Showing papers by "Eva S. Schernhammer published in 2004"

Insulin-like growth factors and neoplasia.

Abstract: The insulin-like growth factor 1 (IGF1) signalling pathway has important roles in regulating cellular proliferation and apoptosis. Converging results from epidemiological research and in vivo carcinogenesis models indicate that high levels of circulating IGF1 are associated with increased risk of several common cancers. Ongoing research seeks to clarify the mechanisms underlying these observations and to determine the extent to which IGF physiology influences patterns of cancer incidence. Various therapeutic strategies that target the IGF1 receptor have demonstrated impressive antineoplastic activity in laboratory models, and clinical trials of several novel drug candidates are planned.

Suicide Rates Among Physicians: A Quantitative and Gender Assessment (Meta-Analysis)

Abstract: OBJECTIVE: Physicians’ suicide rates have repeatedly been reported to be higher than those of the general population or other academics, but uncertainty remains. In this study, physicians’ suicide rate ratios were estimated with a meta-analysis and systematic quality assessment of recent studies. METHOD: Studies of physicians’ suicide rates were located in MEDLINE, PsycINFO, AARP Ageline, and the EBM Reviews: Cochrane Database of Systematic Reviews with the terms “physicians,” “doctors,” “suicide,” and “mortality.” Studies were included if they were published in or after 1960 and gave estimates of age-standardized suicide rates of physicians and their reference population or reported extractable data on physicians’ suicide; 25 studies met the criteria. Reviewers extracted data and scored each study for quality. The studies were tested for heterogeneity and publication bias and were stratified by publication year, follow-up, and study quality. Effect sizes were pooled by using fixed-effects (women) and ran...

A Prospective Study of Sleep Duration and Mortality Risk in Women

Abstract: adjusting for age, smoking, alcohol, exercise, depression, snoring, obesity, and history of cancer and cardiovascular disease, sleeping less than 6 hours or more than 7 hours remained associated with an increased risk of death. The relative mortality risk for sleeping 5 hours or less was 1.15 (95% confidence interval [CI], 1.02-1.29) for 6 hours, 1.01 (95% CI, 0.941.08), for 7 hours, 1.00 (reference group), for 8 hours, 1.12 (95% CI, 1.051.20), and for 9 or more hours 1.42 (95% CI, 1.27-1.58). Conclusions: These results confirm previous findings that mortality risk in women is lowest among those sleeping 6 to 7 hours. Further research is needed to understand the mechanisms by which short and long sleep times can affect health.

A Prospective Study of Aspirin Use and the Risk for Colorectal Adenoma

Abstract: Taking aspirin regularly is associated with a reduced risk for colorectal adenoma. The greatest effect occurred at substantially higher doses than those recommended for prevention of cardiovascular...

Melatonin and cancer risk: does light at night compromise physiologic cancer protection by lowering serum melatonin levels?

Abstract: The suprachiasmatic nuclei in the hypothalamus, one of the most important physiological determinants of alertness and performance, drive a circadian pacemaker in mammals, with an intrinsic period averaging 24 h. Light is the primary stimulus to the disruption and resetting of this pacemaker, which is expressed in changing melatonin rhythms. Melatonin production in humans decreases when people are exposed to light at night. Since melatonin shows potential oncostatic action in a variety of tumours, it is possible that lowered serum melatonin levels caused by exposure to light at night enhance the general tumour development. Cancer is the second leading cause of death in industrialised countries like the United States, where a significant proportion of workers engage in shift work, making a hypothesised relation between light exposure at night and cancer risk relevant. Observational studies support an association between night work and cancer risk. We hypothesise that the potential primary culprit for this observed association is the lack of melatonin, a cancer-protective agent whose production is severely diminished in people exposed to light at night.

A Prospective Study of Aspirin Use and the Risk of Pancreatic Cancer in Women

Abstract: Background: In vitro experiments and limited animal studies suggest that aspirin and nonsteroidal anti-inflammatory drugs may inhibit pancreatic carcinogenesis. Because few studies have examined the association between aspirin use and pancreatic cancer in humans and the results have been inconsistent, we examined the relationship between aspirin use and the development of pancreatic cancer in the Nurses’ Health Study. Methods: Among 88 378 women without cancer at baseline, we documented 161 cases of pancreatic cancer during 18 years of follow-up. Aspirin use was first assessed at baseline in 1980 and updated biennially thereafter. All statistical tests were two-sided. Results: Participants were classified according to history of aspirin use. In a multivariable analysis, the risk of pancreatic cancer was not associated with current regular aspirin use (defined as two or more standard tablets per week; relative risk [RR] 1.20, 95% confidence interval [CI] 0.87 to 1.65), compared with use of fewer than two tablets per week. Increasing duration of regular aspirin use, compared with non-use, was associated with a statistically significant increase in risk: Women who reported more than 20 years of regular aspirin use had an increased risk of pancreatic cancer (RR 1.58, 95% CI 1.03 to 2.43; P trend .01). Among women who reported aspirin use on at least two of three consecutive biennial questionnaires compared with consistent non-users of aspirin, the risk increased with dose (one to three tablets per week: RR 1.11, 95% CI 0.70 to 1.76; four to six tablets per week: RR 1.29, 95% CI 0.70 to 2.40; seven to 13 tablets per week: RR 1.41, 95% CI 0.76 to 2.61; and >14 tablets per week: RR 1.86, 95% CI 1.03 to 3.35) (Ptrend .02). Conclusion: Extended periods of regular aspirin use appear to be associated with a statistically signi ficantly increased risk of pancreatic cancer among women. [J Natl Cancer Inst 2004;96:22‐8] Pancreatic cancer, the fourth leading cause of cancer-related mortality in the United States (1), is a rapidly fatal malignancy with limited effective treatment. Nonetheless, other than cigarette smoking, few risk factors have been consistently linked to the risk of pancreatic cancer. Clearly, further studies are needed to identify potential causes and chemopreventive agents for the disease. There is considerable evidence that nonsteroidal antiinflammatory drugs (NSAIDs), particularly aspirin, reduce the risk of several cancers and premalignant lesions. Observational and intervention studies (2) consistently demonstrate the value of these drugs as chemopreventive agents for colorectal neoplasia. Although the mechanism by which aspirin reduces the risk

