Faculty Bibliography

Thyroid adenoma incidence in a cohort of 2657 infants given X-ray treatment for a supposedly enlarged thymus gland, along with 4833 unirradiated siblings, has been ascertained for an average of 37 years since irradiation. Estimated thyroid doses ranged from 0.03 to > 8 Gy, with 62% receiving < 0.5 Gy. After excluding 4 adenoma cases with concurrent or previous thyroid cancer, there were 86 cases with pathologically diagnosed thyroid adenomas in the irradiated group and 11 in the sibling controls. The estimated excess relative risk (ERR) was 6.3 per gray (90% CI = 3.7, 11.2). Once the dose group with > or = 6 Gy, which was producing downward curvature in the dose-response function, was removed, the curve was compatible with linearity and the ERR was 7.8 per gray. Thyroid adenoma rates were elevated even at low doses: the lowest dose group (< 0.25 Gy) showed a significant elevation in risk. The relative risk appeared to be constant over time and was comparable for both sexes. Excess adenoma risk was observed in the irradiated group to the maximum follow-up interval of about 50 years. A number of potential risk factors for thyroid adenoma were examined both as risk factors in their own right and as modifiers of the radiogenic risk. Parity and use of hormones in relation to menopause were significantly associated with thyroid adenoma risk in women, while education, Jewish origin, history of hyperthyroidism or hypothyroidism, and family history of cancer were also adenoma risk factors in both sexes. An examination of interactions between possible risk factors and radiation suggested that women with a history of oral contraceptive use or hysterectomy and persons with a family history of cancer may have greater risk (per unit dose) of radiogenic thyroid adenomas than their counterparts

The available information on the induction of thyroid cancer in humans by ionizing radiation is summarized and weaknesses or gaps in assessing risk are identified. Issues to be addressed include: average estimates of thyroid cancer risk from external irradiation, the effects of age on thyroid cancer induction, shape of the dose-response curve for acute irradiation, magnitude of risk at low doses, effects of dose fractionation or dose protraction, the relative effectiveness of iodine-131 (131I) in inducing thyroid cancer compared to external radiation, the temporal course of radiogenic thyroid cancer risk, mortality caused by thyroid cancer, host-susceptibility factors for radiogenic thyroid cancer, and biological factors in risk. It is concluded that the most important needs are to obtain more information on thyroid cancer risks following low-level or highly fractionated radiation exposures and following 131I exposure in children

Epidemiologic data are increasingly being used to assess cancer risk from chemicals as their value is recognized and as more and better studies become available. Weight-of-evidence approaches are now available for classifying the experimental and epidemiological evidence regarding human carcinogenicity. When the human data are extensive and of good quality, they should be given substantial weight in assessing risk. Both the positive and the negative epidemiologic data should be used in a quantitative risk assessment (QRA), because only then can an unbiased risk assessment be derived. Good-quality epidemiological studies are those with sound methodology, lack of bias, long enough follow-up times to observe a carcinogenic response, adequate exposure information, and dose-response information. Before a lack of carcinogenicity can be inferred, it is essential that the exposures be of substantial duration and intensity, and that the number of exposed persons be reasonably large. Epidemiologists need to give more attention to exposure assessment, because lack of quantitative exposure information is often the limiting factor that prevents the use of epidemiologic data in QRA. Development of methods to estimate historical workplace exposure intensities from surrogate industrial hygiene variables should receive high research priority, since they have the potential to increase the usefulness in QRA of many epidemiologic studies that have limited exposure information. Several frequently used surrogates for exposure measurements have limitations or pitfalls in their use. In particular, the use of 'ever/never' exposed has a large potential to produce falsely negative results by means of a 'dilution' effect, especially in the common case where the exposure distribution is skewed. Duration of exposure (rather than duration x intensity) may also give misleading results. There is little information to suggest that synergistic exposures to multiple toxicants in an industrial environment are likely to invalidate QRAs, probably because few studies have identified a group of workers with major workplace exposures to multiple carcinogens that cause the same type of cancer. Most of the interactive effects which have been identified to date are between smoking and some occupational carcinogen, so this possibility needs careful evaluation for smoking-related diseases. It is important to evaluate dose-response gradients in a QRA to obtain maximum precision and accuracy in the resulting risk coefficient. The analysis should take into account an appropriate cancer induction period. Various methods to account for cancer induction times are compared; those that incorporate a lag period or model the induction-time distribution are superior to other methods.(ABSTRACT TRUNCATED AT 400 WORDS)

