A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants in Relation to Risk of Type 1 Diabetes

Background

The incidence of type 1 diabetes in Europe is increasing at a rate of about 3% per year and there is also an increasing incidence throughout the world. Type 1 diabetes is a complex disease caused by multiple genetic and environmental factors. Persistent organochlorine pollutants (POPs) have been suggested as a triggering factor for developing childhood type 1 diabetes. The aim of this case-control study was to assess possible impacts of in utero exposure to POPs on type 1 diabetes.

Methodology/ Principal Findings

The study was performed as a case-control study within a biobank in Malmö, a city located in the Southern part of Sweden. The study included 150 cases (children who had their diagnosis mostly before 18 years of age) and 150 controls, matched for gender and day of birth. 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153) and the major DDT metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p′-DDE) were used as a biomarkers for POP exposure. When comparing the quartile with the highest maternal serum concentrations of PCB-153 with the other quartiles, an odds ratio (OR) of 0.73 (95% confidence interval [CI] 0.42, 1.27) was obtained. Similar results was obtained for p,p′-DDE (OR 0.56, 95% CI 0.29, 1.08).

Conclusions

The hypothesis that in utero exposure to POPs will trigger the risk for developing type 1 diabetes was not supported by the results. The risk estimates did, although not statistically significant, go in the opposite direction. However, it is not reasonable to believe that exposure to POPs should protect against type 1 diabetes.     

Exposure to p,p′-DDE: A Risk Factor for Type 2 Diabetes

Background

Persistent organic pollutants (POPs), such as PCBs, DDT and dioxins have in several cross-sectional studies shown strong associations with type 2 diabetes mellitus. Reversed causality can however not be excluded. The aim of this case-control study was to evaluate whether POPs concentration is a risk factor for type 2 diabetes.

Methodology/Principal Findings

A case-control study was performed within a well-defined cohort of women, age 50–59 years, from the Southern part of Sweden. Biomarkers for POP exposure, 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p′-DDE) were analyzed in stored serum samples, which were collected at the baseline examination when the cohort was established. For 107 out of the 371 cases, serum samples were stored at least three years before their type 2 diabetes was diagnosed. In this data set, CB-153 and p,p′-DDE were not associated with an increased risk to develop type 2 diabetes. However, when only the cases (n = 39) that were diagnosed more than six years after the baseline examination and their controls were studied, the women in the highest exposed quartile showed an increased risk to develop type 2 diabetes (OR of 1.6 [95% 0.61, 4.0] for CB-153 and 5.5 [95% CI 1.2, 25] for p,p′-DDE).

Conclusions/Significance

The results from the present case-control study, including a follow-up design, confirms that p,p′-DDE exposure can be a risk factor for type 2 diabetes.     

Exposure to Organochlorine Pollutants and Type 2 Diabetes: A Systematic Review and Meta-Analysis

Objective

Though exposure to organochlorine pollutants (OCPs) is considered a risk factor for type 2 diabetes (T2DM), epidemiological evidence for the association remains controversial. A systematic review and meta-analysis was applied to quantitatively evaluate the association between exposure to OCPs and incidence of T2DM and pool the inconsistent evidence.

Design and Methods

Publications in English were searched in MEDLINE and WEB OF SCIENCE databases and related reference lists up to August 2013. Quantitative estimates and information regarding study characteristics were extracted from 23 original studies. Quality assessments of external validity, bias, exposure measurement and confounding were performed, and subgroup analyses were conducted to examine the heterogeneity sources.

Results

We retrieved 23 eligible articles to conduct this meta-analysis. OR (odds ratio) or RR (risk ratio) estimates in each subgroup were discussed, and the strong associations were observed in PCB-153 (OR, 1.52; 95% CI, 1.19–1.94), PCBs (OR, 2.14; 95% CI, 1.53–2.99), and p,p′-DDE (OR, 1.33; 95% CI, 1.15–1.54) based on a random-effects model.

Conclusions

This meta-analysis provides quantitative evidence supporting the conclusion that exposure to organochlorine pollutants is associated with an increased risk of incidence of T2DM.     

