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.

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.

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.

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.

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.

Do sunscreens increase risk of melanoma in populations residing at higher latitudes?

BACKGROUND: Sunscreens may allow overexposure to ultraviolet A (UVA) in fair-skinned persons and prevent symptoms of sunburn, but their benefits for the prevention of melanoma are uncertain. METHODS: A PubMed search was performed that identified all known studies of the association of sunscreen use with melanoma risk during 1966-2007. A total of 18 studies were identified, of which 17 met criteria for inclusion in the analysis. Of these, 10 were conducted at latitudes >40 degrees from the equator and 7 at 40 degrees from the equator, the odds ratio was 1.6 (95% C.I. 1.3-1.9; p for heterogeneity = 0.006), whereas it was 0.7 at 40 degrees.

Is ultraviolet B irradiance inversely associated with incidence rates of endometrial cancer: an ecological study of 107 countries.

OBJECTIVE: The purpose of this study was to perform an ecological analysis of the relationship between low levels of ultraviolet B (UVB) irradiance and age-standardized incidence rates of endometrial cancer by country, controlling for known confounders. METHODS: The contributions of UVB irradiance, cloud cover, intake of energy from animal sources, proportion of population overweight, skin pigmentation, per capita cigarette consumption, per capita health expenditure, and total fertility rates, to age-standardized incidence rates of endometrial cancer in 107 countries were assessed using multiple regression. RESULTS: Incidence rates were higher at higher latitudes (R2=0.47, p<0.01). According to multiple regression, UVB irradiance adjusted for cloud cover was negatively associated with incidence rates (p=0.02), while proportion of population overweight (p=0.004), intake of energy from animal sources (p=0.01) and per capita health expenditure (p<0.0001) were positively associated with incidence rates (overall R2=0.73, p<0.0001). CONCLUSION: An association was found between low UVB irradiance, high intake of energy from animal sources, per capita health expenditure, proportion of population overweight, and incidence rates.

Vitamin D and prevention of breast cancer: pooled analysis.

BACKGROUND: Inadequate photosynthesis or oral intake of Vitamin D are associated with high incidence and mortality rates of breast cancer in ecological and observational studies, but the dose-response relationship in individuals has not been adequately studied. METHODS: A literature search for all studies that reported risk by of breast cancer by quantiles of 25(OH)D identified two studies with 1760 individuals. Data were pooled to assess the dose-response association between serum 25(OH)D and risk of breast cancer. RESULTS: The medians of the pooled quintiles of serum 25(OH)D were 6, 18, 29, 37 and 48 ng/ml. Pooled odds ratios for breast cancer from lowest to highest quintile, were 1.00, 0.90, 0.70, 0.70 and 0.50 (p trend<0.001). According to the pooled analysis, individuals with serum 25(OH)D of approximately 52 ng/ml had 50% lower risk of breast cancer than those with serum <13 ng/ml. This serum level corresponds to intake of 4000 IU/day. This exceeds the National Academy of Sciences upper limit of 2000 IU/day. A 25(OH)D level of 52 ng/ml could be maintained by intake of 2000 IU/day and, when appropriate, about 12 min/day in the sun, equivalent to oral intake of 3000 IU of Vitamin D(3). CONCLUSIONS: Intake of 2000 IU/day of Vitamin D(3), and, when possible, very moderate exposure to sunlight, could raise serum 25(OH)D to 52 ng/ml, a level associated with reduction by 50% in incidence of breast cancer, according to observational studies.

Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis.

