Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial.

Importance: Evidence suggests that low vitamin D status may increase the risk of cancer. Objective: To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of cancer among older women. Design, Setting, and Participants: A 4-year, double-blind, placebo-controlled, population-based randomized clinical trial in 31 rural counties (June 24, 2009, to August 26, 2015-the final date of follow-up). A total of 2303 healthy postmenopausal women 55 years or older were randomized, 1156 to the treatment group and 1147 to the placebo group. Duration of treatment was 4 years. Interventions: The treatment group (vitamin D3 + calcium group) received 2000 IU/d of vitamin D3 and 1500 mg/d of calcium; the placebo group received identical placebos. Main Outcomes and Measures: The primary outcome was the incidence of all-type cancer (excluding nonmelanoma skin cancers), which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling. Results: Among 2303 randomized women (mean age, 65.2 years [SD, 7.0]; mean baseline serum 25-hydroxyvitamin D level, 32.8 ng/mL [SD, 10.5]), 2064 (90%) completed the study. At year 1, serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group. A new diagnosis of cancer was confirmed in 109 participants, 45 (3.89%) in the vitamin D3 + calcium group and 64 (5.58%) in the placebo group (difference, 1.69% [95% CI, -0.06% to 3.46%]; P = .06). Kaplan-Meier incidence over 4 years was 0.042 (95% CI, 0.032 to 0.056) in the vitamin D3 + calcium group and 0.060 (95% CI, 0.048 to 0.076) in the placebo group; P = .06. In unadjusted Cox proportional hazards regression, the hazard ratio was 0.70 (95% CI, 0.47 to 1.02). Adverse events potentially related to the study included renal calculi (16 participants in the vitamin D3 + calcium group and 10 in the placebo group), and elevated serum calcium levels (6 in the vitamin D3 + calcium group and 2 in the placebo group). Conclusions and Relevance: Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL, supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years. Further research is necessary to assess the possible role of vitamin D in cancer prevention. Trial Registration: clinicaltrials.gov Identifier: NCT01052051.

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.

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.

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.

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.

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.

Socioeconomic factors in the diagnosis of allergic fungal rhinosinusitis.

OBJECTIVES: 1) To investigate socioeconomic and demographic factors differentiating allergic fungal rhinosinusitis (AFRS) from other chronic rhinosinusitis (CRS) diagnostic groups. 2) To consider the potential impact of epidemiological differences on AFRS disease course. STUDY DESIGN: Retrospective review. STUDY METHODS: Retrospective review of AFRS patients, CRS patients with nasal polyps (CRSwNP) without AFRS, and CRS patients without polyps (CRSsNP). Analysis of group differences was performed for age at presentation, gender, ethnicity, insurance status, and socioeconomic measures with the use of medical records and a South Carolina demographic database. RESULTS: AFRS presentation age was lower than CRSwNP and CRSsNP (P < 0.001). The AFRS group had more African Americans (P < 0.001) and uninsured or Medicaid patients (P < 0.001) than expected. AFRS patients resided in counties with higher poverty percentage (P = 0.011), lower median income (P = 0.048), and more African American residents (P = 0.020) than CRSsNP patients. No group differences existed for gender or physicians per 1000 county residents. CONCLUSION: Demographic and socioeconomic factors may affect AFRS presentation and treatment.

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.

Correction: Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study.

[This corrects the article DOI: 10.1371/journal.pone.0152441.].

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.

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.

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.

An estimate of cancer mortality rate reductions in Europe and the US with 1,000 IU of oral vitamin D per day.

Solar ultraviolet B (UVB) irradiance and/or vitamin D have been found inversely correlated with incidence, mortality, and/or survival rates for breast, colorectal, ovarian, and prostate cancer and Hodgkin's and non-Hodgkin's lymphoma. Evidence is emerging that more than 17 different types of cancer are likely to be vitamin D-sensitive. A recent meta-analysis concluded that 1,000 IU of oral vitamin D per day is associated with a 50% reduction in colorectal cancer incidence. Using this value, as well as the findings in a multifactorial ecologic study of cancer mortality rates in the US, estimates for reductions in risk of vitamin D-sensitive cancer mortality rates were made for 1,000 IU/day. These estimates, along with annual average serum 25-hydroxyvitamin D levels, were used to estimate the reduction in cancer mortality rates in several Western European and North American countries that would result from intake of 1,000 IU/day of vitamin D. It was estimated that reductions could be 7% for males and 9% for females in the US and 14% for males and 20% for females in Western European countries below 59 degrees. It is proposed that increased fortification of food and increased availability of supplements could help increase vitamin D intake and could augment small increases in production of vitamin D from solar UVB irradiance. Providing 1,000 IU of vitamin D per day for all adult Americans would cost about $1 billion; the expected benefits for cancer would be in the range of $16-25 billion in addition to other health benefits of vitamin D.

