Remote effects of occupational and non-occupational exposure to electromagnetic fields of power-line frequency. Epidemiological studies

A retrospective cohort study of mortality in the personnel of power-supply plants in the European regions of Russia was carried out. The exposure of the personnel to electromagnetic fields of power-line frequency (PF) was taken into account. Statistically non-significant raise of mortality from leukemia was found, compared to low mortality rates due to all other causes including cancer of any type. Standardized mortality ratio (SMR) was equal to 2.03 (95% CI = 0.23-7.31). In the retrospective case-control study the haemoblastosis development risk under occupational PF EMF exposure was evaluated. The data of 571 "cases" and 1208 "controls" interview showed that odd ratio (OR) was 1.64 (95% CI = 0.8-3.1). In another retrospective case-control study the risk of the haemoblastosis development in children due to parents PF EMF occupational exposure was evaluated. The data of 208 "cases" and 319 "controls" interview showed that the odd ratio (OR) was 1.69 (95% CI = 0.7-3.3). A retrospective cohort study of mortality in a settlement situated near a high-voltage (500 kV) substation, which took into account PF EMF levels in residential areas, revealed low mortality rates, except leukemia mortality (SMR 1.3; 95% CI = 0.2-7.0). The obtained data do not allow excluding a possibility of PF EMF leukogenic effect.     

Occupational exposure to immunologically active agents and risk for lymphoma: The European Epilymph case–control study

ObjectivesAllergies and asthma may be protective for the development of lymphoma. We evaluated whether occupational allergens that provoke immune reactivity and asthma through an IgE-mediated pathway are protective for lymphoma.MethodsThe Epilymph study includes histologically or cytologically confirmed Hodgkin, B-cell, and T-cell lymphoma cases from six European countries (Spain, France, Germany, Italy, Ireland, and Czech Republic) recruited in 1998–2004. Controls were frequency matched to cases by age, gender, and study centre. Lifetime occupational exposure to seven high molecular weight (HMW) agents was evaluated through an asthma-specific job-exposure matrix. 2205 lymphoma cases and 2296 controls with complete occupational history could be included in the analysis. Associations between HMW exposures and lymphoma were evaluated using pooled unconditional logistic regression analyses.ResultsIndividuals exposed to HMW agents had a non-statistically significant decreased risk of any lymphoma (OR, 0.88: 95% CI, 0.74–1.05) and of B-cell lymphoma (OR, 0.91; 95% CI, 0.76–1.09), and a significantly decreased risk for Hodgkin lymphoma (OR, 0.62; 95% CI, 0.40–0.98). A decrease in risk for lymphoma was found for exposure to latex (OR, 0.74; 95% CI, 0.55–0.99).ConclusionsFurther epidemiologic and mechanistic research is needed to confirm that occupational exposure to HMW agents predisposing to asthma can reduce the risk of lymphoma.     

Factors associated with blood zinc,chromium, and lead concentrations in residents of the Nam Pong River in Thailand

This cross-sectional analytical study aimed to determine the blood levels of zinc (B-Zn), chromium (B-Cr), and lead (B-Pb) and to identify the factors influencing these levels in the blood of residents of the Nam Pong River. Quantitative data collection was utilized, and systematic random sampling was conducted to obtain 420 samples for measuring serum heavy metals, including B-Zn, B-Cr, and B-Pb. Multiple regression analysis was used to identify factors influencing the accumulation of heavy metals in the population, reported mean differences, 95% confidence intervals, and p values. The average levels of heavy metals were 74.38 ± 14.00 µg/dL (95% confidence interval [CI]: 73.03–75.72) for zinc, 0.28 ± 0.23 µg/L (95% CI: 0.26–0.30) for chromium, and 2.80 ± 1.60 µg/dL (95% CI: 2.64–2.95) for lead, which all were within normal limits. Factors influencing zinc levels included occupational exposure (batteries) (mean diff = 11.56; 95% CI: 1.81–21.32, p value = 0.02) and consumption of fish from the river exceeding 300 grams/meal or three times/week (mean diff = 4.68; 95% CI: 0.09–9.45, p value = 0.05). Factors influencing chromium levels included a history of past illness (mean diff = 0.19; 95% CI: 0.05–0.34, p value = 0.01) and dust/chemical exposure from industry (mean diff = 0.05; 95% CI: 0.00–0.11, p value = 0.05). Factors influencing lead concentrations included gender (mean diff = 1.82; 95% CI: 0.26–1.98, p value = 0.001), smoking (mean diff = 1.03; 95% CI: 0.60–1.45, p value < 0.001), and occupational exposure (garage) (mean diff = 1.11; 95% CI: 0.27–1.94, p value = 0.01).     

