A missense variant in FTCD is associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

Inorganic arsenic (iAs) is a carcinogen, and exposure to iAs via food and water is a global public health problem. iAs-contaminated drinking water alone affects >100 million people worldwide, including ~50 million in Bangladesh. Once absorbed into the blood stream, most iAs is converted to mono-methylated (MMA) and then di-methylated (DMA) forms, facilitating excretion in urine. Arsenic metabolism efficiency varies among individuals, in part due to genetic variation near AS3MT (arsenite methyltransferase; 10q24.32). To identify additional arsenic metabolism loci, we measured protein-coding variants across the human exome for 1,660 Bangladeshi individuals participating in the Health Effects of Arsenic Longitudinal Study (HEALS). Among the 19,992 coding variants analyzed exome-wide, the minor allele (A) of rs61735836 (p.Val101Met) in exon 3 of FTCD (formiminotransferase cyclodeaminase) was associated with increased urinary iAs% (P = 8x10-13), increased MMA% (P = 2x10-16) and decreased DMA% (P = 6x10-23). Among 2,401 individuals with arsenic-induced skin lesions (an indicator of arsenic toxicity and cancer risk) and 2,472 controls, carrying the low-efficiency A allele (frequency = 7%) was associated with increased skin lesion risk (odds ratio = 1.35; P = 1x10-5). rs61735836 is in weak linkage disequilibrium with all nearby variants. The high-efficiency/major allele (G/Valine) is human-specific and eliminates a start codon at the first 5´-proximal Kozak sequence in FTCD, suggesting selection against an alternative translation start site. FTCD is critical for catabolism of histidine, a process that generates one-carbon units that can enter the one-carbon/folate cycle, which provides methyl groups for arsenic metabolism. In our study population, FTCD and AS3MT SNPs together explain ~10% of the variation in DMA% and support a causal effect of arsenic metabolism efficiency on arsenic toxicity (i.e., skin lesions). In summary, this work identifies a coding variant in FTCD associated with arsenic metabolism efficiency, providing new evidence supporting the established link between one-carbon/folate metabolism and arsenic toxicity.

Correction: A missense variant in FTCD is associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

[This corrects the article DOI: 10.1371/journal.pgen.1007984.].

The effect of age on DNA methylation in whole blood among Bangladeshi men and women.

BACKGROUND: It is well-known that methylation changes occur as humans age, however, understanding how age-related changes in DNA methylation vary by sex is lacking. In this study, we characterize the effect of age on DNA methylation in a sex-specific manner and determine if these effects vary by genomic context. We used the Illumina HumanMethylation 450 K array and DNA derived from whole blood for 400 adult participants (189 males and 211 females) from Bangladesh to identify age-associated CpG sites and regions and characterize the location of these age-associated sites with respect to CpG islands (vs. shore, shelf, or open sea) and gene regions (vs. intergenic). We conducted a genome-wide search for age-associated CpG sites (among 423,604 sites) using a reference-free approach to adjust for cell type composition (the R package RefFreeEWAS) and performed an independent replication analysis of age-associated CpGs. RESULTS: The number of age-associated CpGs (p < 5 x 10- 8) were 986 among men and 3479 among women of which 2027(63.8%) and 572 (64.1%) replicated (using Bonferroni adjusted p < 1.2 × 10- 5). For both sexes, age-associated CpG sites were more likely to be hyper-methylated with increasing age (compared to hypo-methylated) and were enriched in CpG islands and promoter regions compared with other locations and all CpGs on the array. Although we observed strong correlation between chronological age and previously-developed epigenetic age models (r ≈ 0.8), among our top (based on lowest p-value) age-associated CpG sites only 12 for males and 44 for females are included in these prediction models, and the median chronological age compared to predicted age was 44 vs. 51.7 in males and 45 vs. 52.1 in females. CONCLUSIONS: Our results describe genome-wide features of age-related changes in DNA methylation. The observed associations between age and methylation were generally consistent for both sexes, although the associations tended to be stronger among women. Our population may have unique age-related methylation changes that are not captured in the established methylation-based age prediction model we used, which was developed to be non-tissue-specific.

