Publications by authors named "Paul T Strickland"

48 Publications

EXPOSURE ASSESSMENT OF RAYONG OIL SPILL CLEANUP WORKERS.

Expo Health 2020 12 5;12(4):617-628. Epub 2019 Sep 5.

Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, United States.

Background: In July of 2013, a pipeline connecting an offshore oil platform to a tanker caused crude oil to spill into the Sea of Rayong off the coast of Thailand. The resulting oil slick, estimated to be between 50 and 190 cubic meters (336-1,200 barrels), washed ashore one day later on the island of Samet. We conducted a study to quantify internal dose of polycyclic aromatic hydrocarbons (PAHs) and benzene in 1,262 oil spill cleanup workers, and to examine factors related to their dose.

Methods: Frozen stored urine samples (n=1343) collected from the workers during the one month cleanup period were used to measure the concentration of 1-hydroxypyrene-glucuronide (1-OHPG), cotinine and creatinine. Data from questionnaires and urinary trans,trans-muconic acid (t,t-MA), a benzene metabolite, measured previously as part of a worker health surveillance plan, were linked with the laboratory data.

Results: The internal dose of urinary 1-OHPG was highest in individuals who worked during the first 3 days of cleanup work (median: 0.97 pmol/ml) and was 66.7% lower (median: 0.32 pmol/ml) among individuals who worked in the final week of the study (days 21-28). After adjusting for age, cotinineand creatinine by regression analysis, the decline in urinary 1-OHPG concentration with days of cleanup remained significant (P-trend <0.001). A decreasing trend by days of cleanup was also observed for detectable urinary t,t-MA percentage (P-trend <0.001).

Conclusion: Rayong oil spill cleanup workers exhibited evidence of elevated levels of PAH and benzene exposure during the early weeks of cleanup, compared to near background levels 4 weeks after cleanup began. Long-term health monitoring of oil spill cleanup workers is advised.
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http://dx.doi.org/10.1007/s12403-019-00320-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876312PMC
December 2020

State of the Science in Dried Blood Spots.

Clin Chem 2018 04 29;64(4):656-679. Epub 2017 Nov 29.

Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.

Background: Advancements in the quality and availability of highly sensitive analytical instrumentation and methodologies have led to increased interest in the use of microsamples. Among microsamples, dried blood spots (DBS) are the most well-known. Although there have been a variety of review papers published on DBS, there has been no attempt at describing the full range of analytes measurable in DBS, or any systematic approach published for characterizing the strengths and weaknesses associated with adoption of DBS analyses.

Content: A scoping review of reviews methodology was used for characterizing the state of the science in DBS. We identified 2018 analytes measured in DBS and found every common analytic method applied to traditional liquid samples had been applied to DBS samples. Analytes covered a broad range of biomarkers that included genes, transcripts, proteins, and metabolites. Strengths of DBS enable its application in most clinical and laboratory settings, and the removal of phlebotomy and the need for refrigeration have expanded biosampling to hard-to-reach and vulnerable populations. Weaknesses may limit adoption in the near term because DBS is a nontraditional sample often requiring conversion of measurements to plasma or serum values. Opportunities presented by novel methodologies may obviate many of the current limitations, but threats around the ethical use of residual samples must be considered by potential adopters.

Summary: DBS provide a wide range of potential applications that extend beyond the reach of traditional samples. Current limitations are serious but not intractable. Technological advancements will likely continue to minimize constraints around DBS adoption.
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http://dx.doi.org/10.1373/clinchem.2017.275966DOI Listing
April 2018

Predictors of polycyclic aromatic hydrocarbon exposure and internal dose in inner city Baltimore children.

J Expo Sci Environ Epidemiol 2017 05 14;27(3):290-298. Epub 2016 Dec 14.

Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.

Polycyclic aromatic hydrocarbons (PAHs), the by-products of incomplete combustion of organic materials, are commonly found on particulate matter (PM) and have been associated with the development of asthma and asthma exacerbation in urban populations. We examined time spent in the home and outdoors as predictors of exposures to airborne PAHs and measured urinary 1-hydroxypyrene-glucuronide (1-OHPG) as internal dose of PAHs in 118 children aged 5-12 years from Baltimore, MD. During weeklong periods (Saturday-Saturday) in each of four seasons: daily activities were assessed using questionnaires, indoor air nicotine and PM concentrations were monitored, and urine specimens were collected on Tuesday (day 3) and Saturday (day 7) for measurement of 1-OHPG. Time spent in non-smoking homes was associated with significantly decreased 1-OHPG concentration in urine (β=-0.045, 95% CI (-0.076, -0.013)), and secondhand smoke (SHS) exposures modified these associations, with higher urinary 1-OHPG concentrations in children spending time in smoking homes than non-smoking homes (P-value for interaction=0.012). Time spent outdoors was associated with increased urinary 1-OHPG concentrations (β=0.097, 95% CI (0.037, 0.157)) in boys only. Our results suggest that SHS and ambient (outdoor) air pollution contribute to internal dose of PAHs in inner city children.
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http://dx.doi.org/10.1038/jes.2016.57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516642PMC
May 2017

Polycyclic aromatic hydrocarbons and childhood asthma.

Eur J Epidemiol 2015 Feb 20;30(2):91-101. Epub 2015 Jan 20.

Program in Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room E7535, Baltimore, MD, USA.

Asthma is the most common chronic illness in children living in developed countries and the leading cause of childhood hospitalization and school absenteeism. Prevalence rates of asthma are increasing and show disparities across gender, geographic regions, and ethnic/racial groups. Common risk factors for developing childhood asthma include exposure to tobacco smoke, previous allergic reactions, a family history of asthma, allergic rhinitis or eczema, living in an urban environment, obesity and lack of physical exercise, severe lower respiratory tract infections, and male gender. Asthma exacerbation in children can be triggered by a variety of factors, including allergens (e.g., pollen, dust mites, and animal dander), viral and bacterial infections, exercise, and exposure to airway irritants. Recent studies have shown that exposure to polycyclic aromatic hydrocarbons (PAHs), a major component of fine particulate matter from combustion sources, is also associated with onset of asthma, and increasing asthmatic symptoms. In this paper, we review sources of childhood PAH exposure and the association between airborne PAH exposure and childhood asthma prevalence and exacerbation.
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http://dx.doi.org/10.1007/s10654-015-9988-6DOI Listing
February 2015

Polycyclic aromatic hydrocarbons and risk of gastric cancer in the Shanghai Women's Health Study.

Int J Mol Epidemiol Genet 2014 22;5(3):140-4. Epub 2014 Oct 22.

Department of Medicine, School of Medicine, Vanderbilt University Nashville, TN, USA.

