Search

Background Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations. Methods We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model. Results In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption. Conclusions In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD.

The majority of suicide decedents die on their initial attempt. To bring attention to suicide decedents without a suicide attempt history, the current study explored their demographic, clinical, and suicide-related characteristics. The data were derived from the Korea National Investigation of Suicide Victims Study, which assessed all suicide cases from 2013 to 2017 recorded in police investigation reports. We compared suicide decedents with and without a history of nonfatal attempts using the Korea Psychological Autopsy Checklist for Police Records (K-PAC). Out of 5228 cases included in our study, 3147 (60.2%) died on their first suicide attempt. Demographically, those who were male, older than 65, employed, and married/widowed were more likely to die on their initial attempt. Clinically, those who died on their initial attempt were more likely to have never been diagnosed with psychiatric disorders, whereas those who died on a repeated attempt were more likely to have been diagnosed with mood disorders. In terms of suicide-related factors, experiencing relationship problems and complaining about physical discomfort were associated with dying on an initial attempt. Depressed affect, self-harming behaviors, and talking about suicide or death were associated with repeated attempts.

There is insufficient evidence of the association between oophorectomy and depression.A nationwide medical records database of South Korea was used to investigate incidence rate ratios (IRRs) of major depressive disorder before and after oophorectomy (n = 36,284) using a self-controlled case series design. Outcomes before and after hysterectomy (n = 25,415) were identified to compare with those around oophorectomy.In all oophorectomy and hysterectomy groups, the risk of depression was increased before and after surgery, peaking immediately before or after the operation, with no significant difference in the pattern of the results according to type of surgery. In the bilateral oophorectomy group, the IRR was increased between 2-3 months before the surgery, peaking immediately before surgery at 1.39 (95% CI: 1.30-1.49, p.0001), and remained heightened for one-year postexposure. Subgroup analyses performed according to ovarian cancer, age group, and hormone replacement therapy produced results similar to those of the main outcome.Because we used claims data, the detailed clinical information related to oophorectomy is lacking. There is possibility that time-varying confounder besides age and season might have affected the results CONCLUSIONS: The risk of depression increased before and after oophorectomy. The increase in risk of depression started before oophorectomy and peaked immediately before or after the operation, but no significant differences between unilateral and bilateral surgery and cancer and noncancer or among age groups were noted.

Objective To investigate the association between thyroidectomy and suicide attempt.Methods A nationwide population-based electronic medical records database of South Korea between January 1, 2009 and June 30, 2016 was used to investigate incidence rate ratios (IRRs) of suicide attempts and probable suicide attempts before and after thyroidectomy using a self-controlled case series design.Results In 2,986 patients who attempted suicide or probable suicide, the IRRs of suicidal behaviors during risk periods one year before and after thyroidectomy were investigated. Generally, after thyroidectomy, there was no increase in IRR compared to the non-risk period. When data were analyzed according to thyroidectomy type, after partial thyroidectomy, IRR increased up to 1.43 (95% CI: 1.03–1.98, p=0.032) in the days 91–181 period. In the subgroup with major depressive disorder (MDD), the IRR increased up to 1.74 (95% CI: 1.21–2.51, p=0.003) before thyroidectomy, and increased up to 1.67 (95% CI: 1.16–2.41, p=0.006) after thyroidectomy.Conclusion Although the general risk of suicide attempt was not increased after thyroidectomy, patients with MDD showed increased risk of suicide attempt before and after thyroidectomy. These results suggest that suicidality should be evaluated when depressive symptoms are present in patients who have undergone thyroidectomy.

BackgroundLittle is known about the health harms associated with low-intensity smoking in Asians who, on average, smoke fewer cigarettes and start smoking at a later age than their Western counterparts.MethodsIn this pooled analysis of 738 013 Asians from 16 prospective cohorts, we quantified the associations of low-intensity (FindingsDuring a mean follow-up of 11.3 years, 92 068 deaths were ascertained. Compared with never smokers, current smokers who consumed twofold risk of lung cancer mortality. Furthermore, current smokers who started smoking after age 35 and smoked ConclusionsOur study showed that smokers who smoked a small number of cigarettes or started smoking later in life also experienced significantly elevated all-cause and major cause-specific mortality but benefited from cessation. There is no safe way to smoke—not smoking is always the best choice.

Background: The number of thyroidectomies in South Korea has been increasing rapidly due to extensive checkups for thyroid cancer. However, few studies have examined the association between thyroid...

Purpose In some patients who receive adjuvant radiotherapy (RT) for the left breast, the stomach is located inside the RT field. This study investigates the incidence of gastric complications following adjuvant RT for breast cancer using data of the Health Insurance Review and Assessment Service in South Korea. Methods We identified 37,966 women who underwent surgery and received adjuvant RT for breast cancer. The cumulative incidence rate of gastric hemorrhage and gastric cancer was calculated and compared for left and right breast cancers. Results Among 37,966 patients, 19,531 (51.4%) and 18,435 (48.6%) had right and left breast cancers, respectively. After a median follow-up duration of 6.3 years, the cumulative incidence of gastric cancer and gastric hemorrhage did not differ between right and left breast cancers (p = 0.414 and p = 0.166, respectively). The multivariable analysis revealed that old age was the only factor associated with the development of gastric cancer (p < 0.001) and gastric hemorrhage (p < 0.001). The incidence of gastric cancer and hemorrhage did not differ between patients who received adjuvant RT for right and left breast cancers. Conclusion Irradiation-related chronic complications of the stomach in patients with breast cancer are minimal. A study with a longer follow-up duration might be needed to assess the risk of gastric cancer.

Background Although a higher risk of other immune-mediated diseases has been reported in inflammatory bowel disease (IBD) patients, the risk factors of immune-mediated diseases development and the effect of concomitant immune-mediated diseases on outcomes remain poorly defined. Aim To determine the risk factors of incident immune-mediated diseases and the impact of comorbid immune-mediated diseases on outcomes in IBD. Methods Using the National Health Insurance claims data for the entire Korean population, we identified 35 581 IBD patients without immune-mediated diseases and 595 IBD patients with immune-mediated diseases from 2012 to 2013, and follow-up until 2016. We selected four controls by age and sex for comparing with cases. Results A total of 35 581 IBD patients without immune-mediated diseases and 142 324 matched controls without immune-mediated diseases were followed from 2014 to 2016 and of these 239 IBD patients and 357 controls developed immune-mediated disease. The overall immune-mediated diseases risk was higher in IBD patients (HR, hazard ratio, 2.47; 95% confidence interval, CI, 2.09-2.91). In a nested case-control study of the IBD cohort, adult patients aged ≥20 years and frequent hospitalisation ≥1 per year were independent risk factors for incident immune-mediated diseases, in contrast, 5-aminosalicylic acid (5-ASA) use had protective effect (odds ratio, 0.61; 95% CI, 0.41-0.90) for developing immune-mediated diseases. In addition, IBD patients with another immune-mediated disease had an increased risk of needing anti-TNF-α agent (HR, 2.40; 95% CI, 2.02-2.84) and developing acute flare (HR, 1.76; 95% CI, 1.37-2.26). Conclusions The incidence of immune-mediated diseases in IBD patients was higher than that of non-IBD population. 5-ASA use may reduce this risk.

Background: Because the suicide mortality depends on the lethality of suicide methods, the identification and prediction of suicide methods are important for suicide prevention.Methods: Examination data of suicide decedents were collected based on police reports. Suicide decedents were divided into groups according to the suicide methods (hanging, gas poisoning, pesticide poisoning, jumping, drug poisoning, and drowning) they used. Predictive factors for each suicide method in comparison to other suicide methods were identified.Results: Among 23,647 subjects, hanging was the most common method of suicide. Regarding gas poisoning, the history of previous suicide attempt was a risk factor and being age of 65 or older was a protective factor. Being age of 65 or older showed a highly strong association with suicide by pesticide poisoning. Being age of 18 or younger and the presence of schizophrenia were associated with jumping. A history of psychiatric outpatient treatment was a risk factor for drug poisoning. Regarding suicide by drowning, schizophrenia was a risk factor, while being age of 65 or older was a protective factor.Limitations: Only eight out of a total of 17 regions in South Korea were examined and included in the data of this study. Also, the methods of suicide were defined as one method that directly caused the death, which could undermine other less fatal methods used.Conclusions: There were differences in predictive factors according to the method of suicide. Predicting the method of suicide in people at high risk for suicide stands to be an important strategy for suicide prevention in clinical settings.

