Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?

BACKGROUND: Vitamin D has been identified as a potential protective factor in the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally. METHODS: In this ecological study, a series of linear and polynomial regression tests were performed between country-specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps. RESULTS: The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates. CONCLUSION: The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population-wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.

25-Hydroxyvitamin D in the range of 20 to 100 ng/mL and incidence of kidney stones.

OBJECTIVES: Increasing 25-hydroxyvitamin D serum levels can prevent a wide range of diseases. There is a concern about increasing kidney stone risk with vitamin D supplementation. We used GrassrootsHealth data to examine the relationship between vitamin D status and kidney stone incidence. METHODS: The study included 2012 participants followed prospectively for a median of 19 months. Thirteen individuals self-reported kidney stones during the study period. Multivariate logistic regression was applied to assess the association between vitamin D status and kidney stones. RESULTS: We found no statistically significant association between serum 25-hydroxyvitamin D and kidney stones (P = .42). Body mass index was significantly associated with kidney stone risk (odds ratio = 3.5; 95% confidence interval = 1.1, 11.3). CONCLUSIONS: We concluded that a serum 25-hydroxyvitamin D level of 20 to 100 nanograms per milliliter has no significant association with kidney stone incidence.

Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D.

We examined the relationship between serum 25-hydroxyvitamin D (25[OH]D) and all-cause mortality. We searched biomedical databases for articles that assessed 2 or more categories of 25(OH)D from January 1, 1966, to January 15, 2013. We identified 32 studies and pooled the data. The hazard ratio for all-cause mortality comparing the lowest (0-9 nanograms per milliliter [ng/mL]) to the highest (> 30 ng/mL) category of 25(OH)D was 1.9 (95% confidence interval = 1.6, 2.2; P < .001). Serum 25(OH)D concentrations less than or equal to 30 ng/mL were associated with higher all-cause mortality than concentrations greater than 30 ng/mL (P < .01). Our findings agree with a National Academy of Sciences report, except the cutoff point for all-cause mortality reduction in this analysis was greater than 30 ng/mL rather than greater than 20 ng/mL.

A prospective study of factors affecting recovery from musculoskeletal injuries.

PURPOSE: Research suggests the importance of psychosocial factors in recovery from musculoskeletal injuries. The objective of this study was to identify predictors of recovery among U.S. Marines who had musculoskeletal injuries of the back, knee, or shoulder. METHODS: A sample of 134 participants was assessed at baseline and followed for 1 year to determine outcome information. RESULTS: The strongest predictor of injury recovery at the 1-year follow-up was recovery expectations. In a multivariate logistic model with key demographic and psychosocial factors controlled, individuals who had high recovery expectations at baseline were over five times as likely to be recovered at follow-up as individuals who had low expectations (OR = 5.18, p\.01). CONCLUSIONS: This finding is consistent with a large body of research that has linked recovery expectations with better recovery outcomes in patients with musculoskeletal injuries as well as with research linking recovery expectations with better outcomes across a wide range of medical conditions.Applied to military populations, interventions designed to modify recovery expectations may have the potential to improve rates of return to duty and to reduce rates of disability discharge.

Serum 25-hydroxyvitamin D and breast cancer in the military: a case-control study utilizing pre-diagnostic serum.

PURPOSE: The objective of this study was to ascertain whether a relationship exists between pre-diagnostic serum levels of 25-hydroxyvitamin D (25(OH)D) and risk of breast cancer in young women. METHODS: About 600 incident cases of breast cancer were matched to 600 controls as part of a nested case-control study that utilized pre-diagnostic sera. Logistic regression was used to assess the relationship between serum 25(OH)D concentration and breast cancer risk, controlling for race and age. RESULTS: According to the conditional logistic regression for all subjects, odds ratios for breast cancer by quintile of serum 25(OH)D from lowest to highest were 1.2, 1.0, 0.9, 1.1, and 1.0 (reference) (p trend = 0.72). After multivariate regression for subjects whose blood had been collected within 90 days preceding diagnosis, odds ratios for breast cancer by quintile of serum 25(OH)D from lowest to highest were 3.3, 1.9, 1.7, 2.6, and 1.0 (reference) (p trend = 0.09). CONCLUSIONS: An inverse association between serum 25(OH)D concentration and risk of breast cancer was not present in the principal analysis, although an inverse association was present in a small subgroup analysis of subjects whose blood had been collected within 90 days preceding diagnosis. Further prospective studies of 25(OH)D and breast cancer risk are needed.

Predictors of psychiatric disorders in combat veterans.

