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Objectives To develop a convolutional neural network system to jointly segment and classify a hepatic lesion selected by user clicks in ultrasound images. Methods In total, 4309 anonymized ultrasound images of 3873 patients with hepatic cyst (n = 1214), hemangioma (n = 1220), metastasis (n = 1001), or hepatocellular carcinoma (HCC) (n = 874) were collected and annotated. The images were divided into 3909 training and 400 test images. Our network is composed of one shared encoder and two inference branches used for segmentation and classification and takes the concatenation of an input image and two Euclidean distance maps of foreground and background clicks provided by a user as input. The performance of hepatic lesion segmentation was evaluated based on the Jaccard index (JI), and the performance of classification was based on accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC). Results We achieved performance improvements by jointly conducting segmentation and classification. In the segmentation only system, the mean JI was 68.5%. In the classification only system, the accuracy of classifying four types of hepatic lesions was 79.8%. The mean JI and classification accuracy were 68.5% and 82.2%, respectively, for the proposed joint system. The optimal sensitivity and specificity and the AUROC of classifying benign and malignant hepatic lesions of the joint system were 95.0%, 86.0%, and 0.970, respectively. The respective sensitivity, specificity, and the AUROC for classifying four hepatic lesions of the joint system were 86.7%, 89.7%, and 0.947. Conclusions The proposed joint system exhibited fair performance compared to segmentation only and classification only systems. Key Points • The joint segmentation and classification system using deep learning accurately segmented and classified hepatic lesions selected by user clicks in US examination. • The joint segmentation and classification system for hepatic lesions in US images exhibited higher performance than segmentation only and classification only systems. • The joint segmentation and classification system could assist radiologists with minimal experience in US imaging by characterizing hepatic lesions.

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.

Retinal artery&ndash, vein (AV) classification is a prerequisite for quantitative analysis of retinal vessels, which provides a biomarker for neurologic, cardiac, and systemic diseases, as well as ocular diseases. Although convolutional neural networks have presented remarkable performance on AV classification, it often comes with a topological error, like an abrupt class flipping on the same vessel segment or a weakness for thin vessels due to their indistinct appearances. In this paper, we present a new method for AV classification where the underlying vessel topology is estimated to give consistent prediction along the actual vessel structure. We cast the vessel topology estimation as iterative vascular connectivity prediction, which is implemented as deep-learning-based pairwise classification. In consequence, a whole vessel graph is separated into sub-trees, and each of them is classified as an artery or vein in whole via a voting scheme. The effectiveness and efficiency of the proposed method is validated by conducting experiments on two retinal image datasets acquired using different imaging techniques called DRIVE and IOSTAR.

OBJECTIVES: The objective of our study was to evaluate the association between occupational exposure to trichloroethylene (TCE), a suspected lymphomagen, and serum levels of miRNAs in a cross-sectional molecular epidemiology study of TCE exposed workers and comparable unexposed controls in China. METHODS: Serum levels of 40 miRNAs were compared in 74 workers exposed to TCE (median: 12 ppm) and 90 unexposed control workers. Linear regression models were used to test for differences in serum miRNA levels between exposed and unexposed workers and to evaluate exposure-response relationships across TCE exposure categories using a three-level ordinal variable (i.e., unexposed

ObjectivesThe occupational exposure limit for trichloroethylene (TCE) in different countries varies from 1 to 100 ppm as an 8-hour time-weighted average (TWA). Many countries currently use 10 ppm as the regulatory standard for occupational exposures, but the biological effects in humans at this level of exposure remain unclear. The objective of our study was to evaluate alterations in immune and renal biomarkers among workers occupationally exposed to low levels of TCE below current regulatory standards.MethodsWe conducted a cross-sectional molecular epidemiology study of 80 healthy workers exposed to a wide range of TCE (ie, 0.4–229 ppm) and 96 comparable unexposed controls in China, and previously reported that TCE exposure was associated with multiple candidate biological markers related to immune function and kidney toxicity. Here, we conducted further analyses of all of the 31 biomarkers that we have measured to determine the magnitude and statistical significance of changes in the subgroup of workers (n=35) exposed to ResultsSix immune biomarkers (ie, CD4+ effector memory T cells, sCD27, sCD30, interleukin-10, IgG and IgM) were significantly decreased (% difference ranged from −16.0% to −72.1%) and one kidney toxicity marker (kidney injury molecule-1, KIM-1) was significantly increased (% difference: +52.5%) among workers exposed to ConclusionOur results suggest that occupational exposure to TCE below 10 ppm as an 8-hour TWA may alter levels of key markers of immune function and kidney toxicity.

Background: We aimed to report the prevalence and correlates of high-risk alcohol consumption and types of alcoholic beverages. Methods: The baseline data of the Health Examinees-Gem (HEXA-G) study participants, including 43,927 men and 85,897 women enrolled from 2005 through 2013, were used for analysis. Joinpoint regression was performed to estimate trends in the age-standardized prevalence of alcohol consumption. Associations of demographic and behavioral factors, perceived health-related effects, social relationships, and the diagnostic history of diseases with alcohol consumption were assessed using multinomial logistic regression. Results: The prevalence of alcohol consumption remained higher in men during the study period and increased in women. The amount of alcohol consumed has increased in women, especially that from beer and makgeolli, a traditional Korean fermented rice wine. Older participants were less likely to be high-risk drinkers (men and women who drink more than 40 or 20 g/day of alcohol, respectively) and drink Soju, a distilled liquor, and beer, and more likely to drink makgeolli. Educational level was negatively associated with high-risk drinking. However, it was positively associated with the consumption of strong spirits and wine. Smoking was associated with high-risk drinking and the consumption of soju and strong spirits. Engaging in regular exercise and having stress were associated with drinking all types of beverages except for soju. Conclusions: Sex-specific trends in alcohol consumption were influenced by demographic, behavioral, and perceived health-related factors. The findings will help improve the understanding of alcohol-related problems and provide evidence for establishing country-specific policies and campaigns in Korea.

OBJECTIVES: This study compared the results of meta-analysis with and without adjustment for the healthy worker effect on the association between working in the semiconductor industry and cancer mortality.METHODS: Six studies that reported standardized mortality ratios (SMRs) for cancers were selected for meta-analysis. Using a random-effects model, the SMR results from each study were combined for all cancers and leukemias to estimate the summary SMRs (95% confidence interval, CI). To adjust for the healthy worker effect, the relative standardized mortality ratio (rSMR=SMRx/SMRnot x) were calculated using observed and expected counts for the specific cause of interest (i.e., all cancers and leukemias) and the observed and expected counts for all other causes of mortality. Then, the rSMR results were combined to estimate the summary rSMRs (95% CIs).RESULTS: The SMRs for all causes of mortality among semiconductor industry workers ranged from 0.25 to 0.80, which reflects a significant healthy worker effect. A remarkable difference was found between the summary SMRs and the summary rSMRs. The summary SMR for all cancers was 0.70 (95% CI, 0.63 to 0.79) whereas the summary rSMR was 1.38 (95% CI, 1.20 to 1.59). The summary SMR for leukemia was 0.88 (95% CI, 0.72 to 1.07), and the summary rSMR was 1.88 (95% CI, 1.20 to 2.95).CONCLUSIONS: Our results suggest that adjustment for the healthy worker effect (i.e., rSMR) may be useful in meta-analyses of cohort studies reporting SMRs.

