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Schernhammer E.S.,Channing Laboratory | Schernhammer E.S.,Harvard University | Razavi P.,University of Southern California | Li T.Y.,Channing Laboratory | And 4 more authors.
Journal of the National Cancer Institute | Year: 2011

Night shift work is associated with increased risk of several cancers, but the risk of skin cancer among night shift workers is unknown. We documented 10799 incident skin cancers in 68336 women in the Nurses' Health Study from June 1988 to June 2006 and examined the relationship between rotating night shifts and skin cancer. We used Cox proportional hazard models, adjusted for confounding variables (phenotypic and established risk factors of skin cancer), and performed stratified analysis to explore the modifying effect of hair color. Working 10 years or more on rotating night shifts was associated with a 14% decreased risk of skin cancer compared with never working night shifts (age-standardized incidence rate: 976 per 100000 person-years (PY) vs 1070 per 100000 PY, respectively; adjusted hazard ratios = 0.86, 95% confidence interval = 0.81 to 0.92, Ptrend <. 001). This association was strongest for cutaneous melanoma; working 10 years or more of rotating night shifts was associated with 44% decreased risk of melanoma, after adjustment for melanoma risk factors (age-standardized incidence rate: 20 per 100000 PY vs 35 per 100000 PY, respectively; adjusted hazard ratios = 0.56, 95% confidence interval = 0.36 to 0.87, Ptrend =. 005). Hair color, a surrogate for an individual's susceptibility to skin cancer, was a statistically significant effect modifier for the observed associations; darker-haired women had the lowest risk (Pinteraction =. 02). © 2011 The Author. Source


Yu Y.,New England Eye Center | Reynolds R.,New England Eye Center | Rosner B.,Channing Laboratory | Daly M.J.,Massachusetts General Hospital | And 3 more authors.
Investigative Ophthalmology and Visual Science | Year: 2012

PURPOSE. Understanding the effect of genes on progression to different stages of age-related macular degeneration (AMD) may suggest stage-specific therapeutic targets and more precise prediction of the development of this disease. METHODS. Progression events and time to each stage of AMD were derived from the longitudinal data of 2560 subjects without advanced AMD. SNPs in 12 AMD risk loci were genotyped. A multistate Markov model for progression from normal to intermediate drusen, then to large drusen, and eventually to neovascular disease (NV) or geographic atrophy (GA) was applied to estimate stage-specific hazard ratios for each SNP. The effects of these genetic factors were also estimated by a multivariate multistate Markov model adjusted for baseline age, sex, smoking, body mass index (BMI), education, antioxidant treatment, and the status of AMD in the fellow eye. RESULTS. Controlling for demographic and behavioral factors and other SNPs, the TT genotype of rs10468017 in LIPC was associated with decreased risk of progression from large drusen to NV (HR = 0.57, P = 0.04) and tended to reduce the risk of progression from normal to intermediate drusen (HR = 0.72, P = 0.07). The SNP rs1883025 (T allele) in ABCA1 was associated with decreased risk of progression from normal to intermediate drusen (HR per allele = 0.82 per allele, P = 9.7 = 10 -3) and from intermediate drusen to large drusen (HR per allele = 0.77, P = 5.2 = 10 -3). The genes CFH, C3, CFB, and ARMS2/HTRA1 were associated with progression from intermediate drusen to large drusen and from large drusen to GA or NV. CONCLUSIONS. Genes in different pathways influence progression to different stages of AMD. © 2012 The Association for Research in Vision and Ophthalmology, Inc. Source


Forman J.P.,Channing Laboratory | Williams J.S.,Harvard University | Fisher N.D.L.,Harvard University
Hypertension | Year: 2010

Vitamin D regulates the renin-angiotensin system (RAS) in experimental animals, but corresponding human data are limited. We examined the relation between plasma 25-hydroxyvitamin D and elements of the RAS in 184 normotensive individuals in high sodium balance; these included circulating levels of plasma renin activity and angiotensin II (Ang II) and the renal plasma flow response to infused Ang II, which is an indirect measure of the intrinsic RAS activity in the kidney. Compared with individuals with sufficient 25-hydroxyvitamin D levels (≥30.0 ng/mL), those with insufficiency (15.0 to 29.9 ng/mL) and deficiency (<15.0 ng/mL) had higher circulating Ang II levels (P for trend=0.03). Moreover, those with vitamin D deficiency had significantly blunted renal plasma flow responses to infused Ang II (mean decrease of 115 mL/min per 1.73 m in renal plasma flow versus 145 mL/min per 1.73 m2 among those with sufficient vitamin D levels; P for trend=0.009). Although plasma renin activity was higher among individuals with insufficient levels of vitamin D, the result was not statistically significant. These data suggest that low plasma 25-hydroxyvitamin D levels may result in upregulation of the RAS in otherwise healthy humans. Copyright © 2010 American Heart Association. All rights reserved. Source


