Validation and Calibration of a Model Used to Reconstruct Historical Exposure to Polycyclic Aromatic Hydrocarbons for Use in Epidemiologic Studies

OBJECTIVES: We previously developed a historical reconstruction model to estimate exposure to airborne polycyclic aromatic hydrocarbons (PAHs) from traffic back to 1960 for use in case–control studies of breast cancer risk. Here we report the results of four exercises to validate and calibrate the model. METHODS: Model predictions of benzo[a]pyrene (BaP) concentration in soil and carpet dust were tested against measurements collected at subjects’ homes at interview. In addition, predictions of air intake of BaP were compared with blood PAH–DNA adducts. These same soil, carpet, and blood measurements were used for model optimization. In a separate test of the meteorological dispersion part of the model, predictions of hourly concentrations of carbon monoxide from traffic were compared with data collected at a U.S. Environmental Protection Agency monitoring station. RESULTS: The data for soil, PAH–DNA adducts, and carbon monoxide concentrations were all consistent with model predictions. The carpet dust data were inconsistent, suggesting possible spatial confounding with PAH-containing contamination tracked in from outdoors or unmodeled cooking sources. BaP was found proportional to other PAHs in our soil and dust data, making it reasonable to use BaP historical data as a surrogate for other PAHs. Road intersections contributed 40–80% of both total emissions and average exposures, suggesting that the repertoire of simple markers of exposure, such as traffic counts and/or distance to nearest road, needs to be expanded to include distance to nearest intersection

Geographic differences in semen quality of fertile U.S. males.

Although geographic variation in semen quality has been reported, this is the first study in the United States to compare semen quality among study centers using standardized methods and strict quality control. We evaluated semen specimens from partners of 512 pregnant women recruited through prenatal clinics in four U.S. cities during 1999-2001; 91% of men provided two specimens. Sperm concentration, semen volume, and motility were determined at the centers, and morphology was assessed at a central laboratory. Study protocols were identical across centers, and quality control was rigorously maintained. Sperm concentration was significantly lower in Columbia, Missouri, than in New York, New York; Minneapolis, Minnesota; and Los Angeles, California. Mean counts were 58.7, 102.9, 98.6, and 80.8 X 10(6)/mL (medians 53.5, 88.5, 81.8, and 64.8 X 10(6)/mL) in Missouri, New York, Minnesota, and California, respectively. The total number of motile sperm was also lower in Missouri than in other centers: 113, 196, 201, and 162 X 10(6) in Missouri, New York, Minnesota, and California, respectively. Semen volume and the percent morphologically normal sperm did not differ appreciably among centers. These between-center differences remained significant in multivariate models that controlled for abstinence time, semen analysis time, age, race, smoking, history of sexually transmitted disease, and recent fever (all p-values < 0.01). Confounding factors and differences in study methods are unlikely to account for the lower semen quality seen in this mid-Missouri population. These data suggest that sperm concentration and motility may be reduced in semirural and agricultural areas relative to more urban and less agriculturally exposed areas

Polycyclic Aromatic Hydrocarbon-DNA Adducts and Breast Cancer: A Pooled Analysis

Polycyclic aromatic hydrocarbon (PAH)-DNA adducts have been associated with breast cancer in several small studies. The authors' pooled analysis included 873 cases and 941 controls from a population-based case-control study. Competitive enzyme-linked immunosorbent assay in peripheral mononuclear cells was conducted in 2 rounds, and results were pooled on the basis of round-specific quantiles. The odds ratio for breast cancer was elevated in relation to detectable PAH-DNA adducts (1.29 as compared with nondetectable adduct levels; 95% confidence interval = 1.05, 1.58), but there was no apparent dose-response relationship with increasing quantiles. No consistent pattern emerged when the results were stratified by PAH sources (e.g., active cigarette smoking or PAH-containing foods), or when the cases were categorized by stage of disease or hormone receptor status. These data provide only modest support for an association between PAH-DNA adducts and breast cancer development