ObjectivesThis study evaluated whether individuals with affected family member adhered to healthy behaviours.Design and settingThis was a cross-sectional study of participants selected from health examinees who underwent the national health check-up programme of Korea in 39 centres between 2004 and 2013.ParticipantsThe baseline data of 128 520 participants enrolled in the Health Examinees-Gem study were used for analysis.Main outcomes and measuresAssociations of family history of diabetes with adherence to regular exercise, healthy diet and body composition, and clusters of healthy behaviours were evaluated while adjusting for potential confounders selected by a directed acyclic graph.ResultsParticipants with a family history of diabetes were more likely to adhere to a regular exercise regimen (OR=1.12, 95% CI 1.06 to 1.18 for men and OR=1.10, 95% CI 1.07 to 1.14 for women) and healthy diet (OR=1.06, 95% CI 1.01 to 1.12 for men and OR=1.06, 95% CI 1.01 to 1.12 for women) but were less likely to have a normal body composition (OR=0.83, 95% CI 0.78 to 0.87 for men and OR=0.83, 95% CI 0.80 to 0.86 for women). These associations were strengthened when the affected family members were siblings, the number of affected members was increased or the age at diagnosis of the affected member was younger than 50 years. In men and women, having a normal body composition is important in determining the cluster of behaviours, and those with a family history of diabetes were less likely to adhere to the normal body composition cluster.ConclusionsThe group with high risk of diabetes showed healthy behaviors, but they did not have a normal body composition. Policies and campaigns targeting integrated health behaviors will be needed to reduce the burden of diseases and improve public health.

The purpose of this study is to evaluate the associations of sleep duration and with metabolic syndrome and its components. A total of 72,673 participants from the Health Examinees Study were analyzed to investigate the association of sleep duration with metabolic syndrome and its components. Using the NCEP-ATP III guideline and multiple logistic regression models, odds ratios (ORs) were estimated, stratified by sex. Long-sleep duration was significantly associated with an increased OR for metabolic syndrome in women (OR 1.53, 95 % CI 1.32–1.78), but not in men (1.19, 0.98–1.46). Both short- and long-sleep duration were significantly associated with elevated triglycerides among men (short and long sleep, respectively: 1.09, 1.00–1.19; 1.26, 1.04–1.52). Women were associated with long-sleep duration and all of metabolic syndrome components, especially triglycerides (1.29, 1.11–1.50). In conclusion, long-sleep duration is significantly associated with metabolic syndrome in women. Moreover, triglycerides revealed association across sleep duration among components of metabolic syndrome.

The objective of this study was to verify a change in the longitudinal trend of blood lead levels for the Korean population, before and after the regulation of leaded gasoline- which occurred between 1987 and 1993 in Korea. A total of 77 reports on blood lead levels among general Korean population between 1981 and 2014 were selected, and the results were summarized to have the variables of year, number of subjects, the subjects' range in age, gender, and blood lead concentrations (arithmetic mean). The annual average atmospheric lead levels for four major cities (i.e., Seoul, Busan, Daegu and Gwangju) were collected from the Air Pollution Monitoring Database from 1991, and pilot studies from 1985 to 1990 before the national air quality monitoring system was launched in 1991. Blood lead levels were visualized in a bubble plot in which the size of each bubble represented the sample size of each study, and the annual average concentrations in ambient air were depicted on line graphs. Blood lead levels in the Korean population tended to gradually increase from the early 1980s (approximately 15-20 μg/dL) until 1990-1992 (20-25 μg/dL). Blood lead levels then began to rapidly decrease until 2014 (

BACKGROUND Though a large proportion of cancer survivors are assumed to be commonly affected by sleep disturbance, few studies have focused on short sleep problems and its correlates among Korean cancer survivors. The purpose of this study was to evaluate the prevalence of short sleep in adult cancer survivors from a nationwide population-based sample and to identify risk factors for short sleep duration. MATERIALS AND METHODS Based on the fourth and fifth Korea National Health and Nutrition Examination Surveys (2007-2012), 1,045 cancer survivors and 33,929 non-cancer controls were analyzed. The prevalence of short sleep was compared between these two groups. Associations between short sleep and its correlates were evaluated using multiple logistic regression among cancer survivors: odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated after adjusting for sociodemographic factors, lifestyle factors, psychological conditions, and cancer-related factors. RESULTS About 8.1% of cancer survivors slept for less than 5 hours per day (6.2% men and 9.3% women), whereas this was the case for only 3.7% of non-cancer controls. Cancer survivors who had the lowest household income level showed a significantly higher likelihood for short sleep (adjusted OR 2.82, 95%CI 1.06-7.54). Self-reported poor health and depressive symptoms were found to be associated with significantly increased likelihood for short sleep in cancer survivors (adjusted OR 3.60, 95%CI 1.40-9.26 and adjusted OR 2.00, 95%CI 1.17-3.42). Gastric cancer survivors had a 3.97-fold increased risk for short sleep (95%CI 1.60-9.90). CONCLUSIONS The prevalence of short sleep occurs at a high rate among the Korean cancer survivors, which may indicate a poorer quality of life and a higher risk of future complications in survivorship. Targeted interventions that can assist cancer survivors to cope with sleep disturbances as well as ensuring psychological stability are warranted to reduce the latent disease burden.

Objectives: The purpose of this study was to assess excavator drivers in order to determine the proportion showing subjective symptoms of musculoskeletal disorders and to evaluate the association between the symptoms and characteristics of the subjects. Methods: A questionnaire survey was conducted to collect the information on participants’ age, average working hours per day, duration of career (years), work-related musculoskeletal symptoms, and more. The final dataset included 141 excavator drivers. Frequency and percentage were summarized and then the associations between the characteristics of the subjects and symptoms were evaluated as odds ratios (ORs) and 95% confidence intervals (CIs) using multiple logistic regression analysis. Results: Seventy-six percent of the currently reported musculoskeletal symptoms. Those who have musculoskeletal symptoms attributed their symptoms to unstable posture at work, mental stress or vibrations. There was a significant association between symptoms of musculoskeletal disorders and career of excavator drivers (P for trend=0.04). Conclusions: The results of this study suggest that the prevalence of musculoskeletal disorders may be high among excavator drivers and warrants well-designed studies on work-related disorders among excavator drivers.