Levels of Polychlorinated Biphenyls (PCBs) and Three Organochlorine Pesticides in Fish from the Aleutian Islands of Alaska

Background

Persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs) and chlorinated pesticides, have been shown to have many adverse human health effects. These contaminants therefore may pose a risk to Alaska Natives that follow a traditional diet high in marine mammals and fish, in which POPs bioaccumulate.

Methods and Findings

This study examined the levels of PCBs and three pesticides [p, p′-DDE, mirex, and hexachlorobenzene (HCB)] in muscle tissue from nine fish species from several locations around the Aleutian Islands of Alaska. The highest median PCB level was found in rock sole (Lepidopsetta bilineata, 285 ppb, wet weight), while the lowest level was found in rock greenling (Hexagrammos lagocephalus, 104 ppb, wet weight). Lipid adjusted PCB values were also calculated and significant interspecies differences were found. Again, rock sole had the highest level (68,536 ppb, lipid weight). Concerning the PCB congener patterns, the more highly chlorinated congeners were most common as would be expected due to their greater persistence. Among the pesticides, p, p′-DDE generally dominated, and the highest level was found in sockeye salmon (Oncorhynchus nerka, 6.9 ppb, wet weight). The methodology developed by U.S. Environmental Protection Agency (USEPA) was used to calculate risk-based consumption limits for the analyzed fish species. For cancer health endpoints for PCBs, all species would trigger strict advisories of between two and six meals per year, depending upon species. For noncancer effects by PCBs, advisories of between seven and twenty-two meals per year were triggered. None of the pesticides triggered consumption limits.

Conclusion

The fish analyzed, mainly from Adak, contain significant concentrations of POPs, in particular PCBs, which raises the question whether these fish are safe to eat, particularly for sensitive populations. However when assessing any risk of the traditional diet, one must also consider the many health and cultural benefits from eating fish.     

The Prognostic Value of Plasma Soluble ST2 in Hospitalized Chinese Patients with Heart Failure

Background

sST2 has been shown to be a risk predictor in heart failure (HF). Our aim was to explore the characteristics and prognostic value of soluble ST2 (sST2) in hospitalized Chinese patients with HF.

Methods and Results

We consecutively enrolled 1528 hospitalized patients with HF. Receiver operating characteristic (ROC) and multivariable Cox proportional hazards analysis were used to assess the prognostic values of sST2. Adverse events were defined as all-cause death and cardiac transplantation. During a median follow-up of 19.1 months, 325 patients experienced adverse events. Compared with patients free of events, sST2 concentrations were significantly higher in patients with events (P<0.001). Univariable and multivariable Cox regression analyses showed sST2 concentrations were significantly associated with adverse events (per 1 log unit, adjusted hazard ratio 1.52, 95% confidence interval: 1.30 to 1.78, P<0.001). An sST2 concentration in the highest quartiles (>55.6 ng/mL) independently predicted events in comparison to the lowest quartile (≤25.2 ng/mL) when adjusted by multivariable model. In ROC analysis, the area under the curve for sST2 was not different from that for NT-proBNP in short and longer term. Over time, sST2 also improved discrimination and reclassification of risk beyond NT-proBNP.

Conclusions

sST2 is a strong independent risk predictor in Chinese patients hospitalized with HF and can significantly provide additional prognostic value to NT-proBNP in risk prediction.     

Urinary Triclosan is Associated with Elevated Body Mass Index in NHANES

Background

Triclosan—a ubiquitous chemical in toothpastes, soaps, and household cleaning supplies—has the potential to alter both gut microbiota and endocrine function and thereby affect body weight.

Methods

We investigated the relationship between triclosan and body mass index (BMI) using National Health and Nutrition Examination Surveys (NHANES) from 2003–2008. BMI and spot urinary triclosan levels were obtained from adults. Using two different exposure measures—either presence vs. absence or quartiles of triclosan—we assessed the association between triclosan and BMI. We also screened all NHANES serum and urine biomarkers to identify correlated factors that might confound observed associations.