Purpose: Polycyclic aromatic hydrocarbons (PAHs) are byproducts of incomplete combustion of organic materials. Sources include tobacco smoke, charbroiled meat, and air pollution. Indirect evidence suggests that PAHs may be associated with carcinogenesis, but the association with gastric cancer is unclear.

Methods: Using a nested case-control study design, we examined prediagnostic urinary concentrations of 1-hydroxypyrene glucuronide (1-OHPG), a PAH metabolite, in 153 gastric cancer cases and 306 matched controls within the Shanghai Women's Health Study. Conditional logistic regression adjusted for potential risk factors was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results: Urinary 1-OHPG concentrations were slightly higher among cases than controls, with medians of 0.29 μmol/mol Cr (interquartile range, 0.16-0.48) and 0.24 μmol/mol Cr (interquartile range, 0.12-0.45), respectively. Increasing concentrations of 1-OHPG appeared to be associated with elevated risk of gastric cancer, but not within the highest category of 1-OHPG (Q4 vs Q1: OR = 1.4; 95% CI = 0.8-2.5).

Conclusions: Our findings suggest that higher concentrations of 1-OHPG are related to gastric cancer risk, but no clear dose-response relationship was observed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214261PMC
November 2014

Arylesterase phenotype-specific positive association between arylesterase activity and cholinesterase specific activity in human serum.

Int J Environ Res Public Health 2014 Jan 27;11(2):1422-43. Epub 2014 Jan 27.

Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.

Context: Cholinesterase (ChE) specific activity is the ratio of ChE activity to ChE mass and, as a biomarker of exposure to cholinesterase inhibitors, has a potential advantage over simple ChE activity.

Objective: To examine the association of several potential correlates (serum arylesterase/paraoxonase activity, serum albumin, sex, age, month of blood collection, and smoking) with plasma ChE specific activity.

Methods: We analyzed data from 195 cancer-free controls from a nested case-control study, accounting for potential confounding.

Results: Arylesterase activity had an independent, statistically significant positive association with ChE specific activity, and its magnitude was the greatest for the arylesterase phenotype corresponding to the QQ PON1192 genotype followed by phenotypes corresponding to QR and RR genotypes. Serum albumin was positively associated with ChE specific activity.

Conclusions: Plasma arylesterase activity was positively associated with plasma ChE specific activity. This observation is consistent with protection conferred by a metabolic phenotype resulting in reduced internal dose.
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http://dx.doi.org/10.3390/ijerph110201422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945546PMC
January 2014

Polycyclic aromatic hydrocarbons: determinants of urinary 1-hydroxypyrene glucuronide concentration and risk of colorectal cancer in the Shanghai Women's Health Study.

BMC Cancer 2013 Jun 11;13:282. Epub 2013 Jun 11.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

Background: Associations between polycyclic aromatic hydrocarbons (PAHs) and colorectal cancer have been reported previously but few studies have characterized PAH exposure using biological measurements. We evaluated colorectal cancer risk in relation to urinary concentration of 1-hydroxypyrene glucuronide (1-OHPG), a polycyclic aromatic hydrocarbon (PAH) metabolite, and assessed determinants of PAH exposure among controls in the Shanghai Women's Health Study (SWHS).

Methods: Concentrations of 1-OHPG were measured in spot urine samples collected from 343 colorectal cancer cases and 343 individually matched controls. Questionnaires were administered to collect information on demographic characteristics and reported exposures. Odds ratios were calculated for risk of colorectal cancer in relation to quartiles of urinary 1-OHPG concentration. Potential determinants of natural log-transformed urinary 1-OHPG concentration were evaluated among a combined sample of controls from this study and another nested case-control study in the SWHS (N(total)=652).

Results: No statistically significant differences in risk of colorectal cancer by urinary 1-OHPG levels were observed. Among controls, the median (interquartile range) urinary 1-OHPG concentration was 2.01 pmol/mL (0.95-4.09). Active and passive smoking, using coal as a cooking fuel, eating foods that were cooked well done, and recent consumption of fried dough (e.g., yóutiáo) were associated with elevated levels of 1-OHPG, though only active smoking and fried dough consumption achieved statistical significance in multivariate analyses.

Conclusions: This study does not provide evidence of an association between urinary levels of 1-OHPG and risk of colorectal cancer among women. Several environmental and dietary sources of PAH exposure were identified. Overall, the levels of 1-OHPG in this population of predominantly non-smoking women were considerably higher than levels typically observed among non-smokers in Europe, North America, and other developed regions.
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http://dx.doi.org/10.1186/1471-2407-13-282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686696PMC
June 2013

Variation in PAH-related DNA adduct levels among non-smokers: the role of multiple genetic polymorphisms and nucleotide excision repair phenotype.

Int J Cancer 2013 Jun 17;132(12):2738-47. Epub 2012 Dec 17.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20852, USA.

Polycyclic aromatic hydrocarbons (PAHs) likely play a role in many cancers even in never-smokers. We tried to find a model to explain the relationship between variation in PAH-related DNA adduct levels among people with similar exposures, multiple genetic polymorphisms in genes related to metabolic and repair pathways, and nucleotide excision repair (NER) capacity. In 111 randomly selected female never-smokers from the Golestan Cohort Study in Iran, we evaluated 21 SNPs in 14 genes related to xenobiotic metabolism and 12 SNPs in eight DNA repair genes. NER capacity was evaluated by a modified comet assay, and aromatic DNA adduct levels were measured in blood by32P-postlabeling. Multivariable regression models were compared by Akaike's information criterion (AIC). Aromatic DNA adduct levels ranged between 1.7 and 18.6 per 10(8) nucleotides (mean: 5.8 ± 3.1). DNA adduct level was significantly lower in homozygotes for NAT2 slow alleles and ERCC5 non-risk-allele genotype, and was higher in the MPO homozygote risk-allele genotype. The sum of risk alleles in these genes significantly correlated with the log-adduct level (r = 0.4, p < 0.001). Compared with the environmental model, adding Phase I SNPs and NER capacity provided the best fit, and could explain 17% more of the variation in adduct levels. NER capacity was affected by polymorphisms in the MTHFR and ERCC1 genes. Female non-smokers in this population had PAH-related DNA adduct levels three to four times higher than smokers and occupationally-exposed groups in previous studies, with large inter-individual variation which could best be explained by a combination of Phase I genes and NER capacity.
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http://dx.doi.org/10.1002/ijc.27953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597757PMC
June 2013

DNA repair gene variants in relation to overall cancer risk: a population-based study.

Carcinogenesis 2013 Jan 1;34(1):86-92. Epub 2012 Oct 1.

Hollings Cancer Center and Division of Epidemiology and Biostatistics, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA.

