Integrative molecular profiling identifies a novel cluster of estrogen receptor‐positive breast cancer in very young women

Park, Charny,Yoon, Kyong‐,Ah,Kim, Jihyun,Park, In Hae,Park, Soo Jin,Kim, Min Kyeong,Jang, Wooyeong,Cho, Soo Young,Park, Boyoung,Kong, Sun‐,Young,Lee, Eun Sook John Wiley and Sons Inc. 2019 Cancer Science Vol.110 No.5

<P>Very young breast cancer patients are more common in Asian countries than Western countries and are thought to have worse prognosis than older patients. The aim of the current study was to identify molecular characteristics of young patients with estrogen receptor (ER)‐positive breast cancer by analyzing mutations and copy number variants (CNV), and by applying expression profiling. The whole exome and transcriptome of 47 Korean young breast cancer (KYBR) patients (age <35) were analyzed. Genomic profiles were constructed using mutations, CNV and differential gene expression from sequencing data. Pathway analyses were also performed using gene sets to identify biological processes. Our data were compared with young ER+ breast cancer patients in The Cancer Genome Atlas (TCGA) dataset. <I>TP53</I>,<I>PIK3CA</I> and <I>GATA3</I> were highly recurrent somatic mutation genes. APOBEC‐associated mutation signature was more frequent in KYBR compared with young TCGA patients. Integrative profiling was used to classify our patients into 3 subgroups based on molecular characteristics. Group A showed luminal A‐like subtype and IGF1R signal dysregulation. Luminal B patients were classified into groups B and C, which showed chromosomal instability and enrichment for APOBEC3A/B deletions, respectively. Group B was characterized by 11q13 (CCND1) amplification and activation of the ubiquitin‐mediated proteolysis pathway. Group C showed 17q12 (ERBB2) amplification and lower ER and progesterone receptor expression. Group C was also distinguished by immune activation and lower epithelial‐mesenchyme transition (EMT) degree compared with group B. This study showed that integrative genomic profiling could classify very young patients with breast cancer into molecular subgroups that are potentially linked to different clinical characteristics.</P>

Deletion of the Serotonin Receptor Type 3A in Mice Leads to Sudden Cardiac Death During Pregnancy.

Park, Hyewon,Oh, Chang-Myung,Park, Junbeom,Park, Hyelim,Cui, Shanyu,Kim, Hyung Suk,Namkung, Jun,Park, Sang-Kyu,Pak, Hui-Nam,Lee, Moon-Hyoung,Kim, Hail,Joung, Boyoung Japanese Circulation Society 2015 CIRCULATION JOURNAL Vol.79 No.8

<P>The serotonin receptor type 3 (Htr3) blocker is associated with QT prolongation and torsades de pointes. However, little is known about effects of Htr3 on the heart arrhythmia.Methods?and?Results:An electrophysiological study Involving knock-out (KO) female mice lacking functional Htr3a (Htr3a(-/-)) and their wild-type littermates during non-pregancy (NP) and late pregnancy (LP) was performed. Htr3a mRNA was present in the wild-type, but not in theHtr3a(-/-)mouse hearts. Serotonin and tryptophan hydroxylase 1 (Tph1), a rate-limiting enzyme of serotonin synthesis in hearts, is increased during pregnancy. The heart weight and size were increased in the pregnant mice regardless of a mutation. The QTc intervals were prolonged after pregnancy in both the wild (NP: 171.216.8 vs. LP: 247.714.3 ms; P<0.001) andHtr3a(-/-)mice (NP: 187.918.7 vs. LP: 275.611.0 ms, P<0.001). Compared with wild-type LP mice,Htr3a(-/-)LP mice had increased spontaneous ventricle tarchycardia (VT; 56% vs. 0%, P=0.002), VT inducibility (66% vs. 25%, P=0.002) and mortality (56% vs. 0%, P=0.002). Pharmacologic administration of serotonin and Htr3 agonists (m-CPBG) decreased the QT interval in wild mice, but not inHtr3a(-/-)mice.</P>

Attribution to Heterogeneous Risk Factors for Breast Cancer Subtypes Based on Hormone Receptor and Human Epidermal Growth Factor 2 Receptor Expression in Korea