Objective Early recognition of a high-risk group impending suicide is important. We aimed to compare warning signs depending on the nature of the psychiatric disorder and whether it was a documented diagnosis. Methods Data of suicide decedents were collected from police records from 2013 to 2017. We evaluate psychiatric symptoms and warning signs in three aspects (language, behavior, and affect) using the Korea-Psychological Autopsy Checklist for Police Records (K-PAC-PR). Results A total of 13,265 suicide decedents were recruited for this study. Of them, 66.9% of females and 46.7% of males diagnosed psychiatric disorders, with depressive disorder being the most common one. Warning signs were observed in 93.0% of suicide decedents. They were observed more in those who were diagnosed with psychiatric disorders, especially in those with a depressive disorder. "Talking about dying or suicide" was the most common warning sign in all groups, and "apathetic behavior" was the most related warning sign for depressive disorder. Especially for "talking about dying or suicide," the proportion of observed "within a week" was high, making it valuable as a warning sign. Conclusion Warning signs were commonly found in suicide decedents regardless of gender. They were more common among the decedents diagnosed with psychiatric disorders, especially among those with a depressive disorder.

The purpose of this study was to compare the characteristics of suicide attempts by drug overdose between young people and adults, and evaluate the cost-effectiveness of a multi-disciplinary emergency consultation system (MECS) for suicide attempters with drug overdose. It was verified by comparing and analyzing data from June 1, 2017 to May 31, 2018 (before the MECS was implemented; pre-MECS), and from June 1, 2018 to May 31, 2019 (after the MECS was implemented; post-MECS). The data were retrospectively reviewed for a total of 251 such patients with suicide attempts by drug overdose who visited the emergency room of a university hospital in Seoul during the period. The young people group were shown to be more likely to use painkillers and less likely to use psychoactive drugs for a suicide attempt (p < 0.01), had more unplanned attempts than planned ones (p < 0.01), and had lower levels of intentionality for suicide (p = 0.04) and of suicide lethality (p = 0.02), compared to the adult group. We defined suicide attempts as being “serious” when there was both high intentionality and lethality. On this basis, the young people group had less serious suicide attempts, compared to the adult group (p = 0.02). Young people in the post-MECS group had lower intensive care unit (ICU) costs (p = 0.01) and lower costs in the 6-months after the suicide attempt (p = 0.02) compared to those in the pre-MECS group. Young people, both with serious (p < 0.01) and non-serious attempts (p < 0.01) in the post-MECS group had lower ICU costs compared to those in the pre-MECS group. Adults with non-serious attempts in the post-MECS group had lower ICU costs (p < 0.01) compared to those in the pre-MECS group. Therefore, it can be concluded that fast and precise cooperation from the multidisciplinary departments for patients who attempted suicide by drug overdose reduced unnecessary ICU treatment and costs, especially in young attempters and those with lower levels of intentionality and lethality.

BACKGROUND: Most previous studies evaluating the association between leisure-time physical activity (LTPA) and risk of death were conducted among generally healthy individuals of European ancestry. We investigated the association of LTPA with all-cause and cause-specific mortality among East Asian populations, including healthy individuals and those with existing chronic diseases, which has been less well characterized. METHODS: We performed pooled analyses among 467 729 East Asian individuals recruited in nine prospective cohorts included in the Asia Cohort Consortium. Cox proportional hazards regressions were used to derive hazard ratios (HRs) and 95% confidence intervals (CIs) associated with LTPA after adjusting for age, sex, education and marital and smoking status. RESULTS: During a mean follow-up period of 13.6 years, 65 858 deaths were identified. Compared with those who reported no or less than 1 h of LTPA per week, an inverse association was observed between the amount of LTPA and all-cause and cause-specific mortality (P for trend < 0.001). The strength of the inverse association was stronger for death due to cardiovascular diseases and causes other than cancer deaths. An inverse association of LTPA with total mortality was observed among individuals with a severe and often life-threatening disease: cancer, stroke or coronary heart disease [hazard ratio (HR) = 0.81, 95% CI = 0.73-0.89 for high vs low LTPA) and those with other chronic diseases such as diabetes or hypertension (HR = 0.86, 95% CI = 0.80-0.93 for high vs low LTPA). No clear modifying effects by sex, body mass index or smoking status were identified. CONCLUSIONS: Regular participation in LTPA is associated with reduced mortality in middle-aged and elder Asians regardless pre-existing health conditions.

An epidemiologic study that evaluated population’s iodine nutrition status and its relationship with thyroid hormones is lacking in iodine-sufficient area. This nationwide study aimed to evaluate the iodine nutrition status in Korea and relationship between urine iodine concentration (UIC) and thyroid hormones. A total of 8318 subjects of the Korea National Health and Nutrition Examination Survey VI (2013–2015) with UIC and thyroid hormone evaluation were included. Median UIC level and estimated 24-h iodine intake were calculated. The prevalence of iodine deficiency or excess was obtained using estimated average requirement or above the tolerable upper intake level cut-point method by estimated iodine intake. We analyzed UIC with regard to age, sex, social economic status, and geographic characteristics. The median UIC in general population and estimated iodine intake in adult population were 293.9 μg/L (above requirement according to World Health Organization classification) and 249.3μg/day, respectively. The prevalence of iodine deficiency and excess was 14.0 and 13.4%. The median UIC was higher among SAC [511 (299.9–948.5)] and lower among seventies [251.2 (98.9–761.6)] compared to other age groups. The median UIC increased with household income level (p for trend

Purpose To determine the optimal radiotherapy technique for gastric mucosa-associated lymphoid tissue lymphoma (MALToma), we compared the dosimetric parameters and the risk of solid secondary cancer from scattered doses among anterior-posterior/posterior-anterior parallel-opposed fields (AP/PA), anterior, posterior, right, and left lateral fields (4_field), 3-dimensional conformal radiotherapy (3D-CRT) using noncoplanar beams, and intensity-modulated radiotherapy composed of 7 coplanar beams (IMRT_co) and 7 coplanar and noncoplanar beams (IMRT_non). Materials and methods We retrospectively generated 5 planning techniques for 5 patients with gastric MALToma. Homogeneity index (HI), conformity index (CI), and mean doses of the kidney and liver were calculated from the dose-volume histograms. Applied the Biological Effects of Ionizing Radiation VII report to scattered doses, the lifetime attributable risk (LAR) was calculated to estimate the risk of solid secondary cancer. Results The best value of CI was obtained with IMRT, although the HI varied among patients. The mean kidney dose was the highest with AP/PA, followed by 4_field, 3D-CRT, IMRT_co, and IMRT_non. On the other hand, the mean liver dose was the highest with 4_field and the lowest with AP/PA. Compared with 4_field, the LAR for 3D-CRT decreased except the lungs, and the LAR for IMRT_co and IMRT_non increased except the lungs. However, the absolute differences were much lower than Conclusion Tailored RT techniques seem to be beneficial because it could achieve adjacent organ sparing with very small and clinically irrelevant increase of secondary solid cancer risk compared to the conventional techniques.

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. © 2017, Springer-Verlag Berlin Heidelberg.

BACKGROUND No nationwide epidemiological study evaluating the prevalence of subclinical and overt forms of hypothyroidism and hyperthyroidism has yet been conducted in Korea. This study aimed to evaluate the reference range of serum thyroid stimulating hormone (TSH) and the national prevalence of thyroid dysfunctions in Korea. METHODS Nation-wide cross-sectional data were analyzed from a representative sample of the civilian, non-institutionalized Korean population (n=6,564) who underwent blood testing for thyroid function and anti-thyroid peroxidase antibody (TPOAb) as part of the Korea National Health and Nutrition Examination Survey VI (2013 to 2015). RESULTS The reference interval of serum TSH in the Korean reference population was 0.62 to 6.68 mIU/L. Based on this reference interval, the prevalence of overt and subclinical hypothyroidism was 0.73% (males 0.40%, females 1.10%) and 3.10% (males 2.26%, females 4.04%), respectively. The prevalence of hypothyroidism increased with age until the age group between 50 to 59 years. Positive TPOAb were found in 7.30% of subjects (males 4.33%, females 10.62%). The prevalence of overt and subclinical hypothyroidism TPOAb-positive subjects was 5.16% and 10.88%, respectively. The prevalence of overt and subclinical hyperthyroidism was 0.54% (males 0.30%, females 0.81%) and 2.98% (males 2.43%, females, 3.59%), respectively. CONCLUSION The Serum TSH reference levels in the Korean population were higher than the corresponding levels in Western countries. Differences were found in the prevalence of hypothyroidism and hyperthyroidism according to age, sex, and TPOAb positivity. This study provides important baseline information for understanding patterns of thyroid dysfunction and diseases in Korea.