The hypothesis that germ-line polymorphisms in DNA repair genes influence cancer risk has previously been tested primarily on a cancer site-specific basis. The purpose of this study was to test the hypothesis that DNA repair gene allelic variants contribute to globally elevated cancer risk by measuring associations with risk of all cancers that occurred within a population-based cohort. In the CLUE II cohort study established in 1989 in Washington County, MD, this study was comprised of all 3619 cancer cases ascertained through 2007 compared with a sample of 2296 with no cancer. Associations were measured between 759 DNA repair gene single nucleotide polymorphisms (SNPs) and risk of all cancers. A SNP in O(6)-methylguanine-DNA methyltransferase, MGMT, (rs2296675) was significantly associated with overall cancer risk [per minor allele odds ratio (OR) 1.30, 95% confidence interval (CI) 1.19-1.43 and P-value: 4.1 × 10(-8)]. The association between rs2296675 and cancer risk was stronger among those aged ≤54 years old than those who were ≥55 years at baseline (P-for-(interaction) = 0.021). OR were in the direction of increased risk for all 15 categories of malignancies studied (P < 0.0001), ranging from 1.22 (P = 0.42) for ovarian cancer to 2.01 (P = 0.008) for urinary tract cancers; the smallest P-value was for breast cancer (OR 1.45, P = 0.0002). The results indicate that the minor allele of MGMT SNP rs2296675, a common genetic marker with 37% carriers, was significantly associated with increased risk of cancer across multiple tissues. Replication is needed to more definitively determine the scientific and public health significance of this observed association.
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http://dx.doi.org/10.1093/carcin/bgs304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534189PMC
January 2013

Exposure to cooking oil fumes and oxidative damages: a longitudinal study in Chinese military cooks.

J Expo Sci Environ Epidemiol 2013 Jan-Feb;23(1):94-100. Epub 2012 Sep 12.

Department of Public Health, National Defence Medical Centre, Taipei, Taiwan, ROC.

Cooking oil fumes (COF) contain polycyclic aromatic hydrocarbons (PAHs), heterocyclic aromatic amines, benzene, and formaldehyde, which may cause oxidative damages to DNA and lipids. We assessed the relations between exposure to COF and subsequent oxidative DNA damage and lipid peroxidation among military cooks and office-based soldiers. The study population, including 61 Taiwanese male military cooks and a reference group of 37 office soldiers, collected urine samples pre-shift of the first weekday and post-shift of the fifth workday. We measured airborne particulate PAHs in military kitchens and offices and concentrations of urinary 1-OHP, a biomarker of PAH exposure, urinary 8-hydroxydeoxyguanosine (8-OHdG), a biomarkers of oxidative DNA damage, and urinary isoprostane (Isop). Airborne particulate PAHs levels in kitchens significantly exceeded those in office areas. The concentrations of urinary 1-OHP among military cooks increased significantly after 5 days of exposure to COF. Using generalized estimating equation analysis adjusting for confounding, a change in log(8-OHdG) and log(Isop) were statistically significantly related to a unit change in log(1-OHP) (regression coefficient (β), β=0.06, 95% CI 0.001-0.12) and (β=0.07, 95% CI 0.001-0.13), respectively. Exposure to PAHs, or other compounds in cooking oil fumes, may cause both oxidative DNA damage and lipid peroxidation.
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http://dx.doi.org/10.1038/jes.2012.87DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029104PMC
June 2013

A multi-day environmental study of polycyclic aromatic hydrocarbon exposure in a high-risk region for esophageal cancer in China.

J Expo Sci Environ Epidemiol 2013 Jan-Feb;23(1):52-9. Epub 2012 Jul 18.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.

Linzhou, China has one of the highest rates of esophageal squamous cell carcinoma in the world. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), may have a role in this increased risk. To better understand PAH sources, we measured PAHs in the air and food of 20 non-smokers over multiple days and compared the concentrations with a urinary PAH biomarker, 1-hydroxypyrene glucuronide (1-OHPG). Sampling occurred over 4 consecutive days. Kitchen air samples (days 2-3) and duplicate diet samples (days 1-4) were analyzed for 14 or more unique PAHs, including BaP. Daily urine samples (days 1-3) were analyzed for 1-OHPG. Mixed-effects models were used to evaluate the associations between air or food PAH concentrations and urine 1-OHPG concentrations. The median kitchen air BaP concentration was 10.2 ng/m(3) (interquartile range (IQR): 5.1-20.2 ng/m(3)). The median daily food BaP concentration and intake were 0.08 ng/g (IQR=0.04-0.16 ng/g) and 86 ng/day (IQR=41-142 ng/day), respectively. The median 1-OHPG concentration was 3.36 pmol/ml (IQR=2.09-6.98 pmol/ml). In mixed-effects models, 1-OHPG concentration increased with same-day concentration of food BaP (P=0.07). Although PAH concentrations in air were not associated with 1-OHPG concentrations, the high concentrations of PAHs in both air and food suggest that they are both important routes of exposure to PAHs in this population. Further evaluation of the role of PAH exposure from air and food in the elevated rates of esophageal cancer in this region is warranted.
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http://dx.doi.org/10.1038/jes.2012.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504638PMC
June 2013

A population-based study of hedgehog pathway gene variants in relation to the dual risk of basal cell carcinoma plus another cancer.

Cancer Epidemiol 2012 Oct 5;36(5):e288-93. Epub 2012 Jun 5.

Department of Radiation Medicine, Georgetown University School of Medicine, Washington, DC, USA.

Introduction: A personal history of basal cell carcinoma (BCC) is associated with increased risk of other malignancies, but the reason is unknown. The hedgehog pathway is critical to the etiology of BCC, and is also believed to contribute to susceptibility to other cancers. This study tested the hypothesis that hedgehog pathway and pathway-related gene variants contribute to the increased risk of subsequent cancers among those with a history of BCC.

Methods: The study was nested within the ongoing CLUE II cohort study, established in 1989 in Washington County, Maryland, USA. The study consisted of a cancer-free control group (n=2296) compared to three different groups of cancer cases ascertained through 2007, those diagnosed with: (1) Other (non-BCC) cancer only (n=2349); (2) BCC only (n=534); and (3) BCC plus other cancer (n=446). The frequencies of variant alleles were compared among these four groups for 20 single nucleotide polymorphisms (SNPs) in 6 hedgehog pathway genes (SHH, IHH, PTCH2, SMO, GLI1, SUFU), and also 22 SNPs in VDR and 8 SNPs in FAS, which have cross-talk with the hedgehog pathway.

Results: Comparing those with both BCC and other cancer versus those with no cancer, no significant associations were observed for any of the hedgehog pathway SNPs, or for the FAS SNPs. One VDR SNP was nominally significantly associated with the BCC cancer-prone phenotype, rs11574085 [per minor allele odds ratio (OR) 1.38, 95% confidence interval (CI) 1.05-1.82; p-value=0.02].

