Concentrations of blood and urinary arsenic species and their characteristics in general Korean population.

Arsenic (As) exposure has been extensively studied by investigating As species (e.g., inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)) in urine, yet recent research suggests that blood could be a possible biomarker of As exposure. These investigations, however, were conducted on iAs-contaminated areas, and evidence on populations exposed to low levels of iAs is limited. This study aimed to describe the levels and distributions of As species in urine and blood, as well as to estimate methylation efficiency and related factors in the Korean population. Biological samples were obtained by the Korean Ministry of Food and Drug Safety. A total of 2025 urine samples and 598 blood samples were utilized in this study. Six As species were measured using ultra-high-performance liquid chromatography with inductively coupled plasma mass spectrometry (UPLC-ICP-MS): As(V), As(III), MMA, DMA, arsenobetaine (AsB), and arsenocholine (AsC). Multiple linear regression models were used to examine the relationship between As species (concentrations and proportions) and covariates. AsB was the most prevalent species in urine and blood. The relative composition of iAs, MMA, DMA, and AsC in urine and blood differed significantly. Consumption of blue-backed fish was linked to higher levels of AsB in urine and blood. Type of drinking water and multigrain rice consumption were associated with increased iAs concentration in urine. Except for iAs, every species had correlations in urine and blood in both univariate and multivariate analyses. Adolescents and smokers presented a lower methylation efficiency (higher %MMA and lower %DMA in urine) and females presented a higher methylation efficiency (lower %iAs, %MMA, and higher %DMA in urine). In conclusion, blood iAs concentration cannot represent urinary iAs; nonetheless, different compositions of urine and blood might reflect distinct information about iAs exposure. Further investigations on exposure factors and health are needed using low-exposure groups.

Joint segmentation and classification of hepatic lesions in ultrasound images using deep learning.

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.

Alterations in immune and renal biomarkers among workers occupationally exposed to low levels of trichloroethylene below current regulatory standards.

OBJECTIVES: The 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. METHODS: We 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 <10 ppm TCE compared with controls. RESULTS: Six 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 <10 ppm compared with the control group. These associations remained noteworthy after taking into account multiple comparisons using the false discovery rate (ie, <0.20). CONCLUSION: Our 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.

Trends and Correlates of High-Risk Alcohol Consumption and Types of Alcoholic Beverages in Middle-Aged Korean Adults: Results From the HEXA-G Study.

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.

Association between occupational exposure to trichloroethylene and serum levels of microRNAs: a cross-sectional molecular epidemiology study in China.

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, < 12 ppm, the median value among workers exposed to TCE) and ≥ 12 ppm)]. Models were adjusted for sex, age, current smoking, current alcohol use, and recent infection. RESULTS: Seven miRNAs showed significant differences between exposed and unexposed workers at FDR (false discovery rate) < 0.20. miR-150-5p and let-7b-5p also showed significant inverse exposure-response associations with TCE exposure (Ptrend= 0.002 and 0.03, respectively). The % differences in serum levels of miR-150-5p relative to unexposed controls were - 13% and - 20% among workers exposed to < 12 ppm and ≥ 12 ppm TCE, respectively. CONCLUSIONS: miR-150-5p is involved in B cell receptor pathways and let-7b-5p plays a role in the innate immune response processes that are potentially important in the etiology of non-Hodgkin lymphoma (NHL). Further studies are needed to replicate these findings and to directly test the association between serum levels of these miRNAs and risk of NHL in prospective studies.

Mortality among diagnostic medical radiation workers in South Korea, 1996-2015.

OBJECTIVES: To evaluate the risk for all-cause and cause-specific mortality in diagnostic medical radiation workers in South Korea. METHODS: The study population included all diagnostic medical radiation workers enrolled in the National Dosimetry Registry (NDR) between 1996 and 2011. NDR data were linked with mortality data obtained from national registries through 2015. Standardised mortality ratios (SMRs) and relative standardised mortality ratios (rSMRs) were calculated for external comparison and for adjustment of the cohort's overall healthiness. RESULTS: A total of 1099 deaths (974 in men and 125 in women) were reported from among 80 837 medical radiation workers. The SMRs for all causes of death were significantly lower than expected in both men (SMR 0.45, 95% CI 0.42 to 0.48) and women (SMR 0.49, 95% CI 0.41 to 0.58). No excesses were observed for any specific cause of death. The findings were similar by job title, calendar year of entry and year of birth. However, relative to all causes of death, mortality from all cancers (rSMR 1.60, 95% CI 1.41 to 1.82), leukaemia, colon cancer, stomach cancer and diseases of the circulatory system increased significantly among male workers. The results for female workers were limited due to small number of deaths; however, the rSMR for all cancers was significantly elevated (rSMR 1.70, 95% CI 1.17 to 2.46). CONCLUSIONS: This cohort showed lower mortality among diagnostic medical radiation workers than in the general population. However, occupational factors may have been involved in the increased relative mortality for several causes of death.

