Cloud cover-adjusted ultraviolet B irradiance and pancreatic cancer incidence in 172 countries.

BACKGROUND: Controversy exists regarding whether vitamin D deficiency could influence the etiology of pancreatic cancer. Several cohort studies have found that high serum 25-hydroxyvitamin D [25(OH)D] concentrations are associated with low risk of pancreatic cancer, while others have not. HYPOTHESIS: Low ultraviolet B irradiance is associated with high incidence of pancreatic cancer. METHODS: Age-standardized pancreatic cancer incidence rates were obtained from GLOBOCAN in 2008. The association between cloud-adjusted UVB irradiance and age-standardized incidence rates of pancreatic cancer was analyzed using regression. RESULTS: Overall, the lower the cloud-adjusted UVB irradiance, the higher the incidence rate of pancreatic cancer. Residents of countries with low UVB irradiance had approximately 6 times the incidence rates as those in countries with high UVB irradiance (p<0.0001 for males and p<0.0001 for females). This association persisted after adjustment for traditional risk factors of pancreatic cancer (p=0.0182 for males and p=0.0029 for females). CONCLUSIONS: There was an inverse association of cloud-adjusted UVB irradiance with incidence of pancreatic cancer that persisted after adjustment. This result is consistent with an inverse association of overall vitamin D deficiency in countries with lower UVB irradiance with risk of pancreatic cancer. Further research on the role of 25(OH)D in reduction of pancreatic cancer in individuals would be desirable to expand the limited avenues available for prevention of this highly fatal disease. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

Low Cloud Cover-Adjusted Ultraviolet B Irradiance Is Associated with High Incidence Rates of Leukemia: Study of 172 Countries.

There are 52,380 cases of leukemia and 24,090 deaths from it in the US annually. Its causes are unknown and no preventive strategies have been implemented. We hypothesized that leukemia is due mainly to vitamin D deficiency, which is due mainly to low solar ultraviolet B (UVB) irradiance. To test this hypothesis, we estimated age-standardized cloud-cover-adjusted winter UVB irradiance using cloud cover data from the International Satellite Cloud Climatology Project, latitudes of population centroids, and standard astronomical calculations. Incidence rates for 172 countries, available from the International Agency for Cancer Research, were plotted according to cloud-adjusted UVB irradiance. We used multiple regression to account for national differences in elevation and average life expectancy. Leukemia incidence rates were inversely associated with cloud-adjusted UVB irradiance in males (p ≤ 0.01) and females (p ≤ 0.01) in both hemispheres. There were few departures from the trend line, which was parabolic when plotted with the equator at the center of the display, northern hemisphere countries on the right side and southern hemisphere countries on the left. The bivariate association displayed by the polynomial trend line indicated that populations at higher latitudes had at least two times the risk of leukemia compared to equatorial populations. The association persisted in males (p ≤ 0.05) and females (p ≤ 0.01) after controlling for elevation and life expectancy. Incidence rates of leukemia were inversely associated with solar UVB irradiance. It is plausible that the association is due to vitamin D deficiency. This would be consistent with laboratory studies and a previous epidemiological study. Consideration should be given to prudent use of vitamin D for prevention of leukemia.

Are low ultraviolet B and vitamin D associated with higher incidence of multiple myeloma?

BACKGROUND: The purpose of this study was to determine whether an inverse association exists between latitude, solar ultraviolet B (UVB) irradiance, and incidence rates of multiple myeloma.Methods Associations of latitude and UVB irradiance with age-standardized incidence rates of multiple myeloma were analyzed for 175 countries while controlling for sex-specific obesity prevalence, cigarette consumption, and alcohol consumption using multiple linear regression.Results Incidence rates of multiple myeloma were greater at higher latitudes (R(2) for latitude for males=0.31, p<0.0001; females R(2)=0.27, p<0.0001). In regression models for males (R(2)=0.62, p<0.0001) and females (R(2)=0.51, p<0.0001), UVB irradiance was independently inversely associated with incidence rates.Conclusions Age-adjusted incidence rates of multiple myeloma were higher in countries with lower solar UVB irradiance. Further investigation is warranted in individuals of the association of prediagnostic serum 25(OH)D with risk.

