Last data update: Apr 28, 2025. (Total: 49156 publications since 2009)
Records 1-13 (of 13 Records) |
Query Trace: Qu S[original query] |
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Combining genomics and epidemiology to track mumps virus transmission in the United States.
Wohl S , Metsky HC , Schaffner SF , Piantadosi A , Burns M , Lewnard JA , Chak B , Krasilnikova LA , Siddle KJ , Matranga CB , Bankamp B , Hennigan S , Sabina B , Byrne EH , McNall RJ , Shah RR , Qu J , Park DJ , Gharib S , Fitzgerald S , Barreira P , Fleming S , Lett S , Rota PA , Madoff LC , Yozwiak NL , MacInnis BL , Smole S , Grad YH , Sabeti PC . PLoS Biol 2020 18 (2) e3000611 ![]() ![]() Unusually large outbreaks of mumps across the United States in 2016 and 2017 raised questions about the extent of mumps circulation and the relationship between these and prior outbreaks. We paired epidemiological data from public health investigations with analysis of mumps virus whole genome sequences from 201 infected individuals, focusing on Massachusetts university communities. Our analysis suggests continuous, undetected circulation of mumps locally and nationally, including multiple independent introductions into Massachusetts and into individual communities. Despite the presence of these multiple mumps virus lineages, the genomic data show that one lineage has dominated in the US since at least 2006. Widespread transmission was surprising given high vaccination rates, but we found no genetic evidence that variants arising during this outbreak contributed to vaccine escape. Viral genomic data allowed us to reconstruct mumps transmission links not evident from epidemiological data or standard single-gene surveillance efforts and also revealed connections between apparently unrelated mumps outbreaks. |
CD4 lymphocyte enumeration and hemoglobin assessment aid for priority decisions: a multisite evaluation of the BD FACSPresto System
Thakar M , Angira F , Pattanapanyasat K , Wu AHB , O'Gorman M , Zeng H , Qu C , Mahajan B , Sukapirom K , Chen D , Hao Y , Gong Y , Indig MA , Graminske S , Orta D , d'Empaire N , Lu B , Omana-Zapata I , Zeh C . Open AIDS J 2017 11 76-90 Background: The BD FACSPresto system uses capillary and venous blood to measure CD4 absolute counts (CD4), %CD4 in lymphocytes, and hemoglobin (Hb) in approximately 25 minutes. CD4 cell count is used with portable CD4 counters in resource-limited settings to manage HIV/AIDS patients. A method comparison was performed using capillary and venous samples from seven clinical laboratories in five countries. The BD FACSPresto system was assessed for variability between laboratory, instrument/operators, cartridge lots and within-run at four sites. Methods: Samples were collected under approved voluntary consent. EDTA-anticoagulated venous samples were tested for CD4 and %CD4 T cells using the gold-standard BD FACSCalibur() system, and for Hb, using the Sysmex((R)) KX-21N() analyzer. Venous and capillary samples were tested on the BD FACSPresto system. Matched data was analyzed for bias (Deming linear regression and Bland-Altman methods), and for concordance around the clinical decision point. The coefficient of variation was estimated per site, instrument/operator, cartridge-lot and between-runs. Results: For method comparison, 93% of the 720 samples were from HIV-positive and 7% from HIV-negative or normal subjects. CD4 and %CD4 T cells venous and capillary results gave slopes within 0.96-1.05 and R(2) >/=0.96; Hb slopes were >/=1.00 and R(2) >/=0.89. Variability across sites/operators gave %CV <5.8% for CD4 counts, <1.9% for %CD4 and <3.2% for Hb. The total %CV was <7.7% across instrument/cartridge lot. Conclusion: The BD FACSPresto system provides accurate, reliable, precise CD4/%CD4/Hb results compared to gold-standard methods, irrespective of venous or capillary blood sampling. The data showed good agreement between the BD FACSPresto, BD FACSCalibur and Sysmex systems. |
Virus genomes reveal factors that spread and sustained the Ebola epidemic.
