Faculty Bibliography

The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (> 10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10(4) PY Gy (EAR/10(4) PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. Based on limited data, there was a suggestion that spreading dose over time (from a few days to > 1 year) may lower risk, possibly due to the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ and is the only tissue with convincing evidence for risk about 1.10 Gy

BACKGROUND: Circumstantial evidence links endogenous estrogens to increased risk of breast cancer in women, but direct epidemiologic support is limited. In particular, only a few small prospective studies have addressed this issue. PURPOSE: Our purpose was to assess breast cancer risk in relation to circulating levels of the two major endogenous estrogens, estrone and estradiol, measured before the clinical onset of the disease. METHODS: The association between serum levels of estrogens and the risk of breast cancer was examined in a prospective cohort study of 14,291 New York City women, 35-65 years of age, who received screening for breast cancer at the time of blood sampling and who had not been diagnosed with breast cancer. During the first 5 1/2 years of study, we identified 130 breast cancers among the postmenopausal group (7063 women, 35,509 person-years). The case subjects and twice as many postmenopausal control subjects were included in a case-control study nested within the cohort. Biochemical analyses for percent free estradiol, percent estradiol bound to sex hormone-binding globulin (SHBG), total estradiol, estrone, and follicle-stimulating hormone were performed on sera that had been kept at -80 degrees C since sampling. RESULTS: For increasing quartiles of total estradiol, the odds ratio (ORs) of breast cancer, as adjusted for Quetelet index (weight in kilograms divided by the square of the height in meters), were 1.0, 0.9, 1.8, and 1.8 (P value for trend = .06); the ORs for increasing quartiles of estrone were 1.0, 2.2, 3.7, and 2.5 (P value for trend = .06). For increasing quartiles of free estradiol, defined as the fraction of estradiol that is not bound to proteins, the Quetelet index-adjusted ORs of breast cancer were 1.0, 1.4, 3.0, and 2.9 (P value for trend < .01). When we considered the percent of estradiol bound to SHBG, the Quetelet index-adjusted ORs were 1.0, 0.70, 0.40, and 0.32 (P value for trend < .01), thus suggesting a strong protective effect. These associations persisted or became even stronger when analyses were restricted to women whose samples had been drawn 2 or more years before breast cancer diagnosis. CONCLUSIONS: These data represent the first confirmation in a large prospective epidemiologic study of a link between circulating estrogens and breast cancer risk. Although estrogen levels appeared to fall within the conventional limits of normality in all women under study, those who subsequently developed breast cancer tended to show higher levels of estrone, total estradiol, and free estradiol, and a lower percent of estradiol bound to SHBG than women who remained free of cancer. IMPLICATIONS: Factors that increase endogenous estrogen production or reduce the binding of estradiol to SHBG may increase a woman's risk of developing breast cancer later in life

A survey was made of second primary cancers among patients who were enrolled in a large case-control investigation of oral and pharyngeal cancer, hereafter called oral cancer, during 1984-1985 in four areas of the United States. Among the original 1090 patients with oral cancer (nearly all squamous cell carcinomas), 107 developed a second cancer (one-half of them squamous cell) by the end of follow-up in June 1989 (average follow-up 2.6 years), with 69% occurring in the oral cavity, pharynx, oesophagus, larynx or lung. Rates of second tumours varied by age and socioeconomic status, but not sex or race, and were higher among those whose initial cancer was localised, even after adjusting for their longer survival. Long-term survival was lower among those with second cancers. Conditional on surviving for 2 years, the survival at 5 years was under 50% and nearly 70%, respectively, for those with versus those without a second cancer in the first 2 years. These findings confirm the exceptionally high rate of second cancers (especially of the aerodigestive tract) following oral cancer, describe the clinical and pathological features of patients with multiple cancers and indicate the importance of preventive measures

The health effects of bathing in coastal waters is an area of scientific controversy. We conducted the first ever randomised ''trial'' of an environmental exposure to measure the health effects of this activity. The trial was spread over four summers in four UK resorts and 1216 adults took part. Detailed interviews were used to collect data on potential confounding factors and intensive water quality monitoring was used to provide more precise indices of exposure. 548 people were randomised to bathing, and the exposure included total immersion of the head. Crude rates of gastroenteritis were significantly higher in the exposed group (14.8 per 100) than the unexposed group (9.7 per 100; p=0.01). Linear trend and multiple logistic regression techniques were used to establish relations between gastroenteritis and microbiological water quality. Of a range of microbiological indicators assayed only faecal streptococci concentration, measured at chest depth, showed a significant dose-response relation with gastroenteritis. Adverse health effects were identified when faecal streptococci concentrations exceeded 32 per 100 mL. This relation was independent of non-water-related predictors of gastroenteritis. We do not suggest that faecal streptococci caused the excess of gastrointestinal symptoms in sea bathers but these microorganisms do seem to be a better indicator of water quality than the traditional coliform counts. Bathing water standards should be revised with these findings in mind

Levels of total estradiol in premenopausal women vary widely over the course of the menstrual cycle with a spike at the time of ovulation and dissimilar patterns pre- and post-ovulation. Evaluating the association between breast cancer and premenopausal measurements of total estradiol when the measurements cannot be taken on a uniform day of the cycle is therefore a difficult methodological challenge. In a matched case-control study of breast cancer nested within a prospective study, premenopausal serum samples obtained up to 7 years before breast cancer diagnosis were available for total estradiol assay. By fitting a three-piece spline model that regressed the logarithm of total estradiol (ln estradiol) on day of menstrual cycle, the authors were able to adjust the measurements for day of the cycle on which they were collected by expressing them in terms of the number of standard deviations above or below the fitted ln estradiol value for that day. Applying the adjusted measurements to the nested case-control study, they found evidence of a 1.5 to 2-fold risk for women in the upper two tertiles of ln estradiol relative to women in the lowest tertile. Conditional logistic regression analysis for day-of-cycle-adjusted ln estradiol treated as a continuous variable resulted in a relative risk estimate of 1.19 (95% confidence interval 0.91-1.55) per standard-deviation increase in adjusted ln estradiol

Epidemiologic studies have focused on the association between diet and breast cancer with conflicting results. Whereas a majority of case-control studies indicate a role for the intake of total fat and saturated fat, most prospective cohort studies either are negative or indicate very modest associations. Only a few authors have examined the role of meat intake in relation to breast cancer risk. The aim of this study was to examine the relation between risk of breast cancer and dietary intake of meat, animal products, fat, and protein. Between 1985 and 1991, we recruited 14,291 New York City women in a prospective cohort study of endogenous hormones, diet, and cancer in which they reported on their recent diet using a food frequency questionnaire self-administered at enrollment. From the cohort, 180 invasive breast cancer cases diagnosed before December 1990 and five times as many controls, individually matched by age, calendar time at enrollment, menopausal status, and, if premenopausal, phase of menstrual cycle, were included in a nested case-control study. There was an evident increase in the relative risk (RR) of breast cancer for increasing consumption of meat. Women in the upper quintile of meat consumption, as compared with the lowest quintile, had an energy-adjusted RR of 1.87 (95% confidence interval = 1.09-3.21). There was a modest RR increase in the upper quintile of total and saturated fat and no apparent association for other types of fat, protein, dairy products, poultry, or fish.(ABSTRACT TRUNCATED AT 250 WORDS)