To describe the study design, methods, and baseline results of a prospective cohort of radiologic technologists which we have initiated in South Korea. The cohort participants were enrolled through a self-administered questionnaire survey administered from April 2012 to May 2013. Survey data were linked with radiation dosimetry, a cancer registry, and health insurance data by personal identification numbers. A nationwide representative survey was also conducted using a stratified random sampling design with face-to-face interviews. A total of 12,387 radiologic technologists were enrolled, which accounted for approximately 63 % of all diagnostic radiologic technologists working in South Korea. For nationwide survey, 585 workers were interviewed using the detailed questionnaire, and buccal cells were also collected by scraping the inside of the cheek. The majority of study subjects were under 50-year-old and male workers. The average annual effective dose of radiation declined both men (from 2.75 to 1.43 mSv) and women (from 1.34 to 0.95 mSv) over the period of 1996–2011. A total of 99 cancers (66 cancers in men and 33 in women) were reported from 1992 to 2010. The standardized incidence ratio of all cancer combined was significantly lower in men (SIR = 0.75, 95 % CI 0.58–0.96) than general population, but the ratios for thyroid cancer were significantly higher than expected among both men and women. This cohort provides comprehensive information on work activities and health status of diagnostic radiologic technologists. In addition, the nationwide representative sample provides unique opportunities compared with previous radiologic technologist studies.

Objectives: By conducting a meta-analysis of cohort studies reporting standardized mortality ratios (SMRs) for workers exposed to trichloroethylene, we attempted to adjust for healthy hired effect by applying the same methods as described in a recent report from the Agricultural Health Study. Methods: Among all cohort studies that evaluated the association between all cancer, non-Hodgkin's lymphoma (NHL), kidney cancer, liver cancer and occupational exposure to trichloroethylene, a total of 10 studies reporting SMR values were selected. A random-effects model was used to estimate the summary SMRs or rSMRs and 95% confidence intervals. Relative SMR (rSMR=SMR /SMR ) was calculated comparing observed and expected counts for all cancer, NHL, kidney cancer, and liver cancer with an independent referent set of values consisting of the observed and expected counts for other causes. Results: The SMR values for all causes ranged from 0.68 to 1.03, suggesting moderate to weak healthy worker effect for the selected studies. When the healthy worker hire effect was taken into account, the summarized risk became statistically significant; the summary SMR of all cancer was 0.95 (0.91-1.00) and the summary rSMR of all cancer was 1.10 (1.04-1.15). The summary SMR of NHL was 1.04 (0.93-1.14) and the summary rSMR of NHL was 1.23 (1.04-1.46). The summary SMR of kidney cancer was 1.08 (0.88-1.33) and the summary rSMR of kidney cancer was 1.23 (1.02-1.49). The summary SMR of liver cancer was 0.88 (0.78-0.99), and the summary rSMR of liver cancer was 0.95 (0.84-1.07).

We propose a framework for localization and classification of masses in breast ultrasound (BUS) images. We have experimentally found that training convolutional neural network based mass detectors with large, weakly annotated datasets presents a non-trivial problem, while overfitting may occur with those trained with small, strongly annotated datasets. To overcome these problems, we use a weakly annotated dataset together with a smaller strongly annotated dataset in a hybrid manner. We propose a systematic weakly and semi-supervised training scenario with appropriate training loss selection. Experimental results show that the proposed method can successfully localize and classify masses with less annotation effort. The results trained with only 10 strongly annotated images along with weakly annotated images were comparable to results trained from 800 strongly annotated images, with the 95% confidence interval of difference -3.00%--5.00%, in terms of the correct localization (CorLoc) measure, which is the ratio of images with intersection over union with ground truth higher than 0.5. With the same number of strongly annotated images, additional weakly annotated images can be incorporated to give a 4.5% point increase in CorLoc, from 80.00% to 84.50% (with 95% confidence intervals 76.00%--83.75% and 81.00%--88.00%). The effects of different algorithmic details and varied amount of data are presented through ablative analysis., Comment: Accepted to IEEE Transactions on Medical Imaging

The carcinogenic potential of trichloroethylene (TCE) continues to generate much controversy, even after the US Environmental Protection Agency raised its classification to 'carcinogenic to humans'. We conducted a meta-analysis of published cohort and case-control studies exploring occupational TCE exposure in relation to five different lymphatic and haematopoietic cancers: non-Hodgkin's lymphoma (NHL, N=24), Hodgkin's lymphoma (HL, N=13), multiple myeloma (MM, N=11), leukaemia (N=12) and chronic/small lymphocytic leukaemia (CLL/SLL, N=7). Studies published between 1950 and 2011 were identified through a PubMed Medline search. All studies included in analyses were classified as those that assessed either occupational TCE exposure specifically ('TCE-exposure' studies) or a broader classification of all chlorinated solvents ('chlorinated solvent-exposure' studies). A significantly raised summary estimate for NHL was seen for all cohort and case-control 'TCE-exposure' studies combined (N=19; relative risk (RR)=1.32, 95% CI 1.14 to 1.54; I(2)=25.20; p-heterogeneity=0.12) and for cohort 'TCE-exposure' studies (N=10; RR=1.52, 95% CI 1.29 to 1.79; I(2)=7.09; p-heterogeneity=0.63). A non-significant but raised summary estimate was seen for NHL case-control 'TCE-exposure' studies. No significant association with NHL risk was detected overall for any 'chlorinated solvent-exposure' studies. Summary estimates for occupational TCE exposure were not associated with risk of HL, MM, leukaemia or CLL/SLL. Our updated meta-analysis of NHL, which incorporates new analytical results from three cohort and four case-control studies, supports an association between occupational TCE exposure and NHL.

We conducted a hospital-based case-control study in Korea to investigate whether apoptosis- and cell cycle control-related genes are associated with childhood brain tumor. Incident brain tumor cases (N = 70) and non-cancer controls (N = 140), frequency-matched by age and gender, were selected from 3 teaching hospitals in Seoul between 2003 and 2006. Tag single nucleotide polymorphisms (SNPs) (N = 297) in 30 genes related to apoptosis and cell cycle control were selected using a pairwise linkage-disequilibrium-based algorithm. Five tag SNPs in 2 genes (AICDA and CASP14) remained significant after adjusted multiple tests. The most significant association with childhood brain tumor risk was for IVS1-401G>C in the AICDA gene [odds ratio (OR) = 2.8; 95% confidence interval (95%CI) = 1.25-6.46]; the polymorphism *9276A>C of CASP14 was associated with decreased brain tumor risk (OR = 0.4; 95%CI = 0.19-0.95). We concluded that genetic polymorphisms in AICDA and CASP14 are associated with risk for brain tumor in Korean children.

