Faculty Bibliography

Acculturation is a complex phenomenon that can serve as a proxy for cultural norms and behaviors affecting care-seeking, prevention behaviors, and, ultimately, health outcomes. The purpose of this study was to assess the effect of acculturation on the oral health of Haitian immigrants in New York City. We hypothesized that acculturation would be a predictor of the oral health status of the participating individuals. An acculturation scale was specifically developed and validated for this study. A sample of 425 adult Haitian immigrants living in NYC was obtained through outreach activities. Oral health examinations were conducted, and a questionnaire was administered to the participants. After adjustment for age, sex, education, income, and marital status, acculturation was negatively associated with measures of decayed teeth, periodontal attachment loss of > or = 4 mm, and the number of missing teeth. Results suggest a positive impact of acculturation on the oral health status of these individuals.

OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women

Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre-diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case-control study was nested within 3 cohorts in New York (USA), Umea (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76-9.72), p(trend) = 0.0008 for estradiol, 3.67 (1.71-7.88), p(trend) = 0.0007 for estrone, 2.15 (1.05-4.40), p(trend) = 0.04 for androstenedione, 1.74 (0.88-3.46), p(trend) = 0.06 for testosterone, 2.90 (1.42-5.90), p(trend) = 0.002 for DHEAS and 0.46 (0.20-1.05), p(trend) = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis

We assessed the association of sex hormone levels with breast cancer risk in a case-control study nested within the cohort of 7054 New York University (NYU) Women's Health Study participants who were postmenopausal at entry. The study includes 297 cases diagnosed between 6 months and 12.7 years after enrollment and 563 controls. Multivariate odds ratios (ORs) (95% confidence interval (CI)) for breast cancer for the highest quintile of each hormone and sex-hormone binding globulin (SHBG) relative to the lowest were as follows: 2.49 (1.47-4.21), P(trend)=0.003 for oestradiol; 3.24 (1.87-5.58), P(trend)<0.001 for oestrone; 2.37 (1.39-4.04), P(trend)=0.002 for testosterone; 2.07 (1.28-3.33), P(trend)<0.001 for androstenedione; 1.74 (1.05-2.89), P(trend)<0.001 for dehydroepiandrosterone sulphate (DHEAS); and 0.51 (0.31-0.82), P(trend)<0.001 for SHBG. Analyses limited to the 191 cases who had donated blood five to 12.7 years prior to diagnosis showed results in the same direction as overall analyses, although the tests for trend did not reach statistical significance for DHEAS and SHBG. The rates of change per year in hormone and SHBG levels, calculated for 95 cases and their matched controls who had given a second blood donation within 5 years of diagnosis, were of small magnitude and overall not different in cases and controls. The association of androgens with risk did not persist after adjustment for oestrone (1.08, 95% CI=0.92-1.26 for testosterone; 1.15, 95% CI=0.95-1.39 for androstenedione and 1.06, 95% CI=0.90-1.26 for DHEAS), the oestrogen most strongly associated with risk in our study. Our results support the hypothesis that the associations of circulating oestrogens with breast cancer risk are more likely due to an effect of circulating hormones on the development of cancer than to elevations induced by the tumour. They also suggest that the contribution of androgens to risk is largely through their role as substrates for oestrogen production

Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umea (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer

INTRODUCTION: Deficiencies in cellular responses to DNA damage can predispose to cancer. Ionizing radiation can cause cluster damage and double-strand breaks (DSBs) that pose problems for cellular repair processes. Three genes (ATM, BRCA1, and BRCA2) encode products that are essential for the normal cellular response to DSBs, but predispose to breast cancer when mutated. DESIGN: To examine the joint roles of radiation exposure and genetic susceptibility in the etiology of breast cancer, we designed a case-control study nested within five population-based cancer registries. We hypothesized that a woman carrying a mutant allele in one of these genes is more susceptible to radiation-induced breast cancer than is a non-carrier. In our study, 700 women with asynchronous bilateral breast cancer were individually matched to 1400 controls with unilateral breast cancer on date and age at diagnosis of the first breast cancer, race, and registry region, and counter-matched on radiation therapy. Each triplet comprised two women who received radiation therapy and one woman who did not. Radiation absorbed dose to the contralateral breast after initial treatment was estimated with a comprehensive dose reconstruction approach that included experimental measurements in anthropomorphic and water phantoms applying patient treatment parameters. Blood samples were collected from all participants for genetic analyses. CONCLUSIONS: Our study design improves the potential for detecting gene-environment interactions for diseases when both gene mutations and the environmental exposures of interest are rare in the general population. This is particularly applicable to the study of bilateral breast cancer because both radiation dose and genetic susceptibility have important etiologic roles, possibly by interactive mechanisms. By using counter-matching, we optimized the informativeness of the collected dosimetry data by increasing the variability of radiation dose within the case-control sets and enhanced our ability to detect radiation-genotype interactions