BACKGROUND: Previous studies, such as the Women's Health Initiative, have shown that a low dose of vitamin D did not protect against colorectal cancer, yet a meta-analysis indicates that a higher dose may reduce its incidence. METHODS: Five studies of serum 25(OH)D in association with colorectal cancer risk were identified using PubMed. The results of all five serum studies were combined using standard methods for pooled analysis. The pooled results were divided into quintiles with median 25(OH)D values of 6, 16, 22, 27, and 37 ng/mL. Odds ratios were calculated by quintile of the pooled data using Peto's Assumption-Free Method, with the lowest quintile of 25(OH)D as the reference group. A dose-response curve was plotted based on the odds for each quintile of the pooled data. Data were abstracted and analyzed in 2006. RESULTS: Odds ratios for the combined serum 25(OH)D studies, from lowest to highest quintile, were 1.00, 0.82, 0.66, 0.59, and 0.46 (p(trend)<0.0001) for colorectal cancer. According to the DerSimonian-Laird test for homogeneity of pooled data, the studies were homogeneous (chi(2)=1.09, df=4, p=0.90. The pooled odds ratio for the highest quintile versus the lowest was 0.49 (p<0.0001, 95% confidence interval, 0.35-0.68). A 50% lower risk of colorectal cancer was associated with a serum 25(OH)D level > or =33 ng/mL, compared to < or =12 ng/mL. CONCLUSIONS: The evidence to date suggests that daily intake of 1000-2000 IU/day of vitamin D(3) could reduce the incidence of colorectal with minimal risk.

Role of ultraviolet B irradiance and vitamin D in prevention of ovarian cancer.

BACKGROUND: There is a north-south gradient in age-adjusted mortality rates of ovarian cancer in the United States, with the highest rates in the Northeast and the lowest in the South through Southwest. This suggests that lower levels of solar irradiance might be associated with higher risk of ovarian cancer. Laboratory findings also suggest that low levels of vitamin D metabolites could play a role in the etiology of ovarian cancer. METHODS: The association of solar ultraviolet B (UVB) irradiance, stratospheric column ozone, and fertility rates at ages 15 to 19 years with incidence rates of ovarian cancer in 175 countries in 2002 were examined using multiple linear regression in 2006. RESULTS: Age-adjusted ovarian cancer incidence rates generally were highest in countries located at higher latitudes (R(2)=0.45, p< or =0.01). According to multivariate analysis, UVB irradiance (p< or =0.002) and fertility rates at ages 15 to 19 (p=0.01) were inversely associated with incidence rates, while stratospheric ozone (p< or =0.0008), which reduces transmission of UVB, was positively associated with incidence (R(2)=0.49, p<0.0001). CONCLUSIONS: Solar UVB irradiance was inversely associated with incidence rates of ovarian cancer in this study, adding new evidence to the theory that vitamin D might play a role in the prevention of ovarian cancer. Cohort studies are needed to confirm this possible association.

Are low ultraviolet B and high animal protein intake associated with risk of renal cancer?

Incidence rates of kidney cancer are thought to be highest in places situated at high latitudes and in populations with high intake of energy from animal sources. This suggests that low 25-hydroxyvitamin D status, due to lower levels of UVB irradiance, and energy from animal sources might be involved in etiology. The association of latitude with age-adjusted incidence rates was determined for all 175 countries in a UN cancer database, GLOBOCAN. The independent association of UVB irradiance, cloud cover and intake of calories from animal sources with age-adjusted incidence rates was assessed using multiple regression in 139 countries that provided dietary data. Renal cancer incidence rates were highest in countries situated at the highest latitudes, in men (R(2) = 0.64, p < 0.01) and women (R(2) = 0.63, p < 0.01). According to multivariate analysis in men, UVB irradiance was inversely associated with renal cancer incidence rates (p = 0.0003), while cloud cover (p = 0.003) and intake of calories from animal sources (p < 0.0001) were independently positively associated (R(2) for model = 0.73, p < 0.0001). In women, UVB irradiance was inversely associated with incidence rates (p = 0.04), while total cloud cover (p = 0.0008) and calories from animal sources (p < 0.0001) were positively associated (R(2) = 0.68, p < 0.0001). Lower levels of UVB irradiance and higher intakes of calories from animal sources were independently associated with higher incidence rates of kidney cancer.

The role of vitamin D in cancer prevention.

Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects.