No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
UV, latitude, and spatial trends in prostate cancer mortality: All sunlight is not the same (United States)
Abstract
We showed previously that Caucasian mortality rates from prostate cancer for 1970-1979 are significantly inversely correlated with ultraviolet (UV) radiation. We now present the analysis of prostate cancer mortality data over a 45-year period (1950-1994) in order to examine the persistence of this pattern. Furthermore, because vitamin D synthesis does not occur during winter months at latitudes higher than 40 degrees N, we examined this relationship above and below 40 degrees N latitude.
We used trend surface and linear regression analyses to characterize the relationship between prostate cancer mortality and UV radiation for U.S. counties at northern and southern latitudes.
For U.S. Caucasians, prostate cancer mortality rates at the county and SEA levels followed a significant north-south spatial trend that is the inverse of UV radiation. We found significant inverse correlations between UV radiation and prostate cancer mortality at all time points over this 45-year period. These correlations were significantly more pronounced at locations north of 40 degrees N latitude.
Our analyses confirm and extend our findings that the geographic distribution of prostate cancer mortality is the inverse of that of UV radiation. This effect is strongest in counties north of 40 degrees N latitude, where vitamin D synthesis is limited to non-winter months. These findings add additional support for the hypothesis that vitamin D insufficiency increases risk for prostate cancer.
... It has been hypothesized that vitamin D deficiency may increase prostate cancer risk (1,2). A meta-analysis of 6 prospective studies published up to 2010 reported that circulating vitamin D concentrations were not related to prostate cancer risk (3); however, it was insufficiently powered to provide robust estimates of risk, especially for important disease subgroups. ...
... A meta-analysis of 6 prospective studies published up to 2010 reported that circulating vitamin D concentrations were not related to prostate cancer risk (3); however, it was insufficiently powered to provide robust estimates of risk, especially for important disease subgroups. While the active hormonal form of vitamin D is 1,25-dihydroxyvitamin D (1,25(OH) ...
Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between pre-diagnostic concentrations of 25-hydroxyvitamin D (25(OH)D) and 1,25(OH)2D and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. Odds ratios (OR) for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest versus lowest study-specific fifth was 1.22, 95% CI 1.13-1.31; P trend<0.001). However, this association varied by disease aggressiveness (Pheterogeneity=0.014); higher circulating 25(OH)D was associated with a higher risk of non-aggressive disease (OR per 80 percentile increase=1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of non-aggressive prostate cancer may be influenced by detection bias.
... Epidemiological data reveal an inverse correlation between the incidence of lethal prostate cancer and resident latitude, which is taken to be indicative of chronic, lifetime exposure to sunlight (3,4). Indeed, serum levels of 25-hydroxyvitamin D 3 (25D 3 ) are induced by exposure to sunlight, expression of VDR in tumors, and single nucleotide polymorphisms (SNP) in the VDR gene or its associated metabolizing enzymes, such as 25-hydroxylase (CYP27A1), are inversely correlated with incidence of the lethal disease (5)(6)(7)(8). ...
... Overexpression of Hic-5 sensitizes epithelial LNCaP cells to the antiproliferative effects of 1,25D 3 A previously unknown function of Hic-5 has been revealed in prostate epithelial cells (49). Within 7 days of castration, Hic-5 expression was de-repressed in both endogenous mouse prostate epithelium and tumor xenografts derived from patients with prostate cancer. ...
