PURPOSE: The high mobility group box 1 (HMGB1) protein has roles in apoptosis and immune responses by acting as a ligand for receptor for advanced glycation end products (RAGE), Toll-like receptors (TLRs), and triggering receptor expressed on myeloid cells 1. In particular, HMGB1/RAGE is involved in tumor metastasis by inducing matrix metalloproteinase 2 (MMP2) and MMP9 expression. We investigated the associations between genetic variations in HMGB1-related genes and disease-free survival (DFS) and overall survival (OS) in Korean female breast cancer patients. METHODS: A total of 2,027 patients in the Seoul Breast Cancer Study were included in the analysis. One hundred sixteen single nucleotide polymorphisms (SNPs) were extracted from eight genes. A multivariate Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) of each SNP. The effects of the SNPs on breast cancer prognosis were assessed at cumulative levels with polygenic risk scores. RESULTS: The SNPs significantly associated with DFS were rs243867 (hazard ratio, 1.26; 95% CI, 1.05–1.50) and rs243842 (hazard ratio, 1.24; 95% CI, 1.03–1.50); both SNPs were in MMP2. The SNPs significantly associated with OS were rs243842 in MMP2 (hazard ratio, 1.33; 95% CI 1.03–1.71), rs4145277 in HMGB1 (hazard ratio, 1.29; 95% CI, 1.00–1.66), rs7656411 in TLR2 (hazard ratio, 0.76; 95% CI, 0.60–0.98), and rs7045953 in TLR4 (hazard ratio, 0.50; 95% CI, 0.29–0.84). The polygenic risk score results for the DFS and OS patients showed third tertile hazard ratios of 1.72 (95% CI, 1.27–2.34) and 2.75 (95% CI, 1.79–4.23), respectively, over their first tertile references. CONCLUSION: The results of the present study indicate that genetic polymorphisms in HMGB1-related genes are related to breast cancer prognosis in Korean women.
Advanced Glycosylation End Product-Specific Receptor ; Apoptosis ; Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Female ; Genetic Predisposition to Disease* ; Genetic Variation ; HMGB1 Protein ; Humans ; Matrix Metalloproteinase 2 ; Myeloid Cells ; Neoplasm Metastasis ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Prognosis* ; Proportional Hazards Models ; Seoul ; Toll-Like Receptors

OBJECTIVES: The purpose of this study was to examine the associations of childbirth, breastfeeding, and their interaction with breast cancer (BC) risk reduction, and to evaluate the heterogeneity in the BC risk reduction effects of these factors by menopause, hormone receptor (HR) status, and pathological subtype. METHODS: BC patients aged 40+ from the Korean Breast Cancer Registry in 2004-2012 and controls from the Health Examinee cohort participants were included in this study after 1:1 matching (12 889 pairs) by age and enrollment year. BC risk according to childbirth, breastfeeding, and their interaction was calculated in logistic regression models using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: BC risk decreased with childbirth (3+ childbirths relative to 1 childbirth: OR, 0.66; 95% CI, 0.56 to 0.78 and OR, 0.80; 95% CI, 0.68 to 0.95 in postmenopausal and premenopausal women, respectively); and the degree of risk reduction by the number of children was heterogeneous according to menopausal status (p-heterogeneity=0.04), HR status (p-heterogeneity < 0.001), and pathological subtype (p-heterogeneity < 0.001); whereas breastfeeding for 1-12 months showed a heterogeneous association with BC risk according to menopausal status, with risk reduction only in premenopausal women (p-heterogeneity < 0.05). The combination of 2 more childbirths and breastfeeding for ≥13 months had a much stronger BC risk reduction of 49% (OR, 0.51; 95% CI, 0.45 to 0.58). CONCLUSIONS: This study suggests that the combination of longer breastfeeding and more childbirths reduces BC risk more strongly, and that women who experience both 2 or more childbirths and breastfeed for ≥13 months can reduce their BC risk by about 50%.
Breast Feeding* ; Breast Neoplasms* ; Breast* ; Child ; Cohort Studies ; Female ; Humans ; Logistic Models ; Menopause ; Odds Ratio ; Parturition* ; Population Characteristics ; Risk Reduction Behavior*

