Biomedical subjects

Paul T Strickland

Publications and source records attributed to Paul T Strickland.

At least 19 recordsLinked to original sources

PubMed2006

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.

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.

Aryl Hydrocarbon Hydroxylases↗

PubMed2006

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.

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.

Alcohol Drinking↗

PubMed2005

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

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.

Adult↗

PubMed2005

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

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).

Anticarcinogenic Agents↗

PubMed2005

Coumarins are competitive inhibitors of cytochrome P450 1B1, with equal potency for allelic variants.

OBJECTIVES: Coumarins are naturally occurring chemicals with potential as chemopreventive agents, several with known action on the cytochrome P450 1A family. We examined whether cytochrome P450 1B1 (CYP1B1) was inhibited by coumarins, whether such inhibition was competitive, and whether inhibition varied between common polymorphic variants of this enzyme. METHODS: We tested the inhibition properties of four coumarins, bergamottin, isopimpinellin, isoimperatorin, and imperatorin in an assay for oxidation of (-)benzo[a]pyrene-7R-trans-7,8-dihyrodiol (B[a]P-7,8-diol) by CYP1B1 using yeast-microsome expressed enzymes. These assays were performed with wild-type enzyme and five single-amino acid polymorphic variants. RESULTS: All four coumarins are competitive inhibitors of CYP1B1, with Ki values equal to 587, 11, 6 and 1 muM respectively. Inhibition parameters were consistent between five haplotypes of CYP1B1, three representing common haplotypes in Asians, African-Americans and European-Americans, and two with baseline kinetic parameters previously shown to be potentially different from wild-type. CONCLUSIONS: Coumarins are capable of inhibiting carcinogen activation by CYP1B1 with varying potencies, and their efficacy as chemopreventive agents is not likely to be affected by polymorphism in this enzyme.

Alleles↗

PubMed2005

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

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.

Environmental Monitoring↗

PubMed2004

Expression of cytochromes P450 1A1 and 1B1 in human lung from smokers, non-smokers, and ex-smokers.

Cytochromes P450 1A1 and 1B1 are known to bioactivate procarcinogens such as polycyclic aromatic hydrocarbons (PAHs) found in cigarette smoke and are inducible via an Ah receptor-mediated mechanism. The aim of this study was to examine the levels of expression of CYP1A1 and CYP1B1 in samples of lung from smokers (n = 18), non-smokers (n = 7), and ex-smokers (n = 7). Using immunoglobulin preparations of highly specific polyclonal antibodies and immunoblot analysis of microsomes from lung tissues, we determined the specific content for CYP1A1 and CYP1B1. For CYP1A1, we found median expression levels of 15.5 pmol/mg microsomal protein in smokers, 6.0 pmol/mg microsomal protein in non-smokers, and 19.0 pmol/mg microsomal protein in ex-smokers. The difference in median expression levels of smokers and ex-smokers compared to non-smokers was statistically significant. For CYP1B1, we found median expression levels of 1.8 pmol/mg microsomal protein in smokers, 1.0 pmol/mg microsomal protein in non-smokers, and 4.4 pmol/mg microsomal protein in ex-smokers. The difference in median expression levels between ex-smokers and non-smokers was statistically significant. These results suggest that levels of expression of CYP1A1 and CYP1B1 protein in lung tissues from smokers and ex-smokers are quantitatively greater than in non-smokers. By immunohistochemical analysis, we demonstrated the expression of CYP1A1 and CYP1B1 in normal human alveolar type I and II cells, ciliated columnar epithelial cells lining bronchoalveolar airways, and alveolar macrophages. These results confirm that CYP1A1 is expressed in normal human lung, appears to be induced in smokers, and show interindividual variation; the similar characteristics of CYP1B1 are demonstrated.

Adolescent↗

PubMed2004

N-acetyltransferase 2 (NAT2) genotypes, cigarette smoking, and the risk of breast cancer.

