Vitamin D status has been hypothesized to protect against development of diabetic retinopathy via its anti-inflammatory and anti-angiogenic properties. Additionally, in vitro and in vivo studies suggest vitamin D favorably influences blood pressure and blood glucose control, strong risk factors for diabetic retinopathy. We examined the association between vitamin D status and prevalent diabetic retinopathy in participants with diabetes from a population-based cohort. Among participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes at visit 3 (1993–1995), 1339 (906 Caucasians, 433 African Americans) had serum 25-hydroxyvitamin (25[OH]D) concentrations assessed at visit 2 (1989–1992) and nonmydriatic retinal photographs taken at visit 3. Dietary intake of vitamin D was assessed at visit 1 (1987–1989). Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for diabetic retinopathy by categories of season-adjusted 25(OH)D (<30 [referent], 30–<50, 50–<75 and ≥75 nmol/L), by quartile of vitamin D intake (IU/day), and use of vitamin D or fish oil supplements (yes/no). P for trend was estimated using continuous 25(OH)D or vitamin D intake. ORs were adjusted for race, and duration of diabetes. We further adjusted for HBA1c and hypertension to examine if 25(OH)D influenced diabetic retinopathy via its effects on either glycemic control or blood pressure. ORs (95 % CIs) for retinopathy, adjusted for race and duration, were 0.77 (0.45–1.32), 0.64 (0.37–1.10), and 0.39 (0.20–0.75), p for trend = 0.001, for participants with 25(OH)D of 30–<50, 50–<75, and ≥75 nmol/L, respectively. Further adjustment for hypertension minimally influenced results (data not show), but adjustment for HBA1c attenuated the OR among those with 25(OH)D ≥75 (0.47 [0.23–0.96], p for trend = 0.030). No statistically significant association was observed between vitamin D intake from foods or supplements and retinopathy. 25(OH)D concentrations ≥75 nmol/L were associated with lower odds of any retinopathy assessed 3 years later. We speculate this may be due in part to vitamin D’s influence on blood glucose control.

Background: Most analyses of spatial clustering of disease have been based on either residence at the time of diagnosis or current residence. An underlying assumption in these analyses is that residence can be used as a proxy for environmental exposure. However, exposures earlier in life and not just those in the most recent period may be of significance. In breast cancer, there is accumulating evidence that early life exposures may contribute to risk. We explored spatio-temporal patterns of risk surfaces using data on lifetime residential history in a case control study of breast cancer, and identified elevated areas of risk and areas potentially having more exposure opportunities, defined as risk surfaces in this study. This approach may be more relevant in understanding the environmental etiology of breast cancer, since lifetime cumulative exposures or exposures at critical times may be more strongly associated with risk for breast cancer than exposures from the recent period.Results: A GIS-based exploratory spatial analysis was applied, and spatio-temporal variability of those risk surfaces was evaluated using the standardized difference in density surfaces between cases and controls. The significance of the resulting risk surfaces was tested and reported asp-values. These surfaces were compared for premenopausal and postmenopausal women, and were obtained for each decade, from the 1940s to 1990s. We found strong evidence of clustering of lifetime residence for premenopausal women (for cases relative to controls), and a less strong suggestion of such clustering for postmenopausal women, and identified a substantial degree of temporal variability of the risk surfaces.Conclusion: We were able to pinpoint geographic areas with higher risk through exploratory spatial analyses, and to assess temporal variability of the risk surfaces, thus providing a working hypothesis on breast cancer and environmental exposures. Geographic areas with higher case densities need further epidemiologic investigation for potential relationships between lifetime environmental exposures and breast cancer risk. Examination of lifetime residential history provided additional information on geographic areas associated with higher risk; limiting exploration of chronic disease clustering to current residence may neglect important relationships between location and disease.