BACKGROUND: Most previous research that has examined mental health among Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) combatants has relied on self-report measures to assess mental health outcomes; few studies have examined predictors of actual mental health diagnoses. The objective of this longitudinal investigation was to identify predictors of psychiatric disorders among Marines who deployed to combat in Iraq and Afghanistan. METHODS: The study sample consisted of 1113 Marines who had deployed to Iraq or Afghanistan. Demographic and psychosocial predictor variables from a survey that all Marines in the sample had completed were studied in relation to subsequent psychiatric diagnoses. Univariate and multivariate logistic regression were used to determine the influence of the predictors on the occurrence of psychiatric disorders. RESULTS: In a sample of Marines with no previous psychiatric disorder diagnoses, 18% were diagnosed with a new-onset psychiatric disorder. Adjusting for other variables, the strongest predictors of overall psychiatric disorders were female gender, mild traumatic brain injury symptoms, and satisfaction with leadership. Service members who expressed greater satisfaction with leadership were about half as likely to develop a mental disorder as those who were not satisfied. Unique predictors of specific types of mental disorders were also identified. CONCLUSIONS: Overall, the study's most relevant result was that two potentially modifiable factors, low satisfaction with leadership and low organizational commitment, predicted mental disorder diagnoses in a military sample. Additional research should aim to clarify the nature and impact of these factors on combatant mental health.

Anxiety and depression in Marines sent to war in Iraq and Afghanistan.

Although the effects of combat deployment on posttraumatic stress disorder have been extensively studied, little is known about the effects of combat deployment on depression and anxiety. This study examined the factors associated with anxiety and depression in a sample of 1560 US Marines who were deployed to Iraq and Afghanistan. Eleven demographic and psychosocial factors were studied in relation to depression and anxiety. Five factors emerged as significant in relation to depression: deployment-related stressors, combat exposure, attitudes toward leadership, mild traumatic brain injury symptoms, and marital status. The same factors, with the exception of marital status, emerged as significant in relation to anxiety. Deployment-related stressors had a stronger association with both depression and anxiety than any other variable, including combat exposure. This finding is important because deployment-related stressors are potentially modifiable by the military.

Low ultraviolet B and increased risk of brain cancer: an ecological study of 175 countries.

BACKGROUND: The purpose of this study was to determine whether an inverse association exists between latitude, solar ultraviolet B (UVB) irradiance, modeled 25-hydroxyvitamin D [25(OH)D] levels and incidence rates of cancer of the brain. METHODS: Associations of latitude and UVB irradiance with age-standardized incidence rates of cancer of the brain were analyzed for 175 countries while controlling for proportion of population overweight, energy from animal sources, fish consumption, cigarette and alcohol consumption and per capita health expenditures, using multiple regression. Serum 25(OH)D levels were modeled for each country, and their association with brain cancer also was determined. RESULTS: The incidence rates of brain cancer were higher at higher latitudes (R(2) for males = 0.45, p ≤ 0.0001; R(2) for females = 0.35, p < 0.0001). After adjustment for potential confounders, UVB irradiance (p ≤ 0.0001) and modeled serum 25(OH)D were inversely associated with incidence rates. CONCLUSIONS: Countries with low solar UVB irradiance and estimated mean serum 25(OH)D levels generally had higher age-standardized incidence rates of brain cancer. Since this was an ecological study, further research would be worthwhile on the association of prediagnostic serum 25(OH)D with incidence rate in studies of cohorts of individuals.

Psychiatric diagnoses and punishment for misconduct: the effects of PTSD in combat-deployed Marines.

BACKGROUND: Research on Vietnam veterans suggests an association between psychological problems, including posttraumatic stress disorder (PTSD), and misconduct; however, this has rarely been studied in veterans of Operation Iraqi Freedom or Operation Enduring Freedom. The objective of this study was to investigate whether psychological problems were associated with three types of misconduct outcomes (demotions, drug-related discharges, and punitive discharges.) METHODS: A population-based study was conducted on all U.S. Marines who entered the military between October 1, 2001, and September 30, 2006, and deployed outside of the United States before the end of the study period, September 30, 2007. Demographic, psychiatric, deployment, and personnel information was collected from military records. Cox proportional hazards regression analysis was conducted to investigate associations between the independent variables and the three types of misconduct in war-deployed (n = 77,998) and non-war-deployed (n = 13,944) Marines. RESULTS: Marines in both the war-deployed and non-war-deployed cohorts with a non-PTSD psychiatric diagnosis had an elevated risk for all three misconduct outcomes (hazard ratios ranged from 3.93 to 5.65). PTSD was a significant predictor of drug-related discharges in both the war-deployed and non-war-deployed cohorts. In the war-deployed cohort only, a specific diagnosis of PTSD was associated with an increased risk for both demotions (hazard ratio, 8.60; 95% confidence interval, 6.95 to 10.64) and punitive discharges (HR, 11.06; 95% CI, 8.06 to 15.16). CONCLUSIONS: These results provide evidence of an association between PTSD and behavior problems in Marines deployed to war. Moreover, because misconduct can lead to disqualification for some Veterans Administration benefits, personnel with the most serious manifestations of PTSD may face additional barriers to care.

