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Recent studies have revealed the possible association between serum cholesterol levels and hematologic malignancy (HM). However, limited information is available about how reproductive factors interact with this association. Therefore, we investigated the roles of serum cholesterol in the risk of HM according to the menopausal status. We finally identified 1,189,806 premenopausal and 1,621,604 postmenopausal women who underwent a national health screening program in 2009 using data from the Korean National Health Insurance Service database. Overall, 5449 (0.19%) developed HM. Among postmenopausal women, the inverse associations were observed between total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) levels, and the risk of overall HM. In premenopausal women, the highest quartile of HDL-C was associated with a reduced risk of HM compared with the lowest quartile of HDL-C consistent with results in postmenopausal women (adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] [0.68–0.95]), whereas the highest quartile of triglyceride (TG) showed an increased risk of HM compared to the lowest quartile of TG, (aHR 1.22, 95% CI [1.02,1.44]) only in premenopausal women. Our finding suggests that lipid profiles are differently associated with HM risk by menopausal status. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to assess the association of smoking cessation and reduction with risk of cardiovascular disease (CVD). Methods and results A total of 897 975 current smokers aged ≥40 years who had undergone two consecutive national health examinations (in 2009 and 2011) were included. Participants were classified as quitters (20.6%), reducers I (≥50% reduction, 7.3%), reducers II (20–50% reduction, 11.6%), sustainers (45.7%), and increasers (≥20% increase, 14.5%). During 5 575 556 person-years (PY) of follow-up, 17 748 stroke (3.2/1000 PY) and 11 271 myocardial infarction (MI) (2.0/1000 PY) events were identified. Quitters had significantly decreased risk of stroke [adjusted hazard ratio (aHR) 0.77 95% confidence interval (CI) 0.74–0.81; absolute risk reduction (ARR) −0.37, 95% CI −0.43 to −0.31] and MI (aHR 0.74, 95% CI 0.70–0.78; ARR −0.27, 95% CI −0.31 to −0.22) compared to sustainers after adjustment for demographic factors, comorbidities, and smoking status. The risk of stroke and MI incidence in reducers I (aHR 1.02, 95% CI 0.97–1.08 and aHR 0.99, 95% CI 0.92–1.06, respectively) and reducers II (aHR 1.00, 95% CI 0.95–1.05 and aHR 0.97, 95% CI 0.92–1.04, respectively) was not significantly different from the risk in sustainers. Further analysis with a subgroup who underwent a third examination (in 2013) showed that those who quit at the second examination but had starting smoking again by the third examination had 42–69% increased risk of CVD compared to sustained quitters. Conclusions Smoking cessation, but not reduction, was associated with reduced CVD risk. Our study emphasizes the importance of sustained quitting in terms of CVD risk reduction. [ABSTRACT FROM AUTHOR]

Background and Aim: Obesity was suggested to increase the incidence of gastric cancer (GC) in women, but results from previous studies were inconsistent. We investigated the relationship between obesity and the risk of GC according to menopausal status. Methods: We enrolled 1 418 180 premenopausal and 4 854 187 postmenopausal women aged ≥ 40 years using the Korean National Health Insurance System Cohort (2009–2014). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for GC incidence according to body mass index (BMI) and waist circumference (WC) using the Cox proportional hazards models. Results: During the mean follow‐up period of 7.2 years, 42 441 women were newly diagnosed with GC. Compared with the group with BMI 18.5–22.9 kg/m2, the adjusted HRs (95% CIs) for GC in the groups with BMI < 18.5, 23–24.9, 25–29.9, and ≥ 30 kg/m2 were 1.12 (0.95–1.33), 0.96 (0.89–1.04), 1.02 (0.94–1.11), and 0.99 (0.83–1.18), respectively, for premenopausal women and 1.07 (1.00–1.14), 1.01 (0.99–1.04), 1.03 (1.00–1.05), and 1.11 (1.10–1.16), respectively, for postmenopausal women. Compared with the group with WC 65–74.9 cm, the adjusted HRs (95% CIs) for GC for the groups with WC < 65, 75–84.9, 85–94.9, and ≥ 90 cm were 1.00 (0.88–1.15), 1.03 (0.96–1.11), 1.10 (0.99–1.22), and 1.02 (0.81–1.27), respectively, for premenopausal women and 1.01 (0.94–1.09), 1.01 (0.99–1.04), 1.09 (1.06–1.13), and 1.14 (1.09–1.19), respectively, for postmenopausal women. Conclusions: We found a positive association between the highest BMI and WC category and risk of GC in postmenopausal women; however, such an association was not evident in premenopausal women. [ABSTRACT FROM AUTHOR]