N-acetyltransferases (NATs) are important catalytic enzymes that metabolize carcinogenic arylamines. NAT2 genotype might modify the role of cigarette smoking, a source of arylamine exposure, in breast cancer. We conducted a nested case-control study to investigate the association between NAT2 genotype, smoking and breast cancer risk among women (110 cases, 113 matched controls) from the CLUE II cohort in Washington County, MD. Compared to women with the slow acetylator genotype, the main effects odds ratios (OR) for NAT2 were 1.4 for the intermediate acetylator genotype (95% confidence limits (CL) 0.7, 2.7) and 3.6 for the homozygous rapid acetylator genotype (95% CL 1.1, 11.4) (P for trend = 0.05). Smoking was associated in the direction of increased breast cancer risk in slow acetylators (e.g., >15 pack-years versus never smokers OR 2.0; 95% CL 0.7, 5.8) but not in rapid acetylators. These associations were not statistically significant in the total study population, but a statistically significant interaction between smoking and NAT2 acetylator status was present in postmenopausal women. The main effect of NAT2 in the direction of increased risk suggests that exposures to NAT2-activated carcinogens other than cigarette smoke may be important in this study population. The results for smoking were consistent with an inactivation role for NAT2 in breast cancer.

Adult↗

PubMed2004

Geostatistics and GIS: tools for characterizing environmental contamination.

Geostatistics is a set of statistical techniques used in the analysis of georeferenced data that can be applied to environmental contamination and remediation studies. In this study, the 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) contamination at a Superfund site in western Maryland is evaluated. Concern about the site and its future clean up has triggered interest within the community because residential development surrounds the area. Spatial statistical methods, of which geostatistics is a subset, are becoming increasingly popular, in part due to the availability of geographic information system (GIS) software in a variety of application packages. In this article, the joint use of ArcGIS software and the R statistical computing environment are demonstrated as an approach for comprehensive geostatistical analyses. The spatial regression method, kriging, is used to provide predictions of DDE levels at unsampled locations both within the site and the surrounding areas where residential development is ongoing.

Dichlorodiphenyl Dichloroethylene↗

PubMed2004

Association among an ornithine decarboxylase polymorphism, androgen receptor gene (CAG) repeat length and prostate cancer risk.

PURPOSE: A single nucleotide substitution of guanine to adenine (A) at base +316 in the ornithine decarboxylase (ODC) gene may be associated with greater ODC expression and increased tumor growth. ODC is induced by androgens in human prostatic epithelial cells, presumably via transcriptional activation of androgen receptor (AR) and also by nicotine. A nested case-control study was done to examine the association between this ODC genotype and prostate cancer risk, and whether it varies by AR gene CAG repeat length and smoking. MATERIALS AND METHODS: A total of 164 cases were matched to 2 controls each from a community based cohort. ODC and AR genotyping was performed using a TaqMan (PE Applied Biosystems, Foster City, California) based assay and automated fragment analysis, respectively. Conditional logistic regression was used to estimate the OR and 95% CI. RESULTS: The presence of the ODC A allele was not significantly associated with an increased risk of prostate cancer (OR 1.33, 95% CI 0.90 to 1.96). However, men who inherited at least 1 ODC A alleles and less than 22 AR CAG repeats were at twice the risk of prostate cancer compared with those with 2 guanine alleles and 22 or greater AR CAG repeats (OR 2.09, 95% CI 1.23 to 3.57). Smoking was associated with prostate cancer only in men carrying a least 1 ODC A allele (p interaction = 0.02). CONCLUSIONS: The ODC A allele was not associated with a statistically significant increased risk of prostate cancer. However, this association may vary according to the number of CAG repeats in the AR receptor and smoking status.

Aged↗

PubMed2004

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

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.

Adolescent↗

PubMed2004

XPD polymorphism and risk of subsequent cancer in individuals with nonmelanoma skin cancer.