Psychosocial predictors of military misconduct.

The objective of this longitudinal study was to determine psychosocial predictors of military misconduct in a cohort of Marine Corps war veterans. The study included data from 20,746 male Marines who completed a life history questionnaire during initial basic training and were subsequently deployed to a combat zone. Associations between psychosocial variables, psychiatric diagnoses, and subsequent misconduct outcomes were analyzed using Cox proportional hazards regression. The strongest predictors of misconduct outcomes (bad conduct discharges and military demotions) were psychiatric diagnoses and young age at first combat deployment. The results indicate that combat-related psychological disorders may manifest in numerous harmful ways, including impulsive, disruptive, and antisocial behavior. We recommend that the association between misconduct and psychiatric disorders be more explicitly acknowledged in research and treatment efforts involving military war veterans and other trauma victims.

Correlates of posttraumatic stress disorder symptoms in Marines back from war.

The effect of combat and operational stress on the mental health of military personnel is a major concern. The objective of this study was to identify factors associated with possible posttraumatic stress disorder (PTSD). A questionnaire was completed by 1,569 Marines who deployed in support of conflicts in Iraq and Afghanistan (2002-2007). Using the PTSD Checklist with a cutoff score of 44, 17.1% of the sample screened positive for possible PTSD. Of 9 demographic and psychosocial factors examined in relation to PTSD, 4 were significant in a multivariate analysis: deployment-related stressors, combat exposure, marital status, and education. Deployment-related stressors had a stronger association with PTSD than any other variable. This is an important finding because deployment-related stressors are potentially modifiable.

Factors associated with antisocial behavior in combat veterans.

The objective of this study was to identify factors associated with antisocial behavior in 1,543 Marines who deployed to combat zones in support of conflicts in Iraq and Afghanistan during 2002-2007. Five factors were associated with antisocial behavior in multivariate analyses: post-traumatic stress disorder (PTSD) symptoms, deployment-related stressors, combat exposure, younger age, and being divorced. PTSD symptoms had a stronger association with antisocial behavior than any other variable. A unique and important finding of this study was the association between deployment-related stressors and a higher incidence of antisocial behavior. Because deployment-related stressors are potentially modifiable, the military may be able to address them in concrete ways such as by shortening deployments and improving communication with home.

Insufficient Sun Exposure Has Become a Real Public Health Problem.

This article aims to alert the medical community and public health authorities to accumulating evidence on health benefits from sun exposure, which suggests that insufficient sun exposure is a significant public health problem. Studies in the past decade indicate that insufficient sun exposure may be responsible for 340,000 deaths in the United States and 480,000 deaths in Europe per year, and an increased incidence of breast cancer, colorectal cancer, hypertension, cardiovascular disease, metabolic syndrome, multiple sclerosis, Alzheimer's disease, autism, asthma, type 1 diabetes and myopia. Vitamin D has long been considered the principal mediator of beneficial effects of sun exposure. However, oral vitamin D supplementation has not been convincingly shown to prevent the above conditions; thus, serum 25(OH)D as an indicator of vitamin D status may be a proxy for and not a mediator of beneficial effects of sun exposure. New candidate mechanisms include the release of nitric oxide from the skin and direct effects of ultraviolet radiation (UVR) on peripheral blood cells. Collectively, this evidence indicates it would be wise for people living outside the tropics to ensure they expose their skin sufficiently to the sun. To minimize the harms of excessive sun exposure, great care must be taken to avoid sunburn, and sun exposure during high ambient UVR seasons should be obtained incrementally at not more than 5-30 min a day (depending on skin type and UV index), in season-appropriate clothing and with eyes closed or protected by sunglasses that filter UVR.

Commentary. On the epidemiology of influenza: reply to Radonovich et al.

On the epidemiology of influenza: reply to Radonovich LJ, Martinello RA, Hodgson M, Milton DK, Nardell EA. Influenza and ultraviolet germicidal irradiation. Virol J. 2008, 5:149.

Vitamin D and prevention of colorectal adenoma: a meta-analysis.