Dudas G , Carvalho LM , Bedford T , Tatem AJ , Baele G , Faria NR , Park DJ , Ladner JT , Arias A , Asogun D , Bielejec F , Caddy SL , Cotten M , D'Ambrozio J , Dellicour S , Caro AD , Diclaro JW , Duraffour S , Elmore MJ , Fakoli LS , Faye O , Gilbert ML , Gevao SM , Gire S , Gladden-Young A , Gnirke A , Goba A , Grant DS , Haagmans BL , Hiscox JA , Jah U , Kugelman JR , Liu D , Lu J , Malboeuf CM , Mate S , Matthews DA , Matranga CB , Meredith LW , Qu J , Quick J , Pas SD , Phan MV , Pollakis G , Reusken CB , Sanchez-Lockhart M , Schaffner SF , Schieffelin JS , Sealfon RS , Simon-Loriere E , Smits SL , Stoecker K , Thorne L , Tobin EA , Vandi MA , Watson SJ , West K , Whitmer S , Wiley MR , Winnicki SM , Wohl S , Wolfel R , Yozwiak NL , Andersen KG , Blyden SO , Bolay F , Carroll MW , Dahn B , Diallo B , Formenty P , Fraser C , Gao GF , Garry RF , Goodfellow I , Gunther S , Happi CT , Holmes EC , Kargbo B , Keita S , Kellam P , Koopmans MP , Kuhn JH , Loman NJ , Magassouba N , Naidoo D , Nichol ST , Nyenswah T , Palacios G , Pybus OG , Sabeti PC , Sall A , Stroher U , Wurie I , Suchard MA , Lemey P , Rambaut A . Nature 2017 544 (7650) 309-315 ![]() The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics. |
Vibration characteristics of golf club heads in their handheld grinding process and potential approaches for reducing the vibration exposure
Chen Q , Lin H , Xiao B , Welcome DE , Lee J , Chen G , Tang S , Zhang D , Xu G , Yan M , Yan H , Xu X , Qu H , Dong RG . Int J Ind Ergon 2016 62 27-41 To control vibration-induced white finger among workers performing the fine grinding of golf club heads, the aims of this study are to clarify the major vibration sources in the grinding process, to identify and understand the basic characteristics of the club head vibration, and to propose potential approaches for reducing the vibration exposure. The vibrations on two typical club heads and two belt grinding machines were measured at a workplace. A simulated test station was also constructed and used to help examine some influencing factors of the club head vibration. This study found that the club head vibration was the combination of the vibration transmitted from the grinding machines and that generated in the grinding process. As a result, any factor that affects the machine vibration, the grinding vibration, and/or the dynamic response of the club head can influence the vibration exposure of the fingers or hands holding the club head in the grinding process. The significant influencing factors identified in the study include testing subject, grinding machine, machine operation speed, drive wheel condition, club head model, mechanical constraints imposed on the club head during the grinding, and machine foot pad. These findings suggest that the vibration exposure can be controlled by reducing the grinding machine vibration, changing the workpiece dynamic properties, and mitigating the vibration transmission in its pathway. Many potential methods for the control are proposed and discussed. Relevance to industry: Vibrations on handheld workpieces can be effectively transmitted to the hands, especially the fingers. As a result, a major component of the hand-arm vibration syndrome - vibration-induced white finger - has been observed among some workers performing the grinding and/or polishing tasks of the handheld workpieces such as golf club heads. The results of this study can be used to develop more effective methods and technologies to control the vibration exposure of these workers. This may help effectively control this occupational disease. |
Economic evaluation of combined diet and physical activity promotion programs to prevent type 2 diabetes among persons at increased risk: A systematic review for the Community Preventive Services Task Force
Li R , Qu S , Zhang P , Chattopadhyay S , Gregg EW , Albright A , Hopkins D , Pronk NP . Ann Intern Med 2015 163 (6) 452-60 BACKGROUND: Diabetes is a highly prevalent and costly disease. Studies indicate that combined diet and physical activity promotion programs can prevent type 2 diabetes among persons at increased risk. PURPOSE: To systematically evaluate the evidence on cost, cost-effectiveness, and cost-benefit estimates of diet and physical activity promotion programs. DATA SOURCES: Cochrane Library, EMBASE, MEDLINE, PsycINFO, Sociological Abstracts, Web of Science, EconLit, and CINAHL through 7 April 2015. STUDY SELECTION: English-language studies from high-income countries that provided data on cost, cost-effectiveness, or cost-benefit ratios of diet and physical activity promotion programs with at least 2 sessions over at least 3 months delivered to persons at