Results

Compared with undetectable triclosan, a detectable level was associated with a 0.9-point increase in BMI (p<0.001). In analysis by quartile, compared to the lowest quartile, the 2nd, 3rd and 4th quartiles of urinary triclosan were associated with BMI increases of 1.5 (p<0.001), 1.0 (p = 0.002), and 0.3 (p = 0.33) respectively. The one strong correlate of triclosan identified in NHANES was its metabolite, 2,4-dichlorophenol (ρ = 0.4); its association with BMI, however, was weaker than that of triclosan. No other likely confounder was identified.

Conclusions

Triclosan exposure is associated with increased BMI. Stronger effect at moderate than high levels suggests a complex mechanism of action.     

Minor Hypospadias: The “Tip of the Iceberg” of the Partial Androgen Insensitivity Syndrome

Background

Androgens are critical in male external genital development. Alterations in the androgen sensitivity pathway have been identified in severely undermasculinized boys, and mutations of the androgen receptor gene (AR) are usually found in partial or complete androgen insensitivity syndrome (AIS).

Objective

The aim of this study was to determine whether even the most minor forms of isolated hypospadias are associated with AR mutations and thus whether all types of hypospadias warrant molecular analysis of the AR.

Materials and Methods

Two hundred and ninety-two Caucasian children presenting with isolated hypospadias without micropenis or cryptorchidism and 345 controls were included prospectively. Mutational analysis of the AR through direct sequencing (exons 1–8) was performed. In silico and luciferase functional assays were performed for unreported variants.

Results

Five missense mutations of the AR were identified in 9 patients with glandular or penile anterior (n = 5), penile midshaft (n = 2) and penile posterior (n = 2) hypospadias, i.e., 3%: p.Q58L (c.173A>T), 4 cases of p.P392S (c.1174C>T), 2 cases of p.A475V (c.1424C>T), p.D551H (c.1651G>C) and p.Q799E (c.2395C>G). None of these mutations was present in the control group. One mutation has never been reported to date (p.D551H). It was predicted to be damaging based on 6 in silico models, and in vitro functional studies confirmed the lowered transactivation function of the mutated protein. Three mutations have never been reported in patients with genital malformation but only in isolated infertility: p.Q58L, p.P392S, and p.A475V. It is notable that micropenis, a cardinal sign of AIS, was not present in any patient.

Conclusion

AR mutations may play a role in the cause of isolated hypospadias, even in the most minor forms. Identification of this underlying genetic alteration may be important for proper diagnosis and longer follow-up is necessary to find out if the mutations cause differences in sexual function and fertility later in life.     

Association between Irrigation Fluids,Washout Volumes and Risk of Local Recurrence of Anterior Resection for Rectal Cancer: A Meta-Analysis of 427 Cases and 492 Controls

Background

Rectal washout can prevent local recurrence after anterior resection of rectal cancer. Few studies have focused particularly on the association between irrigation fluids volume or agents and the risk of local recurrence after anterior resection of rectal cancer.

Objective

To estimate the association between irrigation fluids types, volumes of rectal washout and risk of local recurrence after anterior resection for cancer.

Data Sources

Relevant studies were identified by a search of Medline, Embase, Wiley Online Library, China National Knowledge Infrastructure, Cochrane Oral Health Group Specialized Register, Wanfang databases and Google Website from their inception until October 18,2013.

Study Selection

Studies reporting the association between rectal washout types and volumes and risk of local recurrence after anterior resection for cancer were included.

Interventions

Eligible studies used rectal washout. Control groups were defined as no washout.

Study Appraisal and Synthesis Methods

Random-effects model were used to obtain summary estimates of RR and 95% CI, with Stata version 11 and RevMan 5.2.5 softwares used. The quality of report was appraised in reference to the MINORS item.

Results

Of the 919 rectal cancer patients in 8 included studies, a total of 61(6.64%) cases of local recurrence were reported, with a pooled RR 0.51 (95%CI = 0.28–0.92, P = 0.03). The RRs 0.37 and 0.39 in normal saline and washout volume (≥1500 ml normal saline) subgroup, respectively, indicated that rectal washout with normal saline, or ≥1500 ml in volume could significantly reduce local recurrence (LR) rate (95% CI = 0.17–0.79, P = 0.01; 95% CI = 0.18–0.87, P = 0.02) after anterior resection for cancer.

Limitation

The included studies were non-randomized observational studies, with diversity of study designs.

