Fragile States, Infectious Disease and Health Security: The Case for Timor-Leste

Timor-Leste is a very young and developing nation state. Endemic infectious disease and weakened health security coupled with its growing and inclusive public institutions keep Timor-Leste fragile and in transition on the spectrum of state stability. The objective here is to systematically review Timor-Leste's state and public health successes, showing how a fragile state can consistently improve its status on the continuum of stability and improve health security for the population. The case study follows a state case study approach, together with a disease burden review and a basic description of the health portrait in relation to Timor-Leste's fragile state status. Disease burden and health security are directly proportional to state stability and indirectly proportional to state failure. Timor-Leste is a clear example of how public health can feed into increased state stability. Our discussion attempts to describe how the weak and fragile island nation of Timor-Leste can continue on its current path of transition to state stability by increasing health security for its citizens. We surmise that this can be realized when public policy focuses on primary healthcare access, inclusive state institutions, basic hygiene and preventative vaccination programs. Based on our review, the core findings indicate that by increasing health security, a positive feedback loop of state stability follows. The use of Timor-Leste as a case study better describes the connection between public health and health security; and state stability, development and inclusive state institutions that promote health security

Fragile States, Infectious Disease and Health Security: The Case for Timor-Leste

Timor-Leste is a very young and developing nation state. Endemic infectious disease and weakened health security coupled with its growing and inclusive public institutions keep Timor-Leste fragile and in transition on the spectrum of state stability. The objective here is to systematically review Timor-Leste's state and public health successes, showing how a fragile state can consistently improve its status on the continuum of stability and improve health security for the population. The case study follows a state case study approach, together with a disease burden review and a basic description of the health portrait in relation to Timor-Leste's fragile state status. Disease burden and health security are directly proportional to state stability and indirectly proportional to state failure. Timor-Leste is a clear example of how public health can feed into increased state stability. Our discussion attempts to describe how the weak and fragile island nation of Timor-Leste can continue on its current path of transition to state stability by increasing health security for its citizens. We surmise that this can be realized when public policy focuses on primary healthcare access, inclusive state institutions, basic hygiene and preventative vaccination programs. Based on our review, the core findings indicate that by increasing health security, a positive feedback loop of state stability follows. The use of Timor-Leste as a case study better describes the connection between public health and health security; and state stability, development and inclusive state institutions that promote health security

LINE-1 Methylation Levels in Leukocyte DNA and Risk of Renal Cell Cancer

Leukocyte global DNA methylation levels are currently being considered as biomarkers of cancer susceptibility and have been associated with risk of several cancers. In this study, we aimed to examine the association between long interspersed nuclear elements (LINE-1) methylation levels, as a biomarker of global DNA methylation in blood cell DNA, and renal cell cancer risk.LINE-1 methylation of bisulfite-converted genomic DNA isolated from leukocytes was quantified by pyrosequencing measured in triplicate, and averaged across 4 CpG sites. A total of 328 RCC cases and 654 controls frequency-matched(2∶1) on age(±5years), sex and study center, from a large case-control study conducted in Central and Eastern Europe were evaluated.LINE-1 methylation levels were significantly higher in RCC cases with a median of 81.97% (interquartile range[IQR]: 80.84–83.47) compared to 81.67% (IQR: 80.35–83.03) among controls (p = 0.003, Wilcoxon). Compared to the lowest LINE-1 methylation quartile(Q1), the adjusted ORs for increasing methylation quartiles were as follows: OR(Q2) = 1.84(1.20−2.81), OR(Q3) = 1.72(1.11−2.65) and OR(Q4) = 2.06(1.34−3.17), with a p-trend = 0.004. The association was stronger among current smokers (p-trend<0.001) than former or never smokers (p-interaction = 0.03). To eliminate the possibility of selection bias among controls, the relationship between LINE-1 methylation and smoking was evaluated and confirmed in a case-only analysis, as well.Higher levels of LINE-1 methylation appear to be positively associated with RCC risk, particularly among current smokers. Further investigations using both post- and pre-diagnostic genomic DNA is warranted to confirm findings and will be necessary to determine whether the observed differences occur prior to, or as a result of carcinogenesis