Conclusion: The hedgehog pathway gene SNPs studied, along with the VDR and FAS SNPs studied, are not strongly associated with the BCC cancer-prone phenotype.
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http://dx.doi.org/10.1016/j.canep.2012.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438291PMC
October 2012

A population-based study of DNA repair gene variants in relation to non-melanoma skin cancer as a marker of a cancer-prone phenotype.

Carcinogenesis 2012 Sep 11;33(9):1692-8. Epub 2012 May 11.

Department of Biostatistics, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

For unknown reasons, non-melanoma skin cancer (NMSC) is associated with increased risk of other malignancies. Focusing solely on DNA repair or DNA repair-related genes, this study tested the hypothesis that DNA repair gene variants contribute to the increased cancer risk associated with a personal history of NMSC. From the parent CLUE II cohort study, established in 1989 in Washington County, MD, the study consisted of a cancer-free control group (n 5 2296) compared with three mutually exclusive groups of cancer cases ascertained through 2007: (i) Other (non-NMSC) cancer only (n 5 2349); (ii) NMSC only (n 5 694) and (iii) NMSC plus other cancer (n 5 577). The frequency of minor alleles in 759 DNA repair gene single nucleotide polymorphisms (SNPs) was compared in these four groups. Comparing those with both NMSC and other cancer versus those with no cancer, 10 SNPs had allelic trend P-values <0.01. The two top-ranked SNPs were both within the thymine DNA glycosylase gene (TDG). One was a non-synonymous coding SNP (rs2888805) [per allele odds ratio (OR) 1.40, 95% confidence interval (CI) 1.16-1.70; P-value 5 0.0006] and the other was an intronic SNP in high linkage disequilibrium with rs2888805 (rs4135150). None of the associations had a P-value <6.6310(-5), the threshold for statistical significance after correcting for multiple comparisons. The results pinpoint DNA repair genes most likely to contribute to the NMSC cancer-prone phenotype. A promising lead is genetic variants in TDG, important not only in base excision repair but also in regulating the epigenome and gene expression, which may contribute to the NMSC-associated increase in overall cancer risk.
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http://dx.doi.org/10.1093/carcin/bgs170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514896PMC
September 2012

Comparability and repeatability of methods for estimating the dietary intake of the heterocyclic amine contaminant 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP).

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2012 Aug 9;29(8):1202-11. Epub 2012 May 9.

Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD, USA.

Inconsistent risk estimates for dietary heterocyclic amine (HCA) exposure and cancers may be due to differences in exposure assessment methods and the associated measurement error. We evaluated repeatability and comparability of intake estimates of the HCA 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) among two food frequency questionnaire (FFQ) collections, three diary collections, and three measurements of urinary PhIP and its metabolites in 36 non-smokers in Baltimore, Maryland, during 2004-2005. Collections spanned ∼9 months. Method repeatability was characterised with intraclass correlation coefficients (ICCs). Comparability among methods was assessed with Spearman correlation coefficients. Within-subject variability in PhIP intake was comparably high across all methods (ICCs of 0.20, 0.30, and 0.15 for FFQ, diary, and creatinine-adjusted urinary PhIP, respectively). Mean diary-based PhIP intake and mean urinary PhIP concentration were strongly correlated when restricting the analysis to participants with at least one non-zero diary-based estimate of PhIP intake (n = 15, r = 0.75, p = 0.001), but not in the full study population (n = 36, r = 0.18, p = 0.28). Mean PhIP intake from the FFQ was not associated with that either based on the diary or urinary PhIP separately, but was modestly correlated with a metric that combined the diary- and biomarker-based approaches (r = 0.30, p = 0.08). The high within-subject variability will result in significantly attenuated associations if a single measure is used to estimate exposure within an epidemiologic study. Improved HCA assessment tools, such as a combination of methods or validated biomarkers that capture long term exposure, are needed.
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http://dx.doi.org/10.1080/19440049.2012.682657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412362PMC
August 2012

A community-based study of nucleotide excision repair polymorphisms in relation to the risk of non-melanoma skin cancer.

J Invest Dermatol 2012 May 16;132(5):1354-62. Epub 2012 Feb 16.

Department of Medicine, Division of Epidemiology and Biostatistics, Medical University of South Carolina, Charleston, South Carolina 29425, USA.

Nucleotide excision repair (NER) is responsible for protecting DNA in skin cells against UVR-induced damage. Using a candidate pathway approach, a matched case-control study nested within a prospective, community-based cohort was carried out to test the hypothesis that single-nucleotide polymorphisms (SNPs) in NER genes are associated with susceptibility to non-melanoma skin cancer (NMSC). Histologically confirmed cases of NMSC (n=900) were matched to controls (n=900) on the basis of age, gender, and skin type. Associations were measured between NMSC and 221 SNPs in 26 NER genes. Using the additive model, two tightly linked functional SNPs in ERCC6 were significantly associated with increased risk of NMSC: rs2228527 (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.20-2.05) and rs2228529 (OR 1.57, 95% CI 1.20-2.05). These associations were confined to basal cell carcinoma (BCC) of the skin (rs2228529, OR 1.78, 95% CI 1.30-2.44; rs2228527, OR 1.78, 95% CI 1.31-2.43). These hypothesis-generating findings suggest that functional variants in ERCC6 may be associated with an increased risk of NMSC that may be specific to BCC.
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http://dx.doi.org/10.1038/jid.2012.4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326207PMC
May 2012

Comparison of standard methods for assessing dietary intake of benzo[a]pyrene.

Cancer Epidemiol Biomarkers Prev 2011 May 23;20(5):962-70. Epub 2011 Mar 23.

Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Background: Inconsistent presence and strength of associations between dietary benzo[a]pyrene (BaP) exposure and cancers may be due to differences in exposure assessment methods. Thus, we determined correlations of usual meat and BaP intake among three methods: food frequency questionnaires (FFQ), diet diaries, and a biomarker.

Methods: Thirty-six nonsmokers were recruited in Baltimore, MD during 2004-2005. Meat and BaP intake estimated from baseline and follow-up FFQs combined with a BaP residue database (FFQ-RD), mean meat and BaP intake estimated from three diet diaries coupled with the residue database (Diary-RD), and mean of three urinary 1-hydroxypyrene glucuronide (1-OHPG) measurements were compared using Spearman correlations. Collections spanned approximately nine months.

Results: BaP intakes from meat from the baseline [median = 6.4, interquartile range (IQR) = 13.9 ng/d] and follow-up FFQ-RD (median = 7.3, IQR = 35.7 ng/d) were higher than the Diary-RD (median = 1.1, IQR = 7.4 ng/d). Mean 1-OHPG concentration was weakly correlated with mean meat intake (r = 0.33, P = 0.05) and BaP intake from meat (r = 0.27, P = 0.11) from the Diary-RD. Mean BaP intake estimated from the Diary-RD was positively correlated with the follow-up (r = 0.35, P = 0.04) but not baseline (r = 0.20, P = 0.24) FFQ; the converse was true for meat intake.