Predicting patients who convert to bipolar disorder is important for deciding appropriate treatment for young adults with major depressive disorder (MDD). We focused on the predictive factors of bipolar conversion in a large population of young adults.A nationwide, population-based electronic medical records database from the Health Insurance ReviewAssessment service of South was used to investigate adjusted hazard ratio (HR) of each potential predictor of the bipolar converter group compared to the non-converter group using Cox regression analysis including age of onset, medication use, clinical features, comorbid disorders, admission, self-harm, and negative life events in childhood.Among 291,721 subjects who were initially diagnosed with MDD in young adults, 12,376 subjects experienced diagnostic conversion to bipolar disorder. The cumulative incidence was 6.46% during the average 3.26 years of follow-up. Among the predictive factors during diagnosis of MDD, antipsychotic use (HR 3.12, 95%CI, 2.99-3.26, p 0.0001) and mood stabilizers (HR 2.45, 95%CI, 2.35-2.55, p 0.0001) showed the strongest association with diagnostic conversion to bipolar disorder. In addition, female sex, younger age of onset, mood stabilizer use, recurrent depression, psychotic symptoms, and admission to a psychiatric ward during diagnosis of MDD were also associated with diagnostic conversion to bipolar disorder.In young adults with MDD, antipsychotic and mood stabilizer use during diagnosis of MDD were the strongest predictive factors with diagnostic conversion to bipolar disorder during follow-up. If young adults with MDD need antipsychotics or mood stabilizer, patients should be carefully evaluated for possibility of bipolar disorder.

ObjectiveTo study the association of educational level and risk of death from all causes, cardiovascular disease (CVD) and cancer among Asian populations.DesignA pooled analysis of 15 population-based cohort studies.Setting and participants694 434 Asian individuals from 15 prospective cohorts within the Asia Cohort Consortium.InterventionsNone.Main outcome measuresHRs and 95% CIs for all-cause mortality, as well as for CVD-specific mortality and cancer-specific mortality.ResultsA total of 694 434 participants (mean age at baseline=53.2 years) were included in the analysis. During a mean follow-up period of 12.5 years, 103 023 deaths were observed, among which 33 939 were due to cancer and 34 645 were due to CVD. Higher educational levels were significantly associated with lower risk of death from all causes compared with a low educational level (≤primary education); HRs and 95% CIs for secondary education, trade/technical education and ≥university education were 0.88 (0.85 to 0.92), 0.81 (0.73 to 0.90) and 0.71 (0.63 to 0.80), respectively (ptrend=0.002). Similarly, HRs (95% CIs) were 0.93 (0.89 to 0.97), 0.86 (0.78 to 0.94) and 0.81 (0.73 to 0.89) for cancer death, and 0.88 (0.83 to 0.93), 0.77 (0.66 to 0.91) and 0.67 (0.58 to 0.77) for CVD death with increasing levels of education (both ptrendConclusionHigher educational level was associated with substantially lower risk of death among Asian populations.

ObjectivesTo investigate the association between zolpidem prescription and suicide attempts in people with depressionMethodsA nationwide, population-based electronic medical records database from the Health Insurance Review & Assessment Service of South was used to investigate the incidence rate ratios (IRRs) of suicide attempts and probable suicide attempts in people with depression before and after zolpidem prescription using self-controlled case series design.ResultsIn a total of 445 people who attempted suicide and 23 141 people who attempted probable suicide attempt, the IRRs of suicidal behavior during the risk periods before and after zolpidem prescription increased compared with those at the baseline. The IRRs gradually increased and peaked immediately before the prescription of zolpidem. The IRR was 70.06 (95% CI: 25.58–191.90) on day 2 before zolpidem prescription and 63.35 (95% CI: 22.99–174.59) on day 1 after zolpidem prescription in the suicide attempt group. The IRR was 24.07 (95% CI: 20.50–28.26) on the day before zolpidem prescription and 14.96 (95% CI: 12.21–18.34) on the day after zolpidem prescription in the probable suicide attempt group. The ratios declined eventually after zolpidem was prescribed.ConclusionsAlthough zolpidem prescription was associated with an increased risk of suicide attempts in people with depression, the risk increased and peaked immediately before zolpidem prescription. The risk declined gradually thereafter. This result indicates that the risk of suicide attempts increases at the time of zolpidem prescription. However, zolpidem prescription does not contribute to additional increase in the risk of suicide attempts.

Background: It has not been determined if adjuvant chemotherapy would be helpful for completely resected early-stage lung adenocarcinoma even with unfavorable genetic markers. As the positive anaplastic lymphoma kinase ( ALK ) rearrangement is associated with aggressive clinical feature in lung adenocarcinoma, we evaluated the treatment outcomes of completely resected stage IA lung adenocarcinoma according to initial ALK status. Methods: This is a retrospective cohort study including 309 patients with surgically resected stage IA lung adenocarcinoma from February 2010 to December 2013. Patients were screened for ALK rearrangement using immunohistochemistry. A positive ALK status was defined as an immunohistochemistry score of 2+ or more. Both disease-free survival (DFS) and the initial recurrence pattern were analyzed according to ALK status. Results: Twenty-three (7.4%) patients had ALK -positive adenocarcinoma. During the median follow-up of 35.8 months, recurrence developed in 34 (11.0%) patients. The patients with ALK -positive tumor had significantly lower 5-year DFS rate (62.4%) compared to those with ALK -negative tumor (86.5%; P=0.038). The multivariable analysis showed that ALK rearrangement was associated with a higher risk of disease recurrence (adjusted hazard ratio =2.64; 95% confidence interval, 1.08–6.44). In addition, patient with ALK -positive tumor showed more frequent recurrence in regional lymph nodes compared with those with ALK -negative tumor (83.3% vs . 28.6%; P=0.031). Conclusions: In patients with completely resected stage IA lung adenocarcinoma, ALK rearrangement was associated with unfavorable DFS and more frequent regional lymph node metastasis. Therefore, careful surveillance for recurrence should be performed in this subset of patients.

The aim of the study was to explore the therapeutic potential of menopausal hormone therapy (MHT) in women with mild cognitive impairment (MCI).Thirty-seven postmenopausal women (age range: 57-82 y) with multiple-domain, amnestic subtype MCI were randomly assigned to either placebo (n = 18) or MHT (n = 19) for 24 months (percutaneous estradiol [E2] gel [0.1%, 2 mg/d] and oral micronized progesterone [MP4] [100 mg/d]). All participants received donepezil, and apolipoprotein E genotype was determined. The primary endpoint was general cognitive function: Alzheimer's disease Assessment Scale, cognitive subscale, the Korean version of Mini-Mental State Examination (K-MMSE), and the Korean version of the Montreal Cognitive Assessment (MoCA_K) were performed in-person every 6 months.Twenty-one participants (placebo 13, MHT 8) completed the trial (56.8%). Progression rates to dementia were 52.9% (9/17) in the placebo group and 44.4% (8/18) in the MHT group. Within-group analysis showed that all three tests significantly worsened during the trial in the placebo, but not the MHT groups. Analysis adjusted for ε4 allele demonstrated that MHT significantly reduced deterioration of MoCA_K score, a sensitive tool for assessing global cognition in MCI (P = 0.0261). Compared with the control group, both MoCA_K (P = 0.043; mean difference, 3.85; 95% CI, -0.46 to 8.16) and K-MMSE (P = 0.0319; mean difference, 3.26; 95% CI, 0.04-6.48) scores were significantly better at 24 months in the MHT group.Long-term MHT using percutaneous E2 gel and oral MP4 might attenuate cognitive decline in postmenopausal women with MCI.

