Showing papers by "Eva S. Schernhammer published in 2006"

Social Networks, Social Support, and Survival After Breast Cancer Diagnosis

Abstract: Purpose We prospectively examined social ties and survival after breast cancer diagnosis. Patients and Methods Participants included 2,835 women from the Nurses' Health Study who were diagnosed with stages 1 to 4 breast cancer between 1992 and 2002. Of these women, 224 deaths (107 of these related to breast cancer) accrued to the year 2004. Social networks were assessed in 1992, 1996, and 2000 with the Berkman-Syme Social Networks Index. Social support was assessed in 1992 and 2000 as the presence and availability of a confidant. Cox proportional hazards models were used in prospective analyses of social networks and support, both before and following diagnosis, and subsequent survival. Results In multivariate-adjusted analyses, women who were socially isolated before diagnosis had a subsequent 66% increased risk of all-cause mortality (HR = 1.66; 95% CI, 1.04 to 2.65) and a two-fold increased risk of breast cancer mortality (HR = 2.14; 95% CI, 1.11 to 4.12) compared with women who were socially integrate...

Night work and risk of breast cancer.

Abstract: Background: Melatonin shows potential oncostatic activity and is acutely suppressed by light exposure. Some evidence suggests an association between night work and breast cancer risk, possibly through the melatonin pathway. Methods: In a cohort of premenopausal nurses, we prospectively studied the relation between rotating night shift work and breast cancer risk. Total number of months during which the nurses worked rotating night shifts was first assessed at baseline in 1989 and periodically updated thereafter. We used Cox proportional hazards models to calculate relative risks (RRs) and 95% confidence intervals (CIs). Results: Among 115,022 women without cancer at baseline, 1,352 developed invasive breast cancer during 12 years of follow up. Women who reported more than 20 years of rotating night shift work experienced an elevated relative risk of breast cancer compared with women who did not report any rotating night shift work (multivariate RR 1.79; 95% CI 1.06‐3.01). There was no increase in risk associated with fewer years of rotating night work. Conclusion: Our results suggest a modestly elevated risk of breast cancer after longer periods of rotating night work. Additional studies are warranted to rule out small sample size or uncontrolled sources for confounding as alternative explanations.

The association of self-reported sleep duration, difficulty sleeping, and snoring with cognitive function in older women.

Abstract: We examined the association of sleep duration, snoring, and difficulty sleeping with cognitive function in a cohort of community-dwelling women. Women (n = 1844), aged 70 to 81 years at initial cognitive interview in 2000, are members of the Nurses' Health Study cohort. Women completed six tests of cognitive function encompassing general cognition, verbal memory, category fluency, and attention. We repeated the assessment 2 years later. We used linear regression models to obtain multivariate-adjusted mean differences in initial test performance, and in cognitive decline over time, across categories of sleep duration (< or =5,6,7,8,9+ hours/night), frequency of snoring (never, occasionally, regularly), and sleep difficulties (rarely/never, occasionally, regularly). In analyses of initial test performance, women sleeping < or =5 hours/night scored worse than women sleeping 7 hours/night (mean difference on global score combining all cognitive tests = 0.15 standard units, 95% CI: -0.28, -0.02). Women who regularly had difficulty falling or staying asleep scored 0.11 units lower on the global score (95% CI: -0.22, 0.01) compared with those who rarely had difficulty sleeping. These differences were equivalent to the mean differences in score observed between participants who were 4 to 5 years apart in age. We found no associations with snoring or with any of the sleep variables and cognitive decline over 2 years. Associations between sleep patterns and initial cognitive function may be clinically relevant given that diminished cognition is a risk factor for dementia. However, the lack of an association with prospective cognitive decline warrants further investigation.

Work Characteristics and Incidence of Type 2 Diabetes in Women

Abstract: The authors prospectively investigated associations between potentially stressful work characteristics and type 2 diabetes incidence in 62,574 young and middle-aged women, aged 29-46 years at baseline in 1993, from the Nurses' Health Study II; 365 cases of type 2 diabetes accrued over 6 years of follow-up. Cox proportional hazards regression was used to simultaneously evaluate associations of hours per week in paid employment, years of rotating night-shift work, and job strain with incidence of type 2 diabetes. In multivariate-adjusted analyses, women working less than 20 hours per week had a lower risk of diabetes (relative risk = 0.80, 95% confidence interval: 0.50, 1.30), and those working overtime (> or =41 hours/week) had an elevated risk of diabetes (relative risk = 1.23, 95% confidence interval: 0.98, 1.55) compared with women working 21-40 hours/week (referent) in paid employment (p(trend) = 0.03). In subsequent analysis, the elevated association appeared stronger in unmarried women (p(interaction) = 0.02). A positive association between years in rotating night-shift work and diabetes was mediated entirely by body weight. Job strain was unrelated to risk of type 2 diabetes. In conclusion, working overtime predicted a slightly elevated risk of type 2 diabetes in young and middle-aged female nurses.