Park, Boyoung,Choi, Ji-Yeob,Sung, Ho Kyung,Ahn, Choonghyun,Hwang, Yunji,Jang, Jieun,Lee, Juyeon,Kim, Heewon,Shin, Hai-Rim,Park, Sohee,Han, Wonshik,Noh, Dong-Young,Yoo, Keun-Young,Kang, Daehee,Park, Su Wolters Kluwer Health 2016 Medicine Vol.95 No.14

<▼1><P>Supplemental Digital Content is available in the text</P></▼1><▼2><P><B>Abstract</B></P><P>We conducted a heterogeneous risk assessment of breast cancer based on the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) calculating the risks and population-based attributable fractions (PAFs) for modifiable and nonmodifiable factors.</P><P>Using matched case–control study design from the Seoul Breast Cancer Study and the national prevalence of exposure, the risks and PAFs for modifiable and nonmodifiable factors were estimated for total breast cancers and subtypes.</P><P>The attribution to modifiable factors was different for each subtype (luminal A, PAF = 61.4% [95% confidence interval, CI = 54.3%–69.8%]; luminal B, 21.4% [95% CI = 18.6–24.9%]; HER2-overexpression, 59.4% [95% CI = 47.8%–74.3%], and triple negative tumors [TNs], 27.1% [95% CI = 22.9%–32.4%)], and the attribution to the modifiable factors for the luminal A and HER2-overexpression subtypes was higher than that of the luminal B and TN subtypes (<I>P</I> heterogeneity ≤ 0.001). The contribution of modifiable reproductive factors to luminal A type in premenopausal women was higher than that of the other subtypes (18.2% for luminal A; 3.1%, 8.1%, and −3.1% for luminal B, HER2-overexpression, and TN subtypes, respectively; <I>P</I> heterogeneity ≤ 0.001). Physical activity had the highest impact preventing 32.6% of luminal A, 14.5% of luminal B, 38.0% of HER2-overexpression, and 26.9% of TN subtypes (<I>P</I> heterogeneity = 0.014). Total reproductive factors were also heterogeneously attributed to each breast cancer subtype (luminal A, 65.4%; luminal B, 24.1%; HER2-overexpression, 57.9%, and TN subtypes, −3.1%; <I>P</I> heterogeneity ≤ 0.001).</P><P>Each pathological subtype of breast cancer by HRs and HER2 status may be associated with heterogeneous risk factors and their attributable risk, suggesting a different etiology. The luminal B and TN subtypes seemed to be less preventable despite intervention for alleged risk factors, even though physical activity had a high preventable potential against breast cancer.</P></▼2>

GIS를 이용한 지하광산 디젤 차량의 운반작업 시 탄소배출량 산정

박보영(Boyoung Park),박세범(Sebeom Park),최요순(Yosoon Choi),박한수(Han-Su Park) 한국암반공학회 2015 터널과지하공간 Vol.25 No.4

Ten-Year Changes in the Hepatitis B Prevalence in the Birth Cohorts in Korea : Results From Nationally Representative Cross-Sectional Surveys

Park, Boyoung,Jung, Kyu-Won,Oh, Chang-Mo,Choi, Kui Son,Suh, Mina,Jun, Jae Kwan Williams & Wilkins Co 2015 Medicine Vol.94 No.41

<P><B>Abstract</B></P><P>To compare the prevalence of hepatitis B virus (HBV) infection over a 10-year period in terms of population-level trends, we established hypothetical birth cohorts that represented each 10-year interval age group.</P><P>We used data from the Korean National Health and Nutrition Examination Surveys conducted between 1998 to 2001 and 2008 to 2011. Trends in the HBV infection were calculated using data from individuals aged 20 to 59 years in 1998 to 2001 and those aged 30 to 69 years in 2008 to 2011.</P><P>In 2008 to 2011, the prevalence of HBV infection, as measured using serum HBV surface antigen (HBsAg) seroprevalence, among participants aged 30 to 69 years was 4.2% (95% CI = 3.7–4.7%), which represents a 1.3% absolute change and 20% change in prevalence ratio, which was significant compared with the prevalence among those aged 20 to 59 years in 1998 to 2001 (5.5%, 95% CI = 4.7–6.3%). The prevalence of HBV infection decreased most in the lowest income group, with marginal significance in males (<I>P</I> = 0.06) and significance in females (<I>P</I> = 0.03). In terms of education, females with at least a high school education showed a significant decrease (<I>P</I> = 0.03).</P><P>Using a birth cohort approach, the prognosis for HBV infection in terms of death or hospitalization, or resolution upon antiviral treatment of their HBV infections, identified by a decrease in the HBsAg seroprevalence was worse in the lower income group and in females with higher education. We postulate that these socioeconomic inequalities were caused by alcohol consumption, disparities in liver cancer surveillance, and access to antiviral treatment because of cost and reimbursement guidelines.</P>