In iodine-sufficient areas, autoimmune hypothyroidism has been regarded as the major subtype of hypothyroidism. Non-immune-related hypothyroidism has received little attention because it is considered to be rare. The aim of this study was to evaluate the prevalence of non-immune-related hypothyroidism in Korea and to identify its associating factors. A total of 6434 participants in the Korea National Health and Nutrition Examination Survey VI (2013–2015) without known thyroid disease who were examined for thyroid stimulating hormone, free thyroxine, TPO Ab, and urine iodine concentration (UIC) were enrolled. The weighted proportions, demographic variables, and severity of immune-related and non-immune-related hypothyroidism were compared. To assess the effect of iodine on hypothyroidism in TPO Ab positive or negative populations, the weighted prevalence of hypothyroidism was assessed in each population according to UIC or estimated iodine intake subgroups. The prevalence of undetected hypothyroidism in Korea was 3.8% (n = 233). Of these 233 cases, 171 (71.8%) were non-immune-related. In the TPO Ab negative population, the prevalence of hypothyroidism was increased significantly in the subgroup with UIC between 250 and 749 µg/L (HR 2.12 [1.17, 3.83]) and ≥ 750 µg/L (HR 3.42 [1.93, 6.04]) or the subgroups with estimated iodine intake ≥ 750 µg/day (HR 2.81 [1.64, 4.80]). This nationwide study demonstrated that most cases of hypothyroidism in iodine-sufficient areas are non-immune-related and are associated with excess iodine above a certain level. More attention to this unrecognized but widespread potential health risk is needed.

Background Establishment of the reference interval of thyroid-stimulating hormone (TSH) is critical in the diagnosis of thyroid dysfunction and is affected by age, gender, iodine nutrition, and ethnicity. The aim of this study was to determine the reference intervals of TSH and free thyroxin (FT4) from a large, nationwide data of Korea where iodine intake is more than adequate. Methods We analyzed data from the Korea National Health and Nutrition Examination Survey VI that measured serum TSH, FT4, and thyroid peroxidase antibody from 7,061 individuals (urinary iodine measurement in 6,565). Age- and gender-specific reference intervals were established from 95% confidence limits from the 2.5 to 97.5 percentile of TSH (log-transformed) and FT4 in reference populations. Results The geometric mean of TSH was 2.16 ± 0.01 mIU/L, with the lowest value found in the middle aged group (2.04 ± 0.02 mIU/L) and higher values noted in age groups of 10–19 and over 70 years (2.38 ± 0.02 and 2.32 ± 0.07 mIU/L, respectively). The association of TSH and age was U-shaped. The overall reference interval of TSH was 0.59–7.03 mIU/L. Mean FT4 was 1.25 ± 0.003 ng/dL (16.09 ± 0.039 pmol/L), and it showed a small but continuous decrease after 20 years of age (P < 0.001). There was a significant positive correlation between TSH and urine iodine concentration (r = 0.154, P < 0.001). Conclusions The reference interval of TSH in Korea, where iodine intake is above the requirement, was 0.59–7.03 mIU/L and showed U-shaped change with age, which was a similar pattern to iodine intake. The reference interval of FT4 was 0.92–1.60 ng/dL. The geometric mean and upper limit of TSH were higher than those of Western populations, reflecting the paramount importance of iodine intake on thyroid function.

Background: Few prospective studies have examined the preventive role of fruit and vegetable intake against cancer in Asian populations. Objective: This prospective study evaluated the associations between total fruit intake, total vegetable intake, and total fruit and vegetable intake and total cancer incidence and mortality. Methods: This prospective cohort study included 14,198 men 40–59 y of age enrolled in the Seoul Male Cohort Study from 1991 to 1993. Fruit and vegetable intakes were assessed by a validated food-frequency questionnaire. We used Cox proportional hazard regression models to compute RR ratios and 95% CIs. Results: During the follow-up period from 1993 to 2008, 1343 men were diagnosed with cancer, and 507 died of cancer. Total vegetable intake was linearly associated with cancer incidence but was nonlinearly associated with cancer mortality; by comparing $500 g/d with

Background The Masaoka-Koga staging system has been known as the strongest prognostic factor for both survival and recurrence of thymic epithelial tumor (TET). The purpose of our study was to find prognostic determinants among computed tomography (CT), histopathologic, and clinical features of TET. Methods Two radiologists reviewed retrospectively CT findings of 437 patients (male 242, female 195; mean age, 51 years) with TET. With medical record review, surgico-histopathologic results were subcategorized into Masaoka-Koga stages I through IV and World Health Organization histopathologic classifications A-B1, B2-B3, and carcinoma. Overall survival and progression-free survival were analyzed. Clinical, histopathologic, and CT features were correlated from each other. Results In all, 437 tumors were in Masaoka-Koga stage I (n = 147, 33.6%), stage II (n = 121, 27.7%), stage III (n = 76, 17.4%), or stage IV (n = 93, 21.3%); A and B1 (n = 114, 26.1%) and B2 and B3 TET (n = 223, 51.0%); and thymic carcinoma (n = 100, 22.9%). In multivariable analyses, age, Masaoka-Koga stage IV, thymic carcinoma, and CT stages III and IV were significantly correlated with overall survival ( p p K = 0.621). Conclusions For TET, CT staging is effective in distinguishing both overall survival and progression-free survival, and patients with Masaoka-Koga stage IV or thymic carcinoma or CT stage IV have the worst prognosis.

Purpose To investigate the association between long-term exposure to ambient air pollution and lung cancer incidence in Koreans. Materials and methods This was a population-based case-control study covering 908 lung cancer patients and 908 controls selected from a random sample of people within each Korean province and matched according to age, sex, and smoking status. We developed land-use regression models to estimate annual residential exposure to particulate matter (PM₁₀) and nitrogen dioxide (NO₂) over a 20-year exposure period. Logistic regression was used to estimate odds ratios (ORs) and their corresponding 95% confidence intervals (CI). Results Increases in lung cancer incidence (expressed as adjusted OR) were 1.09 (95% CI: 0.96-1.23) with a ten-unit increase in PM₁₀ (μg/m³) and 1.10 (95% CI: 1.00-1.22) with a ten-unit increase in NO₂ (ppb). Tendencies for stronger associations between air pollution and lung cancer incidence were noted among never smokers, among those with low fruit consumption, and among those with a higher education level. Air pollution was more strongly associated with squamous cell and small cell carcinomas than with adenocarcinoma of the lung. Conclusion This study provides evidence that PM10 and NO₂ contribute to lung cancer incidence in Korea.

The objective of this study is to find single nucleotide polymorphisms (SNPs) associated with a risk of Type 2 diabetes (T2D) in Korean adults and to investigate the longitudinal association between these SNPs and T2D and the interaction effects of iron intake and average hemoglobin level. Data from the KoGES_ Ansan and Ansung Study were used. Gene-iron interaction analysis was conducted using a two-step approach. To select candidate SNPs associated with T2D, a total of 7,935 adults at baseline were included in genome-wide association analysis (step one). After excluding T2D prevalent cases, prospective analyses were conducted with 7,024 adults aged 40-69 (step two). The association of selected SNPs and iron status with T2D and their interaction were determined using a Cox proportional hazard model. A total of 3 SNPs [rs9465871 (CDKAL1), rs10761745 (JMJD1C), and rs163177 (KCNQ1)] were selected as candidate SNPs related to T2D. Among them, rs10761745 (JMJD1C) and rs163177 (KCNQ1) were prospectively associated with T2D. High iron intake was also prospectively associated with the risk of T2D after adjusting for covariates. Average hemoglobin level was positively associated with T2D after adjusting for covariates in women. We also found significant interaction effects between rs10761745 (JMJD1C) and average hemoglobin levels on the risk of T2D among women with normal inflammation and without anemia at baseline. In conclusion, KCNQ1 and JMJD1C may prospectively contribute to the risk of T2D incidence among adults over the age of 40 and JMJD1C, but CDKAL1 may not, and iron status may interactively contribute to T2D incidence in women.