Could vitamin D sufficiency improve the survival of colorectal cancer patients?

PURPOSE: To determine whether a higher serum 25-hydroxyvitamin D [25(OH)D] concentration at diagnosis is associated with longer survival of colorectal cancer patients. METHODS: A meta-analysis was performed of studies of the relationship between 25(OH)D and mortality of patients with colorectal cancer. A random-effects model was used to calculate a pooled hazards ratio. Homogeneity was evaluated through a DerSimonian-Laird test. RESULTS: Higher serum concentrations of 25(OH)D were associated with lower mortality in patients with colorectal cancer. Patients in the highest quintile of 25(OH)D had 37% lower mortality from colorectal cancer compared to those in the lowest quintile of 25(OH)D (pooled odds ratio=0.63, p<0.0001). Dose-response curves showed lower hazard ratios for mortality with higher serum 25(OH)D through at least 40ng/ml. There were no exceptions. CONCLUSIONS: Higher serum 25(OH)D was associated with lower mortality of patients with colorectal cancer. These results suggest that colorectal cancer patients with deficient levels of serum 25(OH)D should have their levels restored to a normal range (30-80ng/ml). This could be done with regular testing of serum 25(OH)D to be confident that an adequate serum level is being maintained. Additional studies would be worthwhile to evaluate confounding or the possibility of reverse causation.

Meta-analysis of vitamin D sufficiency for improving survival of patients with breast cancer.

BACKGROUND/AIM: To determine whether higher serum 25-hydroxyvitamin D [25(OH)D] at diagnosis is associated with longer survival of patients with breast cancer. MATERIALS AND METHODS: A meta-analysis was performed of five studies of the relationship between 25(OH)D and mortality from breast cancer. A pooled hazard ratio was calculated using a random-effects model. The Der Simonian-Laird test was used to assess homogeneity. RESULTS: Higher serum concentrations of 25(OH)D were associated with lower case-fatality rates after diagnosis of breast cancer. Specifically, patients in the highest quintile of 25(OH)D had approximately half the death rate from breast cancer as those in the lowest. CONCLUSION: High serum 25(OH)D was associated with lower mortality from breast cancer. Serum 25(OH)D in all patients with breast cancer should be restored to the normal range (30-80 ng/ml), with appropriate monitoring. Clinical or field studies should be initiated to confirm that this association was not due to reverse causation.

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.

What is the relationship between ultraviolet B and global incidence rates of colorectal cancer?

The purpose of this study is to examine the relationship between ultraviolet B and global incidence of colorectal cancer, while controlling for relevant covariates. Linear regression was used to assess the relationship between latitude and incidence rates of colon cancer in 173 countries. Multiple linear regression was employed to investigate the relationship between ultraviolet B dose and colorectal cancer rates while controlling for per capita intake of energy from animal sources, per capita health expenditure, pigmentation, and life expectancy. Data on all variables were available for 139 countries. Incidence of colon cancer was highest in countries distant from the equator (R(2) = 0.50, p < 0.0001). UV B dose (p < 0.0001) was independently, inversely associated with incidence rates of colorectal cancer after controlling for intake of energy from animal sources, per capita health expenditure, pigmentation, and life expectancy (R(2) for overall model = 0.76, p < 0.0001). Consistent with previous research, UVB was inversely associated with incidence of colon cancer. Further research on vitamin D and prevention of colon cancer in individuals should be conducted, including studies of higher serum 25-hydroxyvitamin D concentrations than have been studied to date.

Does the evidence for an inverse relationship between serum vitamin D status and breast cancer risk satisfy the Hill criteria?

