Prediagnosis dietary pattern and survival in patients with multiple myeloma.

Inflammation and endogenous growth factors are important in multiple myeloma (MM) pathogenesis. Although diets that modulate these biologic pathways may influence MM patient survival, studies have not examined the association of dietary patterns with MM survival. We conducted pooled prospective survival analyses of 423 MM patients from the Nurses' Health Study (1986-2016) and the Health Professionals Follow-up Study (1988-2016) using Cox regression models. We used data from repeated food frequency questionnaires (FFQ) to compute dietary patterns as of the last prediagnosis FFQ, including the Alternate Healthy Eating Index (AHEI)-2010, alternate Mediterranean Diet, Dietary Approaches to Stop Hypertension, Prudent, Western and empirical dietary inflammatory patterns and empirical dietary indices for insulin resistance and hyperinsulinemia. During follow-up, we documented 295 MM-related deaths among 345 total deaths. MM-specific mortality was 15-24% lower per one standard deviation (SD) increase (e.g., toward healthier habits) in favorable dietary pattern scores. For example, the multivariable-adjusted hazard ratio [HR] and 95% confidence interval [CI] per 1-SD increase in AHEI-2010 score were 0.76, 0.67-0.87 (p < 0.001). In contrast, MM-specific mortality was 16-24% higher per 1-SD increase (e.g., toward less healthy habits) in "unhealthy" diet scores; for example, the multivariable-adjusted HR, 95% CI per 1-SD increase in Western pattern score were 1.24, 1.07-1.44 (p = 0.005). Associations were similar for all-cause mortality. In conclusion, our consistent findings for multiple dietary patterns provide the first evidence that MM patients with healthier prediagnosis dietary habits may have longer survival than those with less healthy diets.

Shift Work, Chronotype, and Melatonin Rhythm in Nurses.

BACKGROUND: Previous studies associated night-shift work with melatonin disruption, with mixed evidence regarding the modulating effects of chronotype (i.e., diurnal preference). METHODS: One hundred and thirty active nurses (84 rotating-shift and 46 day-shift workers) in the Nurses' Health Study II wore a head-mounted light meter and collected spontaneous urine voids over 3 days. 6-Sulfatoxymelatonin (aMT6s), the major urinary metabolite of melatonin, was assessed. RESULTS: Rotating-shift workers on night shifts had more light exposure and lower urinary melatonin levels during the night, and urinary melatonin rhythms with smaller peaks [11.81 ng/mg-creatinine/h, 95% confidence interval (CI), 9.49-14.71 vs. 14.83 ng/mg-creatinine/h, 95% CI, 11.72-18.75] and later peak onset (5.71 hours, 95% CI, 4.76-6.85 vs. 4.10 hours, 95% CI, 3.37-4.99), compared with day-shift workers. Furthermore, evening chronotypes' melatonin rhythms had later peak onset compared with morning types (4.90 hours, 95% CI, 3.94-6.09 vs. 3.64 hours, 95% CI, 2.99-4.43). However, among day-shift workers, morning chronotypes had melatonin rhythms with greater mean levels, larger peaks, and earlier peak onset compared with evening chronotypes; patterns were similar comparing evening versus morning chronotypes among rotating-shift workers on night shifts. The interaction of rotating-shift work and chronotype was significant across all parameters (P < 0.05). CONCLUSIONS: As expected, rotating-shift workers on night shifts had greater light exposure and lower urinary melatonin levels during the night compared with day-shift workers. Intriguingly, melatonin rhythms were dependent on both chronotype and rotating-shift work type, and better alignment of rotating-shift work and chronotype appeared to produce less disrupted melatonin rhythms. IMPACT: The joint effects of shift-work type and chronotype require attention in future studies.

Rotating night shift work and colorectal cancer risk in the nurses' health studies.