Conclusion

Rectal washout with normal saline alone can reduce the risk of local recurrence in patients with resectable rectal cancer, and 1.5 liters rectal washout in volume is recommended.     

Association between Soluble (Pro)Renin Receptor Concentration in Cord Blood and Small for Gestational Age Birth: A Cross-Sectional Study

Objective

The (pro)renin receptor [(P)RR] has been recognized as a multifunctional receptor. The purpose of this study was to assess the association between plasma soluble (P)RR [s(P)RR] concentration in human cord blood (i.e., neonatal blood at birth) and small for gestational age (SGA) birth.

Methods

Participants were women with a singleton pregnancy who delivered at the National Center for Child Health and Development between January 2010 and December 2011. Inclusion criteria were availability of maternal pre-pregnancy and paternal body mass index, and the absence of structural anomalies in neonates. s(P)RR concentration in cord blood was measured in 621 neonates. The 621 pairs of mothers and neonates were categorized into four groups based on quartiles of s(P)RR concentrations in cord blood. SGA was defined as a birth weight below the 10^th percentile for gestational age. Logistic regression analysis was performed to assess the association between cord plasma s(P)RR concentration (quartiles) and incidence of SGA births.

Results

Among 621 neonates, 55 (8.9%) were diagnosed as SGA (SGA group) and 566 (91.1%) were not (non-SGA group). Average s(P)RR concentration in cord blood was 66.1±12.6 ng/ml (mean±standard deviation). There were 155 pairs in the first plasma s(P)RR concentration quartile (Q1: <58.2 ng/ml), 153 pairs in the second quartile (Q2: 58.2–65.1 ng/ml), 157 pairs in the third quartile (Q3: 65.1–73.1 ng/ml) and 156 pairs in the fourth quartile (Q4: >73.1 ng/ml). The distribution of SGA births was 18 (11.6%) in Q1, 14 (9.2%) in Q2, 16 (10.2%) in Q3 and 7 (4.5%) in Q4, respectively. The odds ratio of SGA births was 0.24 (95% confidence interval: 0.08–0.71) for the fourth quartile compared to the first quartile in multivariate models. The P-value for trend was also significant (P = 0.020).

Conclusion

High s(P)RR concentration is associated with a lower SGA birth likelihood.     

A Prospective Study of LINE-1DNA Methylation and Development of Adiposity in School-Age Children

Background

Repetitive element DNA methylation is related to prominent obesity-related chronic diseases including cancer and cardiovascular disease; yet, little is known of its relation with weight status. We examined associations of LINE-1 DNA methylation with changes in adiposity and linear growth in a longitudinal study of school-age children from Bogotá, Colombia.

Methods

We quantified methylation of LINE-1 elements from peripheral leukocytes of 553 children aged 5–12 years at baseline using pyrosequencing technology. Anthropometric characteristics were measured periodically for a median of 30 months. We estimated mean change in three age-and sex-standardized indicators of adiposity: body mass index (BMI)-for-age Z-score, waist circumference Z-score, and subscapular-to-triceps skinfold thickness ratio Z-score according to quartiles of LINE-1 methylation using mixed effects regression models. We also examined associations with height-for-age Z-score.

Results

There were non-linear, inverse relations of LINE-1 methylation with BMI-for-age Z-score and the skinfold thickness ratio Z-score. After adjustment for baseline age and socioeconomic status, boys in the lowest quartile of LINE-1 methylation experienced annual gains in BMI-for-age Z-score and skinfold thickness ratio Z-score that were 0.06 Z/year (P = 0.04) and 0.07 Z/year (P = 0.03), respectively, higher than those in the upper three quartiles. The relation of LINE-1 methylation and annual change in waist circumference followed a decreasing monotonic trend across the four quartiles (P trend = 0.02). DNA methylation was not related to any of the adiposity indicators in girls. There were no associations between LINE-1 methylation and linear growth in either sex.

Conclusions

Lower LINE-1 DNA methylation is related to development of adiposity in boys.     

Prospective Association between Dietary Fiber Intake and Breast Cancer Risk

Background

Mechanistic hypotheses suggest a potential effect of dietary fiber on breast carcinogenesis through the modulation of insulin-like growth factor bioactivity, estrogen metabolism and inflammation. An association between dietary fiber intake and breast cancer risk has been suggested in epidemiological studies but remains inconclusive. In particular, data is lacking regarding the different types of dietary fibers.