increased risk for type 2 diabetes. DATA EXTRACTION: Dual abstraction and assessment of relevant study details. DATA SYNTHESIS: Twenty-eight studies were included. Costs were expressed in 2013 U.S. dollars. The median program cost per participant was $653. Costs were lower for group-based programs (median, $417) and programs implemented in community or primary care settings (median, $424) than for the U.S. DPP (Diabetes Prevention Program) trial and the DPP Outcomes Study ($5881). Twenty-two studies assessed the incremental cost-effectiveness ratios (ICERs) of the programs. From a health system perspective, 16 studies reported a median ICER of $13 761 per quality-adjusted life-year (QALY) saved. Group-based programs were more cost-effective (median, $1819 per QALY) than those that used individual sessions (median, $15 846 per QALY). No cost-benefit studies were identified. LIMITATION: Information on recruitment costs and cost-effectiveness of translational programs implemented in community and primary care settings was limited. CONCLUSION: Diet and physical activity promotion programs to prevent type 2 diabetes are cost-effective among persons at increased risk. Costs are lower when programs are delivered to groups in community or primary care settings. PRIMARY FUNDING SOURCE: None. |
High school completion programs: a Community Guide systematic economic review
Qu S , Chattopadhyay SK , Hahn RA . J Public Health Manag Pract 2015 22 (3) E47-56 CONTEXT: On-time high school graduation rate is among the 26 leading health indicators for Healthy People 2020. High school completion (HSC) programs aim to increase the likelihood that students finish high school and receive a high school diploma or complete a GED (General Educational Development) program. This systematic review was conducted to determine the economic impact of HSC interventions, assess variability in cost-effectiveness of different types of programs, and compare the lifetime benefit of completing high school with the cost of intervention. EVIDENCE ACQUISITION: Forty-seven included studies were identified from 5303 articles published in English from January 1985 to December 2012. The economic evidence was summarized by type of HSC program. All monetary values were expressed in 2012 US dollars. The data were analyzed in 2013. EVIDENCE SYNTHESIS: Thirty-seven studies provided estimates of incremental cost per additional high school graduate, with a median cost for HSC programs of $69 800 (interquartile interval = $35 900-$130 300). Cost-effectiveness ratios varied depending on intervention type, study settings, student populations, and costing methodologies. Ten studies estimated the lifetime difference of economic benefits between high school nongraduates and graduates; 4 used a governmental perspective and reported benefit per additional high school to range from $187 000 to $240 000; 6 used a societal perspective and reported a range of $347 000 to $718 000. Benefits exceeded costs in most studies from a governmental perspective and in all studies from a societal perspective. CONCLUSION: Interventions to increase HSC rates produce substantial economic benefits to government and society including averted health care costs. From a societal perspective, the benefits also exceed costs, implying a positive rate of return from investment in HSC programs. |
Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone.
Park DJ , Dudas G , Wohl S , Goba A , Whitmer SL , Andersen KG , Sealfon RS , Ladner JT , Kugelman JR , Matranga CB , Winnicki SM , Qu J , Gire SK , Gladden-Young A , Jalloh S , Nosamiefan D , Yozwiak NL , Moses LM , Jiang PP , Lin AE , Schaffner SF , Bird B , Towner J , Mamoh M , Gbakie M , Kanneh L , Kargbo D , Massally JL , Kamara FK , Konuwa E , Sellu J , Jalloh AA , Mustapha I , Foday M , Yillah M , Erickson BR , Sealy T , Blau D , Paddock C , Brault A , Amman B , Basile J , Bearden S , Belser J , Bergeron E , Campbell S , Chakrabarti A , Dodd K , Flint M , Gibbons A , Goodman C , Klena J , McMullan L , Morgan L , Russell B , Salzer J , Sanchez A , Wang D , Jungreis I , Tomkins-Tinch C , Kislyuk A , Lin MF , Chapman S , MacInnis B , Matthews A , Bochicchio J , Hensley LE , Kuhn JH , Nusbaum C , Schieffelin JS , Birren BW , Forget M , Nichol ST , Palacios GF , Ndiaye D , Happi C , Gevao SM , Vandi MA , Kargbo B , Holmes EC , Bedford T , Gnirke A , Stroher U , Rambaut A , Garry RF , Sabeti PC . Cell 2015 161 (7) 1516-26 ![]() The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission. |
Out-of-school-time academic programs to improve school achievement: a Community Guide health equity systematic review