Background: Matrix metalloproteinase-2 (MMP-2) has been thought of as a predictor of recurrence or metastasis risk or prognostic markers in cancer. We evaluated whether preoperative serum levels of MMP-2 work as a prognostic biomarker in breast cancer prognosis. Methods: Preoperative serum levels of MMP-2 were measured with ELISA in 303 patients with histologically confirmed breast cancer. The median follow-up time for all patients was 4.24 years. The relationship of MMP-2 to survival was investigated using Cox proportional hazard regression model adjusted for the tumor–node–metastasis (TNM) stage and estrogen receptor (ER) status. Results: In the multivariate analysis, disease-free survival (DFS) was worse among patients with the third tertile of MMP-2 level than with the first tertile of MMP-2 level [hazard ratio, 1.80; 95% confidence interval (CI), 1.04–3.11; P = 0.04]. However, when the patients were stratified by age, ER status, histologic grade, and nuclear grade, inverse correlation was shown between serum MMP-2 levels and prognostic factors, and the associations between MMP-2 and DFS were only significant among patients with poor prognostic factors (HR, 2.75; 95% CI, 1.32–5.73 in ER-negative; HR, 2.90; 95% CI, 1.42–5.92 in histologic grade III; and HR, 2.61; 95% CI, 1.26–5.39 in nuclear grade III). Conclusions: Our results suggest that the preoperative serum levels of MMP-2 were associated with the survival in patients with breast cancer in ER-negative, higher histologic grade, or higher nuclear grade breast cancers. Impact: Our results indicate that serum levels of MMP-2 may play a role as prognostic biomarker in breast cancer survival. Cancer Epidemiol Biomarkers Prev; 21(8); 1371–80. ©2012 AACR.

Using the urinary biomarkers 1-hydroxypyrene-glucuronide (1-OHPG), 2-naphthol, and malondialdehyde (MDA), we evaluated seasonal and regional variations in polycyclic aromatic hydrocarbon (PAH) exposure and oxidative stress among Korean adults and children. In total, 322 children (175 male and 147 female) and 332 adults (47 male and 285 female) were recruited in two regions of Korea, one representing a metropolitan area (Seoul/Incheon) and the other an industrial (Pohang) area, from winter 2002 to spring 2003. The subjects voluntarily gathered their first morning urine void, which was immediately transported to our laboratory and stored at -20 °C. Urinary 1-OHPG was measured by synchronous fluorescence spectroscopy, 2-naphthol by HPLC, and urinary MDA by HPLC with a UV detector. The median urinary 1-OHPG concentration tended to be higher in the industrial region than in the metropolitan region (0.92 vs. 0.77 ng/mL; p=0.03), and higher in winter than in spring (0.95 vs. 0.73 ng/mL; p

The methylation profiles of nine cancer-associated genes were compared with the percent of methylation ratio (PMR) using quantitative methylation RT-PCR in 16 normal lung tissue samples and 80 non-small cell lung cancer (NSCLC) tissues samples. The methylation of nine cancer-associated genes showed a significant increase in tumors compared to matched normal lung tissues, and the level of gene methylation in NSCLC patients containing both adjacent nontumor and tumor tissues showed a significant increase compared to normal lung tissues (P

A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 × 10(-12)); however, this association did not achieve genome-wide significance (p ≤ 10(-7)) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 × 10(-8); allelic risk = 0.80, 95% confidence interval (CI) = 0.74-0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67-0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.

It is becoming increasingly clear that there is wide heterogeneity in genetic predisposition to breast cancer and that breast cancer risk is determined by interactive effect between genetic and environmental factors.We investigated the combined effects of antioxidant vitamin intake and NOS3 genetic polymorphisms on breast cancer risk in a Korean population (Seoul Breast Cancer Study). Histologically confirmed breast cancer cases (n = 512) and age, menopause status-matched controls (n = 512) with no present or previous history of cancer were recruited from several teaching hospitals in Seoul during 2001-2003. Two genetic polymorphisms of NOS3 (298G T and -786 T C) were assessed by single base extension assays.No overall association between the individual NOS3 genotypes or diplotypes and breast cancer risk was found, although the difference between cases and controls in the frequency of the NOS3 894 G T polymorphism showed borderline significance (OR = 0.74, 95% CI = 0.52-1.06). There was no significant difference in energy intake or the intake of antioxidant vitamins between cases and controls, with the exception of vitamin E (OR = 0.49 lowest vs. highest quartile, P(trend) 0.01). On the other hand, our results suggest that antioxidant vitamin intake may modify the effects of the NOS3 -786 T C or 894 G T genetic polymorphisms on breast cancer risk. Although a multiplicative interaction was not observed, the protective effect of β-carotene intake on breast cancer risk was observed predominantly in individuals with the TG:TG diplotype of NOS3 (OR = 0.68) but not observed with others diplotype. An inverse association between vitamin E intake and breast cancer risk was observed for individuals with the NOS3 786 TC + TT genotype and the NOS3 894 GG genotype. In addition, folic acid had a protective effect in the NOS3 786 TT and NOS3 894 GT + TT genotype.Our results suggest that intake of antioxidant vitamins might modify the association between genetic polymorphisms of NOS3 and breast cancer risk.

Aberrant DNA methylation is associated with cancer development and progression. There are several types of specimens from which DNA methylation pattern can be measured and evaluated as an indicator of disease status (from normal biological process to pathologic condition) and even of pharmacologic response to therapy. Blood-based specimens such as cell-free circulating nucleic acid and DNA extracted from leukocytes in peripheral blood may be a potential source of noninvasive cancer biomarkers. In this article, we describe the characteristics of blood-based DNA methylation from different biological sources, detection methods, and the factors affecting DNA methylation. We provide a comprehensive literature review of blood-based DNA methylation as a cancer biomarker and focus on the study of DNA methylation using peripheral blood leukocytes. Although DNA methylation patterns measured in peripheral blood have great potential to be useful and informative biomarkers of cancer risk and prognosis, large systematic and unbiased prospective studies that consider biological plausibility and data analysis issues will be needed in order to develop a clinically feasible blood-based assay.

Healthy worker effect (HWE) refers to the consistent tendency for actively employed individuals to have a more favorable mortality experience than the population at large. Although HWE has been well known since the 1970s, only a few studies in occupational epidemiology have attempted to fully define and evaluate HWE. HWE can be separated into effects on the initial hiring into the workforce (healthy worker hire effect) and those on continuing employment (healthy worker survival effect). In this review, we summarize the methods for minimizingor adjusting for the healthy worker effect available in occupational epidemiology. It is noteworthy that healthy worker survival effect appears complicated, considering that employment status plays simultaneous roles as a counfounding variable and intermediate variable, whereas healthy worker hire effect may be adjusted by incorporating health status at baseline into the statistical model. In addition, two retrospective cohort studies for workers in the semiconductor industry and Vietnam veterans in Korea, respectively, were introduced, and their results were explained in terms of healthy worker effect.