Dose-response of serum 25-hydroxyvitamin D in association with risk of colorectal cancer: A meta-analysis.

Fifteen nested case-control or cohort studies in 14 countries have examined the association between serum 25-hydroxyvitamin D [25(OH)D] and risk of colorectal cancer. A meta-analysis of these studies would provide a useful dose-response gradient curve based on pooling of the results of known studies to date. An up-to-date dose-response curve that combines the findings of these studies has not been reported, to our knowledge. This curve would help in designing interventions for future studies. A new meta-analysis would be more precise than any previous analysis due to its larger sample size. Therefore a search of PubMed and other resources was performed in May 2016 for all cohort or nested case-control observational studies that reported risk of colon or colorectal cancer by quantiles of 25(OH)D. All but two of the 15 studies found a trend toward lower risk of colorectal cancer associated with higher serum 25(OH)D. There was a linear reduction in the odds ratio (OR) with each 10ng/ml-increment in 25(OH)D concentration. The lowest quantile of the serum 25(OH)D concentration was generally<20ng/ml. The downward trend in ORs associated with higher serum 25(OH)D concentrations was statistically significant in 3 studies. The pooled OR from all studies comparing highest with lowest quantile of 25(OH)D was 0.67 (95% confidence interval [CI], 0.59-0.76), meaning there was a 33% lower risk associated with the highest compared with the lowest quantile of serum 25(OH)D. A dose-response analysis revealed that a serum 25(OH)D of 50ng/ml was associated with an OR of 0.4 (95% CI, 0.2-1.0) compared with a concentration of 5ng/ml. The formula for the linear relationship was OR=0.008x. For example, individuals with a 25(OH)D concentration of 50ng/ml had an approximately 60% lower risk of colorectal cancer than those with a concentration of 5ng/ml. Those with a 25(OH)D concentration of 30ng/ml had a 33% lower risk than those with a concentration of 5ng/ml. The inverse association between serum 25(OH)D and risk of colorectal cancer overall was strong and statistically significant. There also was a mostly linear dose response relationship between serum 25(OH)D and risk of colorectal cancer when all studies were combined. No study reported significant adverse effects, and there was no evidence of publication bias. Misclassification in some studies could have influenced the association, causing it to appear weaker than the true association.

Self-reported hepatitis and non-Hodgkin lymphoma: an analysis according to the time since hepatitis diagnosis.

PURPOSE: Using data from the Selected Cancers Study, the authors tested whether the association between hepatitis infection and non-Hodgkin lymphoma (NHL) varied according to the time since the diagnosis of hepatitis. METHODS: Cases were 1177 men ages 32-60 diagnosed with NHL between 1984 and 1988. Controls were men with no history of NHL who were frequency-matched to lymphoma cases by age and cancer registry (n = 1852). Interviews were conducted to collect data on risk factors including history of hepatitis. No information on types of hepatitis was obtained. RESULTS: Logistic regression analyses indicated that history of hepatitis diagnosed 3 or more years prior to the reference date was not a significant risk factor for NHL (OR [odds ratio] = 0.92, 95% CI: 0.63-1.35). In contrast, men with a history of hepatitis diagnosed within 3 years prior to the diagnosis date had more than a five-fold increased risk of NHL (OR = 5.77, 95% CI: 1.99-16.74). CONCLUSIONS: Although the study was limited by lack of information on different types of hepatitis, the increased OR for hepatitis diagnosed more closely to the NHL diagnosis suggests that the reported association between hepatitis and NHL might partly result from increased detection of NHL in patients with recently reported hepatitis virus infection.

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.