Objective

The objective was to investigate the prospective relationship between dietary fiber intake and breast cancer risk, taking into account different types of dietary fiber (overall, insoluble, soluble and from different food sources: cereals, vegetables, fruits and legumes).

Design

4684 women from the SU.VI.MAX cohort were included in this analysis as they completed at least three 24h-dietary records within the first two years of follow-up. Among them, 167 incident invasive breast cancers were diagnosed during a median follow-up of 12.6 years (between 1994 and 2007). The associations between quartiles of dietary fiber intake and breast cancer risk were characterized using multivariate Cox proportional hazards models.

Results

Total fiber intake was not associated with breast cancer risk (HR_{Quartile4vs.Quartile1} = 1.29 (95%CI 0.66–2.50), P-trend = 0.5), nor was fiber intake from cereals (P-trend = 0.1), fruits (P-trend = 0.9) and legumes (P-trend = 0.3). In contrast, vegetable fiber intake was related to a decreased risk of breast cancer (HR_Q4vs.Q1 = 0.50 (0.29-0.88), P-trend = 0.03). Overall vegetable intake (in g/day) was not associated with breast cancer risk (P-trend = 0.2).

Conclusion

This prospective study suggests that vegetable fiber intake may contribute to reduce breast cancer risk, in line with experimental mechanistic data.     

Association of the Estimated 24-H Urinary Sodium Excretion with Albuminuria in Adult Koreans: The 2011 Korea National Health and Nutrition Examination Survey

Background

Sodium intake and albuminuria have important roles in blood pressure and renal progression. Although their relationship has been reported, the results have not been consistent and all studies have examined small populations.

Objective

This study investigated the role of the estimated 24-h urinary sodium excretion as a marker of sodium intake and albuminuria.

Design

This investigation included 5,187 individuals age 19 years and older from a cross-sectional, nationally representative, stratified survey: The Korea National Health and Nutrition Examination Survey (KNHANES V-2), in 2011. Albuminuria was defined as a urinary albumin/creatinine ratio ≥30 mg/g. The 24-h urinary sodium excretion was estimated from a spot urine.

Results

On classifying our participants into quartiles based on the estimated 24-h urinary sodium excretion, the prevalence of albuminuria increased with the 24-h urinary sodium excretion (5.3, 5.7, 7.5, and 11.8% in the first through fourth quartiles, respectively, p for trend <0.001). Even after adjusting for age, sex, diabetes, obesity, and hypertension, the significance persisted. In a multiple logistic regression analysis, the second and third quartiles of the estimated 24-h urinary sodium excretion were not associated with the presence of albuminuria with the first quartile as a control. However, the fourth quartile was significantly associated with the presence of albuminuria (odds ratio 1.61 [95% confidence interval 1.71–2.21], p = 0.003) after adjusting for age, sex, diabetes, obesity, and hypertension.

Conclusions

These findings suggest that salt intake is associated with the presence of albuminuria in the general Korean adult population.     

Effect of Prophylactic Low Level Laser Therapy on Oral Mucositis: A Systematic Review and Meta-Analysis

Background

Objective was to determine whether prophylactic low level laser therapy (LLLT) reduces the risk of severe mucositis as compared to placebo or no therapy.

Methods

MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched until February 2014 for randomized controlled trials (RCTs) comparing prophylactic LLLT with placebo or no therapy in patients with cancer or undergoing hematopoietic stem cell transplantation (HSCT). All analyses used random effects models.

Results

Eighteen RCTs (1144 patients) were included. Prophylactic LLLT reduced the overall risk of severe mucositis (risk ratio (RR) 0.37, 95% confidence interval (CI) 0.20 to 0.67; P = 0.001). LLLT also reduced the following outcomes when compared to placebo/no therapy: severe mucositis at the time of anticipated maximal mucositis (RR 0.34, 95% CI 0.20 to 0.59), overall mean grade of mucositis (standardized mean difference −1.49, 95% CI −2.02 to −0.95), duration of severe mucositis (weighted mean difference −5.32, 95% CI −9.45 to −1.19) and incidence of severe pain (RR 0.26, 95% CI 0.18 to 0.37).