Reynolds R.,New England Eye Center | Rosner B.,Channing Laboratory | Seddon J.M.,New England Eye Center | Seddon J.M.,Tufts University
Ophthalmology | Year: 2010

Objective A genetic variant in the high-density lipoprotein (HDL) cholesterol pathway, hepatic lipase (LIPC), was discovered to be associated with advanced age-related macular degeneration (AMD) in a genome-wide association study. In this study, we evaluated whether LIPC is associated with serum lipids, and whether this gene and serum lipids are independently associated with AMD. Design Case-control study. Participants A total of 458 participants from the Progression Study of Macular Degeneration and the Age-Related Eye Disease Ancillary Biomarker Study, including 318 advanced AMD cases with either geographic atrophy (n = 123) or neovascular disease (n = 195) and 140 controls. Methods Participants were genotyped for 8 variants associated with AMD: 2 CFH variants, C2, CFB, C3, CFI, the ARMS2/HTRA1 gene region, and LIPC. Fasting blood specimens were obtained at study onset, and serum levels of total cholesterol, low-density lipoprotein (LDL), HDL, and triglycerides were determined. Logistic and linear regression were used to evaluate associations between serum lipids, LIPC genotype, and AMD. Main Outcome Measures LIPC and serum lipid associations with AMD. Results The minor T allele of the LIPC gene was associated with a reduced risk of AMD (odds ratio, 0.4; 95% confidence interval, 0.20.9; P = 0.01, trend for number of T alleles, controlling for age and gender). Mean level of HDL was lower (P = 0.05) and mean level of LDL (P = 0.03) was higher in cases of advanced AMD compared with controls. Higher total cholesterol and LDL levels were associated with increased risk of AMD, with P for trend = 0.01 for both, in models controlling for environmental and genetic covariates. The T allele of LIPC was associated with higher levels of HDL, although LIPC was associated with advanced AMD independent of HDL level. Conclusions The HDL-raising allele of the LIPC gene (T) was associated with a reduced risk of AMD. Higher total cholesterol and LDL levels were associated with increased risk, whereas higher HDL levels tended to reduce the risk of AMD. The specific mechanisms underlying the association between AMD and LIPC require further investigation. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references. © 2010 American Academy of Ophthalmology. Source


Fung T.T.,Simmons College | Van Dam R.M.,National University of Singapore | Hankinson S.E.,Channing Laboratory | Stampfer M.,Harvard University | And 2 more authors.
Annals of Internal Medicine | Year: 2010

Background: Data on the long-term association between low-carbohydrate diets and mortality are sparse. Objective: To examine the association of low-carbohydrate diets with mortality during 26 years of follow-up in women and 20 years in men. Design: Prospective cohort study of women and men who were followed from 1980 (women) or 1986 (men) until 2006. Low-carbohydrate diets, either animal-based (emphasizing animal sources of fat and protein) or vegetable-based (emphasizing vegetable sources of fat and protein), were computed from several validated food-frequency questionnaires assessed during follow-up. Setting: Nurses' Health Study and Health Professionals' Follow-up Study. Participants: 85 168 women (aged 34 to 59 years at baseline) and 44 548 men (aged 40 to 75 years at baseline) without heart disease, cancer, or diabetes. Measurements: Investigators documented 12 555 deaths (2458 cardiovascular-related and 5780 cancer-related) in women and 8678 deaths (2746 cardiovascular-related and 2960 cancer-related) in men. Results: The overall low-carbohydrate score was associated with a modest increase in overall mortality in a pooled analysis (hazard ratio [HR] comparing extreme deciles, 1.12 [95% CI, 1.01 to 1.24]; P for trend = 0.136). The animal low-carbohydrate score was associated with higher all-cause mortality (pooled HR comparing extreme deciles, 1.23 [CI, 1.11 to 1.37]; P for trend = 0.051), cardiovascular mortality (corresponding HR, 1.14 [CI, 1.01 to 1.29]; P for trend = 0.029), and cancer mortality (corresponding HR, 1.28 [CI, 1.02 to 1.60]; P for trend = 0.089). In contrast, a higher vegetable low-carbohydrate score was associated with lower allcause mortality (HR, 0.80 [CI, 0.75 to 0.85]; P for trend ≤ 0.001) and cardiovascular mortality (HR, 0.77 [CI, 0.68 to 0.87]; P for trend < 0.001). Limitations: Diet and lifestyle characteristics were assessed with some degree of error. Sensitivity analyses indicated that results were probably not substantively affected by residual confounding or an unmeasured confounder. Participants were not a representative sample of the U.S. population. Conclusion: A low-carbohydrate diet based on animal sources was associated with higher all-cause mortality in both men and women, whereas a vegetable-based low-carbohydrate diet was associated with lower all-cause and cardiovascular disease mortality rates. Primary Funding Source: National Institutes of Health. © 2010 American College of Physicians. Source

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