OBJECTIVE: The purpose of this paper is to analyze the effects of precarious employment status on the level of self-rated health, based on various criteria, by participants in the Korean Labor and Income Panel Survey. METHODS: Data were obtained from 3,268 subjects(2,057 men and 1,211 women), who participated in the 2005-2006 Korean Labor and Income Panel Survey. Group A was classified as Non-precarious employment by both the Ministry of Labor (MoLab) and the Korea Labor and Society Institute (KLSI). The group B was classified as Non-precarious employment by the MoLab and as precarious employment by the KLSI. The group C is classified as Non-precarious employment by both MoLab and KLSI. Outcome variables were self-rated health and a panel logistic regression analysis was performed on the data. RESULTS: The level of self-rated health was worse among group B males (OR: 1.45, C.I:1.00~2.11) and group C males (OR: 1.69, C.I:1.35~2.10) compared to group A males. A substantial difference(57.8%) in the level of self-rated health between groups A and B was attributed to the sociodemographic characteristics of the populations. The difference in self-rated health between groups A and C was explained by work environments(15.7%), as well as by sociodemographic characteristics(26.1%). For female workers, the level of self-rated health in group B and C was worse than in group A, but this finding was not statistically significant. CONCLUSIONS: These findings suggested that the policy to improve the working environment, as well as a more comprehensive effort to reduce the disparity, is needed for the precarious employment worker.
Employment ; Female ; Health Status ; Humans ; Korea ; Logistic Models ; Longitudinal Studies ; Male

OBJECTIVES: The present study was designed to determine the characteristics of shift work and the relationship between shift work and the level of self-rated health using the Korean Labor and Income Panel Study (KLIPS) data, which represents urban households in Korea. METHODS: Using the 9th wave of KLIPS, this study analyzed 2,087 male workers aged 25 to 64 years; participants missing data were excluded from analysis. To determine the impact of shift work on the level of self-rated health, logistic regression analysis was applied that controlled for socio-demographic characteristics, labor environment, and health-related behaviors. RESULTS: Shift workers comprised 13.4% of study subjects overall. The majority(69.2%) of participants were in 2-teams and in 2-shifts. Week 1 shift cycle changes were the highest, 56.3%. The risk of poor self-rated health was not significantly higher among shift workers compared to non-shift workers (OR=1.08, 95% CI=0.79~1.48). When divided by tenure, shift workers with more than 10-years experience (OR=1.79, 95% CI=0.91~3.50) tended to show greater risk than non-shift workers at marginal significance. CONCLUSIONS: In the present study, a significantly higher risk of self-rated poor health among shift workers was not observed. However, shift workers with more than 10-years experience tended to show increased health risk compared to non-shift workers. Further studies are required to determine time-series data and to consider both healthy worker effect and information bias.
Aged ; Bias (Epidemiology) ; Family Characteristics ; Healthy Worker Effect ; Humans ; Korea ; Logistic Models ; Male

Cytochrome P450 1A1 (CYP1A1) is involved in the 2-hydroxylation of estrogen, the hormone that plays a critical role in the etiology of breast carcinoma. We evaluated the associations between two CYP1A1 polymorphisms [MspI (rs4646903); Ile462Val (rs1048943)] and breast cancer in a multicenter case-control study of 513 breast cancer cases and 447 controls in Korea. Women carrying the T allele of the CYP1A1 MspI polymorphism were found to have a 1.72-fold (95% CI 1.11-2.68) greater risk of developing breast cancer. No association was found between any CYP1A1 Ile462Val polymorphism and breast cancer. Haplotype analysis of the two loci showed that the CA haplotype was associated with the lowest risk of breast cancer, and CA/CA diplotypes were associated with a lower risk of breast cancer [OR = 0.28 (0.13-0.61)] than others/others diplotypes. Moreover, this reduced risk was more pronounced among women with a lower body mass index (BMI) [OR = 0.18 (0.06-0.58)] or with a shorter lifetime exposure to estrogen [OR = 0.23 (0.07-0.81)]. The results obtained suggest that the CYP1A1 MspI polymorphisms could affect susceptibility to breast cancer.
Adult ; Aged ; Aged, 80 and over ; Body Mass Index ; Breast Neoplasms/*genetics ; Case-Control Studies ; Cytochrome P-450 CYP1A1/*genetics ; *Disease Susceptibility ; Female ; Haplotypes ; Humans ; Korea ; Middle Aged ; *Polymorphism, Genetic