A wide range of epidemiologic and laboratory studies combined provide compelling evidence of a protective role of vitamin D on risk of breast cancer. This review evaluates the scientific evidence for such a role in the context of the A.B. Hill criteria for causality, in order to assess the presence of a causal, inverse relationship, between vitamin D status and breast cancer risk. After evaluation of this evidence in the context of Hill's criteria, it was found that the criteria for a causal relationship were largely satisfied. Studies in human populations and the laboratory have consistently demonstrated that vitamin D plays an important role in the prevention of breast cancer. Vitamin D supplementation is an urgently needed, low cost, effective, and safe intervention strategy for breast cancer prevention that should be implemented without delay. In the meantime, randomized controlled trials of high doses of vitamin D(3) for prevention of breast cancer should be undertaken to provide the necessary evidence to guide national health policy.

Serum 25-hydroxyvitamin D and prevention of breast cancer: pooled analysis.

BACKGROUND: Low serum levels of 25-hydroxyvitamin D [25(OH)D] have been associated with a high risk of breast cancer. Since publication of the most current meta-analysis of 25(OH)D and breast cancer risk, two new nested case-control studies have emerged. MATERIALS AND METHODS: A PubMed search for all case-control studies on risk of breast cancer by 25(OH)D concentration identified 11 eligible studies. Data from all 11 studies were combined in order to calculate the pooled odds ratio of the highest vs. lowest quantile of 25(OH)D across all studies. RESULTS: The overall Peto odds ratio summarizing the estimated risk in the highest compared to the lowest quantile across all 11 studies was 0.61 (95% confidence interval 0.47, 0.80). CONCLUSION: This study supports the hypothesis that higher serum 25(OH)D levels reduce the risk of breast cancer. According to the review of observational studies, a serum 25(OH)D level of 47 ng/ml was associated with a 50% lower risk of breast cancer.

Ultraviolet B and incidence rates of leukemia worldwide.

BACKGROUND: Recent research has suggested a relationship between vitamin D deficiency and risk of leukemia. PURPOSE: Using data from the UN cancer database, GLOBOCAN, this study will determine whether a relationship exists for latitude and ultraviolet B (UVB) irradiance with incidence rates of leukemia in 175 countries. METHODS: Multiple regression was used to analyze the independent association between UVB and age-adjusted incidence rates of leukemia in 139 countries in 2002. This study controlled for dietary data on intake of energy from animal sources and per capita healthcare expenditures. The analyses were performed in 2009. RESULTS: People residing in the highest-latitude countries had the highest rates of leukemia in both men (R(2)=0.34, p<0.0001) and women (R(2)=0.24, p<0.0001). In men, UVB was independently inversely associated with leukemia incidence rates (p≤0.001), whereas animal energy consumption (p=0.02) and per capita healthcare expenditures (p≤0.0001) were independently positively associated (R(2) for model=0.61, p≤0.0001). In women, UVB adjusted for cloud cover was independently inversely associated with leukemia incidence rates (p≤0.01), whereas animal energy consumption (p≤0.05) and per capita healthcare expenditures (p=0.0002) were independently positively associated (R(2) for model=0.51, p<0.0001). CONCLUSIONS: Countries with low UVB had higher age-adjusted incidence rates of leukemia. This suggests the possibility that low serum 25-hydroxyvitamin D status, because of lower levels of UVB, somehow might predict the development of leukemia.

High serum 25-hydroxyvitamin D is associated with a low incidence of stress fractures.

Low serum 25-hydroxyvitamin D [25(OH)D] concentrations are associated with hip fractures, but the dose-response relationship of serum 25(OH)D with risk of stress fractures in young women is unknown. This nested case-control study in a cohort of female Navy recruits was designed to determine whether those with low prediagnostic serum 25(OH)D concentrations had greater risk of stress fracture. Sera were drawn in 2002-2009 from 600 women who were diagnosed subsequently with stress fracture of the tibia or fibula and 600 matched controls who did not experience a stress fracture. The 25(OH)D concentration was measured using the DiaSorin radioimmunoassay method. Controls were individually matched to cases on race (white, black, or other), length of service (±30 days), and day blood was drawn (±2 days). There was approximately half the risk of stress fracture in the top compared with the bottom quintile of serum 25(OH)D concentration (odds ratio [OR] = 0.51, 95% CI 0.34-0.76, p ≤ 0.01). The range of serum 25(OH)D in the lowest quintile was 1.5 to 19.7 (mean 13.9) ng/mL, whereas in the highest it was 39.9 to 112 (mean 49.7) ng/mL. It is concluded that there was a monotonic inverse dose-response gradient between serum 25(OH)D and risk of stress fracture. There was double the risk of stress fractures of the tibia and fibula in women with serum 25(OH)D concentrations of less than 20 ng/mL compared to those with concentrations of 40 ng/mL or greater. A target for prevention of stress fractures would be a serum 25(OH)D concentration of 40 ng/mL or greater, achievable with 4000 IU/d of vitamin D(3) supplementation.