Insulin-like growth factor-I, its binding proteins (IGFBP-1 and IGFBP-3), and growth hormone and breast cancer risk in The Nurses Health Study II

Abstract: Earlier data suggest that the relationship between circulating insulin-like growth factor I (IGF-I) levels and breast cancer risk differs according to menopausal status. We evaluated the association between IGF levels as well as the primary regulator of IGF-I production, growth hormone (GH), and breast cancer risk in the Nurses' Health Study II (NHS II) cohort, a large cohort of primarily premenopausal women. We conducted a case-control study nested within the prospective NHS II cohort. Plasma concentrations of IGF-I, IGF binding protein (IGFBP)-3, IGFBP-1, and GH were measured in blood samples collected between 1996 and 1999. Totally 317 women were identified who had a diagnosis of invasive or in situ breast cancer between the date of blood collection and June 1 2003; 75% of these women were premenopausal at blood collection. To each of the 317 women, two controls were age-matched for a total of 634 controls. We used conditional logistic regression models to estimate the relative risk of breast cancer. Overall, plasma IGF-I, IGFBP-1, IGFBP-3, and GH levels were not associated with breast cancer risk (relative risks, top vs bottom quartile; IGF-I, 0.98, 95% confidence interval (CI), 0.69-1.39; IGFBP-1, 0.95, 95% CI, 0.63-1.41; IGFBP-3, 1.10, 95% CI, 0.78-1.54; GH, 1.09, 95% CI, 0.82-1.46). These risks were similar for premenopausal women of age 45 years or less. Further adjustment for additional breast cancer risk factors did not change these estimates. In conclusion, circulating IGF-I, IGFBP-1, IGFBP-3, and GH levels appear to have no important association with breast cancer risk in a large cohort of premenopausal women.

A Prospective Study on Habitual Duration of Sleep and Incidence of Breast Cancer in a Large Cohort of Women

Abstract: Mounting evidence suggests habitual sleep duration is associated with various health outcomes; both short and long sleep duration have been implicated in increased risk of cardiovascular disease, diabetes, and all-cause mortality. However, data on the relation between sleep duration and cancer risk are sparse and inconclusive. A link between low levels of melatonin, a hormone closely related to sleep, and increased risk of breast cancer has recently been suggested but it is unclear whether duration of sleep may affect breast cancer risk. We explored the association between habitual sleep duration reported in 1986 and subsequent risk of breast cancer in the Nurses' Health Study using Cox proportional hazards models. During 16 years of follow-up, 4,223 incident cases of breast cancer occurred among 77,418 women in this cohort. Compared with women sleeping 7 hours, covariate-adjusted hazard ratios and 95% confidence intervals for those sleeping or =9 hours were 0.93 (0.79-1.09), 0.98 (0.91-1.06), 1.05 (0.97-1.13), and 0.95 (0.82-1.11), respectively. A moderate trend in risk increase towards longer sleep duration was observed when analyses were restricted to participants who reported same sleep duration in 1986 and 2000 (P(trend) = 0.05). In this prospective study, we found no convincing evidence for an association between sleep duration and the incidence of breast cancer.

Urinary 6‐sulfatoxymelatonin levels and their correlations with lifestyle factors and steroid hormone levels