Background and objective Subcentimeter nodules without change in size during long-term follow-up period (for minimum 2 years) are assumed as benign lesions. However, the 2-year stability rule has not been fully verified so far and is still questionable. Thus, we aimed to retrospectively investigate long-term follow-up results for 2-year stable subcentimeter nodules at screening low-dose computed tomography (LDCT). Methods A total of 635 subjects having had follow-up LDCTs for the initial 2-year screening period and additional 3 years thereafter and having had non-calcified subcentimeter nodules were included. By using computed tomography (CT) nodule volumetry software, we measured interval changes in nodule volume. Results A total of 1107 subcentimeter nodules (1037 solid, 70 ground-glass opacity nodules (GGNs)) were detected at baseline CT. Of 1037 solid nodules, 1032 showed no growth during the initial 2-year and 5-year follow-up period. Fifty-nine GGNs were stable for initial 2 years, but two (3.4%) were later proved as adenocarcinomas. Among five solid nodules that showed growth during the initial 2-year follow-up period, one (20%) proved to be an adenocarcinoma, whereas four (36.4%) of 11 GGNs that demonstrated growth were diagnosed as lung cancers. Conclusions All solid subcentimeter nodules having initial 2-year stability at screening LDCT can be considered benign because none shows growth at further follow-up CT. On the other hand, subcentimeter GGNs have more chance of growth than solid nodules and need further follow-up CT for more than 2 years.

Importance: Asia is home to the largest diabetic populations in the world. However, limited studies have quantified the association of diabetes with all-cause and cause-specific mortality in Asian populations. Objectives: To evaluate the association of diabetes with all-cause and cause-specific mortality in Asia and to investigate potential effect modifications of the diabetes-mortality associations by participants' age, sex, education level, body mass index, and smoking status. Design, Setting, and Participants: This pooled analysis incorporated individual participant data from 22 prospective cohort studies of the Asia Cohort Consortium conducted between 1963 and 2006. A total of 1 002 551 Asian individuals (from mainland China, Japan, South Korea, Singapore, Taiwan, India, and Bangladesh) were followed up for more than 3 years. Cohort-specific hazard ratios and 95% confidence intervals for all-cause and cause-specific mortality were estimated using Cox regression models and then pooled using random-effects meta-analysis. Analysis was conducted between January 10, 2018, and August 31, 2018. Exposures: Doctor-diagnosed diabetes, age, sex, education level, body mass index, and smoking status. Main Outcomes and Measures: All-cause and cause-specific mortality. Results: Of 1 002 551 participants (518 537 [51.7%] female; median [range] age, 54.0 [30.0-98.0] years), 148 868 deaths were ascertained during a median (range) follow-up of 12.6 (3.0-38.9) years. The overall prevalence of diabetes reported at baseline was 4.8% for men and 3.6% for women. Patients with diabetes had a 1.89-fold risk of all-cause death compared with patients without diabetes (hazard ratio [HR], 1.89; 95% CI, 1.74-2.04), with the highest relative risk of death due to diabetes itself (HR, 22.8; 95% CI, 18.5-28.1), followed by renal disease (HR, 3.08; 95% CI, 2.50-3.78), coronary heart disease (HR, 2.57; 95% CI, 2.19-3.02), and ischemic stroke (HR, 2.15; 95% CI, 1.85-2.51). The adverse diabetes-mortality associations were more evident among women (HR, 2.09; 95% CI, 1.89-2.32) than among men (HR, 1.74; 95% CI, 1.62-1.88) (P for interaction

Importance Understanding birth cohort–specific tobacco smoking patterns and their association with total and cause-specific mortality is important for projecting future deaths due to tobacco smoking across Asian populations. Objectives To assess secular trends of tobacco smoking by countries or regions and birth cohorts and evaluate the consequent mortality in Asian populations. Design, Setting, and Participants This pooled meta-analysis was based on individual participant data from 20 prospective cohort studies participating in the Asia Cohort Consortium. Between September 1, 2017, and March 31, 2018, a total of 1 002 258 Asian individuals 35 years or older were analyzed using Cox proportional hazards regression analysis and random-effects meta-analysis. The pooled results were presented for mainland China; Japan; Korea, Singapore, and Taiwan; and India. Exposures Tobacco use status, age at starting smoking, number of cigarettes smoked per day, and age at quitting smoking. Main Outcomes and Measures Country or region and birth cohort–specific mortality and the population attributable risk for deaths from all causes and from lung cancer. Results Of 1 002 258 participants (51.1% women and 48.9% men; mean [SD] age at baseline, 54.6 [10.4] years), 144 366 deaths (9158 deaths from lung cancer) were ascertained during a mean (SD) follow-up of 11.7 (5.3) years. Smoking prevalence for men steadily increased in China and India, whereas it plateaued in Japan and Korea, Singapore, and Taiwan. Among Asian male smokers, the mean age at starting smoking decreased in successive birth cohorts, while the mean number of cigarettes smoked per day increased. These changes were associated with an increasing relative risk of death in association with current smoking in successive birth cohorts of pre-1920, 1920s, and 1930 or later, with hazard ratios for all-cause mortality of 1.26 (95% CI, 1.17-1.37) for the pre-1920 birth cohort, 1.47 (95% CI, 1.35-1.61) for the 1920s birth cohort, and 1.70 (95% CI, 1.57-1.84) for the cohort born in 1930 or later. The hazard ratios for lung cancer mortality were 3.38 (95% CI, 2.25-5.07) for the pre-1920 birth cohort, 4.74 (95% CI, 3.56-6.32) for the 1920s birth cohort, and 4.80 (95% CI, 3.71-6.19) for the cohort born in 1930 or later. Tobacco smoking accounted for 12.5% (95% CI, 8.4%-16.3%) of all-cause mortality in the pre-1920 birth cohort, 21.1% (95% CI, 17.3%-24.9%) of all-cause mortality in the 1920s birth cohort, and 29.3% (95% CI, 26.0%-32.3%) of all-cause mortality for the cohort born in 1930 or later. Tobacco smoking among men accounted for 56.6% (95% CI, 44.7%-66.3%) of lung cancer mortality in the pre-1920 birth cohort, 66.6% (95% CI, 58.3%-73.5%) of lung cancer mortality in the 1920s birth cohort, and 68.4% (95% CI, 61.3%-74.4%) of lung cancer mortality for the cohort born in 1930 or later. For women, tobacco smoking patterns and lung cancer mortality varied substantially by countries and regions. Conclusions and Relevance In this study, mortality associated with tobacco smoking continued to increase among Asian men in recent birth cohorts, indicating that tobacco smoking will remain a major public health problem in most Asian countries in the coming decades. Implementing comprehensive tobacco-control programs is warranted to end the tobacco epidemic.

Objectives The aims of this study were to determine the benefits of short-term empirical proton pump inhibitor (PPI) medication on laryngopharyngeal reflux (LPR) and to determine whether scores on the reflux symptom index (RSI) and the reflux finding score (RFS) could be combined to identify subgroups of patients that will more likely to improve with this medication. Methods Fifty-one Korean Otolaryngology Board-certified specialists joined this prospective, multi-center, and open-label observational study. A total of 1,142 adult patients with LPR was enrolled for 12 weeks of rabeprazol medication. According to pre-treatment scores on RSI and RFS, patients were divided into 4 subgroups. RFS and RSI were measured repeatedly with a month interval along the treatment period. Changes of RSI and RFS were analyzed in an overall study cohort as well as in each subgroup. Results Approximately 40% (n=455) of enrolled patients were followed up until 12 weeks of PPI treatment. Significant improvement in RSI was obtained in 29%, 58%, and 75% of patients after 4, 8, and 12 weeks of PPI medication. RFS was improved in 16%, 42%, and 57% of the patients with 4, 8, and 12 weeks of PPI medication. All subgroups showed improvement regardless of their pre-treatment scores on the RSI and RFS. Conclusion Even though RSI and RFS may be used as a general guideline for LPR management, pre-treatment RSI and RFS are not useful in predicting the patients' response to short-term PPI medication in the usual pattern of practice for LPR, which is mostly based on the physical evaluation and history taking.