BACKGROUND: Vitamin D status is associated inversely with risk of colorectal cancer, but the association with adenoma risk is less clear. This meta-analysis examined the overall relationship between circulating (plasma or serum) 25-hydroxyvitamin D [25(OH)D], vitamin D intake (dietary, supplemental, or total), and colorectal adenoma incidence in published studies. METHODS: A meta-analysis composed of 17 epidemiologic studies [1 cross-sectional, 9 case-control, and 7 cohort or nested case-control studies; 7 on 25(OH)D and 12 on vitamin D intake] published before December 2007 was done to examine the association between circulating 25(OH)D, vitamin D intake, and colorectal adenomas. Summary Peto odds ratios (OR) were computed for overall and stratified analyses. RESULTS: Circulating 25(OH)D was inversely associated with risk of colorectal adenomas: the OR was 0.70 [95% confidence interval (95% CI), 0.56-0.87] for high versus low circulating 25(OH)D. The highest quintile of vitamin D intake was associated with an 11% marginally decreased risk of colorectal adenomas compared with low vitamin D intake (OR, 0.89; 95% CI, 0.78-1.02). For recurrent adenomas, there was a decreased risk of 12% (95% CI, 0.72-1.07) among individuals with high versus low vitamin D intake. The inverse associations appeared stronger for advanced adenoma [OR, 0.64; 95% CI, 0.45-0.90 for serum 25(OH)D and OR, 0.77; 95% CI, 0.63-0.95 for vitamin D intake], but the number of studies was small. CONCLUSIONS: Both circulating 25(OH)D and vitamin D intake were inversely associated with colorectal adenoma incidence and recurrent adenomas. These results further support a role of vitamin D in prevention of colorectal adenoma incidence and recurrence.

On the epidemiology of influenza.

The epidemiology of influenza swarms with incongruities, incongruities exhaustively detailed by the late British epidemiologist, Edgar Hope-Simpson. He was the first to propose a parsimonious theory explaining why influenza is, as Gregg said, "seemingly unmindful of traditional infectious disease behavioral patterns." Recent discoveries indicate vitamin D upregulates the endogenous antibiotics of innate immunity and suggest that the incongruities explored by Hope-Simpson may be secondary to the epidemiology of vitamin D deficiency. We identify - and attempt to explain - nine influenza conundrums: (1) Why is influenza both seasonal and ubiquitous and where is the virus between epidemics? (2) Why are the epidemics so explosive? (3) Why do they end so abruptly? (4) What explains the frequent coincidental timing of epidemics in countries of similar latitude? (5) Why is the serial interval obscure? (6) Why is the secondary attack rate so low? (7) Why did epidemics in previous ages spread so rapidly, despite the lack of modern transport? (8) Why does experimental inoculation of seronegative humans fail to cause illness in all the volunteers? (9) Why has influenza mortality of the aged not declined as their vaccination rates increased? We review recent discoveries about vitamin D's effects on innate immunity, human studies attempting sick-to-well transmission, naturalistic reports of human transmission, studies of serial interval, secondary attack rates, and relevant animal studies. We hypothesize that two factors explain the nine conundrums: vitamin D's seasonal and population effects on innate immunity, and the presence of a subpopulation of "good infectors." If true, our revision of Edgar Hope-Simpson's theory has profound implications for the prevention of influenza.

Relationship between low ultraviolet B irradiance and higher breast cancer risk in 107 countries.

Epidemiological data show an inverse relationship between vitamin D levels and breast cancer incidence. This study investigates the relationship of modeled and measured serum 25-hydroxyvitamin D [25(OH)D] levels with age-standardized incidence rates of breast cancer in 107 countries. The hypothesis being tested is that breast cancer incidence is inversely related to geographically-dependent cutaneous sunlight exposure. A multiple regression approach was used to examine the contributions of ultraviolet B (UVB) irradiance to age-standardized incidence rates of breast cancer in the 107 countries with data on these covariates-total column ozone thickness, per capita intake of alcohol and energy from animal and vegetable sources, cigarettes, proportion of female population overweight, and total fertility. Age-standardized incidence rates were substantially higher at latitudes distant from the equator (R2 = 0.43, p < 0.0001). The dose-response gradient between modeled serum 25(OH)D levels and incidence rates of breast cancer followed a standard inverse dose-response curve. Increasing increments in serum 25(OH)D in the range above 22 ng/mL were associated with incrementally lower incidence rates of breast cancer. According to multiple regression, UVB irradiance adjusted for cloud cover was inversely associated with incidence rates (p = 0.04) after controlling for covariates. Intake of energy from animal sources was also positively associated with incidence rates (p < 0.01). The overall coefficient of determination, R2, was 0.81 (p < 0.0001). There was a protective effect of UVB irradiance on risk of breast cancer that was independent of fertility rate, proportion of the population overweight, alcohol intake, animal energy intake, and other covariates.