Abstract: Exposure to light at night, as experienced by rotating night shift workers, has been related to lower circulating levels of melatonin, a hormone with recognized cancer protective properties. However, little is known about the relationship of other lifestyle factors or endogenous sex steroid hormones with melatonin levels. We examined cross-sectional associations of age, reproductive and menopausal factors, body mass index (BMI), alcohol consumption, smoking history, night shift work, as well as several other breast cancer risk factors, and circulating sex steroid hormone levels with creatinine-adjusted morning urinary melatonin (6-sulfatoxymelatonin, aMT6s) levels. Participants were 459 healthy, primarily premenopausal (age range 33-50 yr) women from the Nurses' Health Study II (NHS II). Using multiple linear regression, we computed least-square mean hormone levels across categories of lifestyle factors. Age was inversely related to aMT6s levels, particularly before menopause (premenopausal women, or=49 yr; aMT6s, 20.8 ng/mg versus 11.8 ng/mg creatinine; P for trend, 0.02). In multivariate analyses, BMI was significantly and inversely associated with aMT6s levels (P for trend, <0.01). Higher pack-years of smoking were associated with significantly lower aMT6s levels (never smoker versus 15+ pack-years, aMT6s = 17.4 ng/mg versus 12.3 ng/mg creatinine; P for trend, 0.04). We also observed a positive association between parity and aMT6s levels (P for trend, <0.01), but no other reproductive factors nor any of the sex hormones (estradiol, progesterone, estrone, estrone sulfate, dehydroepiandrostenedione, dehydroepiandrostenedione sulfate, testosterone, and androstenedione), as measured either in the luteal or the follicular phase of the menstrual cycle, were significantly associated with aMT6s. In conclusion, higher age, BMI, and heavy smoking were significantly related to lower levels of melatonin, whereas parity was significantly associated with higher aMT6s levels. Melatonin levels may be one mechanism through which these factors influence the development of cancer, but more studies are needed to elucidate these mechanisms definitively.

A Prospective Study of Night Shift Work, Sleep Duration, and Risk of Parkinson's Disease

Abstract: The authors prospectively investigated whether working rotating night shifts was associated with the risk of Parkinson’s disease among 84,794 female nurses who reported years of night shift work in 1988 (the US Nurses’ Health Study). After 975,912 person-years of follow-up (1988–2000), 181 incident Parkinson’s disease cases were documented. Compared with nurses who never worked rotating night shifts, those with 15 years or more of night shift work had a 50% lower risk of Parkinson’s disease after adjustment for age and smoking (95% confidence interval: 0.26, 0.97; ptrend ¼ 0.01). Sleep duration was positively associated with Parkinson’s disease risk: The relative risk was 1.84 (95% confidence interval: 0.99, 3.42) when comparing nurses who reported 9 or more hours of sleep per day with those who slept 6 hours or less (ptrend ¼ 0.005). These data suggest that working night shifts may be protective against Parkinson’s disease or that low tolerance for night shift work is an early marker of Parkinson’s disease. Conversely, habitual longer sleep duration may be an earlier marker of Parkinson’s disease. Because of the novelty and the exploratory nature of these findings, confirmation is needed.

Cancer and rhythm.

Abstract: In a recent editorial comment, Denise Duboule [1] emphasized that ‘‘animal development is, in fact, nothing but time.’’ In this issue of Cancer Causes and Control, several papers will substantiate that not only developmental, but also neoplastic processes may be linked to what Duboule [1] and Halberg [2] referred to as ‘chronomics’: timing and rhythm. Moreover, there is reason to believe that timing and rhythm may have been underappreciated in current therapeutic settings [3]. The papers in this issue of Cancer Causes and Control are from leading researchers in the field of cancer and body rhythms. Each one addresses a specific aspect of the topic, and their work is cited below in this overview editorial. Evidence from observational studies is growing [4] that the disturbance of body rhythms, in particular, circadian disruption e.g., shift work [5–8] or chronic jet-lag [9–12] contribute significantly to the development of breast cancer. Figure 1 compares the relative impact of rhythm disturbances to other exposures of significance in breast tumor development [13]. Reproductive risk factors such as parity and age at first birth, age at menarche, and age at menopause each confer a change in risk of roughly 20–30%. Only family history in a first degree confers a relative risk comparable in magnitude to that of female flight attendants. Unlike for other cancers for which primary risk factors have been identified (e.g., smoking and lung cancer risk), to date, no single environmental risk factor has been identified that can account for a major proportion of breast cancers, the incidence of which is still rising. Thus, there is a need for continued, vigorous search of breast cancer risk factors. Disruption of circadian rhythms, which can be caused by a wide variety of factors, may play an important role, not only for breast—but also other cancers, but results are still premature. Disruption of clock gene function may increase cancer risk: In mice, clock genes stabilize the genome and help maintain important repair mechanisms such as the apoptosis of damaged cells [14]. Per-2 gene deprived mice lack a circadian rhythm [15] and have been shown to develop cancer rapidly and spontaneously. The difference between wild type and rhythm-deprived mice was found to be most striking after exposure to ionizing radiation. In suprachiasmatic nuclei (SCN) ablated mice, disruption of circadian rhythms was associated with accelerated growth of Dedication This special issue of CCC is dedicated to Gunther Hildebrandt (Marburg, Germany) and Franz Halberg (Minnesota, USA), two great pioneers of Chronobiology.