The contribution of parent-to-offspring transmission of telomeres to the heritability of telomere length in humans.

Leukocyte telomere length (LTL) is a heritable trait with two potential sources of heritability (h2): inherited variation in non-telomeric regions (e.g., SNPs that influence telomere maintenance) and variability in the lengths of telomeres in gametes that produce offspring zygotes (i.e., "direct" inheritance). Prior studies of LTL h2 have not attempted to disentangle these two sources. Here, we use a novel approach for detecting the direct inheritance of telomeres by studying the association between identity-by-descent (IBD) sharing at chromosome ends and phenotypic similarity in LTL. We measured genome-wide SNPs and LTL for a sample of 5069 Bangladeshi adults with substantial relatedness. For each of the 6318 relative pairs identified, we used SNPs near the telomeres to estimate the number of chromosome ends shared IBD, a proxy for the number of telomeres shared IBD (Tshared). We then estimated the association between Tshared and the squared pairwise difference in LTL ((ΔLTL)2) within various classes of relatives (siblings, avuncular, cousins, and distant), adjusting for overall genetic relatedness (ϕ). The association between Tshared and (ΔLTL)2 was inverse among all relative pair types. In a meta-analysis including all relative pairs (ϕ > 0.05), the association between Tshared and (ΔLTL)2 (P = 0.01) was stronger than the association between ϕ and (ΔLTL)2 (P = 0.43). Our results provide strong evidence that telomere length (TL) in parental germ cells impacts TL in offspring cells and contributes to LTL h2 despite telomere "reprogramming" during embryonic development. Applying our method to larger studies will enable robust estimation of LTL h2 attributable to direct transmission of telomeres.

Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signal.

BACKGROUND: Leucocyte telomere length (TL) is a potential biomarker of ageing and risk for age-related disease. Leucocyte TL is heritable and shows substantial differences by race/ethnicity. Recent genome-wide association studies (GWAS) report ~10 loci harbouring SNPs associated with leucocyte TL, but these studies focus primarily on populations of European ancestry. OBJECTIVE: This study aims to enhance our understanding of genetic determinants of TL across populations. METHODS: We performed a GWAS of TL using data on 5075 Bangladeshi adults. We measured TL using one of two technologies (qPCR or a Luminex-based method) and used standardised variables as TL phenotypes. RESULTS: Our results replicate previously reported associations in the TERC and TERT regions (P=2.2×10-8 and P=6.4×10-6, respectively). We observed a novel association signal in the RTEL1 gene (intronic SNP rs2297439; P=2.82×10-7) that is independent of previously reported TL-associated SNPs in this region. The minor allele for rs2297439 is common in South Asian populations (≥0.25) but at lower frequencies in other populations (eg, 0.07 in Northern Europeans). Among the eight other previously reported association signals, all were directionally consistent with our study, but only rs8105767 (ZNF208) was nominally significant (P=0.003). SNP-based heritability estimates were as high as 44% when analysing close relatives but much lower when analysing distant relatives only. CONCLUSIONS: In this first GWAS of TL in a South Asian population, we replicate some, but not all, of the loci reported in prior GWAS of individuals of European ancestry, and we identify a novel second association signal at the RTEL1 locus.

Individual-, maternal- and household-level factors associated with stunting among children aged 0-23 months in Bangladesh.