Summary Dendrite aberration is a common feature of neurodegenerative diseases caused by protein toxicity, but the underlying mechanisms remain largely elusive. Here, we show that nuclear polyglutamine (polyQ) toxicity resulted in defective terminal dendrite elongation accompanied by a loss of Golgi outposts (GOPs) and a decreased supply of plasma membrane (PM) in Drosophila class IV dendritic arborization (da) (C4 da) neurons. mRNA sequencing revealed that genes downregulated by polyQ proteins included many secretory pathway-related genes, including COPII genes regulating GOP synthesis. Transcription factor enrichment analysis identified CREB3L1/CrebA , which regulates COPII gene expression. CrebA overexpression in C4 da neurons restores the dysregulation of COPII genes, GOP synthesis, and PM supply. Chromatin immunoprecipitation (ChIP)-PCR revealed that CrebA expression is regulated by CREB-binding protein (CBP), which is sequestered by polyQ proteins. Furthermore, co-overexpression of CrebA and Rac1 synergistically restores the polyQ-induced dendrite pathology. Collectively, our results suggest that GOPs impaired by polyQ proteins contribute to dendrite pathology through the CBP-CrebA-COPII pathway. [ABSTRACT FROM AUTHOR]

Prostate cancer is the fourth most common cause of cancer in men in Korea, and there has been a rapid increase in cases. In the present study, we constructed a risk prediction model for prostate cancer using representative data from Korea. Participants who completed health examinations in 2009, based on the Korean National Health Insurance database, were eligible for the present study. The crude and adjusted risks were explored with backward selection using the Cox proportional hazards model to identify possible risk variables. Risk scores were assigned based on the adjusted hazard ratios, and the standardized points for each risk factor were proportional to the β-coefficient. Model discrimination was assessed using the concordance statistic (c-statistic), and calibration ability was assessed by plotting the mean predicted probability against the mean observed probability of prostate cancer. Among the candidate predictors, age, smoking intensity, body mass index, regular exercise, presence of type 2 diabetes mellitus, and hypertension were included. Our risk prediction model showed good discrimination (c-statistic: 0.826, 95% confidence interval: 0.821–0.832). The relationship between model predictions and actual prostate cancer development showed good correlation in the calibration plot. Our prediction model for individualized prostate cancer risk in Korean men showed good performance. Using easily accessible and modifiable risk factors, this model can help individuals make decisions regarding prostate cancer screening. [ABSTRACT FROM AUTHOR]

Simple Summary: From the representative data in Korea, we developed individual lung cancer risk prediction model of Korean adults. Our model would serve as a tool to screen high-risk individuals who would benefit from participating in lung cancer screening in a clinical setting applicable to health examinees or the general adult population. We believe that interactive approaches between healthcare providers and examinees using an easily accessible and visualized risk score can be used for the development of health policies for lung cancer prevention. Early detection of lung cancer by screening has contributed to reduce lung cancer mortality. Identifying high risk subjects for lung cancer is necessary to maximize the benefits and minimize the harms followed by lung cancer screening. In the present study, individual lung cancer risk in Korea was presented using a risk prediction model. Participants who completed health examinations in 2009 based on the Korean National Health Insurance (KNHI) database (DB) were eligible for the present study. Risk scores were assigned based on the adjusted hazard ratio (HR), and the standardized points for each risk factor were calculated to be proportional to the b coefficients. Model discrimination was assessed using the concordance statistic (c-statistic), and calibration ability assessed by plotting the mean predicted probability against the mean observed probability of lung cancer. Among candidate predictors, age, sex, smoking intensity, body mass index (BMI), presence of chronic obstructive pulmonary disease (COPD), pulmonary tuberculosis (TB), and type 2 diabetes mellitus (DM) were finally included. Our risk prediction model showed good discrimination (c-statistic, 0.810; 95% CI: 0.801–0.819). The relationship between model-predicted and actual lung cancer development correlated well in the calibration plot. When using easily accessible and modifiable risk factors, this model can help individuals make decisions regarding lung cancer screening or lifestyle modification, including smoking cessation. [ABSTRACT FROM AUTHOR]