BACKGROUND: Individuals with nonmelanoma skin cancer (NMSC) are at increased risk of developing subsequent cancers. Genetic predisposition to reduced DNA repair capacity may be an underlying susceptibility factor explaining the excess risk of malignancies. To test this hypothesis, a cohort study was conducted to examine the association between XPD Lys751Gln polymorphism and risk of a second primary cancer in individuals with NMSC. METHODS: A subgroup of 481 individuals with a history of NMSC who participated in the CLUE II community-based cohort was followed for the development of a second primary cancer. Blood specimens donated in 1989 were genotyped for the XPD Lys751Gln polymorphism using the 5' nuclease assay. Cox proportional regression with delayed entry was used to calculate the incidence rate ratio (IRR) and 95% confidence interval (95% CI) for risk of developing a second primary cancer according to XPD genotype. All statistical tests were two sided. RESULTS: Eighty individuals developed a second primary cancer. The most frequent occurring cancers were of the prostate (18%), lung (15%), and breast (15%). Persons with at least one Gln allele had an increased risk of a second primary cancer compared with the reference Lys/Lys genotype (adjusted IRR 2.22, 95% CI 1.30-3.76). When the reference category was limited to never smokers with the Lys/Lys genotype, the risk of developing a second primary cancer associated with having at least one Gln allele was increased >3-fold in both never smokers (IRR 3.93, 95% CI 1.36-11.36) and ever smokers (IRR 6.14, 95% CI 2.17-17.37). CONCLUSION: These findings suggest that individuals with NMSC who have the variant XPD Gln allele are at increased risk of developing a second primary cancer.

Age Distribution↗

PubMed2003

Multiple biomarkers study in painters in a shipyard in Korea.

Shipbuilding workers are exposed to a variety of genotoxic compounds including polycyclic aromatic hydrocarbons (PAHs). A limited number of studies have been conducted to evaluate biomarkers related to PAH exposure in painters in the shipyard industry. We examined this in 208 workers recruited from a shipyard located in South Korea. Employees were grouped into three exposure groups: (1) 111 painters using coal tar paints, (2) 70 painters using general paints, and (3) 27 on-site controls using no paints. Levels of urinary 1-hydroxypyrene glucuronide (1-OHPG), as internal dose of PAH exposure, were measured by synchronous fluorescence spectroscopy. Glutathione S-transferase (GST) M1 and T1 genotypes were assessed by a multiplex polymerase chain reaction (PCR)-based method, aromatic-DNA adducts in peripheral white blood cells were measured by 32P-postlabeling, and glycophorin A (GPA) variant frequencies in red blood cells were assessed by flow cytometry. Information on demographic characteristics, smoking habits, diet, job title and use of personal protective equipment (e.g. respiratory and dermal) were collected by self-administered questionnaire. Average urinary 1-OHPG levels in coal tar paint (2.24 micromol/mol creatinine) and general paint (1.38 micromol/mol creatinine) users were significantly higher than in on-site controls (0.62 micromol/mol creatinine) (P<0.001). Paint use, irrespective of the type of paints, and smoking (yes/no) were positively associated with urinary 1-OHPG levels, whereas green tea consumption (yes/no) was negatively associated with the 1-OHPG levels. No significant effect in the 1-OHPG levels were observed for the GSTM1 and GSTT1 genotypes. Aromatic-DNA adduct levels tended to be higher in coal tar paint users (P = 0.06) and painters (P = 0.07) compared to on-site controls. No differences in adduct levels were observed, between the two groups of painters, and the combined group showed greater adduct levels than on-site controls (P = 0.05). GPA mutation frequencies measured in 55 individuals with MN heterozygote genotypes were not significantly different among the three exposure groups, and no correlation was observed between urinary 1-OHPG levels and aromatic-DNA adducts or GPA mutation frequency. These results suggest that painters in the shipyard were exposed to significant amounts of PAHs and possibly to other genotoxic aromatic compounds, and that urinary 1-OHPG may be a potential biomarker of PAH exposure in this population.