OBJECTIVE: Childhood stunting remains a major public health concern in Bangladesh. To accelerate the reduction rate of stunting, special focus is required during the first 23 months of a child's life when the bulk of growth takes place. Therefore the present study explored individual-, maternal- and household-level factors associated with stunting among children under 2 years of age in Bangladesh. DESIGN: Data were collected through a nationwide cross-sectional survey conducted between October 2015 and January 2016. A two-stage cluster random sampling procedure was applied to select 11 428 households. In the first stage, 210 enumerations areas (EA) were selected with probability proportional to EA size (180 EA from rural areas, thirty EA from urban slums). In the second stage, an average of fifty-four households were selected from each EA through systematic random sampling. SETTING: Rural areas and urban slums of Bangladesh.ParticipantsA total of 6539 children aged 0-23 months. RESULTS: Overall, 29·9 % of the children were stunted. After adjusting for all potential confounders in the modified Poisson regression model, child's gender, birth weight (individual level), maternal education, age at first pregnancy, nutrition (maternal level), administrative division, place of residence, socio-economic status, food security status, access to sanitary latrine and toilet hygiene condition (household level) were significantly associated with stunting. CONCLUSIONS: The study identified a number of potentially addressable multilevel risk factors for stunting among young children in Bangladesh that should be addressed through comprehensive multicomponent interventions.

Screening for gene-environment (G×E) interaction using omics data from exposed individuals: an application to gene-arsenic interaction.

Identifying gene-environment interactions is a central challenge in the quest to understand susceptibility to complex, multi-factorial diseases. Developing an understanding of how inter-individual variability in inherited genetic variation alters the effects of environmental exposures will enhance our knowledge of disease mechanisms and improve our ability to predict disease and target interventions to high-risk sub-populations. Limited progress has been made identifying gene-environment interactions in the epidemiological setting using existing statistical approaches for genome-wide searches for interaction. In this paper, we describe a novel two-step approach using omics data to conduct genome-wide searches for gene-environment interactions. Using existing genome-wide SNP data from a large Bangladeshi cohort study specifically designed to assess the effect of arsenic exposure on health, we evaluated gene-arsenic interactions by first conducting genome-wide searches for SNPs that modify the effect of arsenic on molecular phenotypes (gene expression and DNA methylation features). Using this set of SNPs showing evidence of interaction with arsenic in relation to molecular phenotypes, we then tested SNP-arsenic interactions in relation to skin lesions, a hallmark characteristic of arsenic toxicity. With the emergence of additional omics data in the epidemiologic setting, our approach may have the potential to boost power for genome-wide interaction research, enabling the identification of interactions that will enhance our understanding of disease etiology and our ability to develop interventions targeted at susceptible sub-populations.

Exploring the gap between coverage, access, and utilization of long-lasting insecticide-treated nets (LLINs) among the households of malaria endemic districts in Bangladesh.

BACKGROUND: Malaria is still a major public health concern in Bangladesh in spite of mass distribution of long-lasting insecticide-treated nets (LLINs) as a key preventive strategy. There might be a considerable gap between coverage and actual use of nets by the population in endemic areas. This study intended to assess the gap between coverage, access to and use of LLINs among the households in malaria-endemic settings in Bangladesh. METHODS: This cross-sectional study collected data from 2640 households of 13 endemic districts of Bangladesh through three-stage cluster random sampling. The gap between coverage, access and use of LLINs were calculated using the procedure established by the Roll Back Malaria Monitoring and Evaluation Reference Group. To support the quantitative findings, qualitative data were also collected through in-depth interview, focus group discussion and key informant interview and analysed accordingly. RESULTS: Of 2640 total households, 77.4% (n = 2044) possessed at least two LLINs, 56.8% (n = 1499) had insufficient access, and 18.8% (n = 495) had excess LLINs. Members of 77.9% (n = 2056) households had used LLINs the previous night and 6.0% (n = 68) did not use LLINs despite having sufficient access. LLIN use was lower in non-hill track areas, in Bengali community, in richer households and households with more than four members. Moreover, qualitative findings revealed that the major reasons behind not using LLINs were insufficient access, sleeping outside the home, migration, perceived low efficacy of LLINs, or fear of physical side effects. CONCLUSION: Closing the access gap by providing enough nets through solid investment and well-designed behavioural change interventions are crucial for achieving and sustaining universal coverage.