Knopf JA , Hahn RA , Proia KK , Truman BI , Johnson RL , Muntaner C , Fielding JE , Jones CP , Fullilove MT , Hunt PC , Qu S , Chattopadhyay SK , Milstein B . J Public Health Manag Pract 2015 21 (6) 594-608 CONTEXT: Low-income and minority status in the United States are associated with poor educational outcomes, which, in turn, reduce the long-term health benefits of education. OBJECTIVE: This systematic review assessed the extent to which out-of-school-time academic (OSTA) programs for at-risk students, most of whom are from low-income and racial/ethnic minority families, can improve academic achievement. Because most OSTA programs serve low-income and ethnic/racial minority students, programs may improve health equity. DESIGN: Methods of the Guide to Community Preventive Services were used. An existing systematic review assessing the effects of OSTA programs on academic outcomes (Lauer et al 2006; search period 1985-2003) was supplemented with a Community Guide update (search period 2003-2011). MAIN OUTCOME MEASURE: Standardized mean difference. RESULTS: Thirty-two studies from the existing review and 25 studies from the update were combined and stratified by program focus (ie, reading-focused, math-focused, general academic programs, and programs with minimal academic focus). Focused programs were more effective than general or minimal academic programs. Reading-focused programs were effective only for students in grades K-3. There was insufficient evidence to determine effectiveness on behavioral outcomes and longer-term academic outcomes. CONCLUSIONS: OSTA programs, particularly focused programs, are effective in increasing academic achievement for at-risk students. Ongoing school and social environments that support learning and development may be essential to ensure the longer-term benefits of OSTA programs. |
Effects of mental health benefits legislation: a Community Guide systematic review
Sipe TA , Finnie RK , Knopf JA , Qu S , Reynolds JA , Thota AB , Hahn RA , Goetzel RZ , Hennessy KD , McKnight-Eily LR , Chapman DP , Anderson CW , Azrin S , Abraido-Lanza AF , Gelenberg AJ , Vernon-Smiley ME , Nease DE Jr . Am J Prev Med 2015 48 (6) 755-766 CONTEXT: Health insurance benefits for mental health services typically have paid less than benefits for physical health services, resulting in potential underutilization or financial burden for people with mental health conditions. Mental health benefits legislation was introduced to improve financial protection (i.e., decrease financial burden) and to increase access to, and use of, mental health services. This systematic review was conducted to determine the effectiveness of mental health benefits legislation, including executive orders, in improving mental health. EVIDENCE ACQUISITION: Methods developed for the Guide to Community Preventive Services were used to identify, evaluate, and analyze available evidence. The evidence included studies published or reported from 1965 to March 2011 with at least one of the following outcomes: access to care, financial protection, appropriate utilization, quality of care, diagnosis of mental illness, morbidity and mortality, and quality of life. Analyses were conducted in 2012. EVIDENCE SYNTHESIS: Thirty eligible studies were identified in 37 papers. Implementation of mental health benefits legislation was associated with financial protection (decreased out-of-pocket costs) and appropriate utilization of services. Among studies examining the impact of legislation strength, most found larger positive effects for comprehensive parity legislation or policies than for less-comprehensive ones. Few studies assessed other mental health outcomes. CONCLUSIONS: Evidence indicates that mental health benefits legislation, particularly comprehensive parity legislation, is effective in improving financial protection and increasing appropriate utilization of mental health services for people with mental health conditions. Evidence was limited for other mental health outcomes. |
Legislations and policies to expand mental health and substance abuse benefits in health insurance plans: a community guide systematic economic review