Conclusions: Diary-RD estimates were supported by biomarker measurements, but considerable unexplained variability remained. Limited correlation among the dietary BaP exposure assessment methods could be due to differences in timeframes covered by the assessments, interpersonal variability in metabolism, deficiencies in the residue database, or nondietary exposures to BaP.

Impact: Limited correlation in estimated BaP intake among standard methods may contribute to inconsistent epidemiology of BaP and cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-10-1344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618457PMC
May 2011

An engineering intervention resulting in improvement in lung function and change in urinary 8-hydroxydeoxyguanosine among foundry workers in Taiwan.

Int Arch Occup Environ Health 2011 Feb 24;84(2):175-83. Epub 2010 Sep 24.

Institute of Occupational Safety and Health, Council of Labour Affairs, Executive Yuan, Taipei, 221, Taiwan, R.O.C.

Purpose: To assess changes in oxidative DNA damage and lung function amongst a group of foundry workers resulting from an engineering intervention to reduce air respirable dust in their working environment.

Methods: We studied all 22 workers recruited from a typical small Taiwanese iron foundry plant before and 3 months after improvements to air exhaust control. The effectiveness of the air exhaust intervention in reducing respirable dust and SiO₂ was determined by personal breathing-zone air sampling. Initial baseline biomarker measurements were taken of lung function and urinary 8-hydroxy-deoxyguanosine (8-OHdG) in all of the workers, with follow-up measurements taken 3 months after the engineering control was put in place. Generalized estimating equations were used to assess the effect of the intervention on lung function and oxidative DNA damage.

Results: Following the intervention, respirable dust density decreased from 2.87 ± 1.38 mg/m³ to 1.60 ± 0.70 mg/m³ (p = 0.07), and SiO₂ concentration decreased from 0.43 ± 0.25 mg/m³ to 0.18 ± 0.11 mg/m³ (p < 0.05). Compared to initial baseline, significant improvements were found in lung function (FVC, FEV1, FVC%pred and FEV1%pred) amongst the workers after the engineering intervention. A significant increase in concentration of urinary 8-OHdG was observed after the engineering intervention in smokers, but not in non-smokers.

Conclusions: These findings indicate that reductions in workplace respirable dust and SiO₂ concentration can result in improved lung function amongst foundry workers.
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http://dx.doi.org/10.1007/s00420-010-0580-9DOI Listing
February 2011

The association between skin characteristics and skin cancer prevention behaviors.

Cancer Epidemiol Biomarkers Prev 2009 Oct 15;18(10):2613-9. Epub 2009 Sep 15.

Department of Biostatistics, Bioinformatics, and Epidemiology, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Post Office Box 250955, Charleston, SC 29425, USA.

Background: Behaviors such as sunscreen use and wearing sun-protective clothing are thought to prevent certain types of skin cancer and precancerous lesions, but few studies have examined differences in these prevention behaviors by skin type.

Methods: We carried out a cross-sectional study (n = 6,858) nested within a community-based prospective cohort in Washington County, Maryland. We measured the associations between skin type, complexion, freckling, and eye color, and sunscreen and sun-protective clothing use.

Results: The prevalence of regular sunscreen use was 23% and regular sun-protective clothing use was 21%. There were consistent trends indicating those with the most sun-sensitive skin type were most likely to engage in prevention behaviors. For example, compared with those who tan without burning, those who develop blistering sunburns were more likely to use sunscreen [odds ratio (OR), 6.04; 95% confidence interval (95% CI), 2.82-12.95 men; OR, 4.89; 95% CI, 3.34-7.16 women] and sun-protective clothing (OR, 2.87; 95% CI, 1.71-4.80 men; OR, 4.44; 95% CI, 2.88-6.85 women). Health-related characteristics such as body mass index and cigarette smoking were also significantly inversely associated with prevention behaviors.

Conclusion: The overall prevalence of prevention behaviors was low. Those with phenotypic risk factors for skin cancer were most likely to use sunscreen and sun-protective clothing. Those with high-risk skin cancer phenotypes may also be those who are most receptive to skin cancer prevention educational interventions.
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http://dx.doi.org/10.1158/1055-9965.EPI-09-0383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759861PMC
October 2009

Copy number variants of GSTM1 and GSTT1 in relation to lung cancer risk in a prospective cohort study.

Ann Epidemiol 2009 Aug 25;19(8):546-52. Epub 2009 Apr 25.

Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

Purpose: Previous studies did not discriminate wild-type from hemizygous genotypes of GSTM1 and GSTT1. In this study, we investigated wild-type, hemizygous deletion, and homozygous deletion genotypes of GSTM1 and GSTT1 and lung cancer risk.

Methods: We conducted a nested case-control study of 143 primary incident lung cancer cases matched to 447 cancer-free controls. Genotyping was carried out using a real-time polymerase chain reaction (PCR)-based assay. Conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI).

Results: Compared to GSTM1 wild-type carriers, the relative odds of lung cancer increased from 1.49 (95% CI=0.66-3.40) to 1.80 (95% CI=0.81-4.02) for the hemizygous and homozygous deletion genotypes, respectively (p-trend=0.13). The strongest associations were seen among those who smoked less than one pack per day and had greater than or equal to one deletion variant of GSTM1 (OR=3.25; 95% CI=0.93-11.34; p-trend=0.07) whereas the reverse was observed for smokers who smoked greater than or equal to one pack per day (OR=0.80; 95% CI=0.24-2.67; p-interaction=0.08). No clear associations were observed for GSTT1 genotypes.

Conclusions: Risk of lung cancer increased as the number of deletion variants increased for GSTM1, although the associations were nonsignificant. Discriminating between the wild-type, hemizygous, and homozygous deletion GSTM1 genotypes permitted a more precise characterization of the associations between GSTM1 deletion variants and lung cancer.
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http://dx.doi.org/10.1016/j.annepidem.2009.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720160PMC
August 2009

Involuntary tobacco smoke exposure and urinary levels of polycyclic aromatic hydrocarbons in the United States, 1999 to 2002.

Cancer Epidemiol Biomarkers Prev 2009 Mar 3;18(3):884-93. Epub 2009 Mar 3.

Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room W7503, Baltimore, MD 21205, USA.