Simple Summary: The inverse association between smoking, alcohol intake, and thyroid cancer has been suggested by observational studies. From the representative data in Korea, we identified the epidemiologic evidence to elucidate the true effect between smoking, alcohol intake, and thyroid cancer incidence by exploring the effect of changes in smoking and alcohol consumption habits. To elucidate potential causality between smoking and alcohol intake on thyroid cancer incidence, we explored the effect of changes in smoking and alcohol consumption habits. From the Korean National Health Insurance database, we identified 4,430,070 individuals who participated in the national health screening program in 2009 and 2011. The level of smoking and alcohol consumption was measured twice, once in 2009 and again in 2011. The risk of thyroid cancer according to their changes was estimated using the Cox proportional hazard model. During the mean follow-up period of 6.32 ± 0.72 years, 29,447 individuals were diagnosed with thyroid cancer. Compared to those who sustained not smoking, non-smokers who initiated smoking to light (adjusted hazard ratio (aHR) 0.96, 95% confidence interval (CI) 0.81–1.15), moderate (aHR 0.90, 95% CI 0.78–1.04), and heavy level (aHR 0.81, 95% CI 0.69–0.96) had a decreased risk of thyroid cancer. Heavy smokers who quit smoking had an increased risk of thyroid cancer (aHR 1.23, 95% CI 1.06–1.42) compared to those who sustained heavy smoking. Change in drinking status was not significantly associated with thyroid cancer risk compared to drinking at the same level, although a non-significant trend of increased risk was noted in quitters. Participants who initiated both smoking and drinking (HR 0.80, 95% CI 0.69–0.93) had a lower risk of thyroid cancer compared with those who continued not to smoke and drink. Our findings provide further evidence that smoking, and possibly alcohol consumption, would have true protective effects on the development of thyroid cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: There is also growing evidence for metabolic syndrome as a risk factor for BC. However, no studies have yet looked at how the risk of developing breast cancer varies with changes in metabolic syndrome status. It is important to identify the risk of BC among women who develop or recover from metabolic syndrome in disease prevention. Therefore, this study aimed to investigate the association between changes in metabolic syndrome and subsequent breast cancer occurrence. As a result, the risk of breast cancer differed significantly according to the changes of metabolic syndrome status. Individuals who improved from metabolic syndrome had the same risk of breast cancer as those who were sustained non-metabolic syndrome. Thus, efforts to improve metabolic syndrome may provide an added benefit of a reduced risk of breast cancer. Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC. [ABSTRACT FROM AUTHOR]

Parkin, an E3 ubuquitin ligase associated with Parkinson's disease (PD), has recently been implicated in mediating innate immunity. However, molecular details regarding parkin-mediated immune response remain to be elucidated. Here, we identified mitochondrial TSPO-VDAC complex to genetically interact with parkin in mediating responses against infection and wound in Drosophila . The loss-of-function mutation in parkin results in defective immune response against bacterial infection. Additionally, parkin mutant larvae showed hypersensitivity against wound regardless of bacterial infection. Interestingly, the combinatorial trans-heterozygotic mutations in parkin and TSPO , or parkin and VDAC showed similar lethal tendency with parkin homozygous mutants. Furthermore, knockdown of TSPO alone also resulted in defective responses to infection and wound analogously to parkin mutants. Taken together, we propose that parkin cooperates with TSPO-VDAC complex to mediate responses against infection and wound. [ABSTRACT FROM AUTHOR]