Conclusion

Prophylactic LLLT reduced severe mucositis and pain in patients with cancer and HSCT recipients. Future research should identify the optimal characteristics of LLLT and determine feasibility in the clinical setting.     

Risk of Primary Liver Cancer Associated with Gallstones and Cholecystectomy: A Meta-Analysis

Background

Recent epidemiological evidence points to an association between gallstones or cholecystectomy and the incidence risk of liver cancer, but the results are inconsistent. We present a meta-analysis of observational studies to explore this association.

Methods

We identified studies by a literature search of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and relevant conference proceedings up to March 2014. A random-effects model was used to generate pooled multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Between-study heterogeneity was assessed using Cochran’s Q statistic and the I².

Results

Fifteen studies (five case-control and 10 cohort studies) were included in this analysis. There were 4,487,662 subjects in total, 17,945 diagnoses of liver cancer, 328,420 exposed to gallstones, and 884,507 exposed to cholecystectomy. Pooled results indicated a significant increased risk of liver cancer in patients with a history of gallstones (OR = 2.54; 95% CI, 1.71–3.79; n = 11 studies), as well as cholecystectomy (OR = 1.62; 95% CI, 1.29–2.02; n = 12 studies), but there was considerable heterogeneity among these studies. The effects estimates did not vary markedly when stratified by gender, study design, study region, and study quality. The multivariate meta-regression analysis suggested that study region and study quality appeared to explain the heterogeneity observed in the cholecystectomy analysis.

Conclusions

Our results suggest that individuals with a history of gallstones and cholecystectomy may have an increased risk of liver cancer.     

Residential Dampness and Molds and the Risk of Developing Asthma: A Systematic Review and Meta-Analysis

Context

Studies from different geographical regions have assessed the relations between indoor dampness and mold problems and the risk of asthma, but the evidence has been inconclusive.

Objective

To assess the relations between indicators of indoor dampness and mold problems and the risk of developing new asthma, and to investigate whether such relations differ according to the type of exposure.

Data sources

A systematic literature search of PubMed database from 1990 through March 2012 and the reference lists of recent reviews and of relevant articles identified in our search.

Study selection

Cohort/longitudinal and incident case-control studies assessing the relation between mold/dampness and new asthma were included.

Data extraction

Three authors independently evaluated eligible articles and extracted relevant information using a structured form.

Synthesis

Sixteen studies were included: 11 cohort and 5 incident case-control studies. The summary effect estimates (EE) based on the highest and lowest estimates for the relation between any exposure and onset of asthma were 1.50 (95% confidence interval [CI] 1.25–1.80, random-effects model, Q-statistic 38.74 (16), P = 0.001) and 1.31 (95% CI 1.09–1.58, random-effects model, Q-statistic 40.08 (16), P = 0.000), respectively. The summary effect estimates were significantly elevated for dampness (fixed-effects model: EE 1.33, 95% CI 1.12–1.56, Q-statistic 8.22 (9), P = 0.413), visible mold (random-effects model; EE 1.29, 95% CI 1.04–1.60, 30.30 (12), P = 0.001), and mold odor (random-effects model; EE 1.73, 95% CI 1.19–2.50, Q-statistics 14.85 (8), P = 0.038), but not for water damage (fixed-effects model; EE 1.12, 95% CI 0.98–1.27). Heterogeneity was observed in the study-specific effect estimates.

Conclusion

The evidence indicates that dampness and molds in the home are determinants of developing asthma. The association of the presence of visible mold and especially mold odor to the risk of asthma points towards mold-related causal agents.     

Contribution of Risk Factors to Extremely,Very and Moderately Preterm Births – Register-Based Analysis of 1,390,742 Singleton Births

Background

Preterm birth, defined as birth occurring before 37 weeks gestation, is one of the most significant contributors to neonatal mortality and morbidity, with long-term adverse consequences for health, and cognitive outcome.

Objective

The aim of the present study was to identify risk factors of preterm birth (≤36+6 weeks gestation) among singleton births and to quantify the contribution of risk factors to socioeconomic disparities in preterm birth.