Inter-individual variation in DNA repair capacity is thought to modulate breast cancer risk. The phenotypic mutagen sensitivity assay (MSA) measures DNA strand breaks in lymphocytes; women with familial and sporadic breast cancers have a higher mean number of breaks per cell (MBPC) then women without breast cancer. Here, we explore the relationships between the MSA and the Rad51 gene, which encodes a DNA repair enzyme that interacts with BRCA1 and BRCA2, in BRCA1 mutation carriers and women with sporadic breast cancer. Peripheral blood lymphoblasts from women with known BRCA1 mutations underwent the MSA (n = 138 among 20 families). BRCA1 and Rad51 genotyping and sequencing were performed to identify SNPs and haplotypes associated with the MSA. Positive associations from the study in high-risk families were subsequently examined in a population-based case-control study of breast cancer (n = 1170 cases and 2115 controls). Breast cancer diagnosis was significantly associated with the MSA among women from BRCA1 families (OR = 3.2 95%CI: 1.5-6.7; p = 0.004). The Rad51 5'UTR 135 C>G genotype (OR = 3.64; 95% CI: 1.38, 9.54; p = 0.02), one BRCA1 haplotype (p = 0.03) and in a polygenic model, the E1038G and Q356R BRCA1 SNPs were significantly associated with MBPC (p = 0.009 and 0.002, respectively). The Rad51 5'UTR 135C genotype was not associated with breast cancer risk in the population-based study. Mutagen sensitivity might be a useful biomarker of penetrance among women with BRCA1 mutations because the MSA phenotype is partially explained by genetic variants in BRCA1 and Rad51.

Cancer patients are at risk for malnutrition; the aim of this study was to provide a cost-effectiveness analysis of dietary supplementation in cancer survivors. We estimated prevalence of supplementation, hospitalization rates, quality of life (QOL), cost of care and mortality among cancer survivors. We built a decision analytic model to simulate life-long costs of health care and supplementation and QOL among cancer survivors with and without supplementation. Cost of supplements was derived from national pharmacy databases including single- and multivitamin formularies. One-way and probabilistic sensitivity analysis were performed to evaluate the robustness of the incremental cost-effectiveness ratio (ICER) to changes in supplementation costs and duration. The study cohort represented the national cancer survivor population (average age 61 years, 85% white, 52% male, and 94% insured). Hospitalization rates for supplement users and non-users were 12% and 21%, respectively. The cost of hospitalization was $4030. Supplementation was associated with an additional 0.48 QALYs (10.26 vs. 9.78) at the incremental cost of $2094 ($236,933 vs. $234,839) over the remaining lifetime of survivors (on average 13 years). Adequate nutrition provides a cost-effective strategy to achieving potentially optimum health. Further studies are needed to determine the effects of specific nutrient doses and supplementation on long-term outcomes per cancer type.

End-stage Fuchs' endothelial corneal dystrophy is a leading cause of corneal blindness, with a higher prevalence in females than in males. Few modifiable risk factors have been identified. We examined associations between menopausal hormone therapy use (never/past/current), duration of hormone therapy use, estimated lifetime exposure to endogenous estrogen, and serum estradiol with incident Fuchs' endothelial corneal dystrophy in a cohort of postmenopausal women. This was a prospective analysis in the Women's Health Initiative Observational Study. Incident cases of Fuchs' endothelial corneal dystrophy were identified from the Women's Health Initiative Observational Study baseline (1993-1998) through 2019 using Medicare claims data. In 22,980 women, 1382 incident cases of Fuchs' endothelial corneal dystrophy (annualized incidence rate and 95 % confidence interval = 5.0 [4.8-5.3] cases per 1000 person-years) were identified. The adjusted hazard ratios and 95 % confidence intervals for Fuchs' endothelial corneal dystrophy were 1.02 (0.88-1.18) and 0.89 (0.79-0.997) for past and current hormone therapy use (vs. never use) at baseline, respectively. Adjusted hazard ratios (95 % confidence interval) were 0.90 (0.79-1.03) and 0.95 (0.84-1.08), p-trend = 0.36, for ≤10 and > 10 years, respectively, of hormone therapy use compared with no use; and the adjusted hazard ratio (95 % confidence interval) was 1.01 (0.88-1.15), p-trend = 0.87, for 46.7-59.0 versus 13.8-41.0 years of estimated lifetime exposure to endogenous estrogen. No statistically significant associations were observed with serum estradiol concentrations in a subset of participants. In this cohort of postmenopausal women, current hormone therapy use (vs. never use) showed evidence of protection against the development of Fuchs' endothelial corneal dystrophy; however, duration of hormone therapy use, estimated lifetime exposure to endogenous estrogen, or serum estradiol concentrations were not significantly associated with a decreased risk of Fuchs' endothelial corneal dystrophy.