Faculty Bibliography

OBJECTIVE: The aim of the study was to investigate the reproducibility of a food frequency questionnaire (FFQ) used in a cohort of 14,290 women enrolled in the NYU Women's Health Study. DESIGN: A subset of 474 cohort subjects who completed the dietary questionnaire at baseline (FFQ-1) were approached again on the occasion of a second visit to the mammography study centre and asked to complete the questionnaire a second time (FFQ-2) two to four years after FFQ-1. Two to three months later the questionnaire was mailed to the subjects, and they were asked to complete it a third time (FFQ-3). SETTING: A breast cancer screening clinic. SUBJECTS: Of the 474 subjects selected, 100% completed the second questionnaire while only 56% completed and mailed back FFQ-3. This made it possible to compare the long-term reproducibility of dietary intake measurements and baseline dietary habits between the two groups of subjects 'respondents', who agreed to complete the questionnaire a third time, and 'non-respondents', who did not. RESULTS: Among respondents (56% of study subjects), energy-adjusted correlation coefficients for short-term reproducibility between FFQ-2 and FFQ-3 ranged from 0.50-0.64 for nutrients, and from 0.44-0.67 for foods. The long-term reproducibility was lower, ranging from 0.36-0.53 for nutrients, and from 0.31-0.48 for specific food groups. Among those who did not respond to FFQ-3, crude correlations for long-term reproducibility, unadjusted for energy intake, were generally lower than among respondents. Nevertheless, after adjustment for energy intake, correlations for long-term reproducibility (FFQ-2 to FFQ-1) were of similar magnitude in both groups. In addition, 'non-respondents' reported lower intake of fruit and vegetables and higher intake of meat. CONCLUSIONS: The results of this study suggest that subjects who volunteer to participate in substudies on the validity or reproducibility of dietary questionnaire measurements may tend to provide more accurate responses to the questionnaire. The phenomenon seems related more to accuracy of reporting of absolute intake levels than of the relative composition of diet, self-selection may be associated with differences in dietary habits

The authors examined the relation between postmenopausal serum levels of testosterone and dehydroepiandrosterone sulfate (DHEAS) and subsequent risk of breast cancer in a case-control study nested within the New York University Women's Health Study cohort. A specific objective of their analysis was to examine whether androgens had an effect on breast cancer risk independent of their effect on the biologic availability of estrogen. A total of 130 cases of breast cancer were diagnosed prior to 1991 in a cohort of 7,054 postmenopausal women who had donated blood and completed questionnaires at a breast cancer screening clinic in New York City between 1985 and 1991. For each case, two controls were selected, matching the case on age at blood donation and length of storage of serum specimens. Biochemical analyses were performed on sera that had been stored at -80 degrees C since sampling. The present report includes a subset of 85 matched sets, for whom at least 6 months had elapsed between blood donation and diagnosis of the case. In univariate analysis, testosterone was positively associated with breast cancer risk (odds ratio (OR) for the highest quartile = 2.7, 95% confidence interval (CI) 1.1-6.8, p < 0.05, test for trend). However, after including % estradiol bound to sex hormone-binding globulin (SHBG) and total estradiol in the statistical model, the odds ratios associated with higher levels of testosterone were considerably reduced, and there was no longer a significant trend (OR for the highest quartile = 1.2, 95% CI 0.4-3.5). Conversely, breast cancer risk remained positively associated with total estradiol levels (OR for the highest quartile = 2.9, 95% CI 1.0-8.3) and negatively associated with % estradiol bound to SHBG (OR for the highest quartile = 0.05, 95% CI 0.01-0.19) after adjustment for serum testosterone levels. These results are consistent with the hypothesis that testosterone has an indirect effect on breast cancer risk, via its influence on the amount of bioavailable estrogen. No evidence was found of an association between DHEAS and risk of breast cancer in postmenopausal women

The relation between diet and female colorectal cancer was analyzed in a prospective study of 14,727 women aged 34-65 years, who were enrolled at mammographic screening clinics in New York and Florida from 1985 to 1991. They were followed through the end of 1994 (average 7.1 yrs) by a combination of direct contact through mail and telephone and record linkages with regional tumor registries, resulting in 100 incident cases of colorectal cancer. There was no overall positive or inverse association of colorectal cancer risk with intakes of total calories, total or subclasses of fat, carbohydrate, or dietary fiber, whereas there was an inverse association with total protein. Among major food groups, there was a progressive decline in risk of colorectal cancer with increasing intake of fish and shellfish (relative risk for 4th vs. 1st quartile = 0.49, 95% confidence interval = 0.27-0.89). A similar inverse association was also observed for consumption of dairy products, and this association was explained mainly by calcium, not by other nutrients, such as fat or protein. The results of the present study indicated that certain dietary components of fish or dairy products may protect against colorectal cancer, whereas the relations with red meat or total fat remained unclear

A number of topics are discussed related to the potential for and pitfalls in undertaking epidemiologic studies of the late effects of nasopharyngeal radium irradiation. The available evidence indicates that linear extrapolation of risk estimates from high-dose studies is a reasonable basis for estimating risk from radium exposure or other situations in which the radiation exposures were fairly low and fractionated. Epidemiologic study of populations given nasopharyngeal radium irradiation is worthwhile scientifically if several criteria can be met. It is very important that any such study has adequate statistical power, which is a function of the doses to the organs of interest and the radiation risk coefficients for those organs, as well as the available sample size. If the organ doses are low, a prohibitively large sample size would be required. Other problems with low-dose studies include the likelihood of false-positive results when a number of health end points are evaluated and the impact of dose uncertainties, small biases, and confounding factors that make the interpretation uncertain. Cluster studies or studies of self-selected cohorts of irradiated patients are not recommended because of the potential for severe bias with such study designs. The ability to define subgroups of the population who have heightened genetic susceptibility may become a reality in the next few years as genes conferring susceptibility to brain cancers or other head and neck tumors are identified; this scientific advance would have the potential to alter greatly the prospects and approaches of epidemiologic studies

