Faculty Bibliography

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.]

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

BACKGROUND: Excessive body weight is known to increase the risk of postmenopausal, but not premenopausal breast cancer. Some studies have suggested that being overweight is protective against premenopausal breast cancer, but the evidence is not compelling. Much less is known about the role of body fat distribution in either pre- or postmenopausal breast cancer. METHODS: Breast cancer risk was examined in relation to body weight, height, Quetelet index (kg/m2), and waist/hip ratio (WHR) in the New York University Women's Health Study, a prospective cohort study. Cases were 109 premenopausal and 150 postmenopausal women diagnosed with breast cancer between 1985 and 1994. Non-cases were 8,157 cohort members free of breast cancer. RESULTS: Among premenopausal women, there was an increasing risk of breast cancer with increasing WHR. The relative risk (RR) of breast cancer increased to 1.72 (95% confidence interval [CI]: 1.0-3.1) in the upper quartile of WHR. The association was limited to subjects who had elevated Quetelet index, but not among those with lower weight. Overall, Quetelet index itself was not related to breast cancer risk in the premenopausal group, but there was a protective association among those ranking below the median WHR. In postmenopausal women, the RR for breast cancer increased to 2.36 (95% CI: 1.4-3.9) in the upper quartile of Quetelet index, but there was no association with WHR. Height was not associated with breast cancer in this study. CONCLUSIONS: The study confirms that excessive body weight increases breast cancer risk in postmenopausal women. On the contrary, in premenopausal women, excessive body weight may be protective among women who have a lower-body type of fat accumulation (low WHR). An upper-body fat accumulation (high WHR) is a predictor of breast cancer risk in premenopausal women, and this effect is especially pronounced among subjects who are overweight

While irregular menstruations have been associated with lower cumulative exposure to the ovarian steroids, shorter regular cycles have been postulated to increase the cumulative exposure. Epidemiological correlates with menstrual patterns were analyzed among 4900 premenopausal women aged 45 or younger from the New York University Women's Health Study. The length of regular menstrual cycles increased with increasing age at menarche, body mass index and parity, but decreased with age, nonwhite racial background and current smoking. The likelihood of irregular cycles increased with increasing age, body mass index and number of cigarettes smoked per day. With adjustment for age, body mass index and number of cigarettes smoked per day, the risk of irregular cycles was marginally positively associated with total fat intake

Lower serum folate and higher serum homocysteine levels are known risk factors for various conditions. Thus, epidemiologic correlates with these measurements were studied for 256 multivitamin users and 230 non-users who were middle-aged women. Both serum folate and homocysteine levels increased with advancing age in both multivitamin users (P < 0.01 and P < 0.01) and non-users (P = 0.08 and P < 0.01). Among non-users, higher intake of vegetables, fruits, cold cereals and total protein were associated positively with serum folate and inversely with homocysteine levels. There were 25-74% increases in serum folate and 10-15% decreases in serum homocysteine between 1st and 4th quartiles of intake of these food/nutrients. In addition, 26% lower serum folate and 18% higher serum homocysteine were observed for those smoking 20 or more cigarettes per day compared with non-smokers. Among multivitamin users, body weight was correlated inversely with serum folate (P < 0.01) and positively with serum homocysteine levels (P = 0.04), while no correlates were found among lifestyle factors. Regular use of multivitamins increased serum folate about fourfold and decreased homocysteine twofold. These results suggest that multivitamin use can offset the effects of an unhealthy lifestyle on these serum markers, and that levels of serum folate and homocysteine can also be favorably influenced by healthier diet and abstinence from smoking

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

Accumulated evidence suggests that increased body iron stores may increase the risk of colorectal cancer, possibly via catalyzing oxidation reactions. We examined the relationship between iron status and colorectal cancer in a case-control study nested within the New York University Women's Health Study cohort. For 105 incident cases of colorectal cancer with an average follow-up of 4.7 years and 523 individually matched controls, baseline levels of serum iron, ferritin, total iron binding capacity (TIBC) and transferrin saturation were determined as indicators of body iron stores, and total iron intake was assessed based on their diet and supplement intake. Overall, there were no associations between the risk of colorectal cancer and any of these indices except for serum ferritin, which showed a significant inverse association. When analyzed by subsite, there was an increasing trend in risk of cancer of the proximal colon with increasing total iron intake (p-value for trend = 0.04). In addition, a significantly increased risk of colorectal cancer associated with higher total iron intake [odds ratio (OR) = 2.50; 95% confidence interval (CI): 1.06-5.87] was observed among subjects with higher intake of total fat. Our results do not support a role of increased body iron stores in the development of colorectal cancer, but suggest that luminal exposure to excessive iron may possibly increase the risk in combination with a high fat diet