Sun-Seog Kweon

South Korean time trade-off values for EQ-5D health states: modeling with observed values for 101 health states.

OBJECTIVES This study establishes the South Korean population-based preference weights for EQ-5D based on values elicited from a representative national sample using the time trade-off (TTO) method. METHODS The data for this paper came from a South Korean EQ-5D valuation study where 1307 representative respondents were invited to participate and a total of 101 health states defined by the EQ-5D descriptive system were directly valued. Both aggregate and individual level modeling were conducted to generate values for all 243 health states defined by EQ-5D. Various regression techniques and model specifications were also examined in order to produce the best fit model. Final model selection was based on minimizing the difference between the observed and estimated value for each health state. RESULTS The N3 model yielded the best fit for the observed TTO value at the aggregate level. It had a mean absolute error of 0.029 and only 15 predictions out of 101 had errors exceeding 0.05 in absolute magnitude. CONCLUSIONS The study successfully establishes South Korean population-based preference weights for the EQ-5D. The value set derived here is based on a representative population sample, limiting the interpolation space and possessing better model performance. Thus, this EQ-5D value set should be given preference for use with the South Korean population.

Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk

Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted a genome-wide association study of CRC in East Asians with 14,963 cases and 31,945 controls and identified 6 new loci associated with CRC risk (P = 3.42 × 10−8 to 9.22 × 10−21) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcriptional regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9), and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the involvement of new biological pathways.

Relative contribution of body composition to bone mineral density at different sites in men and women of South Korea

We examined the relative contribution of body composition to bone mineral density (BMD) at various sites in 1406 Korean rural men and women, aged 19–80 years, from July to August 2004. The BMD was measured at peripheral (distal forearm and calcaneus) and central (lumbar spine at L1–L4, femoral neck, trochanter, and Wards triangle) using dual-energy X-ray absorptiometry. In multivariate analyses, the linear regression models were adjusted for relevant covariates. In premenopausal women, only lean mass had a significant positive correlation with BMD at all sites. In postmenopausal women, fat mass was significantly positively correlated with BMD at all sites, except the Wards triangle; fat mass was the only determinant of BMD at the lumbar, distal forearm, and calcaneus sites, whereas both lean and fat mass contributed to BMD at the hip, with the effect of lean mass being slightly greater than that of fat mass. In younger men, lean mass had a significant positive contribution to BMD at all sites, whereas fat mass appeared to contribute negatively to BMD at all sites, except the calcaneus. In older men, lean mass made a significant positive contribution to the BMD at all sites; fat mass also made a significant positive contribution to the BMD at the forearm and calcaneus. These data indicate that in the Korean rural population, lean mass may be an important determinant of the BMD, whereas fat mass may contribute positively to BMD only in postmenopausal women and older men.

Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1

In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified 3 genetic loci newly associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene; P = 8.82 × 10−9), rs10474352 at 5q14.3 (near the ARRDC3 gene; P = 1.67 × 10−9) and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene; P = 4.25 × 10−8). We replicated these associations in 16,003 cases and 41,335 controls of European ancestry (P = 0.030, 0.004 and 0.010, respectively). Data from the ENCODE Project suggest that variants rs4951011 and rs10474352 might be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.

BRCA1 and XRCC1 polymorphisms associated with survival in advanced gastric cancer treated with taxane and cisplatin

This study evaluated the influence of genetic polymorphism influencing drug metabolism on survival in taxane‐ and cisplatin‐treated advanced gastric cancer (AGC). Peripheral blood samples from 207 AGC patients treated with first‐line chemotherapy of taxane and cisplatin were used. We investigated polymorphisms that influenced the metabolism of taxane (ATP‐binding cassette transporter B1 (ABCB1)), cisplatin (glutathione S‐transferase M1 (GSTM1), glutathione S‐transferase P1 (GSTP1), glutathione S‐transferase T1 (GSTT1), excision repair cross complementing 1 (ERCC1), X‐ray Cross Complementing group 3 (XRCC3), X‐ray Cross Complementing group 4 (XRCC4), X‐ray Cross Complementing group 1 (XRCC1), breast cancer (BRCA1)), and 5‐fluorouracil (methylene tetrahydrofolate reductase (MTHFR), thymidylate synthase (TYMS)). A total of 207 patients were enrolled between May 2004 and Dec 2008, and 200 patients were analyzed. The overall response rate was 38.5%. Time to progression and overall survival time were 4.3 ± 0.19 months and 11.9 ± 1.05 months, respectively. There was no significant association between genetic polymorphism and response rate. However, the BRCA1 mutant TT homozygote was associated with significant prolongation of overall survival (hazard ratio [HR] = 0.43; 95% confidence interval [CI], 0.20–0.92; P = 0.03) and progression‐free survival (HR = 0.51; 95% CI, 0.26–1.00; P = 0.05). Also, the XRCC1 194 CT genotype was associated with inferior overall survival, relative to the XRCC1 194 CC homozygotes (HR = 1.49; 95% CI, 0.11–2.07; P = 0.018).These findings suggest that BRCA1 TT and XRCC1 194 CT genotypes could be modest prognostic markers of AGC response in taxane‐ and cisplatin‐treated patients.