Objectives: In order to evaluate the association between occupational exposure to chloroethylene (TCE) and risk of non-Hodgkin lymphoma (NHL), we conducted a meta-analysis of retrospective cohort studies and casecontrol studies and attempted to summarize the evidence of the association from molecular-epidemiological studies and experiments with human cells. Methods: In the meta-analysis, we restricted the analysis to those studies with data for chlorinated solvents, degreasers, or TCE. Studies involving dry cleaners or launderers were excluded from the analysis because use of TCE as a dry cleaning fluid has been rare since the 1960s. The data were combined using a random-effects model to estimate the summary risks (OR and RR) and 95% confidence intervals (CIs). Molecular evidence of the effect of TCE on human immune system were also reviewed and summarized. Results: Occupational exposure to TCE was strongly associated with NHL among cohort studies (number of studies=13, summary RR=1.33, 95% CI=1.04-1.70) whereas the association was not statistically significant among case-control studies (number of studies=15, summary OR=1.10, 0.98-1.23). When exposure level was considered, it became statistically significant for the highest exposure level (number of studies=5, summary OR=1.70, 1.25-2.32). Molecular evidences showed that TCE exposure in human or cultured human cells may cause a significant decrease immune cell subsets and changes in hormone levels related to immune response. Conclusions: Our results from meta-analysis and additional molecular evidence suggest that occupational exposure to TCE may cause NHL. However, unmeasured potential confounding and unclear dose-response relationships warrant further study on the role of TCE exposure in NHL carcinogenesis.

Recent compelling evidence indicates that mutation, aberrant expression, and dysregulation of microRNA (miRNA) biogenesis are implicated in cancer development and progression. Based on the important role of miRNA biogenesis pathway in carcinogenesis, we hypothesized that genetic variations in this pathway genes may play a role as susceptibility factors for breast cancer. To test this hypothesis, we investigated the associations between 41 single nucleotide polymorphisms (SNPs) in 14 genes involved in miRNA biogenesis pathway and breast cancer risk in a case–control study of 559 Korean breast cancer cases and 567 controls frequency-matched by age. In all women, 3 SNPs (AGO1 rs595055, AGO2 rs3864659, and p68 rs1991401) were significantly associated with breast cancer risk. In stratified analysis by menopausal status, altered risk associations were observed for 7 SNPs in postmenopausal breast cancer. When subjects were grouped by the number of high-risk genotypes, we found a progressive increase in gene-dosage effect (P trend = 9.46E−7). The protective effects of AGO2 rs3864659 and HIWI rs11060845 were more pronounced in progesterone receptor-positive (PR+) cancer than in progesterone receptor-negative (PR−) cancer (odds ratio (OR), 0.50; 95% confidence interval (CI), 0.30–0.84 vs. OR, 0.94; 95% CI, 0.60–1.84; P heterogeneity = 0.04 and OR, 0.57; 95% CI, 0.37–0.88 vs. OR, 0.97; 95% CI, 0.65–1.44; P heterogeneity = 0.02, respectively), and the DROSHA rs644236 had stronger association with estrogen receptor-negative (ER−) cancer than for estrogen receptor-positive (ER+) cancer (OR, 1.39; 95% CI, 1.08–1.78 vs. OR, 1.05; 95% CI, 0.85–1.29; P heterogeneity = 0.04). Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer risk, and the modifiable effects might be different according to the menopausal status and hormone receptor status.

Ataxia telangiectasia mutated (ATM) cells exist under a constant state of oxidative stress with high levels of reactive oxygen species, which are removed by cellular antioxidant vitamins. We investigated the independent and combined effect of antioxidant vitamins intake and the ATM genotype or diplotype on the breast cancer risk. Analyses included 323 cases and age-matched controls who participated in the Korean Breast Cancer Study during 2001-2003 with complete dietary information. The vitamin A (P0.01) and α-tocopherol (P0.01) were associated with lower breast cancer risk as well as some water-soluble vitamins including vitamin B(2) (P = 0.01), vitamin C (P0.01), and folic acid (P = 0.02) intake. No five single nucleotide polymorphisms (ATM-5144AT (rs228589), IVS21 + 1049TC (rs664677), IVS33-55TC (rs664982), IVS34+60GA (rs664143), and 3393TG (rs4585)) studied showed significant differences in their allele frequencies between the cases and controls. On the other hand, compared with the diploid of ATTGT/ATTGT, as the number of ATTGT haplotype decreased, the risk of breast cancer increased (P = 0.04). The association between ATM diplotype and the breast cancer risk was predominantly among women with low intake of antioxidant vitamins including vitamin A, vitamin C, and folic acid. This study suggested that some antioxidant vitamins intake may modify the effect of ATM diplotype on the breast cancer risk among Korean women.

We conducted a genome-wide association study of childhood acute lymphoblastic leukemia (ALL) in a case–control study conducted in Korea. Incident childhood ALL cases (n = 50) and non-cancer controls (n = 50) frequency-matched to cases by age and sex, recruited from three teaching hospitals in Seoul between 2003 and 2008, were genotyped using Affymetrix SNP Array 6.0 platform. ALL risks were estimated as odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age and birth weight. The false discovery rate (FDR) was used for adjusting multiple tests. Of these 1 million SNPs, six SNPs in 4 genes (HAO1 rs6140264, EPB41L2 rs9388856, rs9388857, rs1360756, C2orf3 12105972, MAN2A1 rs3776932) were strongly associated with childhood ALL risk (Pdominant ≤ 0.0001 and Ptrend < 0.006). These SNPs remained significant after FDR adjustment (FDR value

DNA methylation is the main epigenetic modification that occurs at the early stages of carcinogenesis. We performed a genome-wide DNA methylation profiling to evaluate whether the DNA methylation state is different in the estrogen receptor (ER) and progesterone receptor (PR) status of breast cancer. Twelve ER+/PR+ and 12 ER-/PR- breast cancer tissues were selected from the biorepository of the Seoul Breast Cancer Study for Infinium Methylation Assay. The difference of the DNA methylation state of 27 578 methylation sites in 14 000 genes between two groups was evaluated by Student's t-test. False discovery rate (FDR) was estimated to evaluate the probability of false positive associations. Of the 27 578 sites, 148 sites (0.54%) were significantly different between ER+/PR+ and ER-/PR- breast cancers (P < 0.001); 93 hypermethylated and 55 hypomethylated. Five genes, FAM124B (P = 7.26 × 10(-7)), MANEAL (P = 3.38 × 10(-7)), ST6GALNAC1 (P = 2.85 × 10(-6)), NAV1 (P = 5.94 × 10(-6)) and PER1 (P = 6.45 × 10(-6)) remained significant after correction for multiple tests (FDR < 0.05). In a subsequent replication study for five genes, four of the five genes were validated; FAM124B and ST6GALNAC1 were significantly hypermethylated, and NAV1 and PER1 were significantly hypomethylated in ER+/PR+ breast cancers (P < 0.05). In the first genome-wide DNA methylation profiling according to the receptor status of breast cancer, we found that ER/PR status affects the DNA methylation state of FAM124B, ST6GALNAC1, NAV1 and PER1 in breast cancer.

