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The incidence of thyroid cancer has been rapidly increasing in the United States, but few risk factors have been established. The authors prospectively examined the associations of self-reported medical history, anthropometric factors, and behavioral factors with thyroid cancer risk among 90,713 US radiologic technologists (69,506 women and 21,207 men) followed from 1983 through 2006. Incident thyroid cancers in 242 women and 40 men were reported. Elevated risks were observed for women with benign thyroid conditions (hazard ratio (HR) = 2.35, 95% confidence interval (CI): 1.73, 3.20), benign breast disease (HR = 1.56, 95% CI: 1.08, 2.26), asthma (HR = 1.68, 95% CI: 1.00, 2.83), and body mass index > or =35.0 versus 18.5-24.9 kg/m(2) (HR = 1.74, 95% CI: 1.03, 2.94; P-trend = 0.04). Current smoking was inversely associated with thyroid cancer risk (HR = 0.54). No clear associations emerged for reproductive factors, other medical conditions, alcohol intake, or physical activity. Despite few thyroid cancers in men, men with benign thyroid conditions had a significantly increased risk of thyroid cancer (HR = 4.65, 95% CI: 1.62, 13.34), and results for other risk factors were similar to those for women. Consistent with prior studies, obesity and benign thyroid conditions increased and current smoking decreased the risk of thyroid cancer. The novel findings for benign breast disease and asthma warrant further investigation.

Childhood radiation exposure has been associated with an increased risk for developing several neoplasms, particularly benign and malignant thyroid tumors, but little is known about the risk of developing acoustic neuromas. The aim of this study was to confirm whether there is a risk for acoustic neuromas and, if so, to determine its magnitude and duration. We investigated the time trend and dose-response relationships for acoustic neuroma incidence in a cohort of 3,112 individuals who were irradiated as children between 1939 and 1962. Most of the patients were treated to reduce the size of their tonsils and adenoids and received substantial radiation exposure to the cerebellopontine angle, the site of acoustic neuromas. Forty-three patients developed benign acoustic neuromas, forty of them surgically resected, far in excess of what might be expected from data derived from brain tumor registries. The mean dose (+/-SD) to the cerebellopontine angle was 4.6 +/- 1.9 Gy. The relative risk per Gy was 1.14 (95% confidence interval 1.0-1.3). The earliest case occurred 20.4 years after exposure and the latest 55 years after exposure (mean 38.3 +/- 10.1 years). Our study provides support for an association between acoustic neuromas and childhood radiation exposure. Although acoustic neuromas are usually benign and often asymptomatic, many cause significant morbidity. Following childhood radiation exposure, they appear after a long latency and continue to occur many decades afterward. Any symptoms of an acoustic neuroma in a patient with a history of radiation to the head and neck area should be investigated carefully, and the threshold for employing imaging should be lowered.

We evaluated breast cancer mortality through 1997 among 69 525 female radiologic technologists who were certified in the United States from 1926 through 1982 and who responded to our questionnaire. Risk of breast cancer mortality was examined according to work history and practices and was adjusted for known risk factors. Breast cancer mortality risk was highest among women who were first employed as radiologic technologists prior to 1940 (relative risk [RR] = 2.92, 95% confidence interval [CI] = 1.22 to 7.00) compared with risk of those first employed in 1960 or later and declined with more recent calendar year of first employment (P for trend = .002). Breast cancer mortality risk increased with increasing number of years of employment as a technologist prior to 1950 (P for trend = .018). However, risk was not associated with the total number of years a woman worked as a technologist. Technologists who first performed fluoroscopy (RR = 1.69, 95% CI = 1.02 to 3.11) and multifilm procedures (RR = 1.87, 95% CI = 1.04 to 3.34) before 1950 had statistically significantly elevated risks compared with technologists who first performed these procedures in 1960 or later. The high risks of breast cancer mortality for women exposed to occupational radiation prior to 1950 and the subsequent decline in risk are consistent with the dramatic reduction in recommended radiation exposure limits over time.