BACKGROUND. We conducted a case-control analysis to determine the contribution made to mortality by intermittent ST depression (STD) among patients enrolled in the already completed Beta Blocker Heart Attack Trial. METHODS AND RESULTS. STD was determined by computer analysis of 24-hour ECG tapes as a change in ST level by +/- 0.1 mV or more from the median value of ST of all normally conducted complexes for greater than or equal to 1 minute. All computer-detected ST events were verified by trained readers. To estimate risk of dying associated with STD, 261 deaths were compared with controls matched for age, sex, drug status, and time elapsed since acute myocardial infarction. In a model including relevant covariates, STD had a relative risk (RR) of 1.73 (95% confidence interval, 1.09-2.73). The RR was 2.56 (1.39-4.71) in untreated patients and 0.98 (0.48-2.00) in propranolol-treated patients. A history of angina, although not independently significant, was found to enhance these RRs. A gradient of risk was shown in the placebo group by a RR of 1.91 in those with 1-30 minutes of STD and 4.33 in those with greater than 30 of STD (p = 0.001, trend test). CONCLUSIONS. The findings in this large study show a significant contribution to mortality among untreated early post-myocardial infarction survivors from transient STD on 24-hour monitoring. The absence or reduction of effect in the treated group also suggests an anti-ischemic mechanism by which propranolol exerts a protective effect on mortality. Trials to determine whether reduction of STD improves survival would be warranted

The Japanese atomic bomb survivors and three other cohorts of children exposed to radiation are analyzed, and evidence is found for a reduction in the radiation-induced relative risk of cancers other than leukemia with time following exposure. Multiplicative adjustments to the excess risk either of the form exp[-delta.(time since exposure)] or of the form [time since exposure] gamma give equivalent goodness of fit. Using the former type of adjustment an annual overall reduction of 6.9-8.6% in excess relative risk is indicated (depending on the year after which this reduction might take effect). Using the second type of multiplier an adjustment to the excess relative risk varying between [time after exposure]-2.0 and [time after exposure]-3.2 fits best overall. All these reductions are statistically significant at the 5% level. There is no significant variation by cohort, by sex, by cancer type, or by age at exposure group in the degree of annual reduction in excess relative risk. Although time-adjusted relative and absolute risk models give equivalently good fits within each cohort, there is significant variation between cohorts in the degree of increase of risk with time in the absolute risk formulation, in contrast to the lack of such heterogeneity for the relative risk formulation. It is shown that if the range of observed reductions in relative risk is assumed to operate 40 or more years after exposure in the youngest age groups, the calculated UK population risks would be reduced by 30-45% compared to those based on a constant relative risk model

To investigate whether hair dye use increases the risk of breast cancer, a case-control study was conducted among patients attending a screening center in New York City. The study group consisted of 398 breast cancer cases identified at the screening center between 1977 and 1981, and 790 randomly selected controls screened during the same period. Subjects were interviewed by telephone to obtain information on known risk factors for breast cancer, along with a complete history of hair dye use detailing type of dye, color, duration, frequency, and temporal periods of use. Most subjects (77%) had used hair dye at least once, 38% of the subjects at least 100 times. However, little increased risk of breast cancer was found among hair dye users. The adjusted odds ratio for ever having used hair dye was 0.8 (95% confidence interval 0.6-1.1), and there was no evidence of a trend in risk with increasing number of hair dye uses. The results were the same whether all past exposures were considered or only exposures more than 10 years before disease. Breast cancer risk did not increase with increasing intensity of exposure, as measured by frequency of use or darkness of color. No effect was seen for different types or colors of dye, or for use during different periods of reproductive life. Although personal hair dye use was unrelated to breast cancer risk, there was an adjusted odds ratio of 3.0 (95% confidence interval 1.1-7.8) for 5 or more years of work as a beautician. Overall, the results of this study, taken in conjunction with the findings of other epidemiologic studies, do not implicate hair dye use as an important cause of human breast cancer