Adult↗

PubMed2003

Prospective detection of codon 249 mutations in plasma of hepatocellular carcinoma patients.

A specific missense mutation in the p53 tumor gene at codon 249 has been reported in over 50% of hepatocellular carcinoma (HCC) tumors and in paired blood samples from areas of high dietary exposure to aflatoxin B1, including Qidong, People's Republic of China. Using a combination of pre-digestion with HaeIII, PCR and mass spectrometry, the temporality of this mutation in plasma before and after the clinical diagnosis of HCC was examined. Sixteen liver cancer cases, diagnosed between 1997 and 2001, were selected from a prospective cohort of 1638 high-risk individuals in Qidong on the basis of available annual plasma samples spanning the years before and after diagnosis. The codon 249 mutation was detected in plasma samples obtained after diagnosis in seven of the 15 cases (46.7%) with PCR amplifiable DNA, which is in accord with the reported prevalence of this mutation in HCC. The persistent detection of this mutation in plasma collected annually following diagnosis was statistically significant (P = 0.024, two-tailed) in repetitive samples following diagnosis. Moreover, the mutation was detected in the plasma of four of eight cases positive at the time of diagnosis at least 1 year and in one case 5 years prior to diagnosis. Tracking of the marker in pre-diagnostic samples was borderline statistically significant (P = 0.066). None of the 18 healthy US control plasma samples had any detectable mutations. We have therefore found that pre-diagnosis biomarkers of specific p53 mutations can be measured in plasma and this suggests a paradigm for developing these markers for use in prevention and intervention trials.

Adult↗

PubMed2003

Single amino acid mutations, but not common polymorphisms, decrease the activity of CYP1B1 against (-)benzo[a]pyrene-7R-trans-7,8-dihydrodiol.

Genetic differences that underlie inter-individual variation in the metabolism of common carcinogens are important potential sources of cancer susceptibility. Cytochrome P450 1B1 (CYP1B1), a central enzyme in the activation of the ubiquitous environmental carcinogen benzo[a]pyrene (B[a]P), has several genetic variants. This study investigated six rare mutations and four common polymorphisms for their effects on B[a]P metabolism. Five missense mutations associated with congenital glaucoma (Gly61Glu, Gly365Trp, Asp374Asn, Pro437Leu and Arg469Tryp) dramatically decreased the capacity of CYP1B1 to convert (-)benzo[a]pyrene-7R-trans-7,8-dihyrodiol (B[a]P-7,8-diol) to (+/-)benzo[a]pyrene-r-7,t-8-dihydrodiol-9,10-epoxides. These five mutations resulted in enzymes with 3-12% of normal activity when assayed in vitro using an Saccharomyces cerevisiae microsomal expression system. A 10 bp deletion mutation produced no detectable protein or activity. In contrast, proteins containing all possible combinations of four common single nucleotide polymorphisms (Arg48Gly, Ala199Ser, Val432Leu, Asn453Ser) had modest effects on B[a]P-7,8-diol metabolism. Michaelis-Menten analysis suggested that two alleles, Arg48, Ala119, Val432, Ser453 (RAVS) and Arg48, Ala119, Leu432, Ser453 (RALS), have KM values 2-fold lower than Arg48, Ala119, Val432, Ser453 (RAVN): 1.4+/-0.3 and 1.3+/-0.4 microM, respectively, compared with 2.8+/-0.8 microM (P<0.05). However, these differences could not be confirmed with direct measurements of rate at low substrate concentration. There were no significant differences for either of two other kinetic parameters, kcat or kcat/KM. Allele frequency analysis in three populations reveals the Ser453 variant is rare among those of Asian (<1%) and African ancestry (<4%), and more common in individuals of European ancestry (16%). Haplotypes containing the Ser453 variant were uncommon; only RALS was detectable in our small populations. The RALS allele occurred between 0.5% in Asians and 15% in Europeans. Our study demonstrates that rare, disease-associated mutations in CYP1B1 significantly decrease the enzyme's metabolism of B[a]P-7,8-diol; however, our results do not identify any major differences in this metabolism due to four common single amino acid polymorphisms.