The authors examined risk factors for benign thyroid nodules and their influence on radiation effects among 544 subjects who were exposed to childhood radiation treatment for benign head and neck conditions at a Chicago, Illinois hospital during 1939-1962. In follow-up through 1991, benign thyroid nodules were diagnosed in 131 patients. The risk of benign nodules was elevated in women (relative risk (RR) = 2.2, 95% confidence interval (CI) 1.6-3.2), Jews (RR = 1.7, 95% CI 1.2-2.5), college graduates (RR = 1.8, 95% CI 1.2-2.8), and subjects whose mother had cancer (RR = 1.7, 95% CI 1.2-2.5). There were increasing trends for risk with increasing body mass index in women and decreasing height in men. Risk was increased for women who never married (RR = 3.7, 95% CI 1.6-7.3) or who never had a full-term pregnancy (RR = 2.0, 95% CI 1.1-3.3). A significant radiation dose-response relationship was observed that was not modified by sex, education, Jewish religion, or reproductive factors. The data suggest that there are genetic, life-style (including ascertainment), and hormonal factors associated with the development of benign thyroid nodules.

BACKGROUND Between 1920 and 1965, radiation treatment to the ovaries and/or pituitary gland was used for refractory hormonal infertility and amenorrhoea. The potential carcinogenic effects of hormonal infertility, as well as exposure to relatively low doses of ovarian and pituitary radiation can be studied among patients receiving these treatments. METHODS A cohort of 816 patients treated between 1925 and 1961 was identified from the medical records of a New York City radiologist. The mortality experience for 84% of these women was determined and radiation doses for individual patients were estimated. Doses were, on average, 87, 64, 54, and 29 cGy to the ovary, brain, colon, and active bone marrow, respectively. RESULTS Compared with mortality rates in the US population, the risk of death was less than expected (standardized mortality ratio [SMR] = 0.87; 95% confidence interval [CI]: 0.75-1.00). Deaths due to circulatory and digestive diseases were significantly below expectation. Cancer mortality was about 10% higher than that expected based on New York City mortality rates. Based on a small number of cases, no increase was found for cancers of the ovary or brain, or leukaemia, sites for which direct radiation exposure occurred, but significant excesses of colon cancer and non-Hodgkin's lymphoma were observed. A deficit in mortality from female genital cancers was surprising, since nulliparity has been a consistently reported risk factor for cancers of the endometrium and ovary. Breast cancer mortality was close to expectation. CONCLUSIONS Overall, this study provided little evidence that either infertility or its treatment with radiation increased the risk of total or cancer mortality.

Between 1950 and 1960 about 20,000 israeli children were treated for tinea capitis by x-ray therapy as part of a large public health campaign to eradicate the disease. Dosimetric studies determined that these children were subjected to a mean brain dose of 130 rads. Almost 20 years later, possible radiation effects on the central nervous system were evaluated by comparing several measures of mental and brain function in approximately 11,000 of the irradiated children and in two nonirradiated, tinea-free comparison groups: (a) ethnic, sex- and age-matched individuals from the general population, and (b) siblings. While not all comparisons were statistically significant, there was a consistent trend for the irradiated subjects to exhibit signs of central nervous system inpairment more often than either comparison group. The irradiated children had lower examination scores on scholastic aptitude, intelligence quotient (IQ) and psychologic tests, completed fewer school grades, and had an increased risk for mental hospital admissions for certain disease categories. A slightly higher frequency of mental retardation was also suggested. These-long-lasting scholastic and mental health effects lead the authors to conclude that radiation to the immature brain may cause damage to the central nervous system.

The mortality experience of 10,834 children treated with x-rays for ringworm of the scalp between 1948 and 1960, 10,834 matched comparison subjects, and 5,392 siblings was evaluated over an average follow-up period of 26 years. Mortality was ascertained by linking unique personal identification numbers of study subjects with the national death registry. Radiotherapy in childhood was associated with an increased risk of death due to tumors of the head and neck (relative risk (RR) = 3) and leukemia (RR = 2.3). No other causes of death were significantly elevated after irradiation. The excess of brain tumors (average intracranial dose = 150 rads) confirms that the central nervous system of the child is sensitive to the induction of cancers by radiation. The bone marrow dose averaged over the entire body was approximately 30 rad, and the estimated risk coefficient of 0.9 excess leukemias per million per year per rad is consistent with other studies of whole-body exposure. A significant excess of bone and soft tissue sarcomas (RR = 9) was also observed. The pattern of cancer risk over time was bimodal; an early peak due to excess leukemias occurred within a few years of exposure, whereas excesses of solid tumors were most apparent after about 15 years. Despite the excess of cancers among exposed persons, over 50% of the deaths in the entire study population were from external events, mainly accidents or events related to military service. An estimate of the total impact of radiogenic cancer after childhood irradiation will require additional years of observation since the population irradiated is just now entering the age ranges normally associated with high cancer risk.