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.

Ultraviolet B irradiance and vitamin D status are inversely associated with incidence rates of pancreatic cancer worldwide.

OBJECTIVES: To determine if an inverse association exits between latitude, ultraviolet B (UVB) irradiance and incidence rates of pancreatic cancer worldwide. METHODS: Multiple linear regression was used to investigate the relationship and between UVB irradiance incidence rates of pancreatic cancer and while controlling for cigarette, alcohol and sugar consumption, and proportion overweight. Serum 25-hydroxyvitamin D [25(OH)D] levels were estimated, and their association with incidence rates also was analyzed. RESULTS: Incidence rates were higher at higher latitudes (R2 for latitude for men, 0.51; P < 0.001; R2 for latitude for women, 0.32; P < 0.001). Ultraviolet B irradiance also was independently inversely associated with incidence in men (P < 0.01) and women (P = 0.02). Alcohol (P < 0.0001) and cigarette (P < or = 0.01) consumption were positively associated with incidence in men (R2 for overall model for men, 0.76; P < 0.0001). Alcohol (P < 0.0001) and sugar (P = 0.001) consumption were positively associated with incidence rates in women (R2 for overall model for women, 0.64; P < 0.0001). Incidence rates were half as high in countries with estimated serum 25(OH)D >30 ng/mL (75 nmol/L) than in those with < or =30 ng/mL. CONCLUSIONS: Countries with lower UVB irradiance had higher incidence rates of pancreatic cancer in both hemispheres, with occasional exceptions.

Ultraviolet B irradiance and incidence rates of bladder cancer in 174 countries.

BACKGROUND: Although nearly half of bladder cancer cases are due to smoking, the cause of nearly half is unexplained. PURPOSE: This study aims to determine whether an inverse association exists between ultraviolet B (UVB) irradiance and incidence rates of bladder cancer worldwide. METHODS: This study used an ecologic approach. Age-adjusted incidence rates of bladder cancer from 2002 were obtained for all 174 countries in GLOBOCAN, a database of the International Agency for Research on Cancer. The relationship of latitude and estimated serum 25-hydroxyvitamin D [25(OH)D] with incidence rates was determined. The independent contributions to incidence rates of bladder cancer of UVB, per capita cigarette consumption in 1980, and per capita health expenditure for 2001 were assessed using multiple regression. The analyses were performed in July 2008. RESULTS: Bladder cancer incidence rates were higher in countries at higher latitudes than those nearer to the equator (r=-0.66, 95% CI=-0.74, -0.57, p<0.01). Ultraviolet B irradiance was independently inversely associated with incidence rates of bladder cancer after controlling for per capita cigarette consumption (beta=-0.28, 95% CI=-0.51, -0.05; R(2) for model=0.38, p<0.0001). Further, UVB irradiance was also inversely associated with incidence rates after controlling for per capita health expenditure (beta=-0.23, 95% CI=-0.36, -0.01; R(2) for model=0.49, p<0.0001) in a separate regression model. CONCLUSIONS: Further investigation is needed to confirm the associations identified in this study using observational studies of individuals. The focus of this research should include the association of serum 25(OH)D levels with risk of bladder cancer.

Vitamin D for cancer prevention: global perspective.