Breast cancer, the most common cancer in women, results from combined effects of genetic and environmental factors. Although a number of preventive measures have been suggested to reduce the risk of breast cancer, only a few (e.g., regular mammogram, etc.) proved to be efficient preventive modalities. Among many potential reasons, differences in individual susceptibility factors may complicate the efficacy of the intervention. A growing body of evidence shows that the strength of association between various dietary, behavioral (exercise and obesity), and environmental exposures, and breast cancer risk may be modified by individual genetic factors. Preventive strategies against breast cancer will be discussed considering the findings of the gene-environment interaction of breast cancer. These include behavior modification for high-risk subjects (primary prevention), early detection and extensive monitoring of genetically susceptible subjects and noninvasive treatment of early stage cancer cases (secondary prevention), and finally prophylactic and therapeutic intervention to slow the progression of diseases (tertiary prevention). The accumulating evidences of the gene-environment interactions provide a better understanding of the breast cancer development and enable us to adopt individualized preventive strategies for personalized health care.

To evaluate the immunosuppressive effects of job stress in female nurses, an 8-month longitudinal study was conducted at a major university hospital. Four groups of ten subjects each were constructed to represent high versus low objective stress and high versus low subjective stress based on their responses to a job stress questionnaire and objective stress ratings of the hospital’s work units. Number of white blood cells (i.e., T cells, B cells, and natural killer cells), and lymphocytic proliferation to mitogens (concanavalin A, phytohemagglutinin, and pokeweed) and toxoid (tetanus) were measured by flow cytometry and radioimmunoassay. Serum levels of hydrocortisol, IL-1β, IFN-γ, and TNF-α, and salivary IgA were measured by enzyme-linked immunosorbent assay. The data were analyzed by repeated measures analysis of variance controlling for age and smoking. The level of white blood cells was lower among high objective stress group (median: 7,170/m3; range: 5,386–10,057) compared with that among low objective stress group (8,063; 5,888–9,875) (P = 0.03), however, no other cellular blood variables were found to be significant. In terms of humoral immuno-biomarkers, the level of TNF-α was moderately lower among high objective stress group (1.7 ng/ml; 0.3–2.7) compared with that among low objective stress group (2.2; 0.5–3.5) (P = 0.07), whereas the level of total sIgA was significantly higher among higher objective stress group (72.9 end-point titer/mg/ml/min; 14.4–153.4) compared with that among low objective stress group (44.8; 9.9–123.8) (P = 0.02). The results of the study suggest that psychological job stress affects the levels of some immunological biomarkers in female nurses.

Evidences supporting gene-environment interaction are accumulating in terms of environmental exposure including lifestyle factors and related genetic variants. One form of defense mechanism against cancer development involves a series of genes whose role is to metabolize (activation/detoxification) and excrete potentially toxic compounds and to repair subtle mistakes in DNA. The purpose of this article is to provide a brief review of the notion of gene-environment interaction, environmental/occupational carcinogens and related cancers, and previous studies of gene-environment interaction on cancers caused by exposure to carcinogenesis. With a number of studies on the interaction between lifestyle factors (e.g., smoking and diet) and genetic polymorphisms in genes involved in xenobiotic metabolism and DNA repair excluded, only several studies have been conducted on the interactive effects between polymorphisms of CYPs, GSTs, ERCCs, XRCCs and environmental/occupational carcinogens such as vinyl chloride, benzo[a]pyrene, and chloroform on carcinogenesis or genotoxicity. Future studies may need to be conducted with sufficient number of subjects and based on occupational cohorts to provide useful information in terms of advanced risk assessment and regulation of exposure level.

Genetic variation may be an important risk factor for multiple myeloma. A hallmark of tumor formation and growth is cell cycle dysregulation and apoptosis avoidance. We previously reported the association of genetic variation in caspase genes, the apoptotic-regulating family, and multiple myeloma risk. To further examine if genetic variation in key cell cycle and apoptosis genes alters multiple myeloma risk, we genotyped 276 tag SNPs in 27 gene regions in a population-based case–control study of non-Hispanic Caucasian women (108 cases; 482 controls) in Connecticut. Logistic regression assessed the effect of each SNP on multiple myeloma risk and the minP test assessed the association at the gene region level. Three gene regions were significantly associated with risk of multiple myeloma ( BAX minP = 0.018, CASP9 minP = 0.025, and RIPK1 minP = 0.037). Further explorations identified the most significant variant of BAX , RIPK1 , and CASP9 to be rs1042265, rs9391981, and rs751643, respectively. The A variant at rs1042265 (OR GA+AA = 0.40, 95% CI = 0.21–0.78) and the C variant at rs9391981 (OR GC+CC = 0.32, 95% CI = 0.12–0.81) were associated with a decreased risk of multiple myeloma. The G variant at rs7516435 was associated with an increased risk of multiple myeloma (OR AG = 1.48, 95% CI = 0.94–2.32; OR GG = 2.59, 95% CI = 1.30–5.15; p trend = 0.005). Haplotype analyses supported the SNP findings. These findings suggest that genetic variation in cell cycle and apoptosis genes may play a key role in multiple myeloma and warrant further investigation through replication studies.

Although widely studied over the past forty years, personal use of hair dye generally has not been associated with overall cancer risk. The association between hair dye use and risk of bladder and hematopoietic cancers has been less conclusive. Most hair dye studies have been case-control studies conducted in Caucasian populations. We examined the relationship between personal hair dye use and cancer risk in a prospective cohort of 70,366 Chinese women. After an average of 7 years of follow-up, 2,437 women were newly diagnosed with cancer by December 31, 2005. Cox proportional hazard models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) of cancer risk associated with hair dye use, adjusting for potential confounding factors. Compared with women who reported no hair dye use, ever users had an overall cancer risk of 0.89 (95% CI: 0.82, 0.97). No significant association was observed for several common cancers, including cancers of the breast (RR: 0.93, 95% CI: 0.78, 1.09), lung (RR: 0.81, 95% CI: 0.62, 1.09), stomach (RR: 0.90, 95% CI: 0.66, 1.21), and colorectum (RR=1.04, 95% CI: 0.84, 1.28). We also found no significant association with most other cancers, including bladder cancer (RR: 1.14, 95% CI: 0.56, 2.35) and hematopoietic cancers overall (RR: 0.89, 95% CI: 0.59, 1.35) or their subtypes, including non-Hodgkin lymphoma, multiple myeloma, and leukemia. We generally found no evidence of an association between personal use of hair dye and cancer risk, although our study is limited by small numbers for certain cancer types.