Jacob V , Qu S , Chattopadhyay S , Sipe TA , Knopf JA , Goetzel RZ , Finnie R , Thota AB . J Ment Health Policy Econ 2015 18 (1) 39-48 BACKGROUND: Health insurance plans have historically limited the benefits for mental health and substance abuse (MH/SA) services compared to benefits for physical health services. In recent years, legislative and policy initiatives in the U.S. have been taken to expand MH/SA health insurance benefits and achieve parity with physical health benefits. The relevance of these legislations for international audiences is also explored, particularly for the European context. AIMS OF THE STUDY: This paper reviews the evidence of costs and economic benefits of legislative or policy interventions to expand MH/SA health insurance benefits in the U.S. The objectives are to assess the economic value of the interventions by comparing societal cost to societal benefits, and to determine impact on costs to insurance plans resulting from expansion of these benefits. METHODS: The search for economic evidence covered literature published from January 1950 to March 2011 and included evaluations of federal and state laws or rules that expanded MH/SA benefits as well as voluntary actions by large employers. Two economists screened and abstracted the economic evidence of MH/SA benefits legislation based on standard economic and actuarial concepts and methods. RESULTS: The economic review included 12 studies: eleven provided evidence on cost impact to health plans, and one estimated the effect on suicides. There was insufficient evidence to determine if the intervention was cost-effective or cost-saving. However, the evidence indicates that MH/SA benefits expansion did not lead to any substantial increase in costs to insurance plans, measured as a percentage of insurance premiums. DISCUSSION AND LIMITATIONS: This review is unable to determine the overall economic value of policies that expanded MH/SA insurance benefits due to lack of cost-effectiveness and cost-benefit studies, predominantly due to the lack of evaluations of morbidity and mortality outcomes. This may be remedied in time when long-term MH/SA patient-level data becomes available to researchers. A limitation of this review is that legislations considered here have been superseded by recent legislations that have stronger and broader impacts on MH/SA benefits within private and public insurance: Mental Health Parity and Addiction Equity Act of 2008 (MHPAEA) and the Patient Protection and Affordable Care Act of 2010 (ACA). IMPLICATIONS FOR FUTURE RESEARCH: Economic assessments over the long term such as cost per QALY saved and cost-benefit will be feasible as more data becomes available from plans that implemented recent expansions of MH/SA benefits. Results from these evaluations will allow a better estimate of the economic impact of the interventions from a societal perspective. Future research should also evaluate the more downstream effects on business decisions about labor, such as effects on hiring, retention, and the offer of health benefits as part of an employee compensation package. Finally, the economic effect of the far reaching ACA of 2010 on mental health and substance abuse prevalence and care is also a subject for future research. |
Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients
Lee N , Leo YS , Cao B , Chan PK , Kyaw WM , Uyeki TM , Tam WW , Cheung CS , Yung IM , Li H , Gu L , Liu Y , Liu Z , Qu J , Hui DS . Eur Respir J 2015 45 (6) 1642-52 We aimed to study factors influencing outcomes of adults hospitalised for seasonal and pandemic influenza. Individual-patient data from three Asian cohorts (Hong Kong, Singapore and Beijing; N=2649) were analysed. Adults hospitalised for laboratory-confirmed influenza (prospectively diagnosed) during 2008-2011 were studied. The primary outcome measure was 30-day survival. Multivariate Cox regression models (time-fixed and time-dependent) were used. Patients had high morbidity (respiratory/nonrespiratory complications in 68.4%, respiratory-failure in 48.6%, pneumonia in 40.8% and bacterial superinfections in 10.8%) and mortality (5.9% at 30 days and 6.9% at 60 days). 75.2% received neuraminidase inhibitors (NAI) (73.8% received oseltamivir and 1.4% received peramivir/zanamivir; 44.5% of patients received NAI 2 days and 65.5% 5 days after onset of illness); 23.1% received systemic corticosteroids. There were fewer deaths among NAI-treated patients (5.3% versus 7.6%; p=0.032). NAI treatment was independently associated with survival (adjusted hazard ratio (HR) 0.28, 95% CI 0.19-0.43), adjusted for treatment-propensity score and patient characteristics. Superinfections increased (adjusted HR 2.18, 95% CI 1.52-3.11) and chronic statin use decreased (adjusted HR 0.44, 95% CI 0.23-0.84) death risks. Best survival was shown when treatment started within 2 days (adjusted HR 0.20, 95% CI 0.12-0.32), but there was benefit with treatment within 3-5 days (adjusted HR 0.35, 95% CI 0.21-0.58). Time-dependent analysis showed consistent results of NAI treatment (adjusted HR 0.39, 95% CI 0.27-0.57). Corticosteroids increased superinfection (9.7% versus 2.7%) and deaths when controlled for indications (adjusted HR 1.73, 95% CI 1.14-2.62). Early NAI treatment was associated with shorter length of stay in a subanalysis. NAI treatment may improve survival of hospitalised influenza patients; benefit is greatest from, but not limited to, treatment started within 2 days of illness. Superinfections and corticosteroids increase mortality. Antiviral and non-antiviral management strategies should be considered. |