Radiation and the Risk of Chronic Lymphocytic and Other Leukemias among Chornobyl Cleanup Workers

Background: Risks of most types of leukemia from exposure to acute high doses of ionizing radiation are well known, but risks associated with protracted exposures, as well as associations between radiation and chronic lymphocytic leukemia (CLL), are not clear.
 Objectives: We estimated relative risks of CLL and non-CLL from protracted exposures to low-dose ionizing radiation.
 Methods: A nested case–control study was conducted in a cohort of 110,645 Ukrainian cleanup workers of the 1986 Chornobyl nuclear power plant accident. Cases of incident leukemia diagnosed in 1986–2006 were confirmed by a panel of expert hematologists/hematopathologists. Controls were matched to cases on place of residence and year of birth. We estimated individual bone marrow radiation doses by the Realistic Analytical Dose Reconstruction with Uncertainty Estimation (RADRUE) method. We then used a conditional logistic regression model to estimate excess relative risk of leukemia per gray (ERR/Gy) of radiation dose.
 Results: We found a significant linear dose response for all leukemia [137 cases, ERR/Gy = 1.26 (95% CI: 0.03, 3.58]. There were nonsignificant positive dose responses for both CLL and non-CLL (ERR/Gy = 0.76 and 1.87, respectively). In our primary analysis excluding 20 cases with direct in-person interviews less than 2 years from start of chemotherapy with an anomalous finding of ERR/Gy = –0.47 (95% CI: less than –0.47, 1.02), the ERR/Gy for the remaining 117 cases was 2.38 (95% CI: 0.49, 5.87). For CLL, the ERR/Gy was 2.58 (95% CI: 0.02, 8.43), and for non-CLL, ERR/Gy was 2.21 (95% CI: 0.05, 7.61). Altogether, 16% of leukemia cases (18% of CLL, 15% of non-CLL) were attributed to radiation exposure.
 Conclusions: Exposure to low doses and to low dose-rates of radiation from post-Chornobyl cleanup work was associated with a significant increase in risk of leukemia, which was statistically consistent with estimates for the Japanese atomic bomb survivors. Based on the primary analysis, we conclude that CLL and non-CLL are both radiosensitive.

Genomic characterization of chronic lymphocytic leukemia (CLL) in radiation-exposed Chornobyl cleanup workers

Background Chronic lymphocytic leukemia (CLL) was the predominant leukemia in a recent study of Chornobyl cleanup workers from Ukraine exposed to radiation (UR-CLL). Radiation risks of CLL significantly increased with increasing bone marrow radiation doses. Current analysis aimed to clarify whether the increased risks were due to radiation or to genetic mutations in the Ukrainian population. Methods A detailed characterization of the genomic landscape was performed in a unique sample of 16 UR-CLL patients and age- and sex-matched unexposed general population Ukrainian-CLL (UN-CLL) and Western-CLL (W-CLL) patients (n = 28 and 100, respectively). Results Mutations in telomere-maintenance pathway genes POT1 and ATM were more frequent in UR-CLL compared to UN-CLL and W-CLL (both p < 0.05). No significant enrichment in copy-number abnormalities at del13q14, del11q, del17p or trisomy12 was identified in UR-CLL compared to other groups. Type of work performed in the Chornobyl zone, age at exposure and at diagnosis, calendar time, and Rai stage were significant predictors of total genetic lesions (all p < 0.05). Tumor telomere length was significantly longer in UR-CLL than in UN-CLL (p = 0.009) and was associated with the POT1 mutation and survival. Conclusions No significant enrichment in copy-number abnormalities at CLL-associated genes was identified in UR-CLL compared to other groups. The novel associations between radiation exposure, telomere maintenance and CLL prognosis identified in this unique case series provide suggestive, though limited data and merit further investigation

Vehicular Traffic–Related Polycyclic Aromatic Hydrocarbon Exposure and Breast Cancer Incidence: The Long Island Breast Cancer Study Project (LIBCSP)

BackgroundPolycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in laboratory animals. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major ambient source of PAH exposure.ObjectivesOur study aim was to evaluate the association between residential exposure to vehicular traffic and breast cancer incidence.MethodsResidential histories of 1,508 participants with breast cancer (case participants) and 1,556 particpants with no breast cancer (control participants) were assessed in a population-based investigation conducted in 1996–1997. Traffic exposure estimates of benzo[a]pyrene (B[a]P), as a proxy for traffic-related PAHs, for the years 1960–1995 were reconstructed using a model previously shown to generate estimates consistent with measured soil PAHs, PAH–DNA adducts, and CO readings. Associations between vehicular traffic exposure estimates and breast cancer incidence were evaluated using unconditional logistic regression.ResultsThe odds ratio (95% CI) was modestly elevated by 1.44 (0.78, 2.68) for the association between breast cancer and long-term 1960–1990 vehicular traffic estimates in the top 5%, compared with below the median. The association with recent 1995 traffic exposure was elevated by 1.14 (0.80, 1.64) for the top 5%, compared with below the median, which was stronger among women with low fruit/vegetable intake [1.46 (0.89, 2.40)], but not among those with high fruit/vegetable intake [0.92 (0.53, 1.60)]. Among the subset of women with information regarding traffic exposure and tumor hormone receptor subtype, the traffic–breast cancer association was higher for those with estrogen/progesterone-negative tumors [1.67 (0.91, 3.05) relative to control participants], but lower among all other tumor subtypes [0.80 (0.50, 1.27) compared with control participants].ConclusionsIn our population-based study, we observed positive associations between vehicular traffic-related B[a]P exposure and breast cancer incidence among women with comparatively high long-term traffic B[a]P exposures, although effect estimates were imprecise.CitationMordukhovich I, Beyea J, Herring AH, Hatch M, Stellman SD, Teitelbaum SL, Richardson DB, Millikan RC, Engel LS, Shantakumar S, Steck SE, Neugut AI, Rossner P Jr., Santella RM, Gammon MD. 2016. Vehicular traffic–related polycyclic aromatic hydrocarbon exposure and breast cancer incidence: the Long Island Breast Cancer Study Project (LIBCSP). Environ Health Perspect 124:30–38; http://dx.doi.org/10.1289/ehp.130773

Residential Environmental Exposures and other Characteristics Associated with Detectable PAH-DNA Adducts in Peripheral Mononuclear Cells in a Population-Based Sample of Adult Females

The detection of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human lymphocytes may be useful as a surrogate end point for individual cancer risk prediction. In this study, we examined the relationship between environmental sources of residential PAH, as well as other potential factors that may confound their association with cancer risk, and the detection of PAH-DNA adducts in a large population-based sample of adult women. Adult female residents of Long Island, New York, aged at least 20 years were identified from the general population between August 1996 and July 1997. Among 1556 women who completed a structured questionnaire, 941 donated sufficient blood (25+ ml) to allow use of a competitive ELISA for measurement of PAH-DNA adducts in peripheral blood mononuclear cells. Ambient PAH exposure at the current residence was estimated using geographic modeling (n=796). Environmental home samples of dust (n=356) and soil (n=360) were collected on a random subset of long-term residents (15+ years). Multivariable regression was conducted to obtain the best-fitting predictive models. Three separate models were constructed based on data from : (A) the questionnaire, including a dietary history; (B) environmental home samples; and (C) geographic modeling. Women who donated blood in summer and fall had increased odds of detectable PAH-DNA adducts (OR=2.65, 95% confidence interval (CI)=1.69, 4.17; OR=1.59, 95% CI=1.08, 2.32, respectively), as did current and past smokers (OR=1.50, 95% CI=1.00, 2.24; OR=1.46, 95% CI=1.05, 2.02, respectively). There were inconsistent associations between detectable PAH-DNA adducts and other known sources of residential PAH, such as grilled and smoked foods, or a summary measure of total dietary benzo-[a]-pyrene (BaP) intake during the year prior to the interview. Detectable PAH-DNA adducts were inversely associated with increased BaP levels in dust in the home, but positively associated with BaP levels in soil outside of the home, although CIs were wide. Ambient BaP estimates from the geographic model were not associated with detectable PAH-DNA adducts. These data suggest that PAH-DNA adducts detected in a population-based sample of adult women with ambient exposure levels reflect some key residential PAH exposure sources assessed in this study, such as cigarette smoking