Impact of perceived social support on the mental health and health-related quality of life in cancer patients: results from a nationwide, multicenter survey in South Korea

We investigated whether and how perceived social support is associated with depression and quality of life among patients with various cancer diagnoses.

Rapid increase of scrub typhus, South Korea, 2001-2006.

To the Editor: Scrub typhus, or tsutsugamushi disease, is a febrile illness caused by the rickettsial bacteria Orientia tsutsugamushi. Scrub typhus is endemic to a geographically distinct region, the so-called tsutsugamushi triangle, which includes Japan, Taiwan, China, and South Korea (1,2). Scrub typhus is a public health issue in Asia, where 1 billion persons may be at risk for the disease (3). In South Korea, scrub typhus is the most common rickettsial disease, and public health authorities are concerned about its increased incidence. Scrub typhus has been a reportable disease in South Korea since 1994. Physicians who diagnose suspected or confirmed cases must report these cases to their local health bureau and the Korea Centers for Disease Control and Prevention (KCDC) through the National Notifiable Disease Surveillance System (NNDSS). For a patient’s illness to meet the case definition for scrub typhus, the clinical signs (acute febrile illness and skin eschar) must be present or there must be laboratory confirmation (4-fold rise in antibody titer, antigen detected in blood, or genetic material detected by PCR). We analyzed NNDSS data confirmed by KCDC and classified all reported cases into 2 groups according to residential area. Cases with rural administrative address codes “eup” or “myun” were defined as rural cases, whereas cases with a city administrative address code of “dong” were defined as urban cases. All case-patients were classified by occupation as farmer or nonfarmer; all agricultural, fishery, and forest workers from rural areas were defined as farmers. In total, 23,929 cases, including 16,199 (67.7%) serologically confirmed cases, were reported between 2001 and 2006, of which 35.5% were male patients and 64.5% female patients. The greatest number of cases was in the age group 50–69 years, in both male (47.2%) and female (51.7%) patients; however, there were 167 boys (2.0%) and 119 girls (0.8%) <10 years of age. The number of cases peaked in 2005, with 2,331 and 4,449 cases in male and female patients, respectively. In 2006, a total of 6,480 cases (2,364 and 4,116 in males and females patients), which is 2.5× the number reported in 2001, were reported. The autumn epidemic period was from October through November; 96.2% of all cases were reported during this period (Figure). The proportion of cases identified in farmers decreased from 2001 (44.4%) to 2006 (36.4%); the number of cases in nonfarmers reached 4,121 (63.6%) in 2006. The number and proportion of patients living in urban areas increased from 1,059 (40.2%) in 2001 to 3,230 (49.9%) in 2006. This trend was observed in both farmers and nonfarmers. The number of cases among farmers living in urban areas increased from 150 (12.8%) to 443 (18.8%), while the corresponding number of cases in nonfarmers went from 909 (62.0%) to 2,787 (67.6%). In addition, we identified different features of scrub typhus epidemicity, compared with those reported in previous studies (4–7). Many of the values reported in this study (64.5% of cases in female patients, 59.5% in nonfarmers, and 96.2% occurring in autumn) are higher than the values reported previously in Japan (4), Taiwan (5), and China (6). The higher incidence in female workers may be associated with conventional South Korean working behavior. Female workers typically work in a squatting position, with bare hands, and usually in dry fields, whereas male workers tend to work in a standing position, with tools, and in rice fields. Therefore, female workers are more likely to be exposed to infected mites. Figure Monthly occurrence of scrub typhus cases in South Korea, 2001–2006. Previously, farmers were considered a high-risk group, but our results imply that the same or even more attention should be given to nonfarmers. Leptotrombidium pallidum, a common mite in Korea, first appears in September. Its population then peaks in October and November and to a lesser degree in April and May (7). In autumn, especially around Chusok (Korean Thanksgiving), nonfarmers and urban residents also take part in agricultural activities, such as the chestnut harvest, mowing around graves, and assisting their farmer relatives. A sharp peak in the number of cases occurred during October–November, which is inconsistent with a previous report on vector density showing a secondary peak during April–May (7). This finding suggests that many cases are misreported, especially in spring. Unfortunately, there are still no reports on the comprehensiveness of the scrub typhus surveillance system in South Korea. We cannot exclude other modes of exposure such as golf, climbing, and other outdoor leisure activities. A 5-day work week was introduced in 2004, and, as a result, more leisure time has been available to urban residents. In addition, improved surveillance and diagnostic methods as well as changes in atmospheric temperature (8) may have contributed to the increase. We report the rapid increase of scrub typhus and the proportion of infected persons living in urban areas in South Korea. This information will be used to establish strategies for prevention, surveillance, and management in South Korea and in other countries where scrub typhus is endemic.