PURPOSE: Higher serum levels of the main circulating form of vitamin D, 25-hydroxyvitamin D (25(OH)D), are associated with substantially lower incidence rates of colon, breast, ovarian, renal, pancreatic, aggressive prostate and other cancers. METHODS: Epidemiological findings combined with newly discovered mechanisms suggest a new model of cancer etiology that accounts for these actions of 25(OH)D and calcium. Its seven phases are disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition (abbreviated DINOMIT). Vitamin D metabolites prevent disjunction of cells and are beneficial in other phases. RESULTS/CONCLUSIONS: It is projected that raising the minimum year-around serum 25(OH)D level to 40 to 60 ng/mL (100-150 nmol/L) would prevent approximately 58,000 new cases of breast cancer and 49,000 new cases of colorectal cancer each year, and three fourths of deaths from these diseases in the United States and Canada, based on observational studies combined with a randomized trial. Such intakes also are expected to reduce case-fatality rates of patients who have breast, colorectal, or prostate cancer by half. There are no unreasonable risks from intake of 2000 IU per day of vitamin D(3), or from a population serum 25(OH)D level of 40 to 60 ng/mL. The time has arrived for nationally coordinated action to substantially increase intake of vitamin D and calcium.

Ecological studies of ultraviolet B, vitamin D and cancer since 2000.

PURPOSE: The purpose of this review is to summarize ecological studies of solar ultraviolet B (UVB), vitamin D and cancer since 2000. METHODS: The journal literature is surveyed and summarized. RESULTS: The ecological approach has been the primary tool used during the past two decades to extend the applicability of the UVB-vitamin D-cancer theory to include at least 18 types of cancer. Many of these studies were conducted in the United States, which has the advantages of availability of reliable age-standardized cancer incidence and mortality rate data for geographic areas at various spatial resolutions, and an asymmetric solar UVB dose pattern, with higher UVB irradiance in the west and lower in the east, at any particular latitude. In addition, indices for other cancer risk-modifying factors are readily available including those for smoking, alcohol consumption, ethnic background, urban/rural residence, socioeconomic status, air pollution, and in limited fashion, diet. The ecological approach has also been used to identify latitudinal variations in cancer mortality rates in Australia, China, Japan, and Spain, and in multicountry studies. It has been used to investigate the relative roles of solar UVB and dietary factors on a global scale. The ecological approach has also been applied to cancer survival. Studies in Norway and England found that individuals diagnosed with cancer in summer or fall, when serum 25-hydroxyvitamin D levels are highest, had a milder clinical course and longer survival than those diagnosed in winter or spring. CONCLUSION: These findings provide strong evidence that vitamin D status plays an important role in controlling the outcome of cancer. Support for the UVB-vitamin D-cancer theory is now scientifically strong enough to warrant use of vitamin D in cancer prevention, and as a component of treatment. More research studies would help to explore whether there are benefits beyond the substantial effects that have been observed.

A brief history of vitamin d and cancer prevention.

PURPOSE: To review the history of vitamin D and its use in cancer prevention. METHODS: The literature on published studies of vitamin D and its role in human health was reviewed and summarized. RESULTS: The modern history of vitamin D began in the mid-1800s, when it was noticed that city children were more likely to have rickets than rural children. Half a century later, Palm reported that children raised in sunny climates virtually never developed rickets. McCollum isolated vitamin D, and Windaus its precursors, receiving the Nobel Prize. Other scientists later observed that people with skin cancer had lower prevalence of nonskin cancers, and that lower overall mortality rates from all internal cancers combined existed in sunnier areas. These observations went largely unnoticed, and the field stagnated until 1970, when maps were created of cancer mortality rates. Through study of these maps, Cedric and Frank Garland of Johns Hopkins University reported a strong latitudinal gradient for colon cancer mortality rates in 1980, and hypothesized that higher levels of vitamin D compounds in the serum of people in the south were responsible, and that calcium intake also would reduce incidence. Edward Gorham and colleagues carried out cohort and nested studies, including the first study that found an association of a serum vitamin D compound with reduced cancer risk. William B. Grant then carried out numerous ecologic studies that extended the vitamin D-cancer theory to other cancers. CONCLUSIONS: The history of the role of vitamin D in human health is rich and much of that history is yet to be written not only by scientists, but by policy makers with the vision and leadership necessary to bridge the gap between research and policy.