Background: Higher educational levels have been linked to reduced risk of death in previous studies. Most of these studies, however, were conducted in the United States and Europe. Methods: We performed a pooled analysis to evaluate the association between educational levels and risk of death among 694,434 Asian individuals from 15 prospective cohort studies that participated in the Asia Cohort Consortium. The analysis included 103,023 deaths during a mean follow-up period of 12.5 years, among which 33,945 were due to cancer and 34,645 were due to cardiovascular diseases (CVD). We employed Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between educational level and the risk of death after adjusting for potential confounders. Results: Higher educational levels were significantly associated with lower risk of death from all causes; compared to a low educational level (≤ primary school), HRs and 95% CIs for secondary education, trade/technical education, and ≥ university degree were 0.86 (0.83-0.90), 0.80 (0.71-0.89), and 0.68 (0.61-0.75), respectively (Ptrend Conclusions: Higher educational level was associated with substantially lower risk of death in Asian populations including both East and South Asians. Citation Format: Keming Yang, Ying Zhang, Eiko Saito, Yu Chen, Prakash C. Gupta, Yu-Tang Gao, Akiko Tamakoshi, Yong-Bing Xiang, Woon-Puay Koh, Norie Sawada, Kemmyo Sugiyama, Yasutake Tomata, Atsuko Sadakane, Chisato Nagata, San-Lin You, Renwei Wang, Myung-Hee Shin, Habibul Ahsan, Wen-Harn Pan, Mangesh S. Pednekar, Jian-Min Yuan, Xiao-Ou Shu, Hui Cai, Shoichiro Tsugane, Ichiro Tsuji, Seiki Kanemura, Keiko Wada, Yoon-Ok Ahn, Kotaro Ozasa, John D. Potter, Wei Zheng, Hongmei Nan. Association between educational level and mortality: A pooled analysis of over 694,000 individuals in the Asia Cohort Consortium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4234.

Summary Objectives The seroprevalence of hepatitis E virus (HEV) infection in Northeastern Asia is unknown. This study was conducted to gain insight into the epidemiology of HEV that has been obscure in Northeastern China, South Korea and Japan. Methods A total of 1500 samples of serum were collected (300 each) from 5 groups of inhabitants over 40 years of age (Korean Chinese, indigenous Chinese, South Koreans, Koreans living in Japan, and indigenous Japanese) and screened for antibodies to HEV by the antigen–antibody–antigen sandwich Enzyme Linked Immunosorbent Assay system. Results The positivity for HEV antibodies was 50.7% (95%CI: 45.0–56.3) in Korean Chinese, 47.7% (95%CI: 42.1–53.3) in indigenous Chinese, 34% (95%CI: 28.9–39.5) in South Koreans, 14.3% (95%CI: 10.8–18.8) in Koreans living in Japan, and 6.0% (95%CI: 3.8–9.3) in indigenous Japanese. Conclusions This result emphasizes that HEV is endemic in Northeastern Asia and tends to accumulate in developing countries. Further studies are needed to elucidate the genotype of HEV circulating in these areas and its transmission route—water-borne outbreaks, smaller outbreaks or sporadic forms attributed to zoonosis—with reference to past epidemics, food culture, and sanitary conditions.

Introduction. Reduction in renal mass in rats results in progressive proteinuria, hypertension, focal-segmental glomerulosclerosis (FSG), atrophy of tubules (AT), and interstitial expansion. We reported that slow reduction of renal tissue in rats (slow ablation) ending in the removal of 1.5 kidneys is associated, over the next six months, with higher albumin excretion rates (AER) and accelerated development of FSG lesions compared to sudden equivalent renal mass reduction. It was hypothesised that slow reduction of nephron numbers allows for a process of conditioning of residual nephrons that increases their susceptibility to subsequent injury.Methods. To test this idea we treated MünichWistar rats with the angiotensin receptor blocker (ARB) losartan for six weeks during the gradual staged surgical removal of 1.5 kidneys, and compared them to sham operated controls, and parallel groups untreated by losartan.Results. Despite discontinuation of losartan over the subsequent six months, ARB pre-treatment completely prevented proteinuria and hypertension in these slow renal ablation rats. ARB pre-treatment also largely prevented the subsequent development of FSG,AT, and interstitial expansion in these animals. Both losartan-treated and untreated renal ablation groups had glomerular enlargement and compensatory hyperfiltration and this was uninfluenced by losartan.Conclusion. Temporary ARB administration during gradual renal mass reduction resulted in long-term prevention of hypertension and albuminuria and greatly reduced FSG and tubular and interstitial lesions. We hypothesise that the preconditioning of residual nephrons in the gradual ablation model which facilitates their subsequent injury, is blunted by renin-angiotensin system blockade.

The objective of this study was to characterize the familial associations of symptoms or symptom dimensions of schizophrenia, as a component of the effort to delineate suitable phenotypic markers under the homogenous genetic control.Clinical symptoms of the patients were evaluated on a lifetime basis, with the Korean version of the Diagnostic Interview for Genetic Studies and the Krawieka scale. Our sample consisted of 54 sibling pairs who were concordant for Diagnostic and statistical manual of mental disorder-IV schizophrenia or schizoaffective disorder.At the individual symptom level measured by the Diagnostic Interview for Genetic Studies, we observed a statistically significant degree of concordance within the sibling pairs for auditory hallucination (kappa=0.600, chi(2)=15.193, P=0.000). The within-sibling resemblance of this symptom was also indicated by the results of correlation analyses of individual items of the Krawiecka scale (partial correlation coefficient=0.423, P=0.005). Among the individual symptoms or symptom dimensions of the Krawiecka scale, the 'anxious' (partial correlation coefficient=0.469, P=0.001) and the 'affective dimension' (including the items of 'anxious' and 'depressed') (partial correlation coefficient=0.436, P=0.003) were also determined to indicate significant intra-pair correlations after controlling for potential confounding variables, such as sex, duration of illness, and age of onset.The results of this study suggest that familial factors, possibly genetic factors, contribute a liability to the development of auditory hallucinations. This symptom might then prove useful as a phenotype marker in future genetic studies.

Background Prostate cancer incidence and mortality rates in South Korea are relatively low, but rising steadily. Methods We examined age-standardized incidence and mortality trends of prostate cancer in South Korea to gain further insight into prostate cancer etiology. Results Although prostate cancer incidence has been low (7.9 per 100,000 man-years), it has increased up to 28.2% between 1996–1998 and 1999–2001. Prostate cancer mortality increased 12.7-fold over a 20-year period. Despite the increase in prostate cancer incidence and mortality rates, marked differences in rates remain for Koreans, Korean Americans, and Caucasian Americans. Conclusions The rising rates of prostate cancer in South Korea cannot be attributed entirely to PSA screening due to the low PSA screening prevalence; this trend is most likely related to increased westernization among Koreans. Interdisciplinary epidemiological studies incorporating the collection of biological samples are needed to clarify the extent to which lifestyle and genetic factors contribute to the observed racial disparity. Prostate. Published 2006 Wiley-Liss, Inc.

CYP17 gene is involved in steroidogenesis and steroid metabolism. Epidemiologic results on the association between the CYP17 polymorphism and breast cancer risk have been inconsistent. We exam ined the association between the MspAI polymorphism at +27 relative to the start of transcription in the 5’-untranslated region of CYP17 gene and breast cancer risk in Korean women. Four hundred and sixty-two incident cases and 337 controls were recruited from three teaching hospitals in Seoul during 1994-2001. Polymorphism of the CYP17 gene was determined by a single base extension assay. Demographic and lifestyle characteristics were identified using structured questionnaire. Age-adjusted (aOR) and multivariate odds ratios (mOR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression. The proportions of A1/A1, A1/A2 and A2/A2 genotypes among controls were 20.8%, 45.1% and 34.1%, respectively. Compared to the A1/A1 genotype, A1/A2 or A2/A2 genotype was not statis tically significantly assoc ia ted with overa ll breast cancer risk (i.e., mOR = 1.01, 95% CI = 0.69-1.47 and mOR = 0.76, 95% CI = 0.51-1.14, respectively). However, a significant association between CYP17 A2/A2 genotype and breast cancer was observed am ong women aged 50 years or less (mOR = 0.58, 95% CI = 0.34-0.99, P =0.04) and leaner women (body mass index ＜ 22 ㎏/ ㎡) (mOR = 0.48, 95% CI = 0.23-0.97, P = 0.04). Our results suggest that genetic polymorphism in 5’-untranslated region of CYP17 might play a role in breast cancer development in Korean women among younger women aged less than 50 or leaner women with body mass index less than 22 ㎏/㎡.

We evaluated cigarette smoking as a risk factor for prostate cancer in a prospective, population-based cohort study. The subjects were 14,450 males among the participants in the Seoul Male Cancer Cohort Study who had at least 1-year follow-up. They were followed up between 1993 and 2008. During the 16-year follow-up period, 87 cases of prostate cancer occurred over the 207,326 person-years of the study. The age-adjusted relative risks of past and current smokers at entry were 0.60 (95%CI: 0.34-1.06) and 0.70 (95%CI: 0.43-1.13), respectively, suggesting that cigarette smoking may not be a risk factor for prostate cancer. The relationship between prostate cancer and other modifiable factors, such as Westernized diet, should be studied with the goal of establishing prevention programs for prostate cancer.

Objective To compare the therapeutic efficacy of hormone replacement therapy (HRT) and tacrine in Alzheimer's disease. Design Six-month, randomized, open-label study. Setting University hospital. Patient(s) Fifty-five women with mild to moderate Alzheimer's disease were randomly assigned to tacrine (n = 26) or HRT (n = 29). Intervention(s) In the tacrine group, an initial dose of 40 mg/day was increased up to 160 mg/day. In the HRT group, conjugated equine estrogen was given to patients without uteri (n = 3) or together with micronized progesterone to patients with uteri (n = 26). Main outcome measure(s) Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test, Boston Naming Test, Controlled Oral Word Association Test, Geriatric Depression Scale, Hamilton Depression Scale (HDS), and Instrumental Activities of Daily Living (IADL). Result(s) Thirty-three patients who completed the outcome measures (tacrine, 17; HRT, 16) were included in an intent-to-treat analysis. The results did not differ between groups except for IADL, which rated more highly after HRT. Apolipoprotein E genotype effects were assessed. MMSE and HDS scores were improved after tacrine treatment in e4-negative patients. Conclusion(s) Overall efficacy of estrogen plus progesterone combination was similar to tacrine for cognition and mood, but greater for ADL. In e4-negative patients, tacrine is preferable for cognition and mood.

Purpose: To produce the nationwide 5-year survival rates of Korean cancer patients by primary cancer site. Materials and Methods: The study subjects were cancer patients diagnosed in 1995, as documented by the Korea Central Cancer Registry (KCCR) Program. This data was collected in 120 (93%) of 129 nationwide intern-and resident-training hospitals and 75 (94%) of the 80 Korean university hospitals. Follow-up was performed by obtaining information upon vital status (i.e., whether living or dead) from the government administered whole population files. Cumulative observed survival rate (OSR) was calculated by using the life table method and the relative survival rate (RSR) was computed using the life-time table for the years 1995, 1997, and 1999. Results: Of the 55,042 study subjects, the OSR for all Korean cancer patients was 61.4% at 1 year and 38.1% at 5 years. The RSR for all cancers was 62.5% at 1 year and 41.4% at 5 years, and the 5-year RSRs for all cancers in men and women were 32.6% and 53.2%, respectively. Conclusion: This is the first nationwide report upon 5-year cancer survival by primary site in Korea. Men showed a lower survival rate than women in most malignancies. Pancreatic and thyroid cancer had the lowest and highest 5-year survival rates, respectively.

To evaluate the performance of low-dose CT (LDCT) screening for lung cancer (LCA) detection in an Asian population with diverse risks for LCA. LCA screening was performed in 12,427 symptomless Asian subjects using either LDCT (5,771) or chest radiography (CXR) (6,656) in a non-trial setting. Subjects were divided into high-risk and non-high-risk groups. Data were collected on the number of patients with screening-detected LCAs and their survival in order to compare outcomes between LDCT and CXR screening with the stratification of risks considering age, sex and smoking status. In the non-high-risk group, a significant difference was observed for the detection of lung cancer (adjusted OR, 5.07; 95 % CI, 2.72–9.45) and survival (adjusted HR of LCA survival between LDCT vs. CXR group, 0.08; 95 % CI, 0.01–0.62). No difference in detection or survival of LCA was noticed in the high-risk group. LCAs in the non-high-risk group were predominantly adenocarcinomas (96 %), and more likely to be part-solid or non-solid compared with those in the high-risk group (p = 0.023). In the non-high-risk group, LDCT helps detect more LCAs and offers better survival than CXR screening, due to better detection of part solid or non-solid lung adenocarcinomas. • In an Asian non-high-risk group, LDCT helps detect more early-staged LCAs. • CT-detected lung cancers in non-high-risk subjects demonstrate better survival than CXR-detected cancers. • CT-detected lung cancers in non-high-risk subjects are predominantly part-solid or non-solid adenocarcinomas. • Mortality benefit of LDCT screening in non-high-risk subjects needs to be investigated.

Background: In Korea, Cerebrovascular and cardiovascular diseases (CVD) were the second leading cause of deaths in 2011. In 2010, the American Heart Association (AHA) published cardiovascular health metrics (CVHM) aimed at reducing deaths from all CVDs and stroke, and improving the cardiovascular health of the population as a whole. Despite their implications, the AHA’s metrics have not been broadly studied or previously applied to an Asian population. Objectives: This study estimated the combined association of cardiovascular health behaviors on the risk of all-cause and CVD mortality in middle-aged men in Korea. Methods: In total, 14,533 men aged 40-59 years were enrolled in 1993 and followed-up through 2011. CVHM defined the following lifestyles proposed by the AHA: smoking, physical activity, BMI, healthy diet score, total cholesterol, blood pressure, and fasting blood glucose. The CVHMs score was calculated as a single categorical variable, by assigning 1 point to each ideal healthy behavior vs. 0 points otherwise. All subjects were classified as meeting 0-7 CVHM. The principal outcome variables were all-cause and CVD mortality. The Cox proportional hazard regression model was used to estimate the hazard ratio (HR) of cardiovascular health behavior, and CVHMs score. PARs were calculated from significant CVHMs. Results: During 266,482.8 person-years of follow-up, there were 1,314 deaths in total. Current smoking, blood pressure, and fasting blood glucose were significantly associated with all-cause and CVD mortality. The adjusted PARs for the 3 significant metrics combined were 81% (95% CI, 50-94%) and 96% (66-99%) for all-cause and CVD mortality, respectively. More ideal CVHM was significantly associated with lower risks of all-cause and CVD mortality ( p-trend ). The adjusted HRs of the groups with 6-7 vs. 0-2 ideal CVHM were 0.49 (0.35-0.70) and 0.23 (0.10-0.57) for all-cause and CVD mortality, respectively. Conclusions: Among ideal cardiovascular health behaviors, non-smoking, normal blood pressure, and recommended fasting blood glucose levels associated with reduced risks of all-cause and total CVD mortality. There was a strong trend towards decreased all-cause and CVD mortality risk with increasing the number of ideal CVHMs.

The purpose of this study was to estimate the national prevalence of childhood asthma and other allergic diseases in Korea, and to determine potential risk factors for the diseases. Stratified random samples of 42,886 were selected from 34 elementary (6-12 yr olds) and 34 middle schools (12-15 yr olds) nationwide, and 38,955 were in the final analysis. The Korean-translated modified version of the International Study of Asthma and Allergies in Childhood questionnaire was used in this cross-sectional survey. Twelve-month prevalences of the symptoms of asthma, rhinoconjunctivitis, and flexural eczema were 8.7%, 10.5%, 7.3% in 6-12 yr olds, and 8.2%, 10.0%, 3.9% in 12-15 yr olds, respectively. For allergic conjunctivitis, food allergy, and drug allergy, the prevalences in 6-12 yr olds were 11.2%, 6.5%, and 1.5%, respectively. Asthma and flexural eczema decreased significantly with age. Other significant risk factors were also noted. For 6-12 yr-old asthma, adjusted odds ratio (aOR) of body mass index was 1.21 with 95% confidence interval (CI) 1.0-1.48, aOR of passive smoking was 1.37 with 95%CI 1.24-1.51, aOR of carpet use was 1.28 with 95%CI 1.10-1.49. For 6-12 yr-old eczema, aOR of affluence was 1.22 with 95%CI 1.07-1.39. The control of obesity and passive smoking would be the most important preventive measures of allergic diseases.