The association between daily 500 mg calcium supplementation and lower pregnancy-induced hypertension risk in Bangladesh.

BACKGROUND: Evidence suggests that daily supplementation of 1500 to 2000 mg of calcium during pregnancy reduces pregnancy-induced hypertension (PIH). However, the evidence on the efficacy of low-dose calcium supplementation on PIH is limited. This paper assesses the longitudinal correlation between low-dose calcium intake (500 mg daily) and change in blood pressure during pregnancy among a homogeneous population in terms of hypertension and pre-eclampsia. METHODS: The study followed a retrospective cohort study design, and was carried out among 11,387 pregnant women from 10 rural upazilas (sub-districts) of Bangladesh where maternal nutrition initiative (MNI), implemented by Building Resources Across Communities (BRAC), was ongoing. The modified Poisson regression model was used to estimate the association (risk ratio) between consumption of calcium tablets and PIH. RESULTS: The present research found that women who consumed 500 mg/d calcium tablets for more than 6 months during their pregnancy had a 45% lower risk of developing hypertension compared to those who consumed less calcium (RR = 0.55, 95% CI = 0.33-0.93). CONCLUSIONS: Daily supplementation of 500 mg oral calcium during pregnancy for at least 180 tablets is associated with a considerably reduced risk of PIH, but this study is unable to confirm whether this association is causal. The causal relationship needs to be confirmed through a large scale randomized controlled trial.

Mediation analysis demonstrates that trans-eQTLs are often explained by cis-mediation: a genome-wide analysis among 1,800 South Asians.

A large fraction of human genes are regulated by genetic variation near the transcribed sequence (cis-eQTL, expression quantitative trait locus), and many cis-eQTLs have implications for human disease. Less is known regarding the effects of genetic variation on expression of distant genes (trans-eQTLs) and their biological mechanisms. In this work, we use genome-wide data on SNPs and array-based expression measures from mononuclear cells obtained from a population-based cohort of 1,799 Bangladeshi individuals to characterize cis- and trans-eQTLs and determine if observed trans-eQTL associations are mediated by expression of transcripts in cis with the SNPs showing trans-association, using Sobel tests of mediation. We observed 434 independent trans-eQTL associations at a false-discovery rate of 0.05, and 189 of these trans-eQTLs were also cis-eQTLs (enrichment P<0.0001). Among these 189 trans-eQTL associations, 39 were significantly attenuated after adjusting for a cis-mediator based on Sobel P<10-5. We attempted to replicate 21 of these mediation signals in two European cohorts, and while only 7 trans-eQTL associations were present in one or both cohorts, 6 showed evidence of cis-mediation. Analyses of simulated data show that complete mediation will be observed as partial mediation in the presence of mediator measurement error or imperfect LD between measured and causal variants. Our data demonstrates that trans-associations can become significantly stronger or switch directions after adjusting for a potential mediator. Using simulated data, we demonstrate that this phenomenon is expected in the presence of strong cis-trans confounding and when the measured cis-transcript is correlated with the true (unmeasured) mediator. In conclusion, by applying mediation analysis to eQTL data, we show that a substantial fraction of observed trans-eQTL associations can be explained by cis-mediation. Future studies should focus on understanding the mechanisms underlying widespread cis-mediation and their relevance to disease biology, as well as using mediation analysis to improve eQTL discovery.

How many hours do people sleep in Bangladesh? A country-representative survey.