Background: Prostate-specific antigen-based routine screening is not recommended for the general population due to conflicting results with mortality reduction. We aimed to develop a web-based decision aid (DA) for informed decision making for prostate cancer screening., Methods: Using the International Patient Decision Aid Standards (IPDAS) development process model, we developed our DA based on patient and clinician interviews and multidisciplinary expert discussions. The prototype consisted of predicting individual prostate cancer risk and informed decision-making, including knowledge, risk and benefit, cost, personal value, and decision making. We conducted a pilot study on 101 healthy men, evaluating the effectiveness of DA by measuring knowledge, attitude, and intention to screen before and after using the DA, as well as decisional conflict and usefulness after using the DA., Results: Of the 101 participants (median age 60 [50-69] years), 84% had not undergone screening for prostate cancer in the past two years. After using the DA, knowledge on prostate cancer screening increased (mean score [of 10] before versus after: 6.85 ± 1.03 versus 7.57 ± 1.25; P < 0.001), and intention to not screen increased from 27.7% to 51.5% ( P < 0.001), but attitude toward screening did not change ( P = 0.564). After use of the DA, 79 participants reported no decisional conflict, and the usefulness score was high (mean score [of 100] 77.35 ± 7.69), with 85% of participants reporting that the DA helped with decision making., Conclusion: Our web-based DA yielded increased knowledge, decreased screening intention, and high perceived usefulness. These findings indicate potential clinical relevance, especially among younger individuals., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background: Hearing loss (HL) has been suggested to be associated with impaired microcirculation of the inner ear. This cross-sectional study aimed to evaluate an association between HL and serum lipid levels., Methods: The study comprised 10,356 Korean adults who participated in the fifth Korea National Health and Nutrition Examination Survey (2010-2012). We defined HL as the average hearing thresholds exceeding 25 dB at predetermined frequency levels by pure tone audiometry. Serum lipid levels were measured using an enzymatic assay. The associations between lipid levels and HL were evaluated using a multiple logistic regression model after adjusting for covariates including age, sex, hypertension, diabetes, smoking status, alcohol, physical activity, educational level, household income, and noise exposure. Stratified analyses were performed to examine the effect of the covariates on the association between lipid levels and HL., Results: The high-density lipoprotein cholesterol (HDL-C) level was inversely associated with high-frequency (HF)-HL, with an odds ratio (95% confidence interval) of 0.78 (0.64-0.96) for 1-mmol/L increase in the HDL-C level. Neither the triglyceride nor the low-density lipoprotein cholesterol level was associated with HF-HL. For low-frequency HL, association with any of the serum lipid components was absent. A stratified analysis showed that the inverse association between HDL-C levels and HF-HL was evident (P trend <0.05) in some subjects with specific characteristics such as older age (≥65 years), female sex, non-hypertensive state, and non-regular physical activity. However, a significant interaction between HDL-C levels and all of the stratified variables was absent (P for interaction >0.05)., Conclusion: The HDL-C level has a linear inverse association with the risk of HF-HL. Given the known protective role of HDL-C against atherosclerotic changes, this finding seems to support the concept of impaired microcirculation in the inner ear as a mechanism for HF-HL.

Background: Among the potential modifiable risk factors, the association between alcohol consumption and the risk of multiple myeloma remains controversial. We investigated the effects of weekly average alcohol consumption and drinking pattern on the risk of multiple myeloma using a nationwide representative database., Methods: We identified 11,737,467 subjects who participated in the Korean National Health Screening Program in 2009 and 2010. Cox regression analyses were performed to calculate the risk of multiple myeloma according to weekly alcohol consumption, drinking frequency, and amount per session., Results: During a mean follow-up period of 6.8 years after a one-year time lag, 6,981 subjects (3,921 men and 3,060 women) were diagnosed with multiple myeloma. Compared with nondrinkers, all drinkers were at a significantly lower risk for multiple myeloma. The risk of multiple myeloma was reduced in a dose-dependent manner: mild drinkers [adjusted HR (aHR), 0.89; 95% confidence interval (CI), 0.84-0.95], moderate drinkers (aHR, 0.83; 95% CI, 0.76-0.91), and heavy drinkers (aHR, 0.76; 95% CI, 0.69-0.85). Furthermore, both drinking frequency and amount per drinking session showed inverse association with the risk of multiple myeloma., Conclusions: Our large population-based study suggested an inverse dose-dependent association between total average alcohol consumption and the risk of multiple myeloma, and drinking frequency and amount per drinking session seemed to not differ in their relative contribution to the risk of multiple myeloma., Impact: On the basis of the unprecedentedly large number of study population analyzed in this study, our study provides solid epidemiologic evidence of alcohol consumption on multiple myeloma risk., (©2021 American Association for Cancer Research.)