Evidence supports active smoking as a major source of exposure to polycyclic aromatic hydrocarbons (PAH), compounds that are mutagenic and carcinogenic in humans. The influence of involuntary exposure to tobacco smoke on PAH exposure levels among nonsmokers, however, is unknown. This study evaluated the association between both active and involuntary tobacco smoke and biomarkers of PAH exposure in the general U.S. population. A cross-sectional analysis of 5,060 participants>or=6 years of age was done using data from the 1999-2002 National Health and Nutrition Examination Survey (NHANES). PAH exposure was measured by urinary concentrations of 23 monohydroxylated metabolites of nine PAH compounds. Tobacco smoke exposure was defined as no exposure, involuntary exposure, and active exposure by combining serum cotinine levels, smoking status, and presence of household smokers. PAH metabolite levels ranged from 33.9 ng/L for 9-hydroxyphenanthrene to 2,465.4 ng/L for 2-hydroxynaphthalene. After adjustment for age, sex, race/ethnicity, education, household income, and broiled/grilled food consumption, participants involuntarily and actively exposed to tobacco smoke had urinary metabolite concentrations that were increased by a factor of 1.1 to 1.4 and 1.5 to 6.9, respectively, compared with unexposed participants. Associations for involuntary smoking were stronger and statistically significant for 1-hydroxypyrene, 2-hydroxyfluorene, 3-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, and 3-hydroxyphenanthrene compared with other metabolites. Involuntary exposure to tobacco smoke was associated with elevated urinary concentrations of most PAH metabolites in a representative sample of the U.S. population. Policy and educational efforts must continue to minimize PAH exposure through active and involuntary tobacco smoke exposure.
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http://dx.doi.org/10.1158/1055-9965.EPI-08-0939DOI Listing
March 2009

Determinants of urinary 1-hydroxypyrene glucuronide in South Korean children.

Int Arch Occup Environ Health 2009 Aug 20;82(8):961-8. Epub 2008 Nov 20.

Biomedical Research Group, Hanyang Brain Korea 21, Hanyang University, Seoul, Republic of Korea.

Objectives: This study was conducted to investigate the dominant sources of the urinary pyrene metabolite, 1-hydroxypyrene glucuronide (1-OHPG), in South Korean children.

Methods: Urine samples were collected from 102 non-smoking children (aged 10-14). Urinary 1-OHPG was assayed by synchronous fluorescence spectroscopy, following immuno-affinity purification using monoclonal antibody 8E11. Urinary cotinine, a metabolite of nicotine, was measured by GC/MS. Information on environmental tobacco smoke (ETS) exposure, diet, fuel type for heating home, and other possible sources of PAH exposure was collected by self-administered questionnaires.

Results: Mean (+/-SE) 1-OHPG levels were 1.64 (+/-0.06) ng/ml (range 0.04-3.27 ng/ml). Two multiple linear regression analyses (differing in how ETS was approximated: by parental smoking or urinary cotinine) revealed a positive association between urinary 1-OHPG levels and parental smoking at home (P = 0.007), log urinary cotinine (P = 0.165), frequent grilled (shell)fish consumption (P = 0.061), and living in a commercial/other zone (P = 0.007) versus a residential or industrial zone. No consistent associations were found between 1-OHPG and the child's sex, grilled meat consumption, or fuels used to heat the home.

Conclusions: These results support that ETS, frequent grilled fish consumption, and the ambient environment are important predictors of urinary 1-OHPG levels in South Korean children.
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http://dx.doi.org/10.1007/s00420-008-0385-2DOI Listing
August 2009

Nonmelanoma skin cancer and risk for subsequent malignancy.

J Natl Cancer Inst 2008 Sep 26;100(17):1215-22. Epub 2008 Aug 26.

Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA.

Background: Individuals with a personal history of nonmelanoma skin cancer (NMSC) may have an increased risk of subsequent noncutaneous malignancies. To test this hypothesis, we carried out a community-based, prospective cohort study.

Methods: In the CLUE (Give Us a Clue to Cancer and Heart Disease) II cohort, which was established in Washington County, MD, in 1989, the risk of new malignancies was compared among individuals with (n = 769) and without (n = 18,405) a personal history of NMSC (total n = 19,174) during a 16-year follow-up period. Pathologically confirmed NMSC (and other malignancies) were ascertained from the Washington County Cancer Registry. Cox regression analysis with time-dependent covariates was used to determine the hazard ratios (presented as multivariable-adjusted relative risks [RRs]) and 95% confidence intervals (CIs) of second primary malignancies associated with a previously confirmed NMSC diagnosis. All statistical tests were two-sided.

Results: The crude incidence rate (per 10,000 person-years) of subsequent cancers other than NMSC among participants with a positive personal history of NMSC was 293.5 and with a negative history was 77.8. Compared with persons with no personal history of NMSC, those with such a history had a statistically significantly increased risk of being diagnosed with a subsequent cancer other than NMSC (RR = 1.99, 95% CI = 1.70 to 2.33) after adjusting for age, sex, body mass index, smoking status, and educational level. The association was observed for both basal cell carcinoma (multivariable-adjusted RR = 2.03, 95% CI = 1.70 to 2.42) and squamous cell carcinoma (multivariable-adjusted RR = 1.97, 95% CI = 1.50 to 2.59) of the skin. NMSC was a statistically significantly stronger cancer risk factor in younger age groups than in older age groups (P for interaction = .022).

Conclusions: This community-based, prospective cohort study provides evidence for an association between an NMSC diagnosis and an increased risk of subsequent cancer, even after adjusting for individual-level risk factors.
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http://dx.doi.org/10.1093/jnci/djn260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720713PMC
September 2008

Polychlorinated biphenyl levels in peripheral blood and non-Hodgkin's lymphoma: a report from three cohorts.

Cancer Res 2007 Jun;67(11):5545-52

Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

The incidence of non-Hodgkin's lymphoma (NHL) unrelated to HIV infection has steadily increased over the past several decades and remains substantially unexplained. Limited evidence suggests that increased concentrations of polychlorinated biphenyls (PCB) measured in blood or fat tissue are associated with increased risk of NHL. Although PCB congeners vary in their biological activity, the relation between individual congeners and NHL risk has not been examined previously using prospectively collected biospecimens. We examined congener-specific associations in three prospective cohorts. Prediagnostic serum or plasma concentrations of selected PCB congeners were measured among NHL cases and controls from these cohorts: Janus (190 cases and 190 controls) in Norway and CLUE I (74 cases and 147 controls) and the Nurses' Health Study (30 cases and 78 controls) in the United States. All blood samples were collected in the 1970s or 1980s. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the relations between risk of NHL and lipid-corrected plasma or serum concentrations. Several congeners (i.e., 118, 138, and 153) that were present at higher levels and were moderately to highly correlated with each other showed exposure-response trends with risk of NHL in all three cohorts. These associations were observed primarily among subjects diagnosed closer to the date of blood collection in the two cohorts with sufficient cases to permit stratification by time. Among cases diagnosed within the median years of follow-up (16 years in Janus and 12 years in CLUE I), ORs and 95% CIs for increasing fourths of concentration of congener 118 relative to the lowest fourth were as follows: 2.4 (0.9-6.5), 4.9 (1.6-15.3), and 5.3 (1.5-18.8; P(trend) < 0.005) in Janus and 8.1 (1.0-68.9), 6.6 (0.7-59.0), and 13.0 (1.6-106.8; P(trend) < 0.05) in CLUE I. Similar patterns were seen for congeners 138 and 153 and for total PCBs. Limited evidence of exposure-response trends was also observed for several other congeners. The primary 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane metabolite, p,p'-DDE, was not significantly associated with NHL in most analyses but slightly to moderately confounded the PCB associations. The results from these three cohorts suggest that concentrations of certain PCBs in blood are associated with increased risk of NHL.
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http://dx.doi.org/10.1158/0008-5472.CAN-06-3906DOI Listing
June 2007

Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption, and risk of breast cancer.

Alcohol Clin Exp Res 2007 Mar;31(3):467-76

Department of Epidemiology, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.

Background: In vitro, human isoenzymes encoded by genes homozygous for the ADH1C*1 or ADH1B*2 alleles metabolize ethanol to acetaldehyde at a faster rate than those homozygous for the ADH1C*2 or ADH1B*1 allele. Because alcohol is a known risk factor for breast cancer, we evaluated the joint association of genetic variants in ADH and alcohol consumption in relation to breast cancer.

Methods: A nested case-control study of 321 cases and matched controls was conducted. Five single nucleotide polymorphisms (SNPs) in the ADH1C and ADH1B genes were genotyped. Logistic regression was used to assess odds ratios (ORs) and 95% confidence limits (CIs) for each SNP. Haplotype analysis of all 5 SNPs was also undertaken.

Results: Among drinkers, the median intake of total alcohol was 13 g/wk (10th-90th percentiles; 4.5-135.9) in cases and 18 g/wk (10th-90th percentiles; 4.5-104.1) in controls. Women who drank alcohol tended to be at an increased risk of developing breast cancer compared with those who did not drink (OR=1.40%, 95% CI 0.97-2.03), particularly those who were premenopausal at the time of breast cancer diagnosis (OR=2.69%, 95% CI: 1.00-7.26). Of the known functional alleles, breast cancer risk was not significantly increased among carriers of at least 1 ADH1C*1 or ADH1B*2 allele, when compared with those homozygous for the genotype at each locus. However, breast cancer risk tended to be lower among women who inherited the G allele at ADH1B IVS1+896A>G (OR=0.62, 95% CI 0.37-1.04). Overall haplotype frequencies were not significantly different between cases and controls.

Conclusions: In this study low levels of alcohol are associated with a modest increase in breast cancer risk that is not altered by known functional allelic variants of the ADH1B and 1C gene. The protective association conferred by the G allele at ADH1B IVS1+896A>G needs further evaluation.
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http://dx.doi.org/10.1111/j.1530-0277.2006.00334.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787101PMC
March 2007

The influence of genetic polymorphisms in Ahr, CYP1A1, CYP1A2, CYP1B1, GST M1, GST T1 and UGT1A1 on urine 1-hydroxypyrene glucuronide concentrations in healthy subjects from Rio Grande do Sul, Brazil.

Carcinogenesis 2007 Jan 24;28(1):112-7. Epub 2006 Jul 24.

Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS/320, MSC 7232, Rockville, MD 20852, USA.

Polymorphisms in genes encoding polycyclic aromatic hydrocarbon (PAH) metabolizing enzymes may alter metabolism of these carcinogens and contribute to inter-individual difference in urine concentrations. We investigated the influence of genetic polymorphism on PAH metabolism in urine from 199 healthy subjects from Southern Brazil. We measured urine 1-hydroxypyrene glucuronide (1-OHPG) concentrations using immunoaffinity chromatography and synchronous fluorescence spectroscopy and genotyped subjects using standard methods. Genetic variants in CYP1B1 (rs1056827, rs1800440, rs10012) were strongly associated with urine 1-OHPG with P-values < 0.010. Variants in aryl hydrocarbon receptor (Ahr) (rs4986826), CYP1A1 (rs1799814) and CYP1A2 (rs2069514) were also, although less strongly, associated with changes in urine 1-OHPG concentrations. These variants had P-values of 0.074, 0.040 and 0.025, respectively. The median urine 1-OHPG concentrations (pmol/ml) in the homozygous wild-type and homozygous variants for CYP1B1 (rs10012) and the Ahr, CYP1A1 and CYP1A2 variants listed above were 2.16 and 0.10, 2.16 and 0.41, 2.03 and 0.46, 2.19 and 2.79, respectively. We found no effect of deletions in GST M1 or GST T1, or different alleles of UGT1A1*28. Adjusting for age, sex, place of residence, tobacco smoke exposure, maté drinking, cachaça and barbeque preparation had only a minor impact on the associations. A model containing just exposure variables had an r2 of 0.21; a model with single genotypes for Ahr, CYP1A1, CYP1A2 and CYP1B1 had an r2 of 0.10; and a model combining both exposure and genotype information had a total r2 of 0.33. Our results suggest that CYP1B1 genotypes are strongly associated with urine 1-OHPG concentrations in this population.
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http://dx.doi.org/10.1093/carcin/bgl131DOI Listing
January 2007

Higher urine 1-hydroxy pyrene glucuronide (1-OHPG) is associated with tobacco smoke exposure and drinking maté in healthy subjects from Rio Grande do Sul, Brazil.

BMC Cancer 2006 May 26;6:139. Epub 2006 May 26.

Universidade Federal de Santa Maria, Departamento de Clínica Médica, Centro de CIências da Saúde, Santa Maria, RS, Brazil.

Background: The highest rates of esophageal squamous cell carcinoma (ESCC) in Brazil occur in Rio Grande do Sul, the most southern state, which has incidence rates of 20.4/100,000/year for men and 6.5/100,000/year for women. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) through tobacco smoke and other sources may increase the risk of ESCC. The aims of the current study were to investigate the degree and sources of PAH exposure of the inhabitants of this region of southern Brazil.

Methods: Two hundred healthy adults (half smokers, half non smokers, half male and half female) were recruited, given a standardized questionnaire, and asked to provide a urine sample for measurement of 1-hydroxypyrene glucuronide (1-OHPG), a PAH metabolite). Urine 1-OHPG concentrations were measured using immunoaffinity chromatography and synchronous fluorescence spectroscopy and urine cotinine was measured using a dipstick test. We examined factors associated with 1-OHPG concentration using Wilcoxon tests and multiple linear regression.

Results: Urine 1-hydroxypyrene glucuronide (1-OHPG) was successfully measured on 199 subjects. The median (interquartile range) of urine 1-OHPG in the 199 participants was 2.09 pmol/mL (0.51, 5.84). Tobacco smoke exposure and maté drinking were statistically significantly associated with higher urine 1-OHPG concentrations in the multivariate linear regression model.

