Faculty Bibliography

The objective of the study is to characterize the risk of tumors from radiation exposure to the head and neck. A cohort of 2,224 children given x-ray treatment and 1,380 given only topical medications for ringworm of the scalp (tinea capitis) during 1940-1959 have been followed up for a median of 39 y to determine tumor incidence. Follow-ups were by mail/telephone questionnaire, with 84-88% of the original cohort followed and with medical verification of diseases of interest. Sixteen intracranial tumors [7 brain cancers, 4 meningiomas, and 5 acoustic neuromas (vestibular schwannomas)] occurred in the x-irradiated group following an average brain dose of about 1.4 Gy, compared to 1 acoustic neuroma in the control group. The standardized incidence ratio (SIR) for brain cancer was 3.0 [95% confidence interval (CI): 1.3, 5.9]. Even though the dose to the thyroid gland was only about 60 mGy, 2 thyroid cancers were found in the irradiated group vs. none among controls, and 11 vs. 1 thyroid adenomas were found in the respective groups. Following an average dose of about 4 Gy to cranial marrow, 8 cases of leukemia (SIR = 3.2, CI: 1.5, 6.1) were observed in the irradiated group and 1 in the control group. There was also a suggestive excess of blood dyscrasias. There was no difference between the groups in the frequency of other cancers of the head and neck (excluding nonmelanoma skin cancer) or in total mortality

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol

This study was conducted to validate biomarkers for early detection of benzene exposure and effect in 2 phases. The main purpose of phase 1 was to determine whether these biomarkers could reliably detect differences between workers with high exposure levels and unexposed subjects, which is the minimal screening criterion for a biomarker assay. Phase 2 of the study mainly focused on evaluating the exposure-response relation, confounding factors, and sensitivities of biomarkers for low benzene exposures. The Chinese occupational population studied had a broad range of benzene exposures. On the day of biological sample collection, exposures ranged from 0.06 to 122 ppm with a median exposure of 3.2 ppm. The median of the 4-week mean benzene exposures was 3.8 ppm, and the median lifetime cumulative exposure was 51.1 ppm-years. Compared with benzene levels in collected samples, toluene levels were relatively high, with a median of 12.6 ppm (mean, 26.3 ppm), but xylene levels were low, with a median of 0.30 ppm (mean, 0.40 ppm). The biomarkers evaluated were urinary metabolites S-phenylmercapturic acid (S-PMA*), trans,trans-muconic acid (t,t-MA), hydroquinone (HQ), catechol (CAT), and phenol; albumin adducts of benzene oxide and 1,4-benzoquinone (BO-Alb and 1,4-BQ-Alb, respectively) in blood; blood cell counts; and chromosomal aberrations. Blood cell counts in this population, including red blood cells (RBCs), white blood cells (WBCs), and neutrophils, decreased significantly with increased exposures but remained in normal ranges. Chromosomal aberration data showed significant increases of chromatid breaks and total chromosomal aberrations in exposed subjects compared with unexposed subjects. Among the urinary metabolites, the levels of S-PMA and t,t-MA were significantly elevated after benzene exposures. Both markers showed significant exposure-response trends even over the exposure range from 0 to 1 ppm. However, HQ, CAT, and phenol showed significant increases only for benzene exposure levels above 5 ppm. Multiple regression analyses of these urinary metabolites on benzene exposure indicated that toluene exposure, smoking status, and cotinine levels had no significant effects on urinary metabolite levels. A time-course study estimated the half-lives of S-PMA, t,t-MA, HQ, CAT, and phenol to be 12.8, 13.7, 12.7, 15.0, and 16.3 hours, respectively. Both BO-Alb and 1,4-BQ-Alb showed strong exposure-response associations with benzene. Regression analyses showed that after adjustment for potential confounding by smoking, there was still a strong association between benzene exposure and these markers. Furthermore, the analyses for correlations among biomarkers revealed that the urinary metabolites correlated substantially with each other. The albumin adducts also correlated well with the urinary biomarkers, especially with S-PMA. BO-Alb and 1,4-BQ adducts also correlated well with each other (r = 0.74). For benzene exposure monitoring, both S-PMA and t,t-MA were judged to be good and sensitive markers, which detected benzene exposures at around 0.1 ppm and 1 ppm, respectively. But S-PMA was clearly superior to t,t-MA as a biomarker for low levels of benzene exposure

Occupational radiation exposure is often coded as zero when the exposure dose is below the minimum detection level. This leads to an underestimation of the doses received by individuals and can lead to overestimates of risk in occupational epidemiologic studies. The extent of the dose underestimation is increased with the magnitude of the minimum detection level and the frequency of monitoring. The paper proposes a Bayesian approach to estimate the actual dose and the dose distribution parameter when the observed dose is subject to censoring due to minimum detection level. A Gibbs sampling algorithm is developed to implement the method. Simulation studies are used to evaluate the performance of the estimators. The method is applied to a sample of historical occupational radiation exposure data from the Oak Ridge National Laboratory

OBJECTIVE: To examine whether exposures to anti-inflammatory and non-narcotic analgesic drugs are associated with risk of non-Hodgkin's lymphoma (NHL). METHODS: A case-control study was conducted among women living in upstate New York. The study involved 376 cases of NHL identified through the New York State Cancer Registry and 463 controls randomly selected from the Medicare beneficiary files and New York State driver's license records. Information regarding use of common medications in the past 20 years and potential confounding variables was obtained by telephone interview. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using an unconditional logistic regression model. RESULTS: There were non-significant increases in risk associated with ever use of cortisone injections and oral cortisone (OR = 1.44 (CI 0.98-2.11) for injections and 1.21 (CI 0.73-2.00) for oral cortisone, although there was no clear dose-response relationship with either type. On the other hand, the risk of NHL progressively increased with the frequency of use of non-steroidal anti-inflammatory and non-narcotic analgesic drugs (NSAID/NNAD) (p-value for trend 0.008). Women who used any of these medications daily for more than 10 years had an OR of 1.90 (CI 1.01-3.57), compared with those who used it less than once a month on average. The risk associated with long-term use was most pronounced for ibuprofen, intermediate for aspirin, and least for acetaminophen. CONCLUSIONS: Because the population-attributable risk associated with NSAID/NNAD use is potentially large, our results need to be verified in further epidemiologic studies