Frank C. Garland’s research while affiliated with University of California, San Diego and other places

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 (R2 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. Copyright © 2014. Published by Elsevier Ltd.

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.

Recent research has suggested a relationship between vitamin D deficiency and risk of leukemia. 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. 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. 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). 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.

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. 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. 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. 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.

To determine if an inverse association exits between latitude, ultraviolet B (UVB) irradiance and incidence rates of pancreatic cancer worldwide. 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. 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. Countries with lower UVB irradiance had higher incidence rates of pancreatic cancer in both hemispheres, with occasional exceptions.

Although nearly half of bladder cancer cases are due to smoking, the cause of nearly half is unexplained. This study aims to determine whether an inverse association exists between ultraviolet B (UVB) irradiance and incidence rates of bladder cancer worldwide. 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. 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. 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.

The aim of the study was to determine age- and race-related, and overall incidence rates of insulin-requiring diabetes in adults in the US military. Electronic records for admissions to US military and Tricare hospitals during 1990-2005 and visits to military clinics during 2000-2005 were identified using the Career History Archival Medical and Personnel System at the Naval Health Research Center, San Diego, CA, USA. Population data were obtained from the Defense Manpower Data Center and Defense Medical Epidemiology Database. In men there were 2,918 new cases of insulin-requiring diabetes in 20,427,038 person-years at ages 18-44 years (median age 28 years) for a total age-adjusted incidence rate of 17.5 per 100,000 person-years (95% CI 16.4-18.6). Incidence rates were twice as high in black men as in white men (31.5 vs 14.5 per 100,000, p < 0.001). In women there were 414 new cases in 3,285,000 person-years at ages 18-44 years (median age 27 years), for a total age-adjusted incidence rate of 13.6 per 100,000 (95% CI 12.4-14.9). Incidence rates were twice as high in black women as in white women (21.8 vs 9.7 per 100,000, p < 0.001). In a regression model, incidence of insulin-requiring diabetes peaked annually in the winter-spring season (OR 1.46, p < 0.01). Race and seasonal differences persisted in the multivariate analysis. Differences in incidence rates by race and season suggest a need for further research into possible reasons, including the possibility of a contribution from vitamin D deficiency. Cohort studies using prediagnostic serum 25-hydroxyvitamin D should be conducted to further evaluate this relationship.

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. 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. 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.