Subclinical Hypothyroidism after Radioiodine Exposure: Ukrainian–American Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident (1998–2000)

BackgroundHypothyroidism is the most common thyroid abnormality in patients treated with high doses of iodine-131 (131I). Data on risk of hypothyroidism from low to moderate 131I thyroid doses are limited and inconsistent.ObjectiveThis study was conducted to quantify the risk of hypothyroidism prevalence in relation to 131I doses received because of the Chornobyl accident.MethodsThis is a cross-sectional (1998-2000) screening study of thyroid diseases in a cohort of 11,853 individuals &lt; 18 years of age at the time of the accident, with individual thyroid radioactivity measurements taken within 2 months of the accident. We measured thyroid-stimulating hormone (TSH), free thyroxine, and antibodies to thyroid peroxidase (ATPO) in serum.ResultsMean age at examination of the analysis cohort was 21.6 years (range, 12.2-32.5 years), with 49% females. Mean 131I thyroid dose was 0.79 Gy (range, 0-40.7 Gy). There were 719 cases with hypothyroidism (TSH &gt; 4 mIU/L), including 14 with overt hypothyroidism. We found a significant, small association between (131)I thyroid doses and prevalent hypothyroidism, with the excess odds ratio (EOR) per gray of 0.10 (95% confidence interval, 0.03-0.21). EOR per gray was higher in individuals with ATPO &lt; or = 60 U/mL compared with individuals with ATPO &gt; 60 U/mL (p &lt; 0.001).ConclusionsThis is the first study to find a significant relationship between prevalence of hypothyroidism and individual (131)I thyroid doses due to environmental exposure. The radiation increase in hypothyroidism was small (10% per Gy) and limited largely to subclinical hypothyroidism. Prospective data are needed to evaluate the dynamics of radiation-related hypothyroidism and clarify the role of antithyroid antibodies

I-131 Dose Response for Incident Thyroid Cancers in Ukraine Related to the Chornobyl Accident

Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case–control studies, and studies of prevalent cancers

Environmental toxins and breast cancer on Long Island. I. Polycyclic aromatic hydrocarbon DNA adducts

Polycyclic aromatic hydrocarbons (PAH) are potent mammary carcinogens in rodents, but their effect on breast cancer development in women is not clear. To examine whether currently measurable PAH damage to DNA increases breast cancer risk, a population-based case-control study was undertaken on Long Island, NY. Cases were women newly diagnosed with in situ and invasive breast cancer; controls were randomly selected women frequency matched to the age distribution of cases. Blood samples were donated by 1102 (73.0%) and 1141 (73.3%) of case and control respondents, respectively. Samples from 576 cases and 427 controls were assayed for PAH-DNA adducts using an ELISA. The geometric mean (and geometric SD) of the log-transformed levels of PAH-DNA adducts on a natural scale was slightly, but nonsignificantly, higher among cases [7.36 (7.29)] than among controls [6.21 (4.17); p = 0.51]. The age-adjusted odds ratio (OR) for breast cancer in relation to the highest quintile of adduct levels compared with the lowest was 1.51 [95% confidence interval (CI), 1.04 –2.20], with little or no evidence of substantial confounding (corresponding multivariate-adjusted OR, 1.49; 95% CI, 1.00 –2.21). There was no consistent elevation in risk with increasing adduct levels, nor was there a consistent association between adduct levels and two of the main sources of PAH, active or passive cigarette smoking or consumption of grilled and smoked foods. These data indicate that PAH-DNA adduct formation may influence breast cancer development, although the association does not appear to be dose dependent and may have a threshold effect