Faculty Bibliography

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

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

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol

OBJECTIVE: To examine whether exposures to anti-inflammatory and non-narcotic analgesic drugs are associated with risk of non-Hodgkin's lymphoma (NHL). METHODS: A case-control study was conducted among women living in upstate New York. The study involved 376 cases of NHL identified through the New York State Cancer Registry and 463 controls randomly selected from the Medicare beneficiary files and New York State driver's license records. Information regarding use of common medications in the past 20 years and potential confounding variables was obtained by telephone interview. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using an unconditional logistic regression model. RESULTS: There were non-significant increases in risk associated with ever use of cortisone injections and oral cortisone (OR = 1.44 (CI 0.98-2.11) for injections and 1.21 (CI 0.73-2.00) for oral cortisone, although there was no clear dose-response relationship with either type. On the other hand, the risk of NHL progressively increased with the frequency of use of non-steroidal anti-inflammatory and non-narcotic analgesic drugs (NSAID/NNAD) (p-value for trend 0.008). Women who used any of these medications daily for more than 10 years had an OR of 1.90 (CI 1.01-3.57), compared with those who used it less than once a month on average. The risk associated with long-term use was most pronounced for ibuprofen, intermediate for aspirin, and least for acetaminophen. CONCLUSIONS: Because the population-attributable risk associated with NSAID/NNAD use is potentially large, our results need to be verified in further epidemiologic studies

BACKGROUND: There is no consensus concerning management of Spitz nevi. OBJECTIVE: This study was carried out to ascertain how dermatologists manage Spitz nevi. METHODS: A questionnaire was sent to 997 fellows of the American Academy of Dermatology, 284 pediatric dermatologists, and 27 directors of pigmented-lesion clinics. The results are based on the 381 questionnaires returned. RESULTS: The vast majority of responding dermatologists (93%) recommend biopsies of suspected Spitz nevi. Of this group, 43% recommend total biopsies and 55% recommend partial biopsies; 2% would recommend either total or partial biopsies, depending on the clinical situation. Sixty-nine percent of physicians would completely excise a lesion that was histologically diagnosed as an incompletely removed Spitz nevus. Seventy percent of general dermatologists and 80% of pediatric dermatologists would recommend excision with a 1- to 2-mm margin of normal-appearing skin around a Spitz nevus. Nine percent of general dermatologists would recommend margins of 4 mm or more; however, all pediatric dermatologists surveyed would recommend margins less than 4 mm. Physicians were less likely to monitor patients whose Spitz nevi were completely removed. Three fourths (74%) of respondents believe Spitz nevi are entirely benign, 4% believe they are precursors to melanoma, and 22% are not sure. Seven percent of general dermatologists and 4% of pediatric dermatologists have seen metastatic melanomas arise at sites of lesions initially diagnosed histologically as Spitz nevi; 40% of pigmented-lesion clinic directors have seen such lesions. CONCLUSIONS: We believe that the lack of consensus, both in our survey and in the medical literature, reflects to some extent the lack of certainty in the histologic differentiation of Spitz nevi from melanomas and that concern about melanoma influences management. At the pigmented-lesion clinic of the New York University Skin and Cancer Unit, because of this concern about melanoma, it is usually recommended that Spitz nevi be completely excised

The association between aspirin use and lung cancer risk in women was examined in a case-control study nested in the New York University Women's Health Study, a large cohort in New York. Case subjects were all the 81 incident lung cancer cases who had provided information about aspirin use at enrollment and during the 1994-1996 follow up. Ten controls per case were randomly selected from among study participants who matched a case by age, menopausal status, and dates of enrollment and follow-up. Relative to no aspirin use, the odds ratio for lung cancer (all histological sub-types combined) among subjects who reported aspirin use three or more times per week for at least 6 months was 0.66 (95% confidence interval 0.34-1.28), after adjustment for smoking and education. A stronger inverse association was observed in analyses restricted to non-small cell lung cancer (adjusted odds ratio 0.39, 95% confidence interval 0.16-0.96). These results suggest that regular aspirin use might be inversely associated with risk of lung cancer in women, particularly the non-small cell sub-type

BACKGROUND: Epidemiological evidence suggests that chronic inflammation may influence ovarian carcinogenesis. The study objective was to examine the association between the commonly used anti-inflammatory drug aspirin and epithelial ovarian cancer. METHODS: The authors conducted a case-control study based in the New York University Women's Health Study cohort enrolled between 1985 and 1991 in New York City. After a median follow-up period of 12 years, 68 incident cases of epithelial ovarian cancer were identified. Data about regular aspirin use were collected during the 1994-1996 follow-up questionnaire. Using a case-control study design, 10 controls per case were randomly selected among study participants who matched the case by age and menopausal status. Conditional logistic regression analysis was used to study the relationships between aspirin and epithelial ovarian cancer by generating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Relative to no aspirin use, the OR for epithelial ovarian cancer among women who reported aspirin use three or more times per week for a period of at least 6 months was 0.60 (95% CI 0.26, 1.38), after adjustment for age at menarche, parity, oral contraceptive use, and first-degree family history of breast cancer before age 50. Among recent, within the previous 5 years, users of aspirin, the adjusted OR was 0.36 (95% CI 0.11, 1.18). CONCLUSION: Although confidence intervals included unity, the observed risk estimates seem to be compatible with previous studies suggesting that regular aspirin use could be inversely associated with risk of epithelial ovarian cancer

