examinees Study were analyzed by using multinomial logistic regression models. To evaluate whether sociodemographic factors, lifestyle factors, psychological conditions, anthropometry results, and health conditions were associated with short and/or long sleep duration, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with sleep duration of 6-7 hours as the reference group, accounting for putative covariates. Regardless of sexual differences, we found that adverse behaviors and lifestyle factors including low educational attainment, unemployment, being unmarried, current smoking status, lack of exercise, having irregular meals, poor psychosocial well-being, frequent stress events, and poor self-rated health were significantly associated with abnormal sleep duration. Similarly, diabetes mellitus and depression showed positive associations with abnormal sleep duration in both men and women. Our findings suggest that low sociodemographic characteristics, adverse lifestyle factors, poor psychological conditions, and certain disease morbidities could be associated with abnormal sleep duration in middle-aged and elderly Koreans.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123510PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416918PMC
February 2016
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