Prostate cancer is the fourth most common cause of cancer in men in Korea, and there has been a rapid increase in cases. In the present study, we constructed a risk prediction model for prostate cancer using representative data from Korea. Participants who completed health examinations in 2009, based on the Korean National Health Insurance database, were eligible for the present study. The crude and adjusted risks were explored with backward selection using the Cox proportional hazards model to identify possible risk variables. Risk scores were assigned based on the adjusted hazard ratios, and the standardized points for each risk factor were proportional to the β-coefficient. Model discrimination was assessed using the concordance statistic (c-statistic), and calibration ability was assessed by plotting the mean predicted probability against the mean observed probability of prostate cancer. Among the candidate predictors, age, smoking intensity, body mass index, regular exercise, presence of type 2 diabetes mellitus, and hypertension were included. Our risk prediction model showed good discrimination (c-statistic: 0.826, 95% confidence interval: 0.821-0.832). The relationship between model predictions and actual prostate cancer development showed good correlation in the calibration plot. Our prediction model for individualized prostate cancer risk in Korean men showed good performance. Using easily accessible and modifiable risk factors, this model can help individuals make decisions regarding prostate cancer screening.

Background: Dietary supplements (DS) use is known to be common among cancer survivors. However, detailed information on the factors influencing DS use seems insufficient, including cancer-related and psychological factors., Methods: Study subjects were 1,852 Korean adult cancer survivors recruited from cancer survivor clinic of two university-affiliated hospitals. Data were collected retrospectively through review of medical records and self-administered questionnaires. Psychological factors were assessed using Hospital Anxiety and Depression Scale (HADS) and Fear of Cancer Recurrence Inventory-Short Form. Factors associated the DS use were evaluated by multiple logistic regression analysis after adjusting for covariates., Results: The prevalence of long-term DS use was 15.7% in overall (17.5% in female and 11.6% in male). Female survivors were 3.14 times (95% confidence interval [CI], 1.89-5.22) more likely to use DS than male. In male cancer survivors, ever-smoking and previous radiotherapy were positively associated with DS use. In females, breast cancer survivors were 0.32 times less likely to use DS compared with stomach cancer survivors, and survivors with family history of cancer were 1.39 times more likely to use DS than those without. After adjusting for sociodemographic, clinical, and lifestyle factors, survivors with anxiety (HADS ≥8) used DS 1.38 times (95% CI, 1.01-1.91) more frequently, compared with those without anxiety., Conclusion: Diverse factors such as female sex, cancer treatment modality, smoking history, family history and anxiety status were associated with DS use in Korean cancer survivors. Targeted strategies with consideration of these factors are needed for counseling DS use for cancer survivors.

Background: To examine the relationship between obesity measured by waist circumference (WC) and body mass index (BMI) and the incidence of colorectal cancer in premenopausal and postmenopausal women., Methods: A total of 1,418,180 premenopausal and 4,854,187 postmenopausal women without cancer at baseline and ages over 40 were identified using the Korean National Health Insurance System Cohort during 2009 to 2014. The hazard ratio (HR) for colorectal cancer incidence was assessed according to menopausal state using Cox proportional hazards models., Results: During a mean follow-up period of 7.2 years, 7,094 and 57,449 colorectal cancer cases occurred in premenopausal and postmenopausal women, respectively. Compared with the reference group (WC 65-75), the HRs [95% confidence interval (CI)] of colorectal cancer in WC <65, 75-85, 85-95, and >95 groups were 1.01 (0.91-1.11), 1.02 (0.97-1.07), 1.09 (1.00-1.18), and 1.31 (1.12-1.52), respectively, in premenopausal women and 1.01 (0.95-1.17), 1.09 (1.07-1.12), 1.19 (1.00-1.18), and 1.30 (1.25-1.35), respectively, in postmenopausal women. Compared with the reference group (BMI 18.5-22.9), HRs (95% CI) for colorectal cancer in BMI <18.5, 23-25, 25-30, and >30 groups were 0.99 (0.87-1.14), 0.99 (0.94-1.06), 0.98 (0.92-1.04), and 1.06 (0.92-1.20), respectively, in premenopausal women. In postmenopausal women, those values were 0.99 (0.93-1.05), 1.05 (1.03-1.08), 1.11 (1.09-1.13), and 1.20 (1.16-1.25), respectively., Conclusions: WC is associated with the risk of colorectal cancer in both groups of women, but this association was stronger in postmenopausal women than in premenopausal women. BMI increased the incidence of colorectal cancer only in postmenopausal women IMPACT: Obesity has a stronger relationship with colorectal cancer in postmenopausal women than in premenopausal women., (©2020 American Association for Cancer Research.)