The radiologic technologists' health study in South Korea: study design and baseline results.

PURPOSE: To describe the study design, methods, and baseline results of a prospective cohort of radiologic technologists which we have initiated in South Korea. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Trend of blood lead, mercury, and cadmium levels in Korean population: data analysis of the Korea National Health and Nutrition Examination Survey.

This study was performed to assess the recent trends in lead, mercury, and cadmium levels in the blood among Korean adult population. The geometric means and 95 % confidence intervals (CIs) of blood lead, mercury, and cadmium concentrations were calculated using the data of the subjects from the third (2005, n = 1997), fourth (2008, n = 2005; 2009, n = 1991), and fifth (2010, n = 1989; 2011, n = 2014) Korea National Health and Nutrition Examination Survey. Blood lead levels in 2005, 2008, 2009, 2010, and 2011 declined to 2.61 µg/dL (2.51-2.71), 2.32 µg/dL (2.27-2.37), 2.29 µg/dL (2.23-2.35), 2.09 µg/dL (2.04-2.13), and 1.99 µg/dL (1.94-2.05), respectively. Blood mercury levels were 4.19 µg/L (3.99-4.39), 4.73 µg/L (4.57-4.89), 4.25 µg/L (4.09-4.41), 3.64 µg/L (3.49-3.80), and 3.08 µg/L (2.95-3.22), respectively, which indicated an increase in 2008 compared with those in 2005, and a clear downward trend from 2008 to 2011. Blood cadmium levels were 1.52 µg/L (1.47-1.57), 0.93 µg/L (0.89-0.97), 0.94 µg/L (0.90-0.98), 0.89 µg/L (0.87-0.92), 0.86 µg/L (0.83-0.89), respectively, which indicated very high levels in 2005, but a downward trend since 2008. Although the lead, mercury, and cadmium levels in the blood of the Korean adult population are on the decline, they are still relatively high compared with those for the population of the USA, Canada, and Germany. Thus, continuous biological monitoring and measures to reduce these levels are needed in Korea.

Learning Controllable ISP for Image Enhancement.

We present a plug-and-play Image Signal Processor (ISP) for image enhancement to better produce diverse image styles than the previous works. Our proposed method, ContRollable Image Signal Processor (CRISP), explicitly controls the parameters of the ISP that determine output image styles. ISP parameters for high-quality (HQ) image styles are encoded into low-dimensional latent codes, allowing fast and easy style adjustments. We empirically show that CRISP covers a wide range of image styles with high efficiency. On the MIT-Adobe FiveK dataset, CRISP can very closely estimate the reference styles produced by human experts and achieves better MOS with diverse image styles. Compared with the state-of-the-art method, our ISP comprises only 19 parameters, allowing CRISP to have 2× smaller parameters and 100× reduced FLOPs for an image output. CRISP outperforms previous works in PSNR and FLOPs with several scenarios for style adjustments.

Learning to Learn Task-Adaptive Hyperparameters for Few-Shot Learning.

The objective of few-shot learning is to design a system that can adapt to a given task with only few examples while achieving generalization. Model-agnostic meta-learning (MAML), which has recently gained the popularity for its simplicity and flexibility, learns a good initialization for fast adaptation to a task under few-data regime. However, its performance has been relatively limited especially when novel tasks are different from tasks previously seen during training. In this work, instead of searching for a better initialization, we focus on designing a better fast adaptation process. Consequently, we propose a new task-adaptive weight update rule that greatly enhances the fast adaptation process. Specifically, we introduce a small meta-network that can generate per-step hyperparameters for each given task: learning rate and weight decay coefficients. The experimental results validate that learning a good weight update rule for fast adaptation is the equally important component that has drawn relatively less attention in the recent few-shot learning approaches. Surprisingly, fast adaptation from random initialization with ALFA can already outperform MAML. Furthermore, the proposed weight-update rule is shown to consistently improve the task-adaptation capability of MAML across diverse problem domains: few-shot classification, cross-domain few-shot classification, regression, visual tracking, and video frame interpolation.

FQ-UWF: Unpaired Generative Image Enhancement for Fundus Quality Ultra-Widefield Retinal Images.