To describe symptoms associated with human immunodeficiency virus (HIV) seroconversion, we studied a cohort of 366 injection-drug users (IDUs) with a study design that included recall every 3 months to collect symptom histories using a structured questionnaire. Eleven HIV seroconversions were observed in 621.5 person years at risk (PYAR), equivalent to 1.8 seroconversions/100 PYAR. Cox regression analysis showed age < or = 35 years to be a significant risk factor for HIV seroconversion after controlling for gender, race, and the frequency of drug injection. An embedded case-control analysis then compared symptom histories of HIV seroconverters with those of age-(+/- 5 years) and visit number-matched controls who remained HIV seronegative for > or = 3 months longer than the HIV-seroconverters. Multivariate case-control analysis adjusted for injection frequency yielded significant associations of HIV seroconversion with histories of weight loss > or = 4.5 kg (seven of 11 cases; odds ratio [OR] = 11.6, 95% confidence interval [CI] 3.1, 43.1) and oral ulcers (three of 11 cases; OR = 7.6, 95% CI = 1.2, 48.2) in the 3 months before the subjects' first HIV-seropositive study visit. We conclude that histories of recent symptoms reported by HIV-seroconverting IDUs differ from those reported by non-HIV-seroconverting IDUs, and weight loss may be particularly common among IDUs experiencing primary HIV infection

The objective of this study was to determine what sociodemographic, lifestyle, or drug-related characteristics predict temporal changes in self reported drug injection frequencies among HIV-seronegative injection-drug users (IDUs) who were being given HIV testing and risk reduction counseling. The 277 subjects were given 4-11 quarterly interviews including detailed history of drug use and other HIV risk factors, HIV risk reduction counseling, and venipuncture for HIV antibody testing. A regression slope of change over time in drug injection frequency was calculated for each subject, and categories were created of decreasing temporal slope, increasing slope, relapse (decrease initially, then increase), or no substantial change. Only 44% of subjects decreased their drug injection frequencies despite repetitive HIV testing and counseling. In multivariate logistic analyses, decreasing temporal trends were associated with consistent enrollment in methadone maintenance (p < .1), whereas increasing trends conversely were associated with inconsistent enrollment (p < .01) and also with an absence of crack use (p < .01). Relapses were significantly associated with needle sharing with multiple partners and a low frequency of smoking. The data suggest that methadone maintenance facilitates a positive response to HIV risk reduction counseling. However, the fact that only a minority of subjects displayed a decreasing temporal trend in drug injection frequencies emphasizes the need for improved therapeutic and counseling techniques

A positive association between postmenopausal serum levels of total estradiol, percentage of free estradiol, and percentage of estradiol not bound to sex hormone-binding globulin (SHBG) and breast cancer risk was recently reported by the New York University Women's Health Study (P. Toniolo et al., J. Natl. Cancer Inst., 87: 190-197, 1995). Data from this prospective study are used to assess whether the observed associations differ according to estrogen receptor (ER) status of the tumor. Between 1985 and 1991, 7063 postmenopausal women donated blood and completed questionnaires at a large breast cancer screening clinic in New York City. Before 1991, 130 cases of first primary breast cancer were identified by active follow-up of the cohort. For each case, two controls were selected, matching the case on age at first blood donation and length of storage of specimens. Biochemical analyses were performed on sera that had been stored at -80 degrees since sampling. ER information was abstracted from pathology reports. Separate statistical analyses were conducted of ER-positive, ER-negative, and ER-unknown groups (53, 23, and 54 matched sets, respectively). In each of the 3 groups, the mean estradiol and the mean percentage of free estradiol were greater (21-28% and 6-7%, respectively) in cases than in controls. Conversely, the mean percentage of estradiol bound to SHBG was 9-12% lower in cases than in controls. The logistic regression coefficients measuring the strength of the association between estradiol and its free and SHBG-bound fractions and breast cancer risk were similar in the ER-positive, ER-negative, and ER-unknown groups. These data suggest that in postmenopausal women, the association of endogenous estrogens with breast cancer risk is independent of the ER status of the tumor. This result is more compatible with the hypothesis of a progression from ER-positive to ER negative tumors than with the hypothesis that ER status identifies two distinct types of breast cancer

A case-control analysis was conducted to determine the relationship between height and mortality among patients enrolled in the already completed Beta Blocker Heart Attack Trial (BHAT). In a basic model including height (continuous) and relevant covariates the relative risk (RR) per 4-inch reduction in height (approximately 1 standard deviation) was 1.18 (95% confidence interval, 0.92 to 1.51). When sex was considered, the effect of short stature on mortality was found to be restricted to male subjects. The male RR per 4-inch reduction in height was 1.26 (0.96 to 1.63) whereas for women it was 0.89 (0.49 to 1.59). In males not randomized to propranolol (untreated) the effect was further modified with a RR per 4-inch reduction in height of 1.41 (1.00 to 1.99). It is hypothesized that short stature could be a marker for factors operating as far back as childhood that predispose males to mortality from coronary heart disease in later life