Animal and human data have suggested that shift work involving circadian disruption may be carcinogenic for humans, but epidemiological evidence for colorectal cancer remains limited. We investigated the association of rotating night shift work and colorectal cancer risk in two prospective female cohorts, the Nurses' Health Study (NHS) and NHS2, with 24 years of follow-up. In total, 190,810 women (NHS = 77,439; NHS2 = 113,371) were included in this analysis, and 1,965 incident colorectal cancer cases (NHS = 1,527; NHS2 = 438) were reported during followup (NHS: 1988-2012, NHS2: 1989-2013). We used Cox proportional hazards models adjusted for a wide range of potential confounders. We did not observe an association between rotating night work duration and colorectal cancer risk in these cohorts (NHS: 1-14 years: Hazard Ratio (HR) 1.04, 95% CI: 0.94, 1.16; 15+ years: HR 1.15, 95% CI: 0.95, 1.39; Ptrend = 0.14 and NHS2: 1-14 years: HR 0.81, 95% CI: 0.66, 0.99; 15+ years: HR 0.96, 95% CI: 0.56, 1.64 and Ptrend = 0.88). In subsite analysis in NHS, rectal cancer risk increased after long-term (15+ years) rotating night shift work (proximal colon cancer: HR 1.00, 95% CI: 0.75, 1.34, Ptrend = 0.90; distal colon cancer: HR 1.27, 95% CI: 0.87, 1.85, Ptrend = 0.32; rectal cancer: HR 1.60, 95% CI: 1.09, 2.34, Ptrend = 0.02). We found no overall evidence of an association between rotating night shift work and colorectal cancer risk in these two large cohorts of nurses. Risk for rectal cancer significantly increased with shift work duration, suggesting that long-term circadian disruption may play a role in rectal cancer development.

Prediction of Long-term Cognitive Decline Following Postoperative Delirium in Older Adults.

BACKGROUND: Increasing evidence suggests that postoperative delirium may result in long-term cognitive decline among older adults. Risk factors for such cognitive decline are unknown. METHODS: We studied 126 older participants without delirium or dementia upon entering the Successful AGing After Elective Surgery (SAGES) study, who developed postoperative delirium and completed repeated cognitive assessments (up to 36 months of follow-up). Pre-surgical factors were assessed preoperatively and divided into nine groupings of related factors ("domains"). Delirium was evaluated at baseline and daily during hospitalization using the Confusion Assessment Method diagnostic algorithm, and cognitive function was assessed using a neuropsychological battery and the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) at baseline and 6-month intervals over 3 years. Linear regression was used to examine associations between potential risk factors and rate of long-term cognitive decline over time. A domain-specific and then overall selection method based on adjusted R2 values was used to identify explanatory factors for the outcome. RESULTS: The General Cognitive Performance (GCP) score (combining all neuropsychological test scores), IQCODE score, and living alone were significantly associated with long-term cognitive decline. GCP score explained the most variation in rate of cognitive decline (13%), and six additional factors-IQCODE score, cognitive independent activities of daily living impairment, living alone, cerebrovascular disease, Charlson comorbidity index score, and exhaustion level-in combination explained 32% of variation in this outcome. CONCLUSIONS: Global cognitive performance was most strongly associated with long-term cognitive decline following delirium. Pre-surgical factors may substantially predict this outcome.

Urinary Melatonin in Relation to Postmenopausal Breast Cancer Risk According to Melatonin 1 Receptor Status.

Background: Urinary melatonin levels have been associated with a reduced risk of breast cancer in postmenopausal women, but this association might vary according to tumor melatonin 1 receptor (MT1R) expression.Methods: We conducted a nested case-control study among 1,354 postmenopausal women in the Nurses' Health Study, who were cancer free when they provided first-morning spot urine samples in 2000 to 2002; urine samples were assayed for 6-sulfatoxymelatonin (aMT6s, a major metabolite of melatonin). Five-hundred fifty-five of these women developed breast cancer before May 31, 2012, and were matched to 799 control subjects. In a subset of cases, immunohistochemistry was used to determine MT1R status of tumor tissue. We used multivariable-adjusted conditional logistic regression to estimate the relative risk (RR) of breast cancer [with 95% confidence intervals (CI)] across quartiles of creatinine-standardized urinary aMT6s level, including by MT1R subtype.Results: Higher urinary melatonin levels were suggestively associated with a lower overall risk of breast cancer (multivariable-adjusted RR = 0.78; 95% CI = 0.61-0.99, comparing quartile 4 vs. quartile 1; Ptrend = 0.08); this association was similar for invasive vs. in situ tumors (Pheterogeneity = 0.12). There was no evidence that associations differed according to MT1R status of the tumor (e.g., Pheterogeneity for overall breast cancer = 0.88).Conclusions: Higher urinary melatonin levels were associated with reduced breast cancer risk in this cohort of postmenopausal women, and the association was not modified by MT1R subtype.Impact: Urinary melatonin levels appear to predict the risk of breast cancer in postmenopausal women. However, future research should evaluate these associations with longer-term follow-up and among premenopausal women. Cancer Epidemiol Biomarkers Prev; 26(3); 413-9. ©2016 AACR.

Rotating night shift work, sleep, and colorectal adenoma in women.