Methods

A retrospective population–based case-control study using data derived from the Finnish Medical Birth Register. A total population of singleton births in Finland from 1987−2010 (n = 1,390,742) was reviewed.

Results

Among all singleton births (n = 1,390,742), 4.6% (n = 63,340) were preterm (<37 weeks), of which 0.3% (n = 4,452) were classed as extremely preterm, 0.4% (n = 6,213) very preterm and 3.8% (n = 54,177) moderately preterm. Smoking alone explained up to 33% of the variation in extremely, very and moderately preterm birth incidence between high and the low socioeconomic status (SES) groups. Reproductive risk factors (placental abruption, placenta previa, major congenital anomaly, amniocentesis, chorionic villus biopsy, anemia, stillbirth, small for gestational age (SGA) and fetal sex) altogether explained 7.7−25.0% of the variation in preterm birth between SES groups.

Conclusions

Smoking explained about one third of the variation in preterm birth groups between SES groups whereas the contribution of reproductive risk factors including placental abruption, placenta previa, major congenital anomaly, amniocentesis, chorionic villus biopsy, anemia, stillbirth, SGA and fetal sex was up to one fourth.     

Telomere Length and the Risk of Cutaneous Malignant Melanoma in Melanoma-Prone Families with and without CDKN2A Mutations

Introduction

Recent evidence suggests a link between constitutional telomere length (TL) and cancer risk. Previous studies have suggested that longer telomeres were associated with an increased risk of melanoma and larger size and number of nevi. The goal of this study was to examine whether TL modified the risk of melanoma in melanoma-prone families with and without CDKN2A germline mutations.

Materials and Methods

We measured TL in blood DNA in 119 cutaneous malignant melanoma (CMM) cases and 208 unaffected individuals. We also genotyped 13 tagging SNPs in TERT.

Results

We found that longer telomeres were associated with an increased risk of CMM (adjusted OR = 2.81, 95% CI = 1.02–7.72, P = 0.04). The association of longer TL with CMM risk was seen in CDKN2A- cases but not in CDKN2A+ cases. Among CMM cases, the presence of solar injury was associated with shorter telomeres (P = 0.002). One SNP in TERT, rs2735940, was significantly associated with TL (P = 0.002) after Bonferroni correction.

Discussion

Our findings suggest that TL regulation could be variable by CDKN2A mutation status, sun exposure, and pigmentation phenotype. Therefore, TL measurement alone may not be a good marker for predicting CMM risk.     

Association between Blood Cadmium Levels and 10-Year Coronary Heart Disease Risk in the General Korean Population: The Korean National Health and Nutrition Examination Survey 2008–2010

Background

Non-occupational heavy metals are considered risk factors for coronary heart disease (CHD). Several recent epidemiologic studies have evaluated the relationship between non-occupational cadmium exposure and risk factors for cardiovascular disease (CVD). This study was designed to investigate the relationship between non-occupational cadmium exposure and risk factors for CHD using the Framingham estimate of 10 year CHD risk.

Methods

The heavy metal dataset of the Korean National Health and Nutrition Examination Survey for 2008 through 2010, a cross-sectional survey of a representative sample of 4,668 non-institutionalized Koreans, was analyzed. Subjects were stratified into seven age groups to minimize the effects of age. The log-transformed blood cadmium concentrations were compared with the Framingham estimate of 10 year CHD risk in each age stratum.

Results

The Framingham estimate of 10 year CHD risk was significantly associated with the log-transformed blood cadmium concentrations (p<0.05) in all age groups of Korean men, with the lowest regression coefficient (0.254) for men aged 20 to <35 years and the highest (3.354) for men aged 55 to <60 years; similar results, however, were not observed in Korean women. After adjusting for survey year, age, and urinary cotinine concentration, the log-transformed blood cadmium levels among men aged 20 to <35, 40 to <45, 50 to <55, and 60 to <65 years were significantly associated with systolic blood pressure (p<0.05), but not with total and high density lipoprotein (HDL) cholesterol concentrations.

Conclusions

Cadmium exposure, even at non-occupational levels, may be associated with CHD risk in men. Despite the declines in non-occupational cadmium exposure over the past several decades, more efforts are needed.     