Genetic Contributions to the Association between Adult Height and Head and Neck Cancer : A Mendelian Randomization Analysis

Acknowledgements: The authors thank the Italian Association for Research on Cancer (AIRC, IG 2013 n. 14211) and the PRECeDI project (Marie Skłodowska-Curie Research and Innovation Staff Exchange - RISE N°645740) for supporting the work of Roberta Pastorino and Anna Puggina.Peer reviewedPublisher PD

Exposure-Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies

International audienceBACKGROUND:Evidence is limited regarding risk and the shape of the exposure-response curve at low asbestos exposure levels. We estimated the exposure-response for occupational asbestos exposure and assessed the joint effect of asbestos exposure and smoking by sex and lung cancer subtype in general population studies.METHODS:We pooled 14 case-control studies conducted in 1985-2010 in Europe and Canada, including 17,705 lung cancer cases and 21,813 controls with detailed information on tobacco habits and lifetime occupations. We developed a quantitative job-exposure-matrix to estimate job-, time period-, and region-specific exposure levels. Fiber-years (ff/ml-years) were calculated for each subject by linking the matrix with individual occupational histories. We fit unconditional logistic regression models to estimate odds ratios (ORs), 95% confidence intervals (CIs), and trends.RESULTS:The fully adjusted OR for ever-exposure to asbestos was 1.24 (95% CI, 1.18, 1.31) in men and 1.12 (95% CI, 0.95, 1.31) in women. In men, increasing lung cancer risk was observed with increasing exposure in all smoking categories and for all three major lung cancer subtypes. In women, lung cancer risk for all subtypes was increased in current smokers (ORs ~two-fold). The joint effect of asbestos exposure and smoking did not deviate from multiplicativity among men, and was more than additive among women.CONCLUSIONS:Our results in men showed an excess risk of lung cancer and its subtypes at low cumulative exposure levels, with a steeper exposure-response slope in this exposure range than at higher, previously studied levels. (See video abstract at, http://links.lww.com/EDE/B161.)

In-Home Coal and Wood Use and Lung Cancer Risk: A Pooled Analysis of the International Lung Cancer Consortium

10.1289/ehp.1002217Environmental Health Perspectives118121743-174

Comprehensive Analysis of 5-Aminolevulinic Acid Dehydrogenase (ALAD) Variants and Renal Cell Carcinoma Risk among Individuals Exposed to Lead

BACKGROUND: Epidemiologic studies are reporting associations between lead exposure and human cancers. A polymorphism in the 5-aminolevulinic acid dehydratase (ALAD) gene affects lead toxicokinetics and may modify the adverse effects of lead. METHODS: The objective of this study was to evaluate single-nucleotide polymorphisms (SNPs) tagging the ALAD region among renal cancer cases and controls to determine whether genetic variation alters the relationship between lead and renal cancer. Occupational exposure to lead and risk of cancer was examined in a case-control study of renal cell carcinoma (RCC). Comprehensive analysis of variation across the ALAD gene was assessed using a tagging SNP approach among 987 cases and 1298 controls. Occupational lead exposure was estimated using questionnaire-based exposure assessment and expert review. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression. RESULTS: The adjusted risk associated with the ALAD variant rs8177796(CT/TT) was increased (OR = 1.35, 95%CI = 1.05-1.73, p-value = 0.02) when compared to the major allele, regardless of lead exposure. Joint effects of lead and ALAD rs2761016 suggest an increased RCC risk for the homozygous wild-type and heterozygous alleles ((GG)OR = 2.68, 95%CI = 1.17-6.12, p = 0.01; (GA)OR = 1.79, 95%CI = 1.06-3.04 with an interaction approaching significance (p(int) = 0.06). No significant modification in RCC risk was observed for the functional variant rs1800435(K68N). Haplotype analysis identified a region associated with risk supporting tagging SNP results. CONCLUSION: A common genetic variation in ALAD may alter the risk of RCC overall, and among individuals occupationally exposed to lead. Further work in larger exposed populations is warranted to determine if ALAD modifies RCC risk associated with lead exposure