Faculty Bibliography

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

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.

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

OBJECTIVE: Bone fractures are an important cause of morbidity and mortality among the elderly in the US. The present study assesses the possible role of a number of risk factors for postmenopausal bone fractures. METHODS: We analysed the relationships of anthropometric, demographic and lifestyle factors with the risk of bone fracture among 6250 postmenopausal women in a prospective cohort study, the New York University Women's Health Study. RESULTS: After an average of 7.6 years of follow-up, 1025 new incident bone fractures were reported, including 34 hip and 159 wrist fractures (incidence rates; 71.6 and 334.7 per 105 woman-years, respectively). The risk of fracture increased with increasing age, body height and total fat intake, while it was significantly lower among obese and African American women. The relative risk among African Americans was 0.45 (95% CI: 0.32-0.63) compared with non-African Americans. Women taller than 170 cm had a 64% increase in risk of fractures, as compared with those under 155 cm. These associations were generally more pronounced when fractures were limited to those at the hip and wrist. CONCLUSIONS: The present study provides an indication for a potential role of dietary fat in the development of postmenopausal fractures and further evidence to support protective effects of obesity, short stature and African American ethnicity

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

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

BACKGROUND: The use of psychotropic medications may increase the risk of hormone-related cancers in females through increased gonadotropin secretion, but the data from epidemiologic studies are limited to evaluate the hypothesis. METHODS: The association between the use of psychotropic medications and cancer incidence was studied in a prospective cohort study that involves 15,270 women who participated in mammographic screening. The relative risks (RR) and 95 per cent confidence intervals (CIs) for cancer associated with the use of psychotropic medications were estimated by the Cox's proportional hazard model. RESULTS: During an average of 7.3 years of follow-up, 1,130 incident cases of cancer were identified, including 566 breast, 67 endometrial and 47 ovarian cancers. The use of any type of psychotropic medication at baseline was associated with increased risks of breast [relative risk (RR) = 1.39, 95 per cent CI 1.11-1.74], endometrial (RR=1.71; 95 per cent CI 0.93-3.14) and ovarian (RR= 1.48, 95 per cent CI 0.69-3.16) cancers, whereas no increase in risk was observed for other cancers (RR = 1.06). When the subjects were divided by menopausal status at baseline, premenopausal women tended to have higher risk of all hormone-related cancers (RR = 1.73, 95 per cent CI 1.27-2.35) than postmenopausal women (RR=1.23, 95 per cent CI 0.94-1.62). The magnitude of the RR associated with the use of these medications did not change by length of follow-up. Analysis by type of medication did not find that the association was limited to specific types. CONCLUSION: The observed association needs to be confirmed in further studies based on more detailed medication history

Iron overload, expressed as increased body iron stores, has been recognized as a potential hazard because it promotes the generation of oxygen radicals. We analyzed factors associated with serum ferritin levels (an indicator of body iron stores) among middle-aged women with a high prevalence of nutrient supplement use. Serum ferritin concentrations were determined on automated immunoassay for 487 healthy women with the mean age of 57 years who participated in the New York University Women's Health Study. The mean serum ferritin concentration in postmenopausal women was more than twice that in premenopausal women. Serum ferritin concentrations progressively increased with advancing age, but adjustment for menopausal status considerably weakened this association. Among non-dietary factors, nonwhite ethnicity, obesity and cigarette smoking were positively associated with serum ferritin concentrations. After adjustment for these factors and for menopausal status, serum ferritin levels were positively associated with meat intake and multivitamin use and inversely associated with breakfast cereal consumption. However, none of these lifestyle factors positively associated with serum ferritin levels had a significant impact on serum ferritin levels above 100 ng/ml (approximately equal to median concentration). Our results suggest that iron overload seems unlikely among middle aged women through their diet and nutritional supplements

BACKGROUND: Thickness is known to be an important survival prognosticator for cutaneous melanoma, but controversy exists as to whether Clark level of invasion retains prognostic significance once thickness has been accounted for. A recent proposal to eliminate Clark level from the staging system for melanoma of the American Joint Committee on Cancer (AJCC) prompted the authors to investigate whether level adds useful prognostic information to Breslow thickness. They used the data base of the New York University Melanoma Cooperative Group (NYU-MCG) Registry. METHODS: The analysis was based on 919 patients with AJCC Stage I or II melanomas diagnosed between 1972 and 1982 and followed for an average of 10.9 years. Melanoma thicknesses were divided into 4 categories (< or = 0.75, 0.76-1.50, 1.51-4.00, and >4.00 mm). Patients were cross-classified according to tumor thickness and Clark level (II-V). For each combination of thickness and level, the Kaplan-Meier survival curve and 10-year survival proportion were computed, using death from melanoma as the outcome. The impact of Clark level on survival was evaluated for each of the thickness categories. The Cox proportional hazards model was used to assess the simultaneous effect of thickness and level on survival while controlling for other important prognostic factors, i.e., age, tumor location, and presence or absence of ulceration. RESULTS: Level of invasion was a significant predictor of death from melanoma in each of the four thickness categories. Likewise, in the Cox analyses, level was a significant prognostic variable, even after thickness was included in the model and regardless of whether thickness was treated as a categoric or a continuous variable. CONCLUSIONS: These results confirm that both tumor thickness and level of invasion are important independent prognostic factors in AJCC Stage I and II melanomas. The authors recommend that Clark levels be kept as criteria in the AJCC staging system and be included in pathology reports. [See editorial on pages 491-6, this issue.]

Accumulating evidence suggests that folate, which is plentiful in vegetables and fruits, may be protective against colorectal cancer. The authors have studied the relationship of baseline levels of serum folate and homocysteine to the subsequent risk of colorectal cancer in a nested case-control study including 105 cases and 523 matched controls from the New York University Women's Health Study cohort. In univariate analyses, the cases had lower serum folate and higher serum homocysteine levels than controls. The difference was more significant for folate (P < 0.001) than for homocysteine (P = 0.04). After adjusting for potential confounders, the risk of colorectal cancer in the subjects in the highest quartile of serum folate was half that of those in the lowest quartile (odds ratio, OR = 0.52, 95% confidence interval, CI = 0.27-0.97, P-value for trend = 0.04). The OR for the highest quartile of homocysteine, relative to the lowest quartile, was 1.72 (95% CI = 0.83-3.65, P-value for trend = 0.09). In addition, the risk of colorectal cancer was almost twice as high in subjects with below-median serum folate and above-median total alcohol intake compared with those with above-median serum folate and below-median alcohol consumption (OR = 1.99, 95% CI = 0.92-4.29). The potentially protective effects of folate need to be confirmed in clinical trials