Aryl Hydrocarbon Hydroxylases↗

PubMed2003

Reproductive factors, glutathione S-transferase M1 and T1 genetic polymorphism and breast cancer risk.

We conducted a hospital-based case-control study to evaluate the interactive effect of reproductive factors and glutathione S-transferase (GST) M1 and T1 genetic polymorphisms in individual susceptibility to breast cancer. The study population consisted of 189 incident breast cancer cases and 189 age-matched controls with no known malignant diseases. GSTM1/T1 genotypes were determined by a multiplex polymerase chain reaction (PCR) method, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression model. The parity factors were grouped as (1) high-risk status defined as nullipara or para with experience of first full-term pregnancy (FFTP) at or over 30 years, and (2) low-risk status defined as para with experience of FFTP under 30 years. A significant multiplicative interaction was observed between GSTM1 and GSTT1 null genotypes and high-risk status of parity factor in all women and in premenopausal women (P < or = 0.01), but not in postmenopausal women (P > 0.05). The interaction between the combined genotypes of GSTM1 and GSTT1 and status of parity factor was also significant in all women and in premenopausal women (P < 0.01). Our findings suggest that genetic polymorphisms GSTM1/T1 could modify estrogen-related breast cancer risk.

Breast Neoplasms↗

PubMed2003

Risk of non-Hodgkin's lymphoma and prediagnostic serum organochlorines: beta-hexachlorocyclohexane, chlordane/heptachlor-related compounds, dieldrin, and hexachlorobenzene.

Increases in non-Hodgkin's lymphoma (NHL) incidence and mortality rates during the past few decades remain largely unexplained. Studies suggest that organochlorine pesticides may contribute to an increased risk of NHL. In 1974, serum samples were obtained from 25,802 participants in the Campaign Against Cancer and Stroke in Washington County, Maryland (USA), and cryopreserved for future study. We measured prediagnostic levels of chlordane, lindane (gamma-hexachlorocyclohexane), beta-hexachlorocyclohexane, transnonachlor, heptachlor, heptachlor epoxide, oxychlordane, dieldrin, and hexachlorobenzene in serum samples of 74 cases of NHL and 147 matched controls. Previously, we found an association between NHL and serum levels of total PCBs (polychlorinated biphenyls), but not DDT (dichlorodiphenyltrichloroethane) and related compounds. In this instance, there was no evidence of an association between NHL risk and serum levels of any of the individual lipid- and recovery-corrected organochlorines that we evaluated, nor of the summed chlordane-related compounds (transnonachlor, heptachlor, heptachlor epoxide, oxychlordane). These findings do not support the hypothesis that the organochlorine compounds included in this study are strongly linked to the development of NHL. The possibility of a weak association cannot be excluded by these data.

Case-Control Studies↗

PubMed2003

Relationship between concentration of pyrene and aerosol size distribution in traffic exhausts in Taipei, Taiwan.

Variations in pyrene concentrations in motor-vehicle emissions were assessed on the basis of aerodynamic particle size and by the type of vehicle (i.e., car, truck, or bus) that passed through a Taipei, Taiwan, highway toll station. Airborne particles were collected with 8-stage cascade samplers equipped with 34-mm polyvinyl chloride filters and located in the breathing zones of toll-station workers. The authors used gas chromatography/mass spectrometry to analyze 22 polycyclic aromatic hydrocarbons that were collected. The absolute concentration of pyrene was highest in the fine-particle emission fraction for trucks, buses, and passenger cars; however, fine particles in truck and bus exhausts contained higher pyrene concentrations than the corresponding size fraction of particles emitted from passenger cars. Truck and bus emissions contained a higher concentration of pyrene than car emissions because trucks and buses produced greater amounts of fine and coarse particles, and their fine particles contained higher concentrations of pyrene.

Meteorological Concepts↗