Unlabelled:
Patients with prostate cancer treated with androgen deprivation therapy (ADT) eventually develop castrate-resistant prostate cancer (CRPC). 1,25-Dihydroxyvitamin D3 (1,25D3/calcitriol) is a potential adjuvant therapy that confers antiproliferative and pro-differentiation effects in vitro, but has had mixed results in clinical trials. The impact of the tumor microenvironment on 1,25D3 therapy in patients with CRPC has not been assessed. Transforming growth factor β (TGFβ), which is associated with the development of tumorigenic "reactive stroma" in prostate cancer, induced vitamin D3 receptor (VDR) expression in the human WPMY-1 prostate stromal cell line. Similarly, TGFβ enhanced 1,25D3-induced upregulation of CYP24A1, which metabolizes 1,25D3 and thereby limits VDR activity. Ablation of Hic-5, a TGFβ-inducible nuclear receptor coregulator, inhibited basal VDR expression, 1,25D3-induced CYP24A1 expression and metabolism of 1,25D3 and TGFβ-enhanced CYP24A1 expression. A Hic-5-responsive sequence was identified upstream (392-451 bp) of the CYP24A1 transcription start site that is occupied by VDR only in the presence of Hic-5. Ectopic expression of Hic-5 sensitized LNCaP prostate tumor cells to growth-inhibitory effects of 1,25D3 independent of CYP24A1. The sensitivity of Hic-5-expressing LNCaP cells to 1,25D3-induced growth inhibition was accentuated in coculture with Hic-5-ablated WPMY-1 cells. Therefore, these findings indicate that the search for mechanisms to sensitize prostate cancer cells to the antiproliferative effects of VDR ligands needs to account for the impact of VDR activity in the tumor microenvironment.
Implications:
Hic-5 acts as a coregulator with distinct effects on VDR transactivation, in prostate cancer and stromal cells, and may exert diverse effects on adjuvant therapy designed to exploit VDR activity in prostate cancer.
... Each participant answered questions from the validated UV exposure questionnaire (UVQ) [18,19]; shown to be valid and reproducible in skin cancer [20] and renal transplant studies [21]. This questionnaire is designed to calculate the total amount of exposure to UV light from childhood until the current period. ...
... Similarly, we showed that total UV exposure was associated with case status. Early on, Schwartz and Hanchette [21] presented ecologic data from 3073 United States counties showing an inverse association between prostate cancer mortality and UV, where the mortality was significantly lower in the South [5]. Others have also found that cumulative, оutdооr оccupаtiоnѕ and skin type reduce the risk of аdvаncеd ѕtаgе tumоrѕ [1,[24][25][26]. ...
... Each participant answered questions from the validated UV exposure questionnaire (UVQ) [18,19]; shown to be valid and reproducible in skin cancer [20] and renal transplant studies [21]. This questionnaire is designed to calculate the total amount of exposure to UV light from childhood until the current period. ...
... Similarly, we showed that total UV exposure was associated with case status. Early on, Schwartz and Hanchette [21] presented ecologic data from 3073 United States counties showing an inverse association between prostate cancer mortality and UV, where the mortality was significantly lower in the South [5]. Others have also found that cumulative, оutdооr оccupаtiоnѕ and skin type reduce the risk of аdvаncеd ѕtаgе tumоrѕ [1,[24][25][26]. ...
It is well established that exposure to ultraviolet (UV) radiation has beneficial effects in reducing prostate cancer risk. To determine if there is a correlation between UV exposure and prostate cancer risk, we assessed sun exposure in a case-control study of 182 African-American men aged 40 years and older residing in the Metropolitan Washington, DC area. Using data on cumulative exposure per year and adult sunbathing scores derived from a validated questionnaire, analysis revealed significant difference in cumulative sun exposure between cases and controls (p=0.003). Additionally, the outdoor and recreation UV exposures were significantly higher in controls when compared to cases (p=0.003; p=0.03 in age-matched cases and controls). Although the results of conditional logistic regression analysis indicate that there was no association between total UV exposure and risk of prostate cancer after adjusting for age (OR=2.04, 95% CI 0.54-7.70, p=0.29), outdoor UV exposure was associated with decreased prostate cancer risk (OR= 0.31, 95% CI 0.14-0.65, p=0.002). Furthermore, a trend for reduced prostate cancer risk was found among men with early life high sun exposure during childhood ages 0-5 years (OR=0.17, 95% CI 0.03-0.74, p=0.02) and 6-11 years (OR= 0.28, 95% CI 0.07-1.05, p=0.06). Interestingly, this inverse association between prostate cancer risk and early life high sun exposure intensity was also observed among young men at ages 12-17 years although not statistically significant (OR=0.41, 95% CI 0.09-1.95, p=0.26). These findings indicate that UV exposure earlier in life may affect susceptibility to prostate cancer.