Cyclin D1 A870G polymorphism and the risk of colorectal cancer and adenoma

Abstract: Cyclin D1 (CCND1) plays a key role in cell cycle control, particularly in the transition from G1 to S phase, which is regulated by cyclin-dependent kinases. A common adenine to guanine polymorphism (A870G) in the CCND1 gene has been associated with a longer-life protein and an increased risk of colorectal cancer and adenoma in some studies. Among subjects with hereditary nonpolyposis colorectal cancer, the A870G polymorphism has also been associated with a younger age of onset of colorectal cancer. We analysed 181 colorectal cancer cases and 475 matched controls and 524 adenoma cases and 517 matched controls within women in the Nurses' Health Study (NHS) cohort, 171 colorectal cancer cases and 347 matched controls and 372 adenoma cases and 712 matched controls nested within men in the Health Professionals' Follow-Up Study (HPFS) cohort, and 258 colorectal cancer cases and 415 matched controls within men in the Physicians' Health Study (PHS) cohort to assess the risk associated with the CCND1 A870G genotype. Moreover, we assessed whether CCND1 genotype modified the effect of a sporadic (nonsyndromic) family history of colorectal cancer as well as the effect of other dietary and lifestyle risk factors for colorectal cancer and adenoma. In all cohorts combined, the CCND1 polymorphism did not show statistically significant associations to risk of colorectal cancer (odds ratio (OR) for A allele carriers, 1.04; 95% confidence interval (95% CI), 0.82–1.32) or adenoma (OR, 0.96; 95% CI, 0.79–1.18). The CCND1 A870G genotype was associated with a modest, although nonsignificantly elevated risk of colorectal cancer (OR, 1.59; 95% CI, 0.98–2.57) in women. In contrast, the polymorphism was not associated with increased risk of adenoma in either men or women. Among participants with the A870G genotype, a family history of colorectal cancer conferred a substantially greater risk of colorectal cancer in the women (P for interaction=0.06) and adenoma in the men (P for interaction=0.02). Current postmenopausal hormone (PMH) use was associated with a significant reduction in the risk of colorectal cancer and adenoma among women with the A870G genotype, whereas there was no effect of PMH use among those with the GG genotype. The CCND1 polymorphism appeared to confer a modest elevation in the risk of colorectal cancer among women. Moreover, the A870G genotype may enhance the protective effect of postmenopausal oestrogen use on the development of colorectal neoplasia.

Circulating melatonin levels: possible link between Parkinson's disease and cancer risk?

Abstract: Lower rates of cancer mortality/incidence in patients with Parkinson’s disease (PD) have given rise to speculations about risk or preventative factors common to both diseases, including life-style factors (such as smoking) and genetic susceptibility. Melatonin, a hormone known for its sleep regulatory effects, may play an important role in carcinogenesis as suggested by substantial laboratory and less direct epidemiologic evidence. Particularly, a reduction in melatonin, such as experienced by persons who are exposed to light at night, appears to increase cancer risk. Variations in melatonin levels have been linked to PD in several different ways. Some studies show higher morning melatonin levels in PD patients than in healthy controls. One could speculate that the sleep disorders that affect almost two thirds of those suffering from PD and can precede PD motor symptoms by several years may be associated with variations in melatonin levels. Moreover, in animal models, interventions that increase the bioavailability of melatonin appears to increase the severity of parkinsonian symptoms, whereas reduction in melatonin by pinealectomy or exposure to bright light can enhance recovery from parkinsonisms symptoms. Finally, preliminary epidemiological evidence suggests that longer years of working night shifts is associated with a reduced risk of PD among participants of the Nurses’ Health Study (NHS), whereas longer hours of sleep appear to increase their risk. In sum, while lower melatonin concentrations may predict a higher cancer risk, there is also some evidence that they may be associated with a lower risk of PD. We therefore hypothesize that elevated circulating melatonin levels in PD patients may contribute to their lower cancer rates.