It has been suggested that colorectal cancer might not be one homogenous disease entity, based on the distinctive characteristics of its subsite of origin. Incidence data on 4,987 colorectal cancer were obtained from the Seoul Cancer Registry between 1993 and 1995. Age, sex, and subsite-specific incidence rates were compared. The age-standardized annual incidence rates of total colorectal cancer were 26.1 and 18.0 per 100,000 for men and women, respectively. There were no appreciable difference in the rates of colon and rectal cancer for either sex (colon vs rectum: 12.8 vs. 13.2 for men, 9.3 vs. 8.6 for women). The incidence rate of right colon was slightly higher in men than in women, and this discrepancy became even greater in left colon (men vs women: 3.5 vs. 3.0 for right colon, 4.7 vs. 2.9 for left colon). When the incidence rate of right colon was compared with that of left colon, women had a higher rate in the right colon among the elderly, aged 60 yr and over and a lower rate at age 40 yr or less, while the opposite was observed for men. More analytic approaches are needed to identify which factors are related with these descriptive results in colorectal cancer incidence.

Serum levels of sIL-2R can be used to monitor in vivo immune activation and its elevation have been shown to be correlated with T cell mediated immune disease such as atopic dermatitis, psoriasis, lymphoma and systemic sclerosis. Vitiligo is the disease of depigmentation caused by destruction of melanocytes, and there have been extensive studies on the immune pathogenesis. If the pathogenesis of vitiligo is correlated with the activation of T lymphocytes, the change of IL-2R will be detected compared with that of normal control. Therefore we sought the change in sIL-2R to determine whether T lymphocytes from patients with vitiligo show abnormal biological behavior. The quantitation of sIL-2R was done by sandwich enzyme-linked immunosorbent assay (ELISA) from the sera of 79 vitiligo patients and 40 normal controls. The results were summarized as following. The sIL-2R level in vitiligo patients (671.91 +/- 368.59 U/ml) was significantly increased compared with that of controls (370.8 +/- 71.8 U/ml; P < 0.005). According to clinical types, sIL-2R level in focal type of vitiligo patients was significantly higher than those in other types (segmental or generalized; P < 0.05). The sIL-2R level in patients less than 1 year duration was significantly higher than in patients more than 1 year duration (P < 0.05). The sIL-2R levels were not significantly different between active and inactive group. There was no significant differences among sIL-2R levels according to sex or age of onset. Our study showed that sIL-2R level was higher in vitiligo patients compared with that of normal controls, so the activation of T lymphocytes would be an important component in the pathogenesis of vitiligo. The higher sIL-2R levels in recent onset group would suggest that sIL-2R level might be an acute immunologic marker in vitiligo patients.

Objectives This study estimated the association of cardiovascular health behaviors with the risk of all-cause and cardiovascular disease (CVD) mortality in middle-aged men in Korea. Methods In total, 12 538 men aged 40 to 59 years were enrolled in 1993 and followed up through 2011. Cardiovascular health metrics defined the following lifestyle behaviors proposed by the American Heart Association: smoking, physical activity, body mass index, diet habit score, total cholesterol, blood pressure, and fasting blood glucose. The cardiovascular health metrics score was calculated as a single categorical variable, by assigning 1 point to each ideal healthy behavior. A Cox proportional hazards regression model was used to estimate the hazard ratio of cardiovascular health behavior. Population attributable risks (PARs) were calculated from the significant cardiovascular health metrics. Results There were 1054 total and 171 CVD deaths over 230 690 person-years of follow-up. The prevalence of meeting all 7 cardiovascular health metrics was 0.67%. Current smoking, elevated blood pressure, and high fasting blood glucose were significantly associated with all-cause and CVD mortality. The adjusted PARs for the 3 significant metrics combined were 35.2% (95% confidence interval [CI], 21.7 to 47.4) and 52.8% (95% CI, 22.0 to 74.0) for all-cause and CVD mortality, respectively. The adjusted hazard ratios of the groups with a 6-7 vs. 0-2 cardiovascular health metrics score were 0.42 (95% CI, 0.31 to 0.59) for all-cause mortality and 0.10 (95% CI, 0.03 to 0.29) for CVD mortality. Conclusions Among cardiovascular health behaviors, not smoking, normal blood pressure, and recommended fasting blood glucose levels were associated with reduced risks of all-cause and CVD mortality. Meeting a greater number of cardiovascular health metrics was associated with a lower risk of all-cause and CVD mortality.

ObjectiveObesity is a well-known risk factor for many cancers, including those of the esophagus, colon, kidney, breast, and skin. However, there are few reports on the relationship between obesity and thyroid cancer. We conducted this study to determine whether obesity is a risk factor for thyroid cancer by systematically screening a selected population by ultrasonography.Design and methodsWe obtained data from 15 068 subjects that underwent a routine health checkup from 2007 to 2008 at the Health Screening and Promotion Center of Asan Medical Center. Thyroid ultrasonography was included in the checkup, and suspicious nodules were examined by ultrasonography-guided aspiration. Those with a history of thyroid disease or family history of thyroid cancer were excluded from this study.ResultsIn total, 15 068 subjects, 8491 men and 6577 women, were screened by thyroid ultrasonography. Fine-needle aspiration cytology was performed in 1427 of these patients based on the predefined criteria and thyroid cancer was diagnosed in 267 patients. The prevalence of thyroid cancer in women was associated with a high BMI (per 5 kg/m2 increase) (odds ratios (OR)=1.63, 95% CI 1.24–2.10, PP=0.336). There was no association between age, fasting serum insulin, or basal TSH levels and thyroid cancer in either gender.ConclusionsObesity was associated with a higher prevalence of thyroid cancer in women when evaluated in a routine health checkup setting. This association between risk factor and disease was unrelated to serum insulin and TSH levels. Additional studies are needed to understand the mechanism(s) behind the association of obesity with thyroid cancer risk.

Incidence of lung cancer is decreasing among men and increasing among women in developed countries and also in Korea. However, mortality of lung cancer is still the highest among male cancers. Smoking is one of the group 1 carcinogens for lung cancer development, but its prognostic effect on lung cancer survival is not well established. Beta-carotene supplement increased the risk of lung cancer among smokers but the role of multivitamin supplement on the risk and survival of lung cancer is unclear either. We aimed to evaluate the association between smoking and multivitamin use on lung cancer survival by sex. We interviewed 910 pathologically confirmed lung cancer patients who were diagnosed between 2010 and 2012 in Samsung Medical Center. Questionnaire included current smoking status, age at first smoking, daily smoking amount, alcohol intake, past medical history, and multivitamin use. Pathological type, stage, and treatment information was collected from the electronic medical records. We followed the patients until December 31, 2012. Hazard Ratios (HR) and 95% Confidence Intervals (CI) were estimated using Cox's proportional hazard model (SAS9.4). We found significant difference in age at diagnosis, pathological type and stage between male and female patients; Female patients were younger, smoked less, used more multivitamin, and had more adenocarcinoma and earlier stage cancer than male patients. Smoking increased the risk of lung cancer mortality among female patients only. HR for lung cancer mortality for those who smoked more than 40 pack-years compared to those who never smoked was 5.64 (95%CI = 1.43, 22.28) in women and 1.17 (95%CI = 0.61, 2.26) in men (p-interaction = 0.01) when adjusted for age, stage, and pathologic type. Multivitamin use also increased the risk of lung cancer mortality among female patients only. HR for lung cancer mortality for multivitamin users was 4.14(95%CI = 1.77, 9.73) in women and 1.46 (95%CI = 0.71, 3.00) in men (p-interaction = 0.17). The association between multivitamin use and lung cancer mortality was strongest among female non-smokers (HR = 4.10, 95%CI = 1.72, 9.77). In conclusion, smoking and multivitamin use worsen the survival of female lung cancer. Prognostic effect of multivitamin use may be stronger among non-smokers. Citation Format: Mi Yang, Hyun-Kyung Oh, Young Mog Shim, Myung-Hee Shin. Differential prognostic effect of smoking and multivitamin use on lung cancer survival by sex. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3418.