High parental occupational social contact and risk of childhood hematopoietic,brain and bone cancers

BackgroundThe etiology of childhood cancer is largely unknown, though some research suggests an infectious origin of hematopoietic, central nervous system (CNS) and bone cancers.MethodsWe examined parental occupational social contact as a proxy for exposure to infectious agents and risk of childhood cancer. This population-based case-control study utilized a linkage of four Danish data-registries, and included 3581 cases (<17 years, diagnosed 1973–2012) and 358,100 age-matched controls. We examined the risks of leukemia, lymphoma, CNS and bone cancer related to high occupational social contact from (1) conception to birth and (2) birth to diagnosis.ResultsAcute lymphoblastic leukemia (ALL) and bone cancer were inversely associated with high maternal social contact from conception to birth (OR: 0.86, 95% CI: 0.67–1.10) and birth to diagnosis (OR: 0.54, 95% CI: 0.34–0.86). Children of fathers with high social contact from birth to diagnosis had an increased risk of bone cancers, particularly in rural areas (OR: 1.65, 95% CI: 1.03–2.63). Parental social contact was associated with increased risk of astrocytoma, with strongest associations found in first-born children (maternal: OR: 1.54, 95% CI: 1.02–2.32; paternal: OR: 1.82, 95% CI: 1.05–3.17).ConclusionOur results support the notion of a role of infections for some cancer types.     

Occupational exposure to electromagnetic fields. The situation in Greece

PurposeThe management of the occupational exposure to electromagnetic fields (EMF), an Occupational Health and Safety (OHS) issue of great scientific, social and economic significance, was under intense negotiations at European level over the last twenty years; the Directive 2013/35/EU is the new legislative tool. The presented study deals with the practical aspects of the Directive’s implementation.MethodsThe appropriate, extensive measurements and the overall EMF exposure assessments (i.e. exposure mapping, identification of hot spots, proposition of solutions) were conducted in specific workplaces, including power production, railway, broadcasting, clinical Magnetic Resonance Imaging (MRI) systems, industrial and research sites, as well as common office workplaces.ResultsThe vast majority of the performed EMF assessments did not reveal occupational overexposures; moreover in most of the cases, even the general public exposure limits (in the above occupational areas) were not exceeded. The very few localized overexposures detected, were manageable on the basis of the technical and organizational OHS principles.On the contrary, the maintenance procedures of the EMF emitting equipment, as recorded in this survey, presented overexposures revealing a challenging field.ConclusionsThis study lays a firm basis for the clarification of the occupational EMF environment, where potential exposures might be high. The proper risk assessment demands precise exposure identification and deep understanding of the EMF nature and hazards. Misconceptions range from the common exposure overestimation to the rarer case of the maintenance hazards underestimation, while attention is needed concerning the proper application of the complex limiting system of the Directive.     