Ultra-widefield (UWF) retinal imaging stands as a pivotal modality for detecting major eye diseases such as diabetic retinopathy and retinal detachment. However, UWF exhibits a well-documented limitation in terms of low resolution and artifacts in the macular area, thereby constraining its clinical diagnostic accuracy, particularly for macular diseases like age-related macular degeneration. Conventional supervised super-resolution techniques aim to address this limitation by enhancing the resolution of the macular region through the utilization of meticulously paired and aligned fundus image ground truths. However, obtaining such refined paired ground truths is a formidable challenge. To tackle this issue, we propose an unpaired, degradation-aware, super-resolution technique for enhancing UWF retinal images. Our approach leverages recent advancements in deep learning: specifically, by employing generative adversarial networks and attention mechanisms. Notably, our method excels at enhancing and super-resolving UWF images without relying on paired, clean ground truths. Through extensive experimentation and evaluation, we demonstrate that our approach not only produces visually pleasing results but also establishes state-of-the-art performance in enhancing and super-resolving UWF retinal images. We anticipate that our method will contribute to improving the accuracy of clinical assessments and treatments, ultimately leading to better patient outcomes.

Occupational trichloroethylene exposure and risk of lymphatic and haematopoietic cancers: a meta-analysis.

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.

The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia.

Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10(-7) or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30 x 10(-11)). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38 x 10(-11)). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60 x 10(-20), allelic risk = 1.54, 95% Confidence Interval (CI) 1.41-1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40-1.87), and 2.35 (95% CI: 1.95-2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.

A deep learning-based framework for retinal fundus image enhancement.

PROBLEM: Low-quality fundus images with complex degredation can cause costly re-examinations of patients or inaccurate clinical diagnosis. AIM: This study aims to create an automatic fundus macular image enhancement framework to improve low-quality fundus images and remove complex image degradation. METHOD: We propose a new deep learning-based model that automatically enhances low-quality retinal fundus images that suffer from complex degradation. We collected a dataset, comprising 1068 pairs of high-quality (HQ) and low-quality (LQ) fundus images from the Kangbuk Samsung Hospital's health screening program and ophthalmology department from 2017 to 2019. Then, we used these dataset to develop data augmentation methods to simulate major aspects of retinal image degradation and to propose a customized convolutional neural network (CNN) architecture to enhance LQ images, depending on the nature of the degradation. Peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM), r-value (linear index of fuzziness), and proportion of ungradable fundus photographs before and after the enhancement process are calculated to assess the performance of proposed model. A comparative evaluation is conducted on an external database and four different open-source databases. RESULTS: The results of the evaluation on the external test dataset showed an significant increase in PSNR and SSIM compared with the original LQ images. Moreover, PSNR and SSIM increased by over 4 dB and 0.04, respectively compared with the previous state-of-the-art methods (P < 0.05). The proportion of ungradable fundus photographs decreased from 42.6% to 26.4% (P = 0.012). CONCLUSION: Our enhancement process improves LQ fundus images that suffer from complex degradation significantly. Moreover our customized CNN achieved improved performance over the existing state-of-the-art methods. Overall, our framework can have a clinical impact on reducing re-examinations and improving the accuracy of diagnosis.

A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study.

INTRODUCTION: Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent. METHODS: To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls. RESULTS: In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14). CONCLUSIONS: This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.

Estrogen and progesterone receptor status affect genome-wide DNA methylation profile in breast cancer.

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.

Common genetic polymorphisms of microRNA biogenesis pathway genes and breast cancer survival.

BACKGROUND: Although the role of microRNA's (miRNA's) biogenesis pathway genes in cancer development and progression has been well established, the association between genetic variants of this pathway genes and breast cancer survival is still unknown. METHODS: We used genotype data available from a previously conducted case-control study to investigate association between common genetic variations in miRNA biogenesis pathway genes and breast cancer survival. We investigated the possible associations between 41 germ-line single-nucleotide polymorphisms (SNPs) and both disease free survival (DFS) and overall survival (OS) among 488 breast cancer patients. During the median follow-up of 6.24 years, 90 cases developed disease progression and 48 cases died. RESULTS: Seven SNPs were significantly associated with breast cancer survival. Two SNPs in AGO2 (rs11786030 and rs2292779) and DICER1 rs1057035 were associated with both DFS and OS. Two SNPs in HIWI (rs4759659 and rs11060845) and DGCR8 rs9606250 were associated with DFS, while DROSHA rs874332 and GEMIN4 rs4968104 were associated with only OS. The most significant association was observed in variant allele of AGO2 rs11786030 with 2.62-fold increased risk of disease progression (95% confidence interval (CI), 1.41-4.88) and in minor allele homozygote of AGO2 rs2292779 with 2.94-fold increased risk of death (95% CI, 1.52-5.69). We also found cumulative effects of SNPs on DFS and OS. Compared to the subjects carrying 0 to 2 high-risk genotypes, those carrying 3 or 4-6 high-risk genotypes had an increased risk of disease progression with a hazard ratio of 2.16 (95% CI, 1.18- 3.93) and 4.47 (95% CI, 2.45- 8.14), respectively (P for trend, 6.11E-07). CONCLUSIONS: Our results suggest that genetic variants in miRNA biogenesis pathway genes may be associated with breast cancer survival. Further studies in larger sample size and functional characterizations are warranted to validate these results.