... There are a limited number of modifiable risk factors identified for PC, and further studies are needed to identify some modifiable risk factors associated with PC. There are numerous epidemiological studies linking the risk and outcome of vitamin D with PC (5,6,7,8). Vitamin D is a steroid prohormone that dissolves in fat and is produced in skin by contact with sunlight. With various metabolic changes in the body, it becomes a hormone known as calcitriol, which plays an important role in calcium and phosphate metabolism. ...
Objective: Prostate cancer (PC) is the most common malignancy among men worldwide. There are several epidemiological studies linking the risk and outcome of vitamin D with PC. In this study, we aimed to compare vitamin D levels in patients with PC and benign prostatic hyperplasia (BPH).
Materials and Methods: Patients with PC and BPH admitted to our urology outpatient clinic between 2017 and 2019 were included in this case-control study. Serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were measured to assess vitamin D status.
Results: The study was conducted with a total of 256 patients aged between 47 and 86 years between 2018-2019. The mean age of 128 patients with PC was 67.70±7.74 years, and the mean age of 128 patients with BPH was 67.03±7.89 years. There was a statistically significant difference between patients with PC and BPH in terms of 25-hydroxyvitamin D levels. When the patients diagnosed with PC were examined according to their subgroups, the mean 25-hydroxyvitamin D levels of 64 patients with ISUP Grade I tumors were significantly higher than the remaining 64 patients with ISUP Grade II, III and IV tumors.
Conclusion: According to our results, vitamin D levels were found to be significantly lower in patients with PC than in patients with BPH, and a significant decrease was found in vitamin D levels as the Gleason score increased. Since PC has a high prevalence and heterogeneous geographical distribution, randomized controlled trials are needed in order to demonstrate the relationship between vitamin D and cancer.
... The role of vitamin D in prostate tumor growth and aggressiveness is also supported by ecological studies. Several studies have reported inverse associations between prostate cancer-specific mortality (PCSM) and sunlight exposure, geographical latitude, and season of diagnosis [6][7][8][9][10]. There are, however, only a limited number of studies directly linking serum levels of vitamin D with either PCa prognosis or measures of PCa aggressiveness. ...
Objectives:
Ecological, in vitro, and in vivo studies demonstrate a link between vitamin D and prostate tumor growth and aggressiveness. The goal of this study was to investigate whether plasma concentration of vitamin D is associated with survivorship and disease progression in men diagnosed with prostate cancer.
Materials and methods:
We conducted a population-based cohort study of 1476 prostate cancer patients to assess disease recurrence/progression and prostate cancer-specific mortality (PCSM) risks associated with serum levels of 25(OH) vitamin D [25(OH)D].
Results:
There were 325 recurrence/progression and 95 PCSM events during an average of 10.8 years of follow-up. Serum levels of 25(OH)D were not associated with risk of recurrence/progression or mortality. Clinically deficient vitamin D levels were associated with an increased risk of death from other causes.
Conclusions:
We did not find evidence that serum vitamin D levels measured after diagnosis affect prostate cancer prognosis. Lower levels of vitamin D were associated with risk of non-prostate cancer mortality.
... For this reason, it has been hypothesized that vitamin D deficiency could play a role in the pathogenesis of prostate cancer. Indeed, studies suggest higher cancer mortality rates for patients diagnosed in winter (7,8) and at northern latitudes (9,10). For the majority of individuals, approximately 90% of vitamin D is estimated to derive from sunshine, with the liver converting solar UV radiation into 25-hydroxyvitamin D3 (25-OH D3), the form of vitamin D typically measured in blood serum (11). ...
The association between vitamin D and prostate biopsy outcomes has not been evaluated. We examine serum vitamin D levels with prostate biopsy results in men with an abnormal prostate-specific antigen and/or digital rectal examination.
Serum 25-hydroxyvitamin D (25-OH D) was obtained from 667 men, ages 40 to 79 years, prospectively enrolled from Chicago urology clinics undergoing first prostate biopsy. Logistic regression was used to evaluate the associations between 25-OH D status and incident prostate cancer, Gleason score, and tumor stage.
