Depression as a risk factor for overall and hormone-related cancer: the Korean cancer prevention study.

Depression has been hypothesized to be a risk factor of cancer, especially hormone-related cancers. However, few studies have been conducted with large enough sample size and sufficient follow-up period to rigorously estimate these associations. We aim to examine the relationship between depression and risk of registry-documented overall and hormone-related cancers. In this 19 year prospective cohort study of general population, 601,775 Koreans aged 30-64 years had a biennial medical evaluation by the National Health Insurance Service in either 1992 or 1994. Major and minor depression was ascertained by a 9-item depression questionnaire. At baseline, major depression was identified in 7.4% and 10.2% and minor depression in 19.3% and 21.4% in men and women, respectively. During the follow-up, 49,744 cancers were identified in men and 7860 in women. Prostate cancer in men was positively related to minor depression (HR 1.13, 95% CI 1.05, 1.23), and cervical cancer in women was inversely related to major depression (HR 0.90, 95% CI 0.83, 0.98) after adjusting for potential confounders. Regarding overall cancer, major depression was positively related to overall cancer in men (HR 1.04, 95% CI 1.00, 1.08) and inversely related in women (HR 0.90, 95% CI 0.83, 0.98). There was no association between breast cancer and depression. Different direction and magnitude of association among gender and cancer subtypes suggest different psycho-behavioral and biological pathways in which depression may affect later cancer development. Further studies on the association of depression and cancer and the underlying mechanisms should be conducted on specific cancer subtypes.

The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods.

BACKGROUND: This paper describes the background, aim, and design of a prospective birth-cohort study in Korea called the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). COCOA objectives are to investigate the individual and interactive effects of genetics, perinatal environment, maternal lifestyle, and psychosocial stress of mother and child on pediatric susceptibility to allergic diseases. METHODS/DESIGN: The participants in COCOA represents a Korean inner-city population. Recruitment started on 19 November, 2007 and will continue until 31 December, 2015. Recruitment is performed at five medical centers and eight public-health centers for antenatal care located in Seoul. Participating mother-baby pairs are followed from before birth to adolescents. COCOA investigates whether the following five environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e. house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child's neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Cord blood and blood samples from the child are used to assess whether the child's genes and epigenetic changes influence allergic-disease susceptibility. Thus, COCOA aims to investigate the contributions of genetics, epigenetics, and various environmental factors in early life to allergic-disease susceptibility in later life. How these variables interact to shape allergic-disease susceptibility is also a key aim.The COCOA data collection schedule includes 11 routine standardized follow-up assessments of all children at 6 months and every year until 10 years of age, regardless of allergic-disease development. The mothers will complete multiple questionnaires to assess the baseline characteristics, the child's exposure to environmental factors, maternal pre- and post-natal psychological stress, and the child's neurodevelopment, nutritional status, and development of allergic and respiratory illnesses. The child's microbiome, genes, epigenetics, plasma cytokine levels, and neuropsychological status, the microbiome of the residence, and the levels of indoor and outdoor pollutants are measured by standard procedures. DISCUSSION: The COCOA study will improve our understanding of how individual genetic or environmental risk factors influence susceptibility to allergic disease and how these variables interact to shape the phenotype of allergic diseases.

Measuring depression in South Korea: validity and reliability of a brief questionnaire in the Korean Cancer Prevention Study.