The association between the preoperative serum levels of lipocalin-2 and matrix metalloproteinase-9 (MMP-9) and prognosis of breast cancer.

BACKGROUND: Although a number of experimental studies have suggested the role of lipocalin-2 (LCN2) and matrix metalloproteinase-9 (MMP-9) in breast cancer progression, limited numbers of epidemiological studies have examined the relationship between the levels of lipocalin-2 and MMP-9 and breast cancer survival. METHODS: Preoperative serum levels of lipocalin-2 and MMP-9 were measured in 303 breast cancer patients and 74 healthy controls recruited between 2004 and 2007. We examined the association between lipocalin-2 and MMP-9 levels and disease-free survival (DFS) using Cox proportional hazard regression model. RESULTS: The serum levels of lipocalin-2 and MMP-9 were not significantly different between patients and controls (P > 0.05). Elevated lipocalin-2 and MMP-9 levels were associated with reduced DFS of breast cancer ( Ptrend = 0.029 and Ptrend = 0.063, respectively). When lipocalin-2 and MMP-9 levels were categorized based on the combined risk score, patients with higher levels of both lipocalin-2 and MMP-9 exhibited poor DFS compared to patients with lower levels (Ptrend = 0.004). Furthermore, these effects were profound in patients with BMI less than 25 kg/m2 (adjusted hazard ratio (aHR), 3.17; 95% confidence intervals (CI), 1.66-6.06, Ptrend < 0.001) or lymph-node negative breast cancer (aHR, 5.36; 95% CI, 2.18-13.2, Ptrend < 0.001). CONCLUSIONS: Our study suggests that the elevated levels of lipocalin-2 and MMP-9 are associated with reduced breast cancer survival, particularly in patients with lower BMI and lymph-node negative breast cancers.

Occupational trichloroethylene exposure and kidney cancer risk: a meta-analysis.

OBJECTIVES: Inconsistent epidemiological findings, debate over interpretation, and extrapolation of findings from animal studies to humans have produced uncertainty surrounding the carcinogenicity of trichloroethylene (TCE) exposure in occupational settings. We updated meta-analyses of published case-control and cohort studies exploring occupational TCE exposure and kidney cancer risk, incorporating new analytical results from three recently published cohort studies and a case-control study. METHODS: PubMed MEDLINE was searched for studies published from 1950 to 2011 assessing occupational exposure to chlorinated solvents, degreasers or TCE. All cohort (N=15) and case-control (N=13) studies included in analyses were stratified by assessment of occupational exposure to TCE specifically and to any chlorinated solvent. RESULTS: Significantly elevated summary estimates were observed for cohort studies (relative risk (RR) 1.26, 95% CI 1.02 to 1.56; p heterogeneity=0.65), case-control studies (OR 1.35, 95% CI 1.17 to 1.57; p heterogeneity=0.41), and cohort and case-control studies combined (RR 1.32, 95% CI 1.17 to 1.50, p heterogeneity=0.63) that specifically assessed TCE exposure after excluding outlier studies that contributed to heterogeneity. Non-significantly elevated summary estimates were generally observed for studies of workers exposed to chlorinated solvents but who were not assessed for TCE specifically. CONCLUSIONS: Regardless of study design, significant and stronger estimates were only observed in studies specifically assessing occupational exposure to TCE. Estimates were lower in studies assessing occupational exposure to chlorinated solvents. This updated meta-analysis supports an association between occupational TCE exposure and kidney cancer and provides evidence that exposure misclassification may weaken estimates assessing exposure to the broader class of chlorinated solvents.

DNA methylation in peripheral blood: a potential biomarker for cancer molecular epidemiology.

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.