Passive Smoking Exposure from Partners as a Risk Factor for ER+/PR+ Double Positive Breast Cancer in Never-Smoking Chinese Urban Women: A Hospital-Based Matched Case Control Study

Background

The relationship between passive smoking exposure (PSE) and breast cancer risk is of major interest.

Objective

To evaluate the relationship between PSE from partners and breast cancer risk stratified by hormone-receptor (HR) status in Chinese urban women population.

Design

Hospital-based matched case control study.

Setting

Chinese urban breast cancer patients without current or previous active smoking history in China Medical University 1st Hospital, Liaoning Province, China between Jan 2009 and Nov 2009.

Patients

Each breast cancer patient was matched 1∶1 with healthy controls by gender and age (±2 years) from the same hospital.

Measurements

The authors used unconditional logistic regression analyses to estimate odds ratio for women with PSE from partners and breast cancer risk.

Results

312 pairs were included in the study. Women who endured PSE had significantly increased risk of breast cancer (adjusted OR: 1.46; 95% CI: 1.05–2.03; P = 0.027), comparing with unexposed women. Women who exposed to >5 cigarettes/day also had significant increased risk (adjusted OR: 1.99; 95% CI: 1.28–3.10; P = 0.002), as were women exposed to passive smoke for 16–25 years (adjusted OR: 1.87 95% CI: 1.22–2.86; P = 0.004), and those exposed to > 4 pack-years (adjusted OR: 1.71 95% CI: 1.17–2.50; P = 0.004). Similar trends were significant for estrogen receptor (ER)/progesterone receptor (PR) double positive subgroup(adjusted OR: 1.71; 2.20; 1.99; 1.92, respectively), but not for ER+/PR−, ER−/PR+, or ER−/PR− subgroups.

Limitations

limitations of the hospital-based retrospective study, lack of information on entire lifetime PSE and low statistical power.

Conclusions

Our findings provide further evidence that PSE from partners contributes to increased risk of breast cancer, especially for ER/PR double positive breast cancer, in Chinese urban women.     

Genetic Susceptible Locus in NOTCH2 Interacts with Arsenic in Drinking Water on Risk of Type 2 Diabetes

Background

Chronic exposure to arsenic in drinking water is associated with increased risk of type 2 diabetes mellitus (T2DM) but the underlying molecular mechanism remains unclear.

Objectives

This study evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes associated with diabetes and arsenic exposure in drinking water on the risk of developing T2DM.

Methods

In 2009–2011, we conducted a follow up study of 957 Bangladeshi adults who participated in a case-control study of arsenic-induced skin lesions in 2001–2003. Logistic regression models were used to evaluate the association between 38 SNPs in 18 genes and risk of T2DM measured at follow up. T2DM was defined as having a blood hemoglobin A1C level greater than or equal to 6.5% at follow-up. Arsenic exposure was characterized by drinking water samples collected from participants'' tubewells. False discovery rates were applied in the analysis to control for multiple comparisons.

Results

Median arsenic levels in 2001–2003 were higher among diabetic participants compared with non-diabetic ones (71.6 µg/L vs. 12.5 µg/L, p-value <0.001). Three SNPs in ADAMTS9 were nominally associated with increased risk of T2DM (rs17070905, Odds Ratio (OR)  = 2.30, 95% confidence interval (CI) 1.17–4.50; rs17070967, OR = 2.02, 95%CI 1.00–4.06; rs6766801, OR = 2.33, 95%CI 1.18–4.60), but these associations did not reach the statistical significance after adjusting for multiple comparisons. A significant interaction between arsenic and NOTCH2 (rs699780) was observed which significantly increased the risk of T2DM (p for interaction = 0.003; q-value = 0.021). Further restricted analysis among participants exposed to water arsenic of less than 148 µg/L showed consistent results for interaction between the NOTCH2 variant and arsenic exposure on T2DM (p for interaction  = 0.048; q-value = 0.004).

Conclusions

These findings suggest that genetic variation in NOTCH2 increased susceptibility to T2DM among people exposed to inorganic arsenic. Additionally, genetic variants in ADAMTS9 may increase the risk of T2DM.