Conclusion: Tobacco smoke and maté both contribute to high levels of benzo[a]pyrene exposure in the people of southern Brazil. This high PAH exposure may contribute to the high rates of ESCC observed in this population. The increased urine 1-OHPG concentrations associated with maté suggest that contaminants, not just thermal injury, may help explain the increased risk of ESCC previously reported for maté consumption.
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http://dx.doi.org/10.1186/1471-2407-6-139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1539013PMC
May 2006

The effect of clinical UVA/B exposures on urinary urocanic acid isomer levels in individuals with caucasian type (II/III) skin types.

Dermatol Online J 2005 Dec 1;11(3). Epub 2005 Dec 1.

Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, USA.

Terrestrial ultraviolet radiation (UVR) exposure, consisting of ultraviolet A (320-40 nm) and B (290-320 nm), results in the photoisomerizion of epidermal trans-urocanic acid (trans-UCA) to cis-urocanic acid (cis-UCA), a potential suppressor of local and systemic immune responses. This study examines urinary UCA isomers as biomarkers of UVA/B exposure. It presents results measuring both cis- and trans-UCA in human urine samples collected from a group of study subjects (skin types II/III) that underwent controlled UVA/B exposures similar to those administered in commercial suntanning parlors. The UCA isomers were purified from urine using C18 solid-phase extraction columns followed by high-performance liquid chromatography (HPLC) with UV absorbance (268 nm) detection. The UCA biomarker was expressed as the ratio of cis-UCA to trans-UCA (UCA ratio), or as cis-UCA concentration corrected for urine volume using creatinine (cis-UCA-Cr). The UCA ratio increased over baseline in the urine of individuals exposed to UVA/B. A single exposure to approximately 70 percent minimal erythema dose (MED) of UVR (95 % UVA/5 % UVB to approximately 90 % of skin area) produced a 4.75-fold increase in the UCA ratio (p< 0.001) relative to baseline. Repeated daily UV exposures of similar doses produced a minimal increase in UCA ratio above that of the single UV exposure. These findings indicate that UCA cis-trans ratio holds promise as a biomarker for recent solar UV exposure.
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December 2005

Influence of geographic location in modeling blood pesticide levels in a community surrounding a U.S. Environmental protection agency superfund site.

Environ Health Perspect 2005 Dec;113(12):1712-6

Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

In this study we evaluated residential location as a potential determinant for exposure to organochlorine compounds. We investigated the geographic distribution characteristics of organochlorine levels in approximately 1,374 blood samples collected in 1974 from residents of a community with a potential organochlorine source. Street addresses of Washington County, Maryland, residents were obtained and geocoded in a geographic information system. We used multivariate linear regression models to characterize the blood organochlorine levels of these residents that had been analyzed as part of previous studies using both environmental- and individual-level covariates. This was done to evaluate if the geographic distribution of blood levels in participants was related to the environmental source in the community. Model inference was based on generalized least squares to account for residual spatial variation. A significant inverse relationship was found between blood dieldrin levels and residential distance from the potential source. For every mile of distance from the source, blood dieldrin levels decreased 1.6 ng/g in study participants (p-value = 0.042), adjusting for age, sex, education level, smoking status, and drinking water source. 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) levels in the blood did not change significantly based on residential distance from the source, taking the same covariates into account. However, these results are limited by the inability to account for several potential confounders. This study demonstrates that spatially distributed covariates may play an important role in individual exposure patterns. Spatial information may enable researchers to detect a potential exposure pattern that may not be revealed with only nonspatial variables.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1314910PMC
http://dx.doi.org/10.1289/ehp.8154DOI Listing
December 2005

Design issues in cross-sectional biomarkers studies: urinary biomarkers of PAH exposure and oxidative stress.

Mutat Res 2005 Dec 15;592(1-2):138-46. Epub 2005 Aug 15.

Department of Preventive Medicine, Seoul National University, College of Medicine, Institute of Environmental Medicine, SNUMRC, Seoul 110-799, South Korea.

Cross-sectional biomarker studies can provide a snapshot of the frequency and characteristics of exposure/disease in a population at a particular point in time and, as a result, valuable insights for delineating the multi-step association between exposure and disease occurrence. Three major issues should be considered when designing biomarker studies: selection of appropriate biomarkers, the assay (laboratory validity), and the population validity of the selected biomarkers. Factors related to biomarker selection include biological relevance, specificity, sensitivity, biological half-life, stability, and so on. The assay attributes include limit of detection, reproducibility/reliability, inter-laboratory variation, specificity, time, and cost. Factors related to the population validity include the frequency or prevalence of markers, greater inter-individual variation than intra-individual variation, intra-class correlation coefficients (ICC), association with potential confounders, invasiveness of specimen collection, and subject selection. Three studies are selected to demonstrate different features of cross-sectional biomarker studies: (1) characterizing the determinants of the biomarkers (study I: urinary PAH metabolites and environmental particulate exposure), (2) relationship of multiple biomarkers of exposure and effect (study II: relationship between urinary PAH metabolites and oxidative stress), and (3) evaluating gene-environmental interaction (study III: effect of genetic polymorphisms of GSTM1 on the association of green tea consumption and urinary 1-OHPG levels in shipbuilding workers).
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http://dx.doi.org/10.1016/j.mrfmmm.2005.06.009DOI Listing
December 2005

Urinary 1-hydroxypyrene-glucuronide as a biomarker of exposure to various vehicle exhausts among highway toll-station workers in Taipei, Taiwan.

Arch Environ Health 2004 Feb;59(2):61-9

Department of Public Health, National Defense Medical Center, Taipei, Taiwan, Republic of China.

In this cross-sectional study, the authors evaluated urinary 1-hydroxypyrene-glucuronide (1-OHP-gluc) as a potential biomarker of exposure to various traffic exhausts. Subjects were 47 female highway toll-station workers and 27 female office workers in training for toll-station employment in Taipei, Taiwan. The mean concentration of urinary 1 -OHP-gluc was 0.117 micromol/mol creatinine in the exposed group and 0.073 micromol/mol creatinine in the reference group (difference in mean concentrations: 0.044 micromol/mol creatinine [95% confidence interval [CI]: 0.015, 0.072). In the lanes where tolls were collected from passenger cars, there was a significant relationship between cumulative traffic and 1-OHP-gluc concentration (i.e., average increase of 0.015 micromol/mol creatinine [95% CI: 0.003, 0.027] per 1,000 vehicles). The average increase for truck/bus lanes was similar to that identified for the car lanes (i.e., average increase of 0.011 micromol/mol creatinine [95% Cl: -0.024, 0.045] per 1,000 vehicles). The authors determined that exposure to various traffic exhausts increased the urinary concentration of 1-OHP-gluc in a dose-response pattern, which suggests that this chemical may be a useful biomarker for exposure to vehicle exhausts.
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http://dx.doi.org/10.3200/AEOH.59.2.61-69DOI Listing
February 2004
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