Occupational exposure to solar ultraviolet B radiation and risk of prostate cancer in Danish men

ObjectivesFormer epidemiological studies have indicated that solar ultraviolet B radiation (UV) may reduce the risk of prostate cancer, however, the evidence is inconclusive. To contribute with evidence, the present study aimed to evaluate the association between occupational UV exposure and prostate cancer in Danish men.MethodsA total of 12,268 men diagnosed with primary prostate cancer before age 70 were identified via the Danish Cancer Registry. The Danish Civil Registration System was used to randomly select five male controls matched on year of birth, alive and free of prostate cancer at the time of diagnosis of the index case. Full individual-level employment history was retrieved from the Danish Supplementary Pension Fund Register and linked to a job exposure matrix to assess occupational UV exposure. Conditional logistic regression was used to estimate odds ratios (ORs) with corresponding 95 % confidence intervals.ResultsWe observed an inverse association between ever exposure to occupational UV and prostate cancer (OR=0.93, 95 % CI: 0.89–0.97). Longer duration of exposure (≥20 years: OR=0.90, 95 % CI: 0.84–0.96) and highest cumulative exposure (OR=0.90, 95 % CI: 0.84–0.96) were both inversely associated with disease risk.ConclusionsThe present study indicates a modest protective effect from occupational UV exposure on the risk of prostate cancer. This finding needs further attention in future large-scale studies.     

Global DNA methylation (LINE-1) associated with exposure to arsenic-contaminated environment and with type of arsenical skin lesions in Thailand

The effects of chronic arsenic exposure mode on DNA methylation and skin lesion type are unclear. These relationships were investigated in an arsenic-contaminated area of southern Thailand. Cases with arsenical skin lesions (n = 131) and lesion-free controls (n = 163) were selected from an arsenic-contaminated sub-district, as well as 105 controls from a non-contaminated area. Type and severity of skin lesions and salivary global DNA methylation (LINE-1) were determined. Arsenic exposure was characterized as occupational, domestic and current (toe-nail arsenic). Associations were explored using logistic regression. Cases and controls had lower LINE-1 methylation and higher toenail arsenic than external controls (74.65% and 74.61% vs 76.05%, p < 0.001 for each). Cases were more likely to have been exposed domestically (OR_total 1.76, 95% ci 1.00, 3.11; and 2.22, 95% ci 1.22, 4.03; P_trend = 0.005 for exposure <36 and ≥36 years). More severe spotty hyperpigmentation was related to higher LINE-1 methylation (P_trend=0.006). LINE-1 methylation was positively associated with toenail arsenic only among non-symptomatic exposed subjects (OR 1.31, 95% ci 1.06, 1.64; p = 0.014). Exposure to an arsenic-contaminated environment results in global DNA hypomethylation. However, among symptomatic subjects, increased global DNA methylation was associated with increased severity of spotty hyperpigmentation.     

Respiratory symptoms and lung function in taxi drivers and manual workers

The aim of this study, was to determine the prevalence of some respiratory symptoms and possible diseases among taxi drivers and manual workers. This prospective study was performed on 165 Pakistani male drivers, (mean age: 34.5±7.8 years) and 165 Pakistani male manual workers not exposed to dust or fumes, without occupational exposure to driving employed in the Water and Electricity Department and recruited as controls (mean age: 34.6±7.6 years and mean height and weight 169.8±6.0 cm and 71.9±10.9 kg). The data on chronic respiratory symptoms showed that taxi drivers had higher prevalence of symptoms than manual workers, being significantly greater for asthma (RR=1.72; 95% CI=1.00–2.88,P=0.037); allergic rhinitis (RR=2.41; 95% CI=1.46–3.94,P=0.0006); dyspnea (RR=2.13; 95% CI=1.22–3.71,P=0.009); and nasal catarrh (RR=2.19; 95% CI=1.22–3.91,P=0.0106). Thirty percent of taxi drivers and 27% of manual workers were smokers, there was no significant differences in the prevalence of chronic respiratory symptoms between smokers and non-smokers. Lung function parameters in the taxi drivers were significantly lower than in manual workers group (P<0.0001) except PEF parameter. When comparing the measured mean values of lung function parameters in the drivers among smokers and nonsmokers, there was no significant differences between smokers and nonsmokers. Also, a comparison of ventilatory capacity of paired predicted values with measured normal values showed statistically significant differences between predicted and measured values for taxi drivers and manual workers for FVC, FEV₁, FEF_25–75 and PEF parameters except for FEV₁/FVC test in manual workers. In conclusion, the results of the present study provide evidence regarding effects of such as carbon monoxide, nitrogen dioxide, sulfur dioxide and gases exposures on taxi drivers and long-term driving, which may be associated with the development of chronic respiratory symptoms and lung function impairment.     