This study investigated total sleep time in the Bangladeshi population and identified the proportion of the population at greater risk of developing chronic diseases due to inadequate sleep. Using a cross-sectional survey, total sleep time was captured and analysed in 3968 respondents aged between 6 and 106 years in 24 (of 64) districts in Bangladesh. Total sleep time was defined as the hours of total sleep in the previous 24 h. We used National Sleep Foundation (2015) guidelines to determine the recommended sleep hours in different age categories. Less or more than the recommended total sleep time (in hours) was considered 'shorter' and 'longer' sleep time, respectively. Linear and multinomial logistic regression models were used to determine the relationship between demographic variables and estimated risk of shorter and longer total sleep time. The mean (±standard deviation) total sleep time of children (6-13 years), teenagers (14-17 years), young adults and adults (18-64 years) and older adults (≥65 years) were 8.6 (±1.1), 8.1 (±1.0), 7.7 (±0.9) and 7.8 (±1.4) h, respectively, which were significantly different (P < 0.01). More than half of school-age children (55%) slept less than, and 28.2% of older adults slept longer than, recommended. Residents in all divisions (except Chittagong) in Bangladesh were less likely to sleep longer than in the Dhaka division. Rural populations had a 3.96× greater chance of sleeping for a shorter time than urban residents. The Bangladeshi population tends to sleep for longer and/or shorter times than their respective recommended sleep hours, which is detrimental to health.

Arsenic exposure, telomere length, and expression of telomere-related genes among Bangladeshi individuals.

BACKGROUND: Inorganic arsenic is a carcinogen whose mode of action may involve telomere dysfunction. Recent epidemiological studies suggest that chronic arsenic exposure is associated with longer telomeres and altered expression of telomere-related genes in peripheral blood. In this study, we evaluated the association of urinary arsenic concentration with expression of telomere-related genes and telomere length in Bangladeshi individuals with a wide range of arsenic exposure through naturally contaminated drinking water. METHODS: We used linear regression models to estimate associations between urinary arsenic and array-based expression measures for 69 telomere related genes using mononuclear cell RNA samples from 1799 individuals. Association between arsenic exposure and a qPCR-based telomere length measure was assessed among 167 individuals. RESULTS: Urinary arsenic was positively associated with expression of WRN, and negatively associated with TERF2, DKC1, TERF2IP and OBFC1 (all P<0.00035, Bonferroni-corrected threshold). We detected interaction between urinary arsenic and arsenic metabolism efficiency in relation to expression of WRN (P for interaction =0.00008). In addition, we observed that very high arsenic exposure was associated with longer telomeres compared to very low exposure (P=0.02). DISCUSSION: Our findings suggest that arsenic's carcinogenic mode of action may involve alteration of telomere maintenance and/or telomere damage. This study extends our knowledge regarding the effect of arsenic on telomere length and expression of telomere-related genes.

Genome-wide association study of smoking behaviours among Bangladeshi adults.

BACKGROUND: The high prevalence of tobacco use in some developing nations, including Bangladesh, poses several public health challenges for these populations. Smoking behaviour is determined by genetic and environmental factors; however, the genetic determinants of smoking behaviour have not been previously examined in a Bangladeshi or South Asian population. We performed a genome-wide association study (GWAS) of tobacco smoking behaviour among a population-based sample of 5354 (2035 ever smokers and 3319 never smokers) men and women in Bangladesh. METHODS: Genome-wide association analyses were conducted for smoking initiation (ever vs never smokers), smoking quantity (cigarettes per day), age of smoking initiation, and smoking cessation (former vs current smokers). Sex-stratified associations were performed for smoking initiation. RESULTS: We observed associations for smoking initiation in the SLC39A11 region at 17q21.31 (rs2567519, p=1.33×10⁻7) among men and in the SLCO3A1 region at 15q26 (rs12912184, p=9.32×10⁻8) among women. CONCLUSIONS: These findings suggest possible underlying mechanisms related to solute carrier transporter genes, which transport neurotransmitters, nutrients, heavy metals and other substrates into cells, for smoking initiation in a South Asian population in a sex-specific pattern. Genetic markers could have potential translational implications for the prevention or treatment of tobacco use and addiction in South Asian populations and warrant further exploration.

Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

Arsenic contamination of drinking water is a major public health issue in many countries, increasing risk for a wide array of diseases, including cancer. There is inter-individual variation in arsenic metabolism efficiency and susceptibility to arsenic toxicity; however, the basis of this variation is not well understood. Here, we have performed the first genome-wide association study (GWAS) of arsenic-related metabolism and toxicity phenotypes to improve our understanding of the mechanisms by which arsenic affects health. Using data on urinary arsenic metabolite concentrations and approximately 300,000 genome-wide single nucleotide polymorphisms (SNPs) for 1,313 arsenic-exposed Bangladeshi individuals, we identified genome-wide significant association signals (P<5×10(-8)) for percentages of both monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) near the AS3MT gene (arsenite methyltransferase; 10q24.32), with five genetic variants showing independent associations. In a follow-up analysis of 1,085 individuals with arsenic-induced premalignant skin lesions (the classical sign of arsenic toxicity) and 1,794 controls, we show that one of these five variants (rs9527) is also associated with skin lesion risk (P = 0.0005). Using a subset of individuals with prospectively measured arsenic (n = 769), we show that rs9527 interacts with arsenic to influence incident skin lesion risk (P = 0.01). Expression quantitative trait locus (eQTL) analyses of genome-wide expression data from 950 individual's lymphocyte RNA suggest that several of our lead SNPs represent cis-eQTLs for AS3MT (P = 10(-12)) and neighboring gene C10orf32 (P = 10(-44)), which are involved in C10orf32-AS3MT read-through transcription. This is the largest and most comprehensive genomic investigation of arsenic metabolism and toxicity to date, the only GWAS of any arsenic-related trait, and the first study to implicate 10q24.32 variants in both arsenic metabolism and arsenical skin lesion risk. The observed patterns of associations suggest that MMA% and DMA% have distinct genetic determinants and support the hypothesis that DMA is the less toxic of these two methylated arsenic species. These results have potential translational implications for the prevention and treatment of arsenic-associated toxicities worldwide.

Arsenic and lung disease mortality in Bangladeshi adults.

BACKGROUND: Chronic arsenic exposure through drinking water is a public health problem affecting millions of people worldwide, including at least 30 million in Bangladesh. We prospectively investigated the associations of arsenic exposure and arsenical skin lesion status with lung disease mortality in Bangladeshi adults. METHODS: Data were collected from a population-based sample of 26,043 adults, with an average of 8.5 years of follow-up (220,157 total person-years). There were 156 nonmalignant lung disease deaths and 90 lung cancer deaths ascertained through October 2013. We used Cox proportional hazards models to estimate adjusted hazard ratios and 95% confidence intervals (CIs) for lung disease mortality. RESULTS: Creatinine-adjusted urinary total arsenic was associated with nonmalignant lung disease mortality, with persons in the highest tertile of exposure having a 75% increased risk for mortality (95% CI = 1.15-2.66) compared with those in the lowest tertile of exposure. Persons with arsenical skin lesions were at increased risk of lung cancer mortality (hazard ratio = 4.53 [95% CI = 2.82-7.29]) compared with those without skin lesions. CONCLUSIONS: This prospective investigation of lung disease mortality, using individual-level arsenic measures and skin lesion status, confirms a deleterious effect of ingested arsenic on mortality from lung disease. Further investigations should evaluate effects on the incidence of specific lung diseases, more fully characterize dose-response, and evaluate screening and biomedical interventions to prevent premature death among arsenic-exposed populations, particularly among those who may be most susceptible to arsenic toxicity.

Relationship between arsenic skin lesions and the age of natural menopause.