Nitric oxide (NO) induces cytotoxicity and angiogenesis, and may play a role in prostate carcinogenesis, potentially modulated by environmental exposures. We evaluated the association of prostate cancer with genetic polymorphisms in two genes related to intracellular NO: NOS2A [inducible nitric oxide synthase (NOS); −2892T>C, Ex16 + 14C>T (S608L), IVS16 + 88T>G and IVS20 + 524G>A] and NOS3 [endothelial NOS; IVS1 − 762C>T, Ex7 − 43C>T (D258D), IVS7 − 26A>G, Ex8 − 63G>T (E298D) and IVS15 − 62G>T]. Prostate cancer cases (n = 1320) from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were frequency matched to controls (n = 1842), by age, race, time since initial screening and year of blood draw. An antioxidant score [range 3–12; low (3–7) versus high (8–12)] was created by summing the quartile levels of vitamin E, β-carotene and lycopene, which were coded from 1 to 4, respectively. The global tests for all eight single-nucleotide polymorphisms (SNPs) (excluding NOS2A −2892T>C, with low minor allele frequency) were statistically significant for prostate cancer (P = 0.005), especially for aggressive cancer (stage III–IV or Gleason score ≥ 7) (P = 0.01). The NOS2A IVS16 + 88 GT/TT was associated with increased prostate caner risk (odds ratio = 1.24, 95% confidence interval = 1.00–1.54), whereas the IVS20 + 524 AG/GG was associated with decreased risk (0.77, 0.66–0.90). The NOS3 IVS7 − 26GG was associated with increased prostate caner risk (1.33, 1.07–1.64). All these SNPs showed significant associations with aggressive cancer and not for non-aggressive cancer. In the evaluation of effect modification, the effect of the NOS2A IVS16 + 88 GT/TT on aggressive cancer was stronger among subjects with higher antioxidant intake (1.61, 1.18–2.19; Pinteraction = 0.01). Our results suggest that NOS gene polymorphisms are genetic susceptibility factors for aggressive prostate cancer.

Domestic fuel combustion from cooking and heating, to which about 3 billion people worldwide are exposed, is associated with increased lung cancer risk. Lung cancer incidence in Xuanwei is the highest in China, and the attributable risk of lung cancer from unvented smoky coal burning is greater than 90%. To evaluate any lung cancer mortality reduction after changing from unvented stoves to portable stoves, we used lifetime smoky coal users in a retrospective cohort of all farmers born during 1917–1951 and residing in Xuanwei in 1976. Of the 42 422 enrolled farmers, 4054 lifetime smoky coal users changed to portable stoves, 4364 did not change, and 1074 died of lung cancer. Lung cancer morality associated with stove change was assessed by product-limit survival curves and multivariate Cox regression models. Both men (P

WOS: 000256012800016, PubMed ID: 18463401, evaluate the roles of CYP1A1 polymorphisms [Ile (462)Val and (TC)-C-6235 (MspI)] and deletion of GSTM1 and and GSTT1 in lung cancer development in Asian populations, a pooled analysis was conducted on 13 existing studies included in Genetic Susceptibility to Environmental Carcinogenesis database. This pooled analysis included 1,971 cases and 2,130 controls. Lung cancer risk was estimated as odds ratios (OR) and 95% confidence intervals (95% CD using unconditional logistic regression model adjusting for age, sex, and pack-year. The CYP1A1 C-6235 variant was associated with squamous cell lung cancer (TC versus TT: OR, 1.42; 95% CI, 0.96-2.09; CC versus TT: OR, 1.97; 95% CI, 1.26-3.07; P-trend = 0.003). In haplotype analysis, (462)Val-T-6235 and Ile-C haplotypes were associated with lung cancer risk with reference to the Ile-T haplotype (OR, 3.41; 95% CI, 1.78-6.53 and OR, 1.39; 95% CI, 1.12-1.71, respectively). The GSTM1-null genotype increased squamous cell lung cancer risk (OR, 1.36; 95% CI, 1.05-1.77). When the interaction was evaluated with smoking, increasing trend of lung cancer risk as pack-year increased was stronger among those with the CYP1A1 6235 TC/CC genotype compared with those with IT genotype (P-interaction = 0.001) and with the GSTM1-null genotype compared with the present type (Pinteraction 0.08, when no genotype effect with no exposure was assumed). These results suggest that genetic polymorphisms in CYP1A1 and GSTM1 are associated with lung cancer risk in Asian populations. However, further investigation is warranted considering the relatively small sample size when subgroup analyses were done and the lack of environmental exposure data other than smoking., NCI NIH HHS [2P50CA090440-06, P30CA047904-19S1]

This study was conducted to evaluate the potential role of CASP8 genetic polymorphisms in the etiology of breast cancer in a case–control study, Korea. Incident breast cancer cases confirmed histologically (n = 1,599) were recruited from two hospitals in Seoul during 2001–2005. Control subjects (n = 1,536) were selected from the Health Examinee Cohort from Seoul and Gyeonggi Province surrounding Seoul, Korea. Three SNPs (D302H D > H, 5′-UTR C > T, and K337K G > A) were genotyped by the primer extension assay. The CASP8 D302H, which was not polymorphic in 48 samples, was excluded in further genotyping. Odds ratios and 95% confidential intervals (95% CIs) were estimated by unconditional logistic regression model adjusted for age at enrollment, education, age at first full-term pregnancy, cigarette smoking, and family history of breast cancer. The 5′-UTR T allele containing genotypes (CT/TT) were associated with an increased risk of breast cancer, compared with those with the CC genotype (OR = 1.13, 95% CI = 0.95–1.34; and OR = 1.48, 95% CI = 1.04–2.10, respectively; P-trend = 0.02). When stratified by the estrogen and progesterone receptor status, the association between the 5′-UTR T allele and breast cancer risk was prominent in ER(+) and PR(+) cases among pre-menopausal women (OR = 1.31, 95% CI = 1.00–1.72 and OR = 1.40, 95% CI = 1.06–1.85, respectively), whereas the association was found prominent in ER(−) or PR(−) cases (OR = 1.32, 95% CI = 0.93–1.87 and OR = 1.42, 95% CI = 1.04–1.94, respectively) among post-menopausal women. Our results thus suggest that the CASP8 5′-UTR C > T are associated with breast cancer risks and the effect may be modified by estrogen and progesterone receptor status.

Dysregulation of the one-carbon metabolic pathway, which controls nucleotide synthesis and DNA methylation, may promote lymphomagenesis. We evaluated the association between polymorphisms in one-carbon metabolism genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study in Australia. Cases (n = 561) and controls (n = 506) were genotyped for 14 selected single-nucleotide polymorphisms in 10 genes (CBS, FPGS, FTHFD, MTHFR, MTHFS, MTR, SHMT1, SLC19A1, TCN1, and TYMS). We also conducted a meta-analysis of all studies of Caucasian populations investigating the association between MTHFR Ex5+79C > T (a.k.a., 677C>T) and NHL risk. A global test of 13 genotypes was statistically significant for diffuse large B-cell lymphoma (DLBCL; P = 0.008), but not for follicular lymphoma (FL; P = 0.27) or all NHL (P = 0.17). The T allele at MTHFR Ex5+79 was marginally significantly associated with all NHL (OR = 1.25, 95% CI = 0.98–1.59) and DLBCL (1.36, 0.96–1.93). The T allele at TYMS Ex8+157 was associated with a reduced risk of FL (0.64, 0.46–0.91). An elevated risk of NHL was also observed among carriers of the G allele at FTHFD Ex21+31 (all NHL, 1.31, 1.02–1.69; DLBCL, 1.50, 1.05–2.14). A meta-analysis of 11 studies conducted in Caucasian populations of European origin (4,121 cases and 5,358 controls) supported an association between the MTHFR Ex5+79 T allele and increased NHL risk (additive model, P = 0.01). In conclusion, the results of this study suggest that genetic polymorphisms of one-carbon metabolism genes such as MTHFR and TYMS may influence susceptibility to NHL.