PURPOSE: This study aims to investigate the associations of rotating night shift work history and sleep duration with risk of colorectal adenoma. METHODS: We evaluated 56,275 cancer-free participants of the Nurses' Health Study II, who had their first colonoscopy or sigmoidoscopy between 1991 and 2011; rotating night shift work and sleep duration were reported by mailed questionnaire. Multivariable-adjusted logistic regression was used to estimate relative risks (RR) of colorectal adenoma, with 95% confidence intervals (CI), across categories of rotating night shift work history (none, 1-4, 5-9, and ≥10 years) and sleep duration (≤5, 6, 7, 8, and ≥9 h/day). RESULTS: We found no association between duration of rotating night shift work and occurrence of colorectal adenoma (p-trend across shift work categories = 0.5). Women with the longest durations of rotating night shift work (≥10 years) had a similar risk of adenoma compared to women without a history of rotating night shift work (multivariable-adjusted RR = 0.96, 95% CI = 0.83-1.11). Similarly, there were no associations of shorter or longer sleep durations with adenoma risk (p-trend = 0.2 across sleep durations of ≤5 through 7 h/day and p-trend = 0.5 across sleep durations of 7 through ≥9 h/day). Results were similar when we examined associations according to adenoma location and subtype. CONCLUSIONS: Our results do not support an association between rotating night shift work or sleep duration and risk of colorectal adenoma in women.

Association Between Rotating Night Shift Work and Risk of Coronary Heart Disease Among Women.

IMPORTANCE: Prospective studies linking shift work to coronary heart disease (CHD) have been inconsistent and limited by short follow-up. OBJECTIVE: To determine whether rotating night shift work is associated with CHD risk. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 189,158 initially healthy women followed up over 24 years in the Nurses' Health Studies (NHS [1988-2012]: N = 73,623 and NHS2 [1989-2013]: N = 115,535). EXPOSURES: Lifetime history of rotating night shift work (≥3 night shifts per month in addition to day and evening shifts) at baseline (updated every 2 to 4 years in the NHS2). MAIN OUTCOMES AND MEASURES: Incident CHD; ie, nonfatal myocardial infarction, CHD death, angiogram-confirmed angina pectoris, coronary artery bypass graft surgery, stents, and angioplasty. RESULTS: During follow-up, 7303 incident CHD cases occurred in the NHS (mean age at baseline, 54.5 years) and 3519 in the NHS2 (mean age, 34.8 years). In multivariable-adjusted Cox proportional hazards models, increasing years of baseline rotating night shift work was associated with significantly higher CHD risk in both cohorts. In the NHS, the association between duration of shift work and CHD was stronger in the first half of follow-up than in the second half (P=.02 for interaction), suggesting waning risk after cessation of shift work. Longer time since quitting shift work was associated with decreased CHD risk among ever shift workers in the NHS2 (P<.001 for trend). [table: see text] CONCLUSIONS AND RELEVANCE: Among women who worked as registered nurses, longer duration of rotating night shift work was associated with a statistically significant but small absolute increase in CHD risk. Further research is needed to explore whether the association is related to specific work hours and individual characteristics.

Antihypertensive medication use and incident breast cancer in women.

The purpose of this study was to evaluate whether antihypertensive medication use, including long-term use, is associated with increased breast cancer incidence in women. We studied 210,641 U.S. registered nurses participating in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II). Information on antihypertensive medication use was collected on biennial questionnaires in both cohorts, and breast cancer cases were ascertained during this period. Multivariable-adjusted Cox proportional hazard models were used to estimate relative risks of invasive breast cancer over follow-up (1988-2012 in NHS, 1989-2011 in NHS II) across categories of overall antihypertensive medication use and use of specific classes (diuretics, beta blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors). During follow-up, 10,012 cases of invasive breast cancer developed (6718 cases in NHS and 3294 in the NHS II). Overall, current use of any antihypertensive medication was not associated with breast cancer risk compared with past/never use in NHS (multivariable-adjusted relative risk = 1.00, 95 % CI = 0.95-1.06) or NHS II (multivariable-adjusted relative risk = 0.94, 95 % CI = 0.86-1.03). Furthermore, no specific class of antihypertensive medication was consistently associated with breast cancer risk. Results were similar when we considered hypertensive women only, and when we evaluated consistency and duration of medication use over time. Overall, antihypertensive medication use was largely unrelated to the risk of invasive breast cancer among women in the NHS cohorts.

Night shift work at specific age ranges and chronic disease risk factors.