Sympathetic nerve blocks promote anti-inflammatory response by activating the JAK2-STAT3–mediated signaling cascade in rat myocarditis models: A novel mechanism with clinical implications

Park, Hyelim,Park, Hyewon,Mun, Dasom,Kim, Michael,Pak, Hui-Nam,Lee, Moon-Hyoung,Joung, Boyoung Elsevier 2018 Heart rhythm Vol.15 No.5

<P><B>Background</B></P> <P>Left stellectomy has become an important therapeutic option for patients with potentially fatal arrhythmias. However, the antiarrhythmic mechanism of left stellectomy is not well known. The cholinergic anti-inflammatory pathway (CAIP) is a complex immune mechanism that regulates peripheral inflammatory responses.</P> <P><B>Objective</B></P> <P>The purpose of this study was to evaluate the effect of left stellectomy on CAIP using rat experimental autoimmune myocarditis (EAM) models.</P> <P><B>Methods</B></P> <P>EAM was produced by injecting 2 mg of porcine cardiac myosin into the footpads of rats. Left stellectomy was performed before EAM induction. We evaluated the effect of left stellectomy on arrhythmic events, survival, inflammation, and CAIP in rats without and with EAM.</P> <P><B>Results</B></P> <P>Left stellectomy prevented arrhythmia and improved survival in EAM rats. Left stellectomy decreased the levels of tumor necrosis factor α, interleukin 6, and high mobility group box 1 (<I>P</I> < .05 vs EAM) in serum and heart tissues from EAM rats. In heart rate variability analysis, high-frequency peaks of the power spectrum densities, reflecting parasympathetic cardiovagal tone, were significantly decreased in EAM rats, but increased after left stellectomy. The ratios of phosphorylated STAT3/STAT3 (signal transducer and activator of transcription 3) and phosphorylated JAK2/JAK2 (Janus kinase 2) decreased in cell lysates of the spleen, liver, and heart in EAM rats. However, the same ratios significantly increased after left stellectomy. Nuclear factor κB in cell lysates of the spleen, liver, and heart increased in EAM rats, but decreased after left stellectomy.</P> <P><B>Conclusion</B></P> <P>In EAM models, left stellectomy increased survival of the rats while showing antiarrhythmic effects with reduced inflammation via activation of the JAK2-STAT3–mediated signaling cascade. Our findings suggest an exciting opportunity to develop new and novel therapeutics to attenuate cardiac inflammation.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Prevalence and predictors of anxiety and depression among family caregivers of cancer patients: a nationwide survey of patient–family caregiver dyads in Korea

Park, Boyoung,Kim, So Young,Shin, Ji-Yeon,Sanson-Fisher, Robert W.,Shin, Dong Wook,Cho, Juhee,Park, Jong-Hyock Springer-Verlag 2013 Supportive care in cancer Vol.21 No.10

Lack of Effects of Peroxisome Proliferator-Activated Receptor Gamma Genetic Polymorphisms on Breast Cancer Risk: a Case-Control Study and Pooled Analysis

Park, Boyoung,Shin, Aesun,Kim, Kyee-Zu,Lee, Yeon-Su,Hwang, Jung-Ah,Kim, Yeonju,Sung, Joohon,Yoo, Keun-Young,Lee, Eun-Sook Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

A growing body of evidence suggests that the peroxisome proliferator-activated receptor-gamma ($PPAR{\gamma}$) gene may harbor targets for the chemoprevention of breast cancer. However, it is unclear whether polymorphisms in the $PPAR{\gamma}$ gene are associated with the susceptibility of breast cancer. We performed a candidate gene association study between $PPAR{\gamma}$ polymorphisms and breast cancer and a meta-analysis on the association of breast cancer with selected $PPAR{\gamma}$ variants. Six single nucleotide polymorphisms (SNPs) in the $PPAR{\gamma}$ gene were analyzed among 456 breast cancer patients and 461 controls from the National Cancer Center in Korea. Association between the polymorphisms and breast cancer risk were assessed using the Cochrane-Armitage test for trend and a multivariate logistic regression model. Two SNPs, rs3856806 and rs1801282, had been previously analyzed, thus enabling us to perform pooled analyses on their associations with breast cancer susceptibility. Our findings from the candidate gene association study showed no association between the $PPAR{\gamma}$ gene polymorphisms and breast cancer risk. A meta-analysis combining existing studies and our current study also refuted an association of the $PPAR{\gamma}$ gene with breast cancer. Our findings suggest that the $PPAR{\gamma}$ gene may not harbor variants that alter breast cancer susceptibility, although a moderate sample size might have precluded a decisive conclusion.