Superoxide dismutase (SOD) plays a key role in the detoxification of superoxide free radicals. We evaluated the association of prostate cancer with genetic polymorphisms in SOD1 (CuZn-SOD; IVS3-251A>G), SOD2 [MnSOD; Ex2+24T>C (V16A)], and SOD3 (EC-SOD; IVS1+186C>T, Ex3-631C>G, Ex3-516C>T, and Ex3-489C>T), the three main isoforms of SOD. Prostate cancer cases (n = 1,320) from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were frequency matched to nondiseased controls (n = 1,842) by age, race, time since initial screening, and year of blood draw. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI); stratified analysis by the level of antioxidative vitamins was also conducted. The higher activity Ala variant at SOD2 Ex2+24T>C (V16A), which has been hypothesized to suppress prostate carcinogenesis, was associated with elevation of prostate cancer risk in Caucasians (Val/Ala versus Val/Val: OR, 1.17; 95% CI, 0.97-1.42; Ala/Ala versus Val/Val: OR, 1.28; 95% CI, 1.03-1.60; Ptrend = 0.03). Stratification by quartiles of dietary and supplemental vitamin E intake (IU/d) showed risks of prostate cancer tended to be increased among SOD2 Ala allele carriers, except at the highest quartile of vitamin E intake (>222; Pinteraction = 0.06, Q1-Q3 versus Q4). The association between Ala allele and prostate cancer risk among those with lower intake of vitamin E (≤222) was stronger for smokers (OR, 1.44; 95% CI, 1.10-1.90). No significant association with prostate cancer was observed for polymorphic variants in SOD3 or SOD1. These results suggest that the Ala variant of SOD2 is associated with moderately increased risk of prostate cancer, particularly among men with lower intakes of dietary and supplemental vitamin E. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1581–6)

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. Haplo - type 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.

1751 There is increasing recognition that inflammatory pathways contribute to malignant transformation including cancer. We conducted a population-based case-control study in Xuanwei, China, where lung cancer rates are among the country9s highest, and where lung cancer risk is strongly associated with exposure to indoor coal combustion products. We evaluated the role of polymorphisms in immunoregulatory genes in lung cancer development. A total of 122 incident lung cancercases and 122 individually matched controls were enrolled. Fifty single nucleotide polymorphisms (SNPs) in 23 immunoregulatorygenes involved in inflammation (CCR5, ICAM1, IFNG, IFNGR, IL1A/B, IL1RN, IL4, IL4R, IL5, IL8, IL8RA/B, IL10, IL10RA, IL12A/B, IL13, IL16, LTA, MIF, TGFB, and TNF) were genotyped. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression, adjusting for sex, age, smoking and smoky coal use. Haplotype analyses were conducted for selected genes with two or more SNPs using the haplo.stat package, which uses an expectation-maximization algorithm to estimate haplotypes from genotype data. A global test of association for 42 SNPs, which excluded eight SNPs that were in very tight linkage disequilibrium with other SNPs, was statistically significant (P=0.01), suggesting that overall genetic variation in this pathway contributes to lung cancer risk. In addition, the IL1B -1060TT (i.e., -511TT) genotype was associated with increased lung cancer risk compared to the CC genotype (OR=2.27, 95% CI=1.05-4.91). The IL8RA Ex2+860GC or CC (OR=0.27, 95% CI=0.11-0.67), ICAM1 Ex2+31 AT or TT (OR=0.39, 95% CI=0.18-0.88), and IL12A Ex+227 GA or AA (OR=0.43, 95% CI=0.22-0.84)genotypes were significantly associated with decreased lung cancer risk. The protective effect of the IL8RA variant was predominant among subjects with high cumulative smoky coal use (≥130 tons) (OR=0.11, 95% CI=0.03-0.44; Pinteraction=0.03). Haplotype analysis did not reveal associations beyond what was apparent in the single SNP analyses. In conclusion, genetic variation in immunoregulatory genes may play an important role in the development of lung cancer in this population. These findings should be replicated in other populations exposed to indoor fuel combustion products, and extended by analysis of other genetic variants in the inflammatory pathway.

Background In South Korea, a cluster of acute lung disease patients included lung injury disease suspected of being caused by the use of humidifier disinfectants. We examined the relationship between humidifier disinfectant exposure and clinically diagnosed humidifier disinfectant-associated lung injury (HDLI) in a family-based study. Methods This case-control study included 169 clinically confirmed HDLI cases and 303 family controls who lived with the HDLI patients. A range of information on exposure to humidifier disinfectants was obtained using a structured questionnaire and field investigations. Odds ratios (ORs) and confidence intervals (CIs) were estimated using unconditional logistic regression models that were adjusted for age, sex, presence of a factory within 1 km of residence, and the number of household chemical products used. Results HDLI risk increased approximately two-fold or more among the highest quartile compared with the lowest quartile in terms of the hours sleeping in a room with an operating humidifier treated with disinfectant (adjusted OR = 2.0, 95 % CI = 1.1-3.7), average hours of disinfectant-treated humidifier use per day (adjusted OR = 2.1, 95 % CI = 1.0-4.5), airborne disinfectant intensity (adjusted OR = 2.6, 95% CI = 1.2-5.3), and cumulative disinfectant inhalation level (adjusted OR = 2.0, 95% CI = 1.0-4.1). HDLI risk increased as the distance of the bed from humidifier gets shorter; compared with longer distance (> 1 m), the odds ratio was 2.7 for 0.5 to 1 m (95 % CI = 1.5-5.1) and 13.2 for

Leaded gasoline has been one of the main causes of environmental exposure to lead worldwide. In Korea, leaded gasoline began to be banned since 1987 and no more leaded gasoline was sold since 1993....

Some immunological biomarkers have been reported to be associated with job-related stress. This study was conducted to explore the intercorrelation between the psychosocial components of job stress and various immunological biomarkers among female nurses. To assess monthly and weekly job stress, 41 nurses have repeatedly completed questionnaires such as the National Institute for Occupational Safety and Health General Job Stress Questionnaire, the profile of mood states short version and the Center for Epidemiologic Studies-Depression scale. Using flow cytometry and radioimmunoassay, the number of white blood cells, lymphocytic proliferation to mitogens, and toxoid were measured. Moreover, levels of hydrocortisol, interleukin-β, interferon-γ, and tumor necrosis factor-α and salivary immunoglobulin A were evaluated by enzyme-linked immunosorbent assay. When the Pearson correlation coefficients between job stress and immunological biomarkers were estimated after adjusting for age and smoking status, “Clashes: conflict at work” was significantly related to the number of CD4 cells (r = 0.36, p-value