Cohort Profile: The Namwon Study and the Dong-gu Study

These two cohorts were designed to examine the increasing burden of chronic diseases among Korean populations. The studies investigated determinants for stroke, osteoporosis, dementia and cancer among middle-aged and elderly Korean populations. The Namwon Study baseline survey was performed between 2004 and 2007 (n = 10 667), and followed up 4 years later (n = 8157, follow-up rate = 76.5%). The baseline survey of the Dong-gu Study was administered over 2007-2010 (n = 9260), and will be followed up between 2014 and 2015. Questionnaires included assessment of cognitive function, psychiatric health and lifestyle factors. Clinical examinations, biochemical tests and genotyping focused on evaluating the determinants of target diseases and their intermediate phenotypes. Potential collaborators will be invited to contact the chief investigators.

Methylenetetrahydrofolate reductase C677T polymorphism in patients with gastric and colorectal cancer in a Korean population

BackgroundThis study was designed to investigate an association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of gastric and colorectal cancer in the Korean population.MethodsWe conducted a population-based large-scale case-control study involving 2,213 patients with newly diagnosed gastric cancer, 1,829 patients with newly diagnosed colorectal cancer, and 1,700 healthy controls. Genotyping was performed with peripheral blood DNA for MTHFR C677T polymorphisms. The statistical significance was estimated by logistic regression analysis.ResultsThe MTHFR C677T frequencies of CC, CT, and TT genotypes were 35.2%, 47.5%, and 17.3% among stomach cancer, 34%, 50.5%, and 15.5% in colorectal cancer, and 31.8%, 50.7%, and 17.5% in the controls, respectively. The MTHFR 677TT genotype showed a weak opposite association with colorectal cancer compared to the homozygous CC genotype [adjusted age and sex odds ratio (OR) = 0.792, 95% confidence interval (CI) = 0.638-0.984, P = 0.035]. Subjects with the MTHFR 677CT showed a significantly reduced risk of gastric cancer compared whose with the 677CC genotype (age- and sex-adjusted OR = 0.810; 95% CI = 0.696-0.942, P = 0.006). We also observed no significant interactions between the MTHFR C677T polymorphism and smoking or drinking in the risk of gastric and colorectal cancer.ConclusionsThe T allele was found to provide a weak protective association with gastric cancer and colorectal cancer.

Prevalence of osteoporosis and reference data for lumbar spine and hip bone mineral density in a Korean population

The aims of this study were to establish reference data for bone mineral density (BMD) at central skeletal sites using Lunar dual-energy X-ray absorptiometry (DXA), and to estimate the age-and sex-specific prevalence of osteoporosis in a Korean population. We performed a population-based, cross-sectional study. The subjects were 4148 (1810 men and 2338 women) Korean adults, aged 20–79 years. The BMD for central sites (lumbar spine, femoral neck, trochanter, and Ward’s triangle) were measured by DXA. The standardized prevalence of osteoporosis among individual aged 50–79 years in lumbar spine, femoral neck, Ward’s triangle, and trochanter was 40.1%, 12.4%, 28.4%, and 4.4% in women and 6.5%, 5.9%, 3.7%, and 1.6% in men, respectively. In women, peak BMD occurred in the age range 40–49 years for the femoral neck and trochanter, 30–39 years for the lumbar spine, and 20–29 years for Ward’s triangle. In men, peak BMD values were observed at 20–29 years for all measured sites. This study establishes a normative database for BMD at central skeletal sites using dualenergy X-ray absorptiometry and provides more reliable information on the prevalence of osteoporosis in Korea.