Transmission of Seasonal Outbreak of Childhood Enteroviral Aseptic Meningitis and Hand-foot-mouth Disease

Park, Sue K.,Park, Boyoung,Ki, Moran,Kim, Ho,Lee, Kwan,Jung, Cheoll,Sohn, Young Mo,Choi, Sung-Min,Kim, Doo-Kwun,Lee, Dong Seok,Ko, Joon Tae,Kim, Moon Kyu,Cheong, Hae-Kwan The Korean Academy of Medical Sciences 2010 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.25 No.5

<P>This study was conducted to evaluate the modes of transmission of aseptic meningitis (AM) and hand-foot-mouth disease (HFMD) using a case-control and a case-crossover design. We recruited 205 childhood AM and 116 HFMD cases and 170 non-enteroviral disease controls from three general hospitals in Gyeongju, Pohang, and Seoul between May and August in both 2002 and 2003. For the case-crossover design, we established the hazard and non-hazard periods as week one and week four before admission, respectively. In the case-control design, drinking water that had not been boiled, not using a water purifier, changes in water quality, and contact with AM patients were significantly associated with the risk of AM (odds ratio [OR]=2.8, 2.9, 4.6, and 10.9, respectively), while drinking water that had not been boiled, having a non-water closet toilet, changes in water quality, and contact with HFMD patients were associated with risk of HFMD (OR=3.3, 2.8, 6.9, and 5.0, respectively). In the case-crossover design, many life-style variables such as contact with AM or HFMD patients, visiting a hospital, changes in water quality, presence of a skin wound, eating out, and going shopping were significantly associated with the risk of AM (OR=18.0, 7.0, 8.0, 2.2, 22.3, and 3.0, respectively) and HFMD (OR=9.0, 37.0, 11.0, 12.0, 37.0, and 5.0, respectively). Our findings suggest that person-to-person contact and contaminated water could be the principal modes of transmission of AM and HFMD.</P>

Association of Gender With Clinical Outcomes in a Contemporary Cohort of Patients With Atrial Fibrillation Receiving Oral Anticoagulants

Boyoung Joung,Minjeong Kim,Jun Kim,Jin-Bae Kim,Junbeom Park,Jin-Kyu Park,Ki-Woon Kang,Jaemin Shim,Eue-Keun Choi,Young Soo Lee,Hyung Wook Park 대한심장학회 2022 Korean Circulation Journal Vol.52 No.8

Background and Objectives: In patients with atrial fibrillation (AF), females taking vitamin K antagonist are at higher risk of stroke or systemic embolism (SSE), bleeding and all-cause death than males. This study investigated the relationship between sex and adverse clinical events in a contemporary AF patient cohort taking anticoagulation. Methods: This prospective multicenter AF registry study comprised 6,067 patients with AF (mean age, 70±9 years; men, 59%) with intermediate to high risk of stroke (CHA2DS2-VAscore ≥1) and receiving oral anticoagulation therapy. Adverse clinical outcomes, including SSE, bleeding, death were evaluated in patients stratified by sex and anticoagulation patterns. Results: Women were older and used more direct oral anticoagulants (85% vs. 78%, p<0.001) than men. During a median (25th and 75th percentiles) follow-up of 30 (24, 38) months, the incidence rate and risk of SSE (0.7 in women vs. 0.7 in men per 100 person-years) and major bleeding (0.1 in women vs. 0.1 in men per 100 person-years) were not different between the sexes. However, women had a lower all-cause death rate (0.4 in women vs. 0.6 in men per 100 person-years, hazard ratio: 0.48, 95% confidence interval: 0.25–0.91, p=0.025) than men. Conclusions: In contemporary anticoagulation for AF, SSE and major bleeding risks did not differ between sexes. However, women showed a lower risk of all-cause death rate than men, indicating that the use of oral anticoagulants for treating AF in females does not appear to be a risk factor for adverse clinical events.