OBJECTIVE: To examine the validity and reliability of a new questionnaire for measuring depression in a South Korean population, and then to estimate the prevalence of depression in that country using this tool. METHODS: In total, 742,600 individuals (123,725 women), aged 30-64 years at entry into the Korean Cancer Prevention Study, completed a depression symptom in 1992 (baseline enrollment) and again in 1994. We examined the concurrent validity of the depression questionnaire by relating data from it to known socio-demographic and behavioral correlates of depression; its predictive capacity by relating scores from the questionnaire to the occurrence of future hospitalization for depression; and the test-retest reliability by comparing scores from its administration in 1992 to those in 1994. RESULTS: The prevalence of major depression was 7.5% in men and 10.0% in women. Factors significantly related to major depression were being younger (men), being female, not being married, of lower socioeconomic status, being a smoker, a heavy drinker, and not exercising regularly. Men (hazard ratio; 95% confidence interval: 2.0; 1.8, 2.2) and women (1.6; 1.3, 1.9) with questionnaire-ascertained depression experienced an elevated risk of hospitalization for the disorder during follow-up. The rates of agreement between responses to 1992 and 1994 surveys were 91.3% in men and 88.3% in women. CONCLUSIONS: These findings imply validity of the instrument and support its use in future studies directed at links of depression with somatic disease endpoints. LIMITATION: The questions do not have a specified time frame of reference.

Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma.

Activation of the prostaglandin D2 receptor (PTGDR) may contribute to pulmonary vasodilation, bronchoconstriction, recruitment of eosinophils, basophils and T-lymphocytes, and enhanced synthesis of leukotriene C4. We investigated whether polymorphisms of the leukotriene C4 synthase (LTC4S) -444A/C and PTGDR -441T/C were associated with clinical phenotypes and responsiveness to leukotriene receptor antagonist (LTRA) in Korean asthmatic children. We enrolled 270 normal and 870 asthmatic children. We prescribed montelukast (5 mg per day) to 100 of asthmatic children, and analyzed the responsiveness to LTRA by exercise challenge tests. Polymorphisms were genotyped by PCR-restriction fragment length polymorphism. As the number of minor alleles of the PTGDR -441T/C and LTC4S -444A/C polymorphisms increased, the log total eosinophil counts increased in atopic asthmatic children (P-value=0.03). We found a significant association between responsiveness to montelukast and the PTGDR polymorphism (P-value=0.038). However, the LTC4S -444A/C and PTGDR -441T/C were not associated with the susceptibility for asthma (LTC4S, AA versus AC+CC, adjusted odds ratio of 0.98 (95% confidence interval, 0.73-1.31); PTGDR, TT versus TC+CC, adjusted odds ratio of 0.90 (95% confidence interval, 0.68-1.19)) or clinical phenotypes (P-value>0.05). The effects of the PTGDR and LTC4S polymorphisms on the enhancement of eosinophil counts were additive in the Korean children with asthma. In addition, the PTGDR polymorphism seems to be associated with the responsiveness to LTRA. Therefore, therapies that target the PTGDR may be useful for modulating the responsiveness to LTRA.

Polymorphisms in GSDMA and GSDMB are associated with asthma susceptibility, atopy and BHR.

The gasdermin A (GSDMA) and gasdermin B (GSDMB) genes are located at 17q21.2. The GSDM family genes have been studied in the gastrointestinal tract but recent reports suggest that GSDMB is associated with childhood asthma in several populations. We investigated the association of the GSDMA and GSDMB variants with asthma in Korean children, and to assess the effect of these variants on intermediate phenotypes of asthma. Asthmatic (n = 778) and normal (n = 522) children were enrolled and genotypes were determined using PCR-RFLP. Asthma susceptibility was associated with GG of the GSDMA (rs7212938) and TT of GSDMB (rs7216389). And a combination of risk alleles of two polymorphisms was associated with asthma susceptibility and a frequency of those was higher in asthmatic children with increased levels of total IgE (aOR 1.77, 95% CI 1.15-2.72) and BHR (aOR 1.54, 95% CI 0.99-2.40) compared to normal. Also, we observed a significant association between haplotype of two polymorphisms and asthma susceptibility. The region including the GSDMA and GSDMB polymorphisms may be associated with asthma susceptibility and intermediate phenotypes of asthma, such as elevated IgE and BHR, in Korean children with asthma. These results strongly support an important role for the GSDMA and GSDMB in the development of childhood asthma.