Breast cancer has recently become the most common cancer in Korea. Although traditional epidemiological approaches, which are defined as "the study of the distribution and determinants of disease frequency in human population" have increased the understanding of breast cancer development in the human population, it cannot address the importance of the genetic susceptibility of humans to this disease. Therefore, a molecular epidemiological study which uses biological or genetic markers to identify and characterize the disease with the help of advances in molecular biology and human genetics might provide a better understanding of the multi-factorial or multi-step occurrence of human breast cancer. The susceptibility genes involved in the pathogenesis of breast cancer have been categorized into two groups: high penetrance genes (i.e., BRAC1, RB, etc.) and low penetrance genes (i.e., GSTs, XRCC1, etc.). This paper addresses the usefulness of biomarkers in epidemiological research of breast cancer and provides examples of the use of selected low penetrance genes involved in breast carcinogenesis in Korean women. Molecular epidemiological studies of breast cancer have enormous potential in helping researchers understand the gene-environmental interactions involved breast carcinogenesis and provide valuable insights into disease progression and survival.
Biomarkers ; Breast Neoplasms* ; Breast* ; Carcinogenesis ; Disease Progression ; Epidemiologic Studies ; Female ; Genetic Markers ; Genetic Predisposition to Disease ; Genetics, Medical ; Humans ; Korea ; Molecular Biology ; Molecular Epidemiology* ; Penetrance

To evaluate the relationship of genetic polymorphisms of ERCC2 and ERCC4 genes, both involved in nucleotide excision repair (NER), and the risk of breast cancer, a hospital-based case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n=574) and controls (n=502) with no present or previous history of cancer were recruited from three teaching hospitals in Seoul during 1995-2001. Information on selected characteristics was collected by interviewed questionnaire. ERCC2 Asp312Asn (G>A) was genotyped by single-base extension assay and ERCC4 Ser835Ser (T>C) by dynamic allele-specific hybridization system. Although no significant association was observed between the genetic polymorphisms and the risk of breast cancer, women with both ERCC2 A allele- and ERCC4 C allele-containing genotypes showed a 2.6-fold risk (95% CI: 1.02-6.48) of breast cancer compared to women concurrently carrying the ERCC2 GG and ERCC4 TT genotypes. The breast cancer risk increased as the number of "at risk" genotypes increased with a borderline significance (P for trend = 0.07). Interactive effect was also observed between ERCC4 genotype and body mass idnex (BMI) for the breast cancer risk; the ERCC4 C allele containing genotypes posed a 1.7-fold (95% CI: 0.96-2.93) breast cancer risk in obese women (BMI>25 kg/m2) with a borderline significance. Our finding suggests that the combined effect of ERCC2 Asp312Asn and ERCC4 Ser835Ser genotypes might be associated with breast cancer risk in Korean women.
Breast Neoplasms/*genetics ; DNA Helicases/*genetics ; DNA-Binding Proteins/*genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Korea ; Middle Aged ; Obesity/*genetics ; *Polymorphism, Genetic ; Transcription Factors/*genetics

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 examined 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 statistically significantly associated with overall 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 among 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 kg/m2) (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 kg/m2.
5' Untranslated Regions/*genetics ; Breast/metabolism/pathology ; Breast Neoplasms/enzymology/epidemiology/*genetics ; Case-Control Studies ; Comparative Study ; Demography ; Female ; *Genetic Predisposition to Disease ; Genotype ; Humans ; Korea/epidemiology ; Middle Aged ; Odds Ratio ; Polymorphism, Genetic/*genetics ; Questionnaires ; Research Support, Non-U.S. Gov't ; Risk Factors ; Steroid 17-alpha-Hydroxylase/*genetics