The genetic association between osteoprotegerin gene polymorphisms and fracture risk in Chinese Han population

This article put the genetic association exploration of osteoprotegerin (OPG) gene polymorphisms in promoter region (A-163G, T-245G) and fracture risk first and hoped to explain the ethology of fracture. The genotyping of OPG gene polymorphisms was conducted with the method of polymerase chain reaction-restriction fragment length polymorphism in 125 fracture patients and 138 relative controls. The genotype frequencies of selected controls based on OPG gene polymorphisms were checked by the χ² test whether conformed to Hardy–Weinberg equilibrium (HWE). The relative risk was represented with odds ratio (OR) and 95% confidence interval (95% CI) between gene polymorphism and disease. The linkage disequilibrium (LD) and haplotype were also analyzed. The genotypes distributions of selected controls in OPG polymorphisms conformed to HWE. The G allele of A-163G polymorphism carriers had the tendency to suffer from fracture in the same condition, compared with A allele carriers (OR = 1.63, 95% CI = 1.04–2.55). TG and TG/GG genotypes of OPG T-245G polymorphism also showed the increased risk of fracture development, but not TT genotype (OR = 2.22, 95% CI = 1.15–4.28; OR = 2.45, 95% CI = 1.28–4.68). Likely, the mutant allele G had an abnormally higher frequency in cases than controls (14.00% and 6.16%). These two polymorphisms existed the LD and the haplotype G _-163–G _-245 obviously increased the risk of fracture. OPG A-163G, T-245G polymorphisms were associated with the onset of fracture and both the independent risk factors.     

Physical activity and lung cancer among non-smokers: a pilot molecular epidemiological study within EPIC

The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by ³²P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35–0.90), higher GSH levels (+1.87 μmol GSH g^?1 haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38–2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84–1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.     

LINE1 methylation levels associated with increased bladder cancer risk in pre-diagnostic blood DNA among US (PLCO) and European (ATBC) cohort study participants

Global methylation in blood DNA has been associated with bladder cancer risk in case-control studies, but has not been examined prospectively. We examined the association between LINE1 total percent 5-methylcytosine and bladder cancer risk using pre-diagnostic blood DNA from the United States-based, Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) (299 cases/676 controls), and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) cohort of Finnish male smokers (391 cases/778 controls). Logistic regression adjusted for age at blood draw, study center, pack-years of smoking, and sex was used to estimate odd ratios (ORs) and 95% confidence intervals (CIs) using study- and sex-specific methylation quartiles. In PLCO, higher, although non-significant, bladder cancer risks were observed for participants in the highest three quartiles (Q2–Q4) compared with the lowest quartile (Q1) (OR = 1.36, 95% CI: 0.96 -1.92). The association was stronger in males (Q2–Q4 vs. Q1 OR = 1.48, 95% CI: 1.00–2.20) and statistically significant among male smokers (Q2–Q4 vs. Q1 OR = 1.83, 95% CI: 1.14–2.95). No association was found among females or female smokers. Findings for male smokers were validated in ATBC (Q2–Q4 vs. Q1: OR = 2.31, 95% CI: 1.62–3.30) and a highly significant trend was observed (P = 8.7 × 10^?7). After determining that study data could be combined, pooled analysis of PLCO and ATBC male smokers (580 cases/1119 controls), ORs were significantly higher in Q2-Q4 compared with Q1 (OR = 2.03, 95% CI: 1.52–2.72), and a trend across quartiles was observed (P = 0.0001). These findings suggest that higher global methylation levels prior to diagnosis may increase bladder cancer risk, particularly among male smokers.     