BACKGROUND: Chronic exposure to arsenic is associated with neoplastic, cardiovascular, endocrine, neuro-developmental disorders and can have an adverse effect on women's reproductive health outcomes. This study examined the relationship between arsenic skin lesions (a hallmark sign of chronic arsenic poisoning) and age of natural menopause (final menopausal period) in populations with high levels of arsenic exposure in Bangladesh. METHODS: We compared menopausal age in two groups of women--with and without arsenic skin lesions; and presence of arsenic skin lesions was used as an indicator for chronic arsenic exposure. In a cross-sectional study, a total of 210 participants were randomly identified from two ongoing studies--participants with arsenic skin lesions were identified from an ongoing clinical trial and participants with no arsenic skin lesions were identified from an ongoing cohort study. Mean age of menopause between these two groups were calculated and compared. Multivariable linear regression was used to estimate the relationship between the status of the arsenic skin lesions and age of natural menopause in women. RESULTS: Women with arsenic skin lesions were 1.5 years younger (p <0.001) at the time of menopause compared to those without arsenic skin lesions. After adjusting with contraceptive use, body mass index, urinary arsenic level and family history of premature menopause, the difference between the groups' age at menopause was 2.1 years earlier (p <0.001) for respondents with arsenic skin lesions. CONCLUSIONS: The study showed a statistically significant association between chronic exposure to arsenic and age at menopause. Heavily exposed women experienced menopause two years earlier than those with lower or no exposure.

A prospective cohort study of stroke mortality and arsenic in drinking water in Bangladeshi adults.

BACKGROUND: Arsenic in drinking water causes increased coronary artery disease (CAD) and death from CAD, but its association with stroke is not known. METHODS: Prospective cohort study with arsenic exposure measured in well water at baseline. 61074 men and women aged 18 years or older on January 2003 were enrolled in 2003. The cohort was actively followed for an average of 7 years (421,754 person-years) through December 2010. Based on arsenic concentration the population was categorized in three groups and stroke mortality HR was compared to the referent. The risk of stroke mortality Hazard Ratio (HR) and 95% Confidence Interval was calculated in relation to arsenic exposure was estimated by Cox proportional hazard models with adjustment for potential confounders. RESULTS: A total of 1033 people died from stroke during the follow-up period, accounting for 23% of the total deaths. Multivariable adjusted HRs (95% confidence interval) for stroke for well water arsenic concentrations <10, 10-49, and ≥50 µg/L were 1.0 (reference), 1.20 (0.92 to 1.57), and 1.35 (1.04 to 1.75) respectively (Ptrend=0.00058). For men, multivariable adjusted HRs (95%) for well water arsenic concentrations <10, 10-49, and ≥50 µg/L were 1.0 (reference), 1.12 (0.78 to 1.60), and 1.07 (0.75 to 1.51) respectively (Ptrend=0.45) and for women 1.0 (reference),1.31 (0.87 to 1.98), and 1.72 (1.15 to 2.57) respectively (Ptrend=0.00004). CONCLUSION: The result suggests that arsenic exposure was associated with increased stroke mortality risk in this population, and was more significant in women compared to men.

Baseline comorbidities in a skin cancer prevention trial in Bangladesh.

BACKGROUND: Epidemiologic research suggests that increased cancer risk due to chronic arsenic exposure persists for several decades even after the exposure has terminated. Observational studies suggest that antioxidants exert a protective effect on arsenical skin lesions and cancers among those chronically exposed to arsenic through drinking water. This study reports on the design, methods and baseline analyses from the Bangladesh Vitamin E and Selenium Trial (BEST), a population-based chemoprevention study conducted among adults in Bangladesh with visible arsenic toxicity. MATERIALS AND METHODS: Bangladesh Vitamin E and Selenium Trial is a 2 × 2 full factorial, double-blind, randomized controlled trial of 7000 adults having manifest arsenical skin lesions evaluating the efficacy of 6-year supplementation with alpha-tocopherol (100 mg daily) and L-selenomethionine (200 µg daily) for the prevention of nonmelanoma skin cancer. RESULTS: In cross-sectional analyses, we observed significant associations of skin lesion severity with male gender (female prevalence odds ratio (POR) = 0.87; 95% CI = 0.79-0.96), older age (aged 36-45 years, POR = 1.27; 95% CI = 1.13-1.42; aged 46-55 years, POR = 1.44; 95% CI = 1.27-1.64 and aged 56-65 years, POR = 1.50; 95% CI = 1.26-1.78 compared with aged 25-35 years), hypertension (POR = 1.29; 95% CI = 1.08-1.55), diabetes (POR = 2.13; 95% CI = 1.32-3.46), asthma (POR = 1.55; 95% CI = 1.03-2.32) and peptic ulcer disease (POR = 1.20; 95% CI = 1.07-1.35). CONCLUSIONS: We report novel associations between arsenical skin lesions with several common chronic diseases. With the rapidly increasing burden of preventable cancers in developing countries, efficient and feasible chemoprevention study designs and approaches, such as employed in BEST, may prove both timely and potentially beneficial in conceiving cancer chemoprevention trials in Bangladesh and beyond.