To evaluate the interactive effect of methylenetetrahydrofolate reductase (MTHFR) genotype and dietary factors on the development of breast cancer, a hospital based case-control study was conducted in South Korean study population consisting of 189 histologically confirmed incident breast cancer cases and their 189 age-matched controls without present or previous history of cancer. A PCR-RFLP method was used for the genotyping of MTHFR (C677T) and statistical evaluations were performed by unconditional logistic regression analysis. Consumption of some dietary factors, such as green vegetables (OR=0.3, 95% CI: 0.2-0.6), white vegetables (OR=0.3, 95% CI: 0.1-0.7) mushrooms (OR=0.4, 95% CI: 0.3-0.7), and meats (OR=1.7, 95% CI: 1.1-2.8) significantly decreased or increased the risk of breast cancer. Although the breast cancer risk was 1.7-fold (95% CI: 0.8-3.2) increased in women with MTHFR TT genotype, the association was not statistically significant. Women with MTHFR TT genotype and low green vegetable intake increased 5.6-fold (95% CI: 1.2-26.3) risk of breast cancer compared to high green vegetable intake group containing MTHFR CC/CT genotype. However, the interaction was not significant (p for interaction=0.96). Our findings suggest that MTHFR polymorphism did not influence individual susceptibility to breast cancer. However MTHFR (C667T) genotype and green vegetable intakes appeared to have the interactive effect in breast cancer development.
Adult ; Aged ; Alleles ; Breast Neoplasms/enzymology/*genetics ; Case-Control Studies ; *Diet ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Korea ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Middle Aged ; *Polymorphism, Restriction Fragment Length ; Research Support, Non-U.S. Gov't

PURPOSE: A case-control study was conducted to evaluate the association between diet and breast cancer in Korean women. METHODS: The eligible subjects consisted of a series of histologically confirmed incident breast cancer patients (n= 1063) and non-cancer controls (n=1002) admitted to the departments of surgery at four teaching hospitals located in Seoul, Korea (Seoul National University Hospital, Borame Hospital, Samsung Medical Canter, and Asan medical Center) between 1995 and 2002, from whom blood samples were available. After excluding subjects with a previous history of cancer, hysterectomy or oophorectomy, the final study population consisted of 819 cases and 713 controls. The demographic characteristics and other information were collected by interviewed questionnaire. Dietary information obtained by trained interviewer using food frequency questionnaires. RESULTS: Women educated more than 12 years (OR=1.9, 95% CI: 1.4~2.7), with a higher body mass index (BMI) (OR= 1.4, 95% CI: 1.1~2.0) and a positive family history of breast cancer among the first degree relatives (OR=2.5, 95% CI: 1.3~4.3) were significant risk factors for breast cancer. The longer the exposure to estrogen during their lifetime, the higher the observed risk of breast cancer was (p for trend<0.001). The risk for breast cancer was increased with frequent consumption of cereals (OR=1.8, 95% CI: 1.8~2.5), potatoes (OR=1.8, 95% CI: 1.4~2.5), nuts and seeds (OR=1.9, 95% CI: 1.1~3.4), mushrooms (OR=1.5, 95% CI: 1.2~1.8), meats (OR=1.5, 95% CI: 1.2~1.9), eggs (OR=1.6, 95% CI: 1.1~2.3) and fish (OR=1.5, 95% CI: 1.2~1.9), whereas the risk decreased with higher intakes of green vegetables (OR=0.6, 95% CI: 0.4~1.0), fruits (OR=0.7, 95% CI: 0.6~0.9) and seaweeds (OR=0.7, 95% CI: 0.5~1.0). CONCLUSION: Certain diets (e.g., high fat, high carbohydrate, low vegetable or fruit intake, etc.) were significantly associated with the risk of breast cancer in Korea women, which were similar to the findings in Western countries.
Agaricales ; Body Mass Index ; Breast Neoplasms* ; Breast* ; Case-Control Studies* ; Edible Grain ; Chungcheongnam-do ; Diet* ; Eggs ; Estrogens ; Female ; Fruit ; Hospitals, Teaching ; Humans ; Hysterectomy ; Korea ; Meat ; Nuts ; Ovariectomy ; Ovum ; Surveys and Questionnaires ; Risk Factors ; Seoul ; Solanum tuberosum ; Vegetables