Association study in eating disorders: TPH2 associates with anorexia nervosa and self‐induced vomiting

Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self‐induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71–91% of the common variance in candidate genes, stathmin (STMN1), serotonin receptor 1D (HTR1D), tryptophan hydroxylase 2 (TPH2) and brain‐derived neurotrophic factor (BDNF), with AN and EDs characterized by regular SV. The first allele frequencies of all the SNPs were compared between a Dutch case group (182 AN, 149 EDs characterized by SV) and 607 controls. Associations rendering P‐values < 0.05 from this initial study were then tested for replication in a meta‐analysis with two additional independent ED case–control samples, together providing 887 AN cases, 306 cases with an ED characterized by SV and 1914 controls. A significant effect for the minor C‐allele of tryptophan hydroxylase 2 rs1473473 was observed for both AN [odds ratio (OR) = 1.30, 95% CI 1.08–1.57, P < 0.003] and EDs characterized by SV (OR = 1.52, 95% CI 1.28–2.04, P < 0.006). In the combined case group, a dominant effect was observed for rs1473473 (OR = 1.38, 95% CI 1.16–1.64, P < 0.0003). The meta‐analysis revealed that the tryptophan hydroxylase 2 polymorphism rs1473473 was associated with a higher risk for AN, EDs characterized by SV and for the combined group.     

Systematic analysis of long non-coding RNA and mRNA expression changes in ApoE-deficient mice during atherosclerosis

Hypertension (HT), a common age-related disorder, is an important risk factor for cardiovascular disease. This study aims to identify the prevalence of HT in Portuguese centenarians and evaluate whether gene polymorphisms encoding key molecules in blood pressure (BP) regulation are associated with longevity. There were recruited 253 centenarians (100.26?±?1.98 years) and 268 control subjects (67.51?±?3.25 years). Hypertension (ESH/ESC2013 and JNC8) and diabetes (WHO) were evaluate. Genetic polymorphisms of renin-angiotensin-aldosterone system (RAAS) and NOS3 were determined. The prevalence of HT among centenarians was 64.4% and the majority (58.9%) were controlled, differing from control group both on frequency (P?<?0.001) and on their control (P?<?0.001). We found that HT is a risk factor for not achieving longevity (OR 2.531, 95% CI 1.688–3.793, P?<?0.001), the same for diabetes (OR 5.669 95% CI 2.966–10.835, P?<?0.001), and male gender (OR 2.196, 95% CI 1.493–3.29, P?<?0.001). Hypertension, adjusted for gender and diabetes, was independent risk factor anti-longevity (OR 2.007, 95% CI 1320–3.052, P?=?0.001). The ACE_D and NOS3_G alleles were more frequent in centenarians compared to controls (P?<?0.001, both cases). ACE_II and NOS3_TT genotypes, adjusted for BP, gender and diabetes, increased risk in 3.748 (95% CI 1.887–7.444) and 2.533 (95% CI 1.483–4.327), respectively, in relation to ACE_DD (P?<?0.001) and NOS3_GG (P?=?0.001), against longevity. Our findings suggest that the prevalence of hypertension was lower in Portuguese centenarians than in the elderly, reinforcing the importance of better cardiovascular risk profiles to achieve longevity even in the presence of genetic condition.

     

Air pollution-induced placental epigenetic alterations in early life: a candidate miRNA approach

Particulate matter (PM) exposure during in utero life may entail adverse health outcomes in later-life. Air pollution's adverse effects are known to alter gene expression profiles, which can be regulated by microRNAs (miRNAs). We investigate the potential influence of air pollution exposure in prenatal life on placental miRNA expression. Within the framework of the ENVIRONAGE birth cohort, we measured the expression of six candidate miRNAs in placental tissue from 210 mother-newborn pairs by qRT-PCR. Trimester-specific PM_2.5 exposure levels were estimated for each mother's home address using a spatiotemporal model. Multiple regression models were used to study miRNA expression and in utero exposure to PM_2.5 over various time windows during pregnancy. The placental expression of miR-21 (?33.7%, 95% CI: ?53.2 to ?6.2, P = 0.022), miR-146a (?30.9%, 95% CI: ?48.0 to ?8.1, P = 0.012) and miR-222 (?25.4%, 95% CI: ?43.0 to ?2.4, P = 0.034) was inversely associated with PM_2.5 exposure during the 2nd trimester of pregnancy, while placental expression of miR-20a and miR-21 was positively associated with 1st trimester exposure. Tumor suppressor phosphatase and tensin homolog (PTEN) was identified as a common target of the miRNAs significantly associated with PM exposure. Placental PTEN expression was strongly and positively associated (+59.6% per 5 µg/m³ increment, 95% CI: 26.9 to 100.7, P < 0.0001) with 3rd trimester PM_2.5 exposure. Further research is required to establish the role these early miRNA and mRNA expression changes might play in PM-induced health effects. We provide molecular evidence showing that in utero PM_2.5 exposure affects miRNAs expression as well as its downstream target PTEN.     

CYP1A1 rs1048943 and rs4646903 polymorphisms associated with laryngeal cancer susceptibility among Asian populations: a meta‐analysis

Many studies have investigated the association between CYP1A1 rs1048943 and rs4646903 polymorphisms and laryngeal cancer risk, but their results have been inconsistent. The PubMed and CNKI were searched for case–control studies published up to 01 July 2015. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. In this meta‐analysis, we assessed 10 published studies involving comprising 748 laryngeal cancer cases and 1558 controls of the association between CYP1A1 rs1048943 and rs4646903 polymorphisms and laryngeal cancer risk. For CYP1A1 rs1048943 of the homozygote G/G and G allele carriers (A/G + G/G) versus A/A, the pooled ORs were 1.77 (95% CI = 1.28–2.81, P = 0.007 for heterogeneity) and 1.86 (95% CI = 1.45–2.40, P = 0.000 for heterogeneity). For CYP1A1 rs4646903 of the homozygote G/G and G allele carriers (A/G + G/G) versus A/A, the pooled ORs were 1.53 (95% CI = 1.31–2.21, P = 0.012 for heterogeneity) and 1.33(95% CI = 1.04–1.71, P = 0.029 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were found among Asians for both the G allele carriers and homozygote G/G. However, no significant associations were found in Caucasian population all genetic models. These results from the meta‐analysis suggest that CYP1A1 rs1048943 and rs4646903 polymorphisms contribute to risk of laryngeal cancer among Asian populations.     

The properties of human body phantoms used in calculations of electromagnetic fields exposure by wireless communication handsets or hand-operated industrial devices

According to international guidelines, the assessment of biophysical effects of exposure to electromagnetic fields (EMF) generated by hand-operated sources needs the evaluation of induced electric field (E _in) or specific energy absorption rate (SAR) caused by EMF inside a worker's body and is usually done by the numerical simulations with different protocols applied to these two exposure cases. The crucial element of these simulations is the numerical phantom of the human body. Procedures of E _in and SAR evaluation due to compliance analysis with exposure limits have been defined in Institute of Electrical and Electronics Engineers standards and International Commission on Non-Ionizing Radiation Protection guidelines, but a detailed specification of human body phantoms has not been described. An analysis of the properties of over 30 human body numerical phantoms was performed which has been used in recently published investigations related to the assessment of EMF exposure by various sources. The differences in applicability of these phantoms in the evaluation of E _in and SAR while operating industrial devices and SAR while using mobile communication handsets are discussed. The whole human body numerical phantom dimensions, posture, spatial resolution and electric contact with the ground constitute the key parameters in modeling the exposure related to industrial devices, while modeling the exposure from mobile communication handsets, which needs only to represent the exposed part of the human body nearest to the handset, mainly depends on spatial resolution of the phantom. The specification and standardization of these parameters of numerical human body phantoms are key requirements to achieve comparable and reliable results from numerical simulations carried out for compliance analysis against exposure limits or within the exposure assessment in EMF-related epidemiological studies.     

THE FUNDAMENTALS OF PHARMACOPHORE MODELING IN COMBINATORIAL CHEMISTRY*

Abstract

Objective: To better understand the risks of rheumatoid arthritis (RA) and certain subsets conferred by mannose-binding lectin (MBL2) polymorphisms in different races. Materials and methods: Eighteen articles (4810 cases and 4585 controls) were identified from the latest literature search carried out in May 2014 using PubMed, Web of Science, Wanfang Database (Chinese) and Chinese National Knowledge Infrastructure. Three single nucleotide polymorphisms of codon 52, 54 and 57, exonic and extended genotypic variance in MBL2 were synthesized. Results: Codon 54 mutation of MBL2 was unlikely to be a risk factor for RA in overall population, but turned out to be deleterious in East Asian (four studies with 523 cases and 647 controls, pooled OR:1.63, 95% CI: 1.23–2.17). Codon 54 mutation increased the risk of seropositive and erosive RA by 44% and 162%, respectively (three studies with 281 cases and 358 controls, 95% CI: 1.01–2.05; 3 studies with 180 cases and 499 controls, 95% CI: 1.77–3.88). Furthermore, those risks were relatively stronger when restricted in East Asian (two studies with 147 cases and 244 controls, pooled OR: 1.85, 95% CI: 1.19–2.87; 2 studies with 170 cases and 291 controls, pooled OR: 2.78, 95% CI: 1.85–4.20). No remarkable associations were detected regarding codon 52, 57, exon 1 and extended genotype of MBL2. Conclusions: Polymorphism of codon 54 in MBL2 may predispose to RA, especially seropositive or erosive RA, which East Asian appears to be more vulnerable.     

Leptin rs2167270 G > A (G19A) polymorphism may decrease the risk of cancer: A case-control study and meta-analysis involving 19 989 subjects

Accumulating evidence has suggested that leptin (LEP) is very important for the development of cancer. Recently, a number of case-control studies about the relationship of the rs2167270 G > A (G19A) variants in the LEP gene with the risk of cancer have yielded inconsistent results. In this study, we have carried out a case-control study [1063 esophagogastric junction adenocarcinoma (EGJA) cases and 1677 controls] in a Chinese population. Furthermore, we carried out a pooled-analysis of 13 studies involving 8059 cancer patients and 11 930 controls to assess whether the LEP G19A locus was associated with overall cancer susceptibility. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were harnessed to evaluate the potential association. In our case-control study, we found an association between the carriers of LEP 19A allele and EGJA risk. In addition, the results of meta-analysis also suggested significant associations with cancer risk (A vs G: OR = 0.92, 95% CI = 0.88–0.97, P = 0.001; AA vs GG: OR = 0.83, 95% CI = 0.74–0.93, P = 0.001, GA/AA vs GG: OR = 0.93, 95% CI = 0.88–0.99, P = 0.023 and AA vs GG/GA: OR = 0.83, 95% CI = 0.74–0.92, P < 0.001). Upon conducting a stratified analysis, we found that LEP 19A allele might decrease the susceptibility of non-Hodgkin lymphoma (NHL) and colorectal cancer (CRC). In a stratified-by-ethnicity analysis, significant associations were also found in Asians, Caucasians, and mixed populations. We can conclude that the LEP G19A polymorphism constitutes a decreased risk of cancer.