Plasma 25-hydroxyvitamin D concentration and risk of type 2 diabetes and pre-diabetes: 12-year cohort study.

BACKGROUND: It has been reported that higher plasma 25-hydroxyvitamin D is associated with lower risk of type 2 diabetes. However the results to date have been mixed and no adequate data based on a cohort are available for the high end of the normal range, above approximately 32 ng/ml or 80 nmol/L. METHODS: We performed a cohort study of 903 adults who were known to be free of diabetes or pre-diabetes during a 1997-1999 visit to a NIH Lipid Research Centers clinic. Plasma 25(OH)D was measured at Visit 8 in 1977-1979. The mean age was 74 years. The visit also included fasting plasma glucose and oral glucose tolerance testing. Follow-up continued through 2009. RESULTS: There were 47 cases of diabetes and 337 cases of pre-diabetes. Higher 25(OH)D concentrations (> 30 ng/ml) were associated with lower hazard ratios (HR) for diabetes: 30-39 ng/ml or 75-98 nmol/L: HR = 0.31, 95% CI = 0.14-0.70; for 40-49 ng/ml or 100-122 nmol/L: HR = 0.29, CI = 0.12-0.68; for > 50 ng/ml or 125 nmol/L: HR = 0.19, CI = 0.06-0.56. All HRs are compared to < 30 ng/ml or 75 nmol/L. There was an inverse dose-response gradient between 25(OH)D concentration and risk of diabetes with a p for trend of 0.005. Each 10 ng/mL or 25 nmol/L higher 25(OH)D concentration was associated with a HR of 0.64, CI = 0.48-0.86. 25(OH)D concentrations were more weakly inversely associated with pre-diabetes risk, and the trend was not significant. CONCLUSION: Further research is needed on whether high 25(OH)D might prevent type 2 diabetes or transition of prediabetes to diabetes.

Breast cancer risk markedly lower with serum 25-hydroxyvitamin D concentrations ≥60 vs <20 ng/ml (150 vs 50 nmol/L): Pooled analysis of two randomized trials and a prospective cohort.

BACKGROUND: While numerous epidemiologic studies have found an association between higher serum 25-hydroxyvitamin D [25(OH)D] concentrations and lower breast cancer risk, few have assessed this association for concentrations >40 ng/ml. OBJECTIVE: To investigate the relationship between 25(OH)D concentration and breast cancer risk across a broad range of 25(OH)D concentrations among women aged 55 years and older. METHODS: Analyses used pooled data from two randomized clinical trials (N = 1129, N = 2196) and a prospective cohort (N = 1713) to examine a broad range of 25(OH)D concentrations. The outcome was diagnosis of breast cancer during the observation periods (median: 4.0 years). Three analyses were conducted: 1) Incidence rates were compared according to 25(OH)D concentration from <20 to ≥60 ng/ml (<50 to ≥150 nmol/L), 2) Kaplan-Meier plots were developed and 3) multivariate Cox regression was used to examine the association between 25(OH)D and breast cancer risk using multiple 25(OH)D measurements. RESULTS: Within the pooled cohort (N = 5038), 77 women were diagnosed with breast cancer (age-adjusted incidence: 512 cases per 100,000 person-years). Results were similar for the three analyses. First, comparing incidence rates, there was an 82% lower incidence rate of breast cancer for women with 25(OH)D concentrations ≥60 vs <20 ng/ml (Rate Ratio = 0.18, P = 0.006). Second, Kaplan-Meier curves for concentrations of <20, 20-39, 40-59 and ≥60 ng/ml were significantly different (P = 0.02), with the highest proportion breast cancer-free in the ≥60 ng/ml group (99.3%) and the lowest proportion breast cancer-free in the <20 ng/ml group (96.8%). The proportion with breast cancer was 78% lower for ≥60 vs <20 ng/ml (P = 0.02). Third, multivariate Cox regression revealed that women with 25(OH)D concentrations ≥60 ng/ml had an 80% lower risk of breast cancer than women with concentrations <20 ng/ml (HR = 0.20, P = 0.03), adjusting for age, BMI, smoking status, calcium supplement intake, and study of origin. CONCLUSIONS: Higher 25(OH)D concentrations were associated with a dose-response decrease in breast cancer risk with concentrations ≥60 ng/ml being most protective.