We assessed the association of postmenopausal serum levels of oestrogens and sex hormone-binding globulin (SHBG) with endometrial cancer risk in a case-control study nested within the NYU Women's Health Study cohort. Among 7054 women postmenopausal at enrolment, 57 cases of endometrial cancer were diagnosed a median of 5.5 years after blood donation. Each case was compared to 4 controls matched on age, menopausal status at enrolment, and serum storage duration. Endometrial cancer risk increased with higher levels of oestradiol (odds ratio = 2.4 in highest vs lowest tertile, P for trend = 0.02), percent free oestradiol (OR = 3.5, P< 0.001), and oestrone (OR = 3.9, P< 0.001). Risk decreased with higher levels of percent SHBG-bound oestradiol (OR = 0.43, P = 0.03) and SHBG (OR = 0.39, P = 0.01). Trends remained in the same directions after adjusting for height and body mass index. A positive association of body mass index with risk was substantially reduced after adjusting for oestrone level. Our results indicate that risk of endometrial cancer increases with increasing postmenopausal oestrogen levels but do not provide strong support for a role of body mass index independent of its effect on oestrogen levels.

Insulin-like growth factor I (IGF-I) is a systemic hormone with potent mitogenic and anti-apoptotic properties, which could influence the proliferative behavior of normal breast cells. Limited epidemiological observations suggest that the hormone may play a role in the etiology of breast cancer, especially at pre-menopausal ages. In a prospective case-control study nested within a cohort of New York City women, IGF-I, IGF-binding protein 3 (IGFBP-3) and C peptide were measured in frozen serum samples from 172 pre-menopausal and 115 post-menopausal subjects who were subsequently diagnosed with breast cancer. Subjects were eligible if diagnosed 6 months or more after recruitment into the study (7 to 120 months). Cohort members who matched the cases on age, menopausal status, date of blood sampling and day of menstrual cycle at blood collection served as controls. Post-menopausal breast cancer was not associated with serum IGF-I, IGFBP-3 or C-peptide levels. However, the risk of breast cancer increased with increasing serum concentrations of IGF-I in pre-menopausal women. The odds ratio (OR) for the highest quartile of IGF-I (>256 ng/ml) compared to the lowest (<168 ng/ml) was 1.60 [95% confidence interval (CI) 0.91-2. 81]. The OR decreased to 1.49 (95% CI 0.80-2.79) after adjustment for IGFBP-3. In analyses restricted to subjects who were pre-menopausal at the time of blood sampling and whose cancer was diagnosed before age 50, the top vs. bottom quartile OR increased appreciably to 2.30 (95% CI 1.07-4.94). Adjustment for IGFBP-3 reduced the OR to 1.90 (95% CI 0.82-4.42). There was no association between pre-menopausal breast cancer and IGFBP-3, IGF-I:IGFBP-3 ratio or non-fasting levels of C peptide. Elevated circulating levels of IGF-I may be an indicator of increased risk of breast cancer occurring before age 50

OBJECTIVE: To determine the risk for developing malignant melanoma and neurocutaneous melanocytosis (NCM) in patients with large congenital melanocytic nevi. DESIGN: Follow-up data suitable for calculations were available on 160 patients in the New York University Registry of Large Congenital Melanocytic Nevi who had been free of known melanomas or NCM when entered into the Registry. The cumulative 5-year life-table risks for developing melanoma and NCM were calculated. The relative risk for developing melanoma, using a control general population reference group, was determined. RESULTS: The 160 patients (median age at entry: 14 months) were followed prospectively for an average of 5.5 years. Three extracutaneous melanomas developed: 2 were in the central nervous system (CNS) and 1 was retroperitoneal. The 5-year cumulative life-table risk for developing melanoma was 2.3% (95% confidence interval [CI]:.8-6.6) and the relative risk was 101 (95% CI: 21-296). No melanoma occurred within a large congenital melanocytic nevus. Four patients developed manifest NCM, 2 with CNS melanomas. The 5-year cumulative life-table risk for developing NCM was 2.5% (95% CI:.8-7.2). Ten patients were excluded from the calculations because of preexisting disease on entry into the Registry: 5 with manifest NCM and 5 with melanomas (3 in large congenital melanocytic nevi, 1 in nonnevus skin, and 1 unknown primary). CONCLUSIONS: Patients with large congenital melanocytic nevi are at increased risk for developing melanomas. There is also a significant increased risk for developing NCM. The high incidence of CNS involvement may influence decisions concerning treatment of the large congenital melanocytic nevi