A population-based case-control interview study of thyroid cancer (159 cases and 285 controls) was conducted in Connecticut. Prior radiotherapy to the head or neck was reported by 12% of the cases and 4% of the controls [odds ratio (OR) = 2.8; 95% confidence interval = 1.2-6.9]. Risk was inversely related to age at irradiation and was highest among children exposed under age 10. Few persons born after 1945 received prior radiotherapy, consistent with the declining use of radiation to treat benign conditions in the 1950's. Among females the radiogenic risk appeared to be potentiated by the number of subsequent live-births. Other significant risk factors included a history of benign thyroid nodules (OR = 33) or goiter (OR = 5.6). Miscarriage and multiparity increased risk but only among women who developed thyroid cancer before age 35 years. Consumption of shellfish (a rich source of iodine) seemed to increase the risk of follicular thyroid cancer, whereas consumption of goitrogen-containing vegetables appeared to reduce risk of total thyroid cancer, possibly because of their cruciferous nature. A significantly low risk was observed among persons of English descent, whereas Italian ancestry appeared to increase risk. No significant associations were found with a number of suspected risk factors: diagnostic x-rays, radioactive isotope scans, occupational radiation exposure, tonsillectomy, Jewish ethnicity, alcohol intake, cigarette smoking, oral contraceptives, lactation suppressants, menopausal estrogens, most other common medications, and water source. New associations were suggested for obesity among females (OR = 1.5), surgically treated benign breast disease (OR = 1.6), use of spironolactone (OR = 4.3) or vitamin D supplements (OR = 1.8), and a family history of thyroid cancer (OR = 5.2). About 9% of the incident thyroid cancers could be attributed to prior head and neck irradiation, 4% to goiter, and 17% to thyroid nodular disease, leaving the etiology of most thyroid cancers yet to be explained.

The incidence of all thyroid surgery was studied among 10,842 persons whose thyroid glands had been exposed in childhood to an average dose of 9 rads of X-radiation during treatment for tinea capitis and among 2 matched control groups. A statistically significant increased risk for both benign and malignant neoplasms was found in the exposed group. The excess risk was 8.3 cases/year/rad/million population. There were no differences in other surgical conditions between the irradiated and nonirradiated groups. Persons irradiated under age 6 years had the highest excess risk for developing carcinomas. The incidence of thyroid neoplasms was approximately threefold higher in women than in men among the irradiated persons and among the controls, but the relative risk for the irradiated group of women was greater than the addition of the relative risks of the other groups. Low-dose radiation is instrumental in the development of both benign and malignant thyroid neoplasms.

A dietary case-control study based on 818 newly diagnosed breast cancer (BC) patients was conducted in Israel between 1975 and 1978. The role of coffee and total methylxanthine intake from coffee, tea, cola, chocolate, and cocoa drinks was evaluated in the BC patients as compared to that in two matched control populations [surgical controls (SC) and neighborhood controls (NC)]. Because it has been suggested that caffeine enhances mammary carcinogenesis in rats fed high polyunsaturated fat diets, analysis was done also in relation to fat consumption. When comparison was done to both matched control groups, a nonsignificant negative association was found between consumption of cups of coffee and BC (odds ratios of greater than or equal to 4 cups of coffee/day vs. less than or equal to 1 per week = 0.6 for BC/NC and 0.7 for BC/SC). This association was observed in all 3 ethnic subgroups studied. The pattern was stronger among the high-fat consumers after controlling for several hormonal confounding factors (two-tailed P-value for linear trend = 0.06 for SC and P = 0.05 for NC). In addition, when the consumption of methylxanthine of BC patients was compared to that of benign breast patients, adjusted by age and ethnic group, a diminished risk was found (odds ratio for BC of the highest level of methylxanthine vs. lowest level = 0.59).