OBJECTIVES: We examined the association of night shift work history and age when night shift work was performed with cancer and cardiovascular disease risk factors among 54 724 women in the Nurses' Health Study (NHS) II. METHODS: We calculated age-adjusted and socioeconomic status-adjusted means and percentages for cancer and cardiovascular risk factors in 2009 across categories of night shift work history. We used multivariable-adjusted logistic regression to estimate odds ratios (ORs) and 95% CIs for key risk factors among 54 724 participants (72% ever shift workers). We further examined these associations by age (20-25, 26-35, 36-45 and 46+ years) at which shift work was performed. RESULTS: Ever night shift workers had increased odds of obesity (body mass index ≥30 kg/m(2); OR=1.37, 95% CI 1.31 to 1.43); higher caffeine intake (≥131 mg/day; OR=1.16, 95% CI 1.12 to 1.22) and total calorie intake (≥1715 kcal/day; OR=1.09, 95% CI 1.04 to 1.13); current smoking (OR=1.30, 95% CI 1.19 to 1.42); and shorter sleep durations (≤7 h of sleep/day; OR=1.19, 95% CI 1.15 to 1.24) compared to never night shift workers. These estimates varied depending on age at which night work was performed, with a suggestion that night shift work before age 25 was associated with fewer risk factors compared to night shift work at older ages. CONCLUSIONS: Our results indicate that night shift work may contribute to an adverse chronic disease risk profile, and that risk factors may vary depending on the age at which night shift work was performed.

Chronotype and breast cancer risk in a cohort of US nurses.

The aim of this study was to examine the relation between chronotype and breast cancer risk. We analyzed the association between chronotype (definite morning type, probable morning type, probable evening type, definite evening type, or neither morning nor evening type) and breast cancer risk among 72 517 women in the Nurses' Health Study II (NHS II). Chronotype was self-reported in 2009, and 1834 breast cancer cases were confirmed among participants between 1989 and 2007; a 2-yr lag period was imposed to account for possible circadian disruptions related to breast cancer diagnosis. Age- and multivariable-adjusted logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Participants who self-reported as neither morning nor evening type had a 27% increased risk of breast cancer (multivariable-adjusted OR = 1.27, 95% CI = 1.04-1.56), compared with definite morning types. None of the other chronotypes were significantly associated with breast cancer risk (multivariable-adjusted OR = 0.99, 95% CI = 0.87-1.12 for probable morning versus definite morning types; OR = 0.96, 95% CI = 0.84-1.09 for probable evening versus definite morning types; and OR = 1.15, 95% CI = 0.98-1.34 for definite evening versus definite morning types). Overall, chronotype was not associated with breast cancer risk in our study. A modestly increased risk among neither morning nor evening types may indicate circadian disruption as a potentially underlying mechanism; however, more studies are needed to confirm our results.

Total antioxidant capacity of the diet and major neurologic outcomes in older adults.

OBJECTIVE: To evaluate total antioxidant capacity of the diet, measured by the ferric-reducing antioxidant power (FRAP) assay, in relation to risks of dementia and stroke, as well as key structural brain volumes, in the elderly. METHODS: We prospectively studied 5,395 participants in the Rotterdam Study, aged 55 years and older, who were dementia free and provided dietary information at study baseline; 5,285 individuals were also stroke free at baseline, and 462 were dementia and stroke free at the time of an MRI brain scan 5 years after baseline. Dietary data were ascertained using a semiquantitative food-frequency questionnaire, and combined with food-specific FRAP measurements from published tables; this information was aggregated across the diet to obtain "dietary FRAP scores." Multivariable-adjusted Cox proportional hazard models were used to estimate relative risks of dementia and stroke, and multivariable-adjusted linear regression was used to estimate mean differences in structural brain volumes, across tertiles of dietary FRAP scores. RESULTS: During a median 13.8 years of follow-up, we identified approximately 600 cases each of dementia and stroke. In multivariable-adjusted models, we observed no associations between dietary FRAP scores and risk of dementia (p trend = 0.3; relative risk = 1.12, 95% confidence interval = 0.91-1.38, comparing the highest vs lowest FRAP tertiles) or risk of stroke (p trend = 0.3; relative risk = 0.91, 95% confidence interval = 0.75-1.11, comparing extreme FRAP tertiles); results were similar across subtypes of these outcomes. Dietary FRAP scores were unrelated to brain tissue volumes as well. CONCLUSIONS: Total antioxidant capacity of the diet, measured by dietary FRAP scores, does not seem to predict risks of major neurologic diseases.

Total antioxidant capacity of diet in relation to cognitive function and decline.