Publicized sobriety checkpoint programs: a Community Guide systematic review
Bergen G , Pitan A , Qu S , Shults RA , Chattopadhyay SK , Elder RW , Sleet DA , Coleman HL , Compton RP , Nichols JL , Clymer JM , Calvert WB . Am J Prev Med 2014 46 (5) 529-539 CONTEXT: Publicized sobriety checkpoint programs deter alcohol-impaired driving by stopping drivers systematically to assess their alcohol impairment. Sobriety checkpoints were recommended in 2001 by the Community Preventive Services Task Force for reducing alcohol-impaired driving, based on strong evidence of effectiveness. Since the 2001 review, attention to alcohol-impaired driving as a U.S. public health problem has decreased. This systematic review was conducted to determine if available evidence supports the effectiveness of publicized sobriety checkpoint programs in reducing alcohol-impaired driving, given the current context. The economic costs and benefits of the intervention were also assessed. EVIDENCE ACQUISITION: This review focused on studies that evaluated the effects of publicized sobriety checkpoint programs on alcohol-involved crash fatalities. Using Community Guide methods, a systematic search was conducted for studies published between July 2000 and March 2012 that assessed the effectiveness of publicized sobriety checkpoint programs. EVIDENCE SYNTHESIS: Fourteen evaluations of selective breath testing and one of random breath testing checkpoints met the inclusion criteria for the systematic review, conducted in 2012. Ten evaluations assessed the effects of publicized sobriety checkpoint programs on alcohol-involved crash fatalities, finding a median reduction of 8.9% in this crash type (interquartile interval=-16.5%, -3.5%). Five economic evaluations showed benefit-cost ratios ranging from 2:1 to 57:1. CONCLUSIONS: The number of studies, magnitude of effect, and consistency of findings indicate strong evidence of the effectiveness of publicized sobriety checkpoint programs in reducing alcohol-involved crash fatalities. Economic evidence shows that these programs also have the potential for substantial cost savings. |
Prenatal exposure to polycyclic aromatic hydrocarbons, benzo[a]pyrene-DNA adducts, and genomic DNA methylation in cord blood.
Herbstman JB , Tang D , Zhu D , Qu L , Sjodin A , Li Z , Camann D , Perera FP . Environ Health Perspect 2012 120 (5) 733-8 ![]() BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic environmental pollutants generated during incomplete combustion. After exposure and during metabolism, PAHs can form reactive epoxides that can covalently bind to DNA. These PAH-DNA adducts are established markers of cancer risk. PAH exposure has been associated with epigenetic alterations, including genomic cytosine methylation. Both global hypomethylation and hypermethylation of specific genes have been associated with cancer and other diseases in humans. Experimental evidence suggests that PAH-DNA adduct formation may preferentially target methylated genomic regions. Early embryonic development may be a particularly susceptible period for PAH exposure, resulting in both increased PAH-DNA adducts and altered DNA methylation. OBJECTIVE: We explored whether prenatal exposure to PAHs is associated with genomic DNA methylation in cord blood and whether methylation levels are associated with the presence of detectable PAH-DNA adducts. METHODS: In a longitudinal cohort study of nonsmoking women in New York City, we measured PAH exposure during pregnancy using personal air monitors, assessed PAH internal dose using prenatal urinary metabolites (in a subset), and quantified benzo[a]pyrene-DNA adducts and genomic DNA methylation in cord blood DNA among 164 participants. RESULTS: Prenatal PAH exposure was associated with lower global methylation in umbilical cord white blood cells (p = 0.05), but global methylation levels were positively associated with the presence of detectable adducts in cord blood (p = 0.01). CONCLUSIONS: These observations suggest that PAH exposure was adequate to alter global methylation in our study population. Additional epidemiologic studies that can measure site-specific cytosine methylation and adduct formation will improve our ability to understand this complex molecular pathway in vivo. |
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