Mathematical methods exist to determine the fractions of sex hormones bound to albumin, bound to sex hormone binding globulin (SHBG), or unbound, using total hormone concentration and SHBG concentration. We used data from eight prospective studies of postmenopausal women to assess the validity of these estimates for fractions of estradiol (E2) and to investigate the impact of using calculated values in breast cancer relative risk (RR) models. Comparisons were made between measured and calculated concentrations of free and non-SHBG-bound E2 in four studies. Relationships between the hormone fractions were investigated and a sensitivity analysis of the calculation performed. Breast cancer RRs were estimated using conditional logistic regression by quintiles of free E2. There is a high correlation (r > 0.91) between calculated and measured values of both free and non-SHBG-bound E2. The calculation is highly sensitive to total hormone concentration but is relatively insensitive to SHBG concentration. In studies with both measured and calculated values, the RRs of breast cancer by quintile of free E2 were almost identical for both estimates; using calculated values in all possible studies the RR in the highest compared with the lowest quintile of free E2 was 2.29 (95% confidence interval, 1.65-3.19). The mathematical method used to calculate fractions of E2 is valid, and RR analyses using calculated values produce similar results to those using measured values. This suggests that for epidemiological studies, it is only necessary to measure total E2 concentration and SHBG concentration, with hormone fractions being obtained by calculation, producing savings in cost, time, and serum

This article reports an extensive program to monitor individual personal exposures of subjects recruited for a study conducted in a Chinese occupational population to determine whether selected biological markers of exposure to benzene are reliable and sensitive enough to detect low-level benzene exposure in people. The monitoring program reported here was to assure an appropriate range of exposure for subject selection as well as to provide data for the exposure response assessment. The overall study resulted in correlation of the measured exposures with the measured concentrations of two minor urinary benzene metabolites, trans,trans-muconic acid and S-phenylmercapturic acid. The study design and evaluation of biological end points are presented in separate publications. Recruitment of 130 exposed subjects was based on personal exposure measurements collected with passive organic vapor monitors at weekly intervals for 3 to 4 weeks prior to collection of biological samples. Two monitors, side by side, were used for all of the personal monitoring in the first year of the study and about 10 percent of subsequent monitoring. One of each pair was analyzed immediately in Beijing at the Institute of Occupational Medicine, and the other was shipped to the United States and analyzed at the New York University Institute of Environmental Medicine. Exposure concentrations measured over 4-5 weeks were reasonably stable with average coefficients of variation of 0.58, 0.59, and 0.46 for benzene, toluene, and xylene, respectively. Benzene exposure averaged 10 +/- 13 ppm benzene with a median of 3.8 ppm for the recruited exposed workers. Excellent correlation was obtained between samples analyzed for benzene at the two laboratories. The extensive effort to document exposures was important to the exposure-response relationship demonstrated in the full study, which concluded that S-phenylmercapturic acid appears to be a good biomarker for detecting and evaluating benzene exposure at concentrations less than 0.25 ppm

A population-based, incidence case-control study was conducted among women in upstate New York to determine whether histories of certain infections and antibiotic use are associated with risk of non-Hodgkin's lymphoma (NHL). Our study involved 376 cases of NHL identified through the New York State Cancer Registry and 463 controls selected from the Medicare beneficiary files and state driver's license records. Information about use of common medications including antibiotics, history of selected infectious diseases and potential confounding variables was obtained by telephone interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using an unconditional logistic regression model. There was a progressive increase in risk of NHL with increasing frequency and duration of systemic antibiotic use, as assessed over the period of 2-20 years before the interview. The ORs for the highest exposure categories, >/=36 episodes and >/=366 days of use, were 2.56 (95% CI 1.33-4.94) and 2.66 (95% CI 1.35-5.27), respectively. These associations were primarily due to antibiotic use against respiratory infections and dental conditions. Moreover, the association with frequency of antibiotic use for respiratory infections was pronounced for marginal zone B-cell lymphoma and for respiratory tract lymphoma. Analyses by class of antibiotics did not suggest that a general cytotoxic effect of antibiotics was responsible for these increased risks. Although recall bias and selection bias remain potential concerns in our study, the results are generally consistent with the hypothesis that persistent infection/inflammation predisposes individuals to the development of NHL. However, a direct role of antibiotics in NHL induction has not been ruled out