The impact of education and media on contraceptive use in Bangladesh: a multivariate analysis.

In this paper, an attempt is made to show the impact of education and media on contraceptive use and also to identify the factors that associated with the current use of contraception and continuing of contraception. To reach our goal, Bangladesh Demographic and Health Survey (BDHS 2007) data were used. Findings of this study reveal that education, age of the respondents, religion, media exposure, area of residence and if they belong to any of the non-governmental organizations (Grameen Bank, Bangladesh Rural Advancement Committee, ASA, Mother's club, etc.) have significant contribution to current use of contraception and continuing of contraception. Media, particularly TV, and education play the leading role regarding this issue, whereas the others have an indirect relationship. Multivariate analyses showed that contraceptive use were higher among educated women and those women who watch TV at least once a week as compared with their respective counterpart. The results indicate urgent need to give emphasis on education, ensuring electronic media exposure, head-to-head communication programme, institutional-based family planning education and necessary information to learn about the impact of overpopulation for the people all over the country.

Gender and age differences in mixed metal exposure and urinary excretion.

BACKGROUND: Little is known about the variation in exposure to toxic metals by age and gender and other potential modifying factors. We evaluated age and gender differences by measurements of metal/element concentrations in urine in a rural population in Matlab, Bangladesh, in three age groups: 8-12 (N=238), 14-15 (N=107) and 30-88 (N=710) years of age, living in an area with no point sources of metal exposure but where elevated water arsenic concentrations are prevalent. RESULTS: We found marked differences in urine concentrations of metals and trace elements by gender, age, tobacco use, socioeconomic and nutritional status. Besides a clearly elevated urinary arsenic concentration in all age groups (medians 63-85 µg As/L), and despite the low degree of contamination from industries and traffic, the urine concentrations of toxic metals such as cadmium and lead were clearly elevated, especially in children (median 0.31 µg Cd/L and 2.9 µg Pb/L, respectively). In general, women had higher urinary concentrations of toxic metals, especially Cd (median 0.81 µg/L) compared to men (0.66 µg/L) and U (median 10 ng/L in women, compared to 6.4 ng/L in men), while men had higher urinary concentrations of the basic and essential elements Ca (69 mg/L in men, 30-50 years, compared to 52 mg/L in women), Mg (58 mg/L in men compared to 50 mg/L in women), Zn (182 µg/L in men compared to 117 µg/L in women) and Se (9.9 µg/L in men compared to 8.7 µg/L in women). Manganese was consistently higher in females than in males in all age groups, suggesting a biological difference between females and males in Mn metabolism. Increasing socioeconomic status decreased the toxic metal exposure significantly in children and especially in men. Poor iron status was detected in 17% of children, adolescents and women, but only in 6% of men. Also zinc deficiency was more prevalent in females than in males. CONCLUSIONS: Women and children seemed to be more at risk for toxic metal exposure than men and at the same time more vulnerable to micronutrient deficiency. Higher concentrations of the toxic metals in urine in women are likely to reflect an increased gastrointestinal absorption of these metals at micronutrient deficiency, such as low body iron stores and Zn deficiency. Higher urinary concentrations of the essential elements in men likely reflect a better nutritional status. There is a need for information on exposure, lifestyle and socioeconomic factors, stratified by gender and age, for the purpose of conducting balanced risk assessment and management that considers such differences.