Job stress and breast cancer risk: the nurses' health study.

Abstract: Workers tend to perceive certain features of their jobs as harmful to health and are alert to associations between job stress and health outcomes, but few observational studies have evaluated the role of job stress in carcinogenesis. The authors prospectively assessed the association between job strain, measured by Karasek and Theorell's job content questionnaire in four categories (low strain, active, passive, and high strain), and breast cancer risk among participants in the Nurses' Health Study. A total of 37,562 US female registered nurses were followed for up to 8 years (1992-2000), and 1,030 cases of invasive breast cancer were ascertained during that period. All participants were still in the workforce at baseline and completed the job content questionnaire. Adjusted for age, reproductive history, and other breast cancer risk factors, the multivariate relative risks of breast cancer, in comparison with women who worked in low-strain jobs, were 0.83 (95% confidence interval (CI): 0.69, 0.99) for women in active jobs, 0.87 (95% CI: 0.73, 1.04) for women in high-strain jobs, and 0.90 (95% CI: 0.76, 1.06) for women in passive jobs. Findings from this study indicate that job stress is not related to any increase in breast cancer risk.

Caregiving stress, endogenous sex steroid hormone levels, and breast cancer incidence.

Abstract: Stress is hypothesized to be a risk factor for breast cancer. The authors examined associations of hours of, and self-reported levels of stress from, informal caregiving with prospective breast cancer incidence. Crosssectional analyses of caregiving and endogenous sex steroid hormones were also conducted. In 1992 or 1996, 69,886 US women from the Nurses’ Health Study, aged 46–71 years at baseline, answered questions on informal caregiving; 1,700 incident breast cancer cases accrued over follow-up to 2000. A subset of 665 postmenopausal women not taking exogenous hormones returned a blood sample in 1990. Numbers of hours of care provided to an ill adult or to a child were each summed and analyzed as 0 (reference), 1–14, and ≥15 per week. Cox proportional hazards models were used in prospective analyses and linear models in cross-sectional analyses. High numbers of caregiving hours and self-reported stress did not predict a higher incidence of breast cancer. However, compared with women providing no adult care, women providing ≥15 hours of adult care (median, 54) had significantly lower levels of estradiol (geometric mean, 9.21 pg/ml vs. 7.46 pg/ml (95% confidence interval: 6.36, 8.76)) and bioavailable estradiol (geometric mean, 1.86 pg/ml vs. 1.35 pg/ml (95% confidence interval: 1.00, 1.82)). Stress from caregiving did not appear to increase breast cancer risk. breast neoplasms; caregivers; cohort studies; gonadal steroid hormones; stress, psychological

Light at night and cancer risk.

Abstract: Environmental lighting powerfully suppresses the physiologic release of melatonin, which typically peaks in the middle of the night. This decreased melatonin production has been hypothesized to increase the risk of cancer. Evidence from experimental studies supports a link between melatonin and tumor growth. There is also fairly consistent indirect evidence from observational studies for an association between melatonin suppression, using night work as a surrogate, and breast cancer risk.

Phase Ia and Ib Study of Amitriptyline for Ulnar Nerve Block in HumansSide Effects and Efficacy

Abstract: Background: The antidepressant amitriptyline is used as an adjuvant in the treatment of chronic pain conditions. Among its many actions, this drug also blocks Ion channels, such as Na + channels. Preliminary animal studies suggested that amitriptyline would be a longer-lasting local anesthetic than bupivacaine, with potentially fewer side effects. Therefore, the authors investigated the adverse effects and effectiveness of this drug when given for ulnar nerve blockade in human volunteers. Methods: After obtaining written institutional review board approval and informed consent, a typical phase Ia trial was conducted by administration to the ulnar nerve at the level of the wrist in an open-label, dose-escalating fashion. Amitriptyline hydrochloride, 4 ml, at concentrations of 5, 10, and 20 mM (n = 4-9/group) was used for each volunteer. If no major side effects and nerve block were encountered, comparison in a randomized, double-blinded trial of amitriptyline (20 mM) to placebo and bupivacaine (4 mM) (n = 4-9/group), was to follow. A blunt needle was used to grade the pain, and motor blockade was assessed by the Froment test. Results: There was no significant statistical difference in terms of side effects (pain, swelling, erythema, and sedation) among any groups. The analgesic effects of 20 mM amitriptyline and 4 mM bupivacaine solution were significantly higher than those of the placebo solution. Conclusions: Because of the lack of evidence that amitriptyline provides better nerve blockade than current local anesthetics and the potential for neurotoxicity, its use for peripheral nerve blockade in humans seems limited.