BACKGROUND: Epidemiologic evidence on the association of individual antioxidant vitamins and cognition is inconsistent. OBJECTIVE: We evaluated the total antioxidant capacity of diets on the basis of the ferric-reducing antioxidant power (FRAP) assay in relation to cognition in older women. DESIGN: Starting in 1995, we used a telephone-based cognitive assessment to evaluate cognitive function on 3 occasions at 2-y intervals in 16,010 participants aged ≥70 y in the Nurses' Health Study. In 1980, and every 4 y thereafter, we collected dietary information by using a semiquantitative food-frequency questionnaire (FFQ). For each participant, we combined FFQ data with food- and supplement-specific FRAP values to obtain FRAP scores; these data were averaged from 1980 until the initial cognitive interview to reflect long-term diets. We used multivariable-adjusted linear regression to estimate mean differences in initial cognitive function and slopes of decline across quintiles of FRAP scores. RESULTS: In multivariable-adjusted models, there was an association between higher total FRAP scores and better cognitive function at the first interview (P for trend = 0.003 for global scores with all cognitive tests combined; mean difference = 0.04 standard units; 95% CI: 0.01, 0.08 standard units, comparing the highest and lowest quintiles). A weaker association was observed for dietary FRAP scores (excluding supplements) and initial global scores (P for trend = 0.05). However, prospective analyses of cognitive decline indicated no associations with total or dietary FRAP scores in models adjusted for multiple potential confounders (P for trend = 0.3 and 0.5 for global scores, respectively). CONCLUSION: We observed no clear evidence of a consistent association between the total antioxidant capacity of diets and cognition in this cohort of older women.

Dietary antioxidants and long-term risk of dementia.

BACKGROUND: The Rotterdam Study previously found that higher dietary intakes of vitamins E and C related to lower risk of dementia and Alzheimer disease (AD) over 6 years of follow-up. OBJECTIVE: To study consumption of major dietary antioxidants relative to long-term risk of dementia. DESIGN: Population-based prospective cohort study. SETTING: The Rotterdam Study in the Netherlands. PARTICIPANTS: A total of 5395 participants, 55 years and older, who were free of dementia and provided dietary information at study baseline. MAIN OUTCOME MEASURES: Incidence of dementia and AD, based on internationally accepted criteria, relative to dietary intake of vitamin E, vitamin C, beta carotene, and flavonoids. RESULTS: During a mean follow-up period of 9.6 years, dementia developed in 465 participants, of whom 365 were diagnosed as having AD. In multivariate models adjusted for age, education, apolipoprotein E epsilon4 genotype, total energy intake, alcohol intake, smoking habits, body mass index, and supplement use, higher intake of vitamin E at study baseline was associated with lower long-term risk of dementia (P = .02 for trend). Compared with participants in the lowest tertile of vitamin E intake, those in the highest tertile were 25% less likely to develop dementia (hazard ratio, 0.75; 95% confidence interval, 0.59-0.95 with adjustment for potential confounders). Dietary intake levels of vitamin C, beta carotene, and flavonoids were not associated with dementia risk after multivariate adjustment (P > .99 for trend for vitamin C and beta carotene and P = .60 for trend for flavonoids). Results were similar when risk for AD was specifically assessed. CONCLUSION: Higher intake of foods rich in vitamin E may modestly reduce long-term risk of dementia and AD.

Dietary fat intake and cognitive decline in women with type 2 diabetes.

OBJECTIVE: Individuals with type 2 diabetes have high risk of late-life cognitive impairment, yet little is known about strategies to modify risk. Targeting insulin resistance and vascular complications-both associated with cognitive decline-may be a productive approach. We investigated whether dietary fat, which modulates glucose and lipid metabolism, might influence cognitive decline in older adults with diabetes. RESEARCH DESIGN AND METHODS: Beginning in 1995-1999, we evaluated cognitive function in 1,486 Nurses' Health Study participants, aged >or=70 years, with type 2 diabetes; second evaluations were conducted 2 years later. Dietary fat intake was assessed regularly beginning in 1980; we considered average intake from 1980 (at midlife) through initial cognitive interview and also after diabetes diagnosis. We used multivariate-adjusted linear regression models to obtain mean differences in cognitive decline across tertiles of fat intake. RESULTS: Higher intakes of saturated and trans fat since midlife, and lower polyunsaturated to saturated fat ratio, were each highly associated with worse cognitive decline in these women. On a global score averaging all six cognitive tests, mean decline among women in the highest trans fat tertile was 0.15 standard units worse than that among women in the lowest tertile (95% CI -0.24 to -0.06, P = 0.002); this mean difference was comparable with the difference we find in women 7 years apart in age. Results were similar when we analyzed diet after diabetes diagnosis. CONCLUSIONS: These findings suggest that lower intakes of saturated and trans fat and higher intake of polyunsaturated fat relative to saturated fat may reduce cognitive decline in individuals with type 2 diabetes.