Among European American (EA) men, there was an association of 25-OH D <12 ng/mL with higher Gleason score ≥ 4+4 [OR, 3.66; 95% confidence interval (CI), 1.41-9.50; P = 0.008] and tumor stage [stage ≥ cT2b vs. ≤ cT2a, OR, 2.42 (1.14-5.10); P = 0.008]. In African American (AA) men, we find increased odds of prostate cancer diagnosis on biopsy with 25-OH D < 20 ng/mL [OR, 2.43 (1.20-4.94); P = 0.01]. AA men demonstrated an association between 25-OH D < 12 ng/mL and Gleason ≥ 4+4 [OR, 4.89 (1.59-15.07); P = 0.006]. There was an association with tumor stage ≥ cT2b vs. ≤ cT2a [OR, 4.22 (1.52-11.74); P = 0.003].
In AA men, vitamin D deficiency was associated with increased odds of prostate cancer diagnosis on biopsy. In both EA and AA men, severe deficiency was positively associated with higher Gleason grade and tumor stage. Clin Cancer Res; 20(9); 2289-99. ©2014 AACR.
... Vitamin D has been presented to reduce cellular proliferation, increase apoptosis and inhibit invasion, migration, metastasis and angiogenesis [52,53]. The potential role of vitamin D in prostate tumor growth and aggressiveness is supported by environmental and case-control studies demonstrating an inverse relationship between prostate cancer mortality and advanced disease with ultraviolet (UV) exposure, which is the primary source of vitamin D [54][55][56][57]. Additionally, African Americans and older men who have reduced capacity for absorbing UV, presented an increased prostate cancer mortality [58][59]. ...
Recent studies have demonstrated an association between higher body mass index and increased aggressiveness in prostate cancer.The present narrative review, based on a search of Medline® and Embase® databases from October 1982 to October 2012, explores the relationship between higher body mass index and localized prostate cancer. In particular, the current epidemiological and mechanistic evidence for interactions between obesity and prostate cancer are discussed.Obesity is associated with alterations in androgen levels, decreased sex hormone binding globulin and increased estrogen levels, insulin resistance, hyperglycemia, alterations in plasma lipoprotein levels particularly raised triglycerides and reduced high density lipoprotein, decreased levels of adiponectin, and increased levels of circulating insulin-growth factor- 1, leptin and dietary saturated fats. Obese men have more aggressive prostate cancer with a greater percentage prostate involvement, increased tumor volume and higher-grade disease, enlarged prostates, high prostate-specific antigen levels, increased risk of having positive margins and recurrence.Moreover, there is strong evidence of the beneficial effects of functional foods for the treatment of obesity. Additionally, an increasing number of studies support that obesity-induced inflammation plays an important role in the development of obesity-related pathologies. Despite, the beneficial role of nutriment in prostate cancer control, the use of functional foods in prostate cancer is not recommended for lack of large epidemiological studies.This data supports the hypothesis that obese men have more aggressive prostate cancers and that the obesity is a modifiable risk factor of prostate cancer.Key Words: prostate cancer, metabolic syndrome, obesity, high BMI, risk factor, diet, functional foods.
... Although the results of experimental studies of vitamin D and prostate cancer have been uniformly positive, the results of observational studies have been mixed. Numerous ecologic studies replicated the inverse correlation of prostate cancer rates with sunlight (9)(10)(11). Analytic studies support a protective effect of sunlight exposure in individual men, including an effect for exposure during early life (12)(13)(14). ...
The effects of blood levels of 25-hydroxyvitamin D (25-OHD) on the risk of total, low-, and high-grade prostate cancer were examined in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and the Prostate Cancer Prevention Trial (PCPT). In the SELECT study, plasma 25-OHD levels were associated with a linear decrease in prostate cancer risk for high-grade cancers in African American men and an apparent "U"-shaped effect in other men. The "U-shaped" curve may reflect detection bias. In the PCPT study, in which detection bias was minimized, serum 25-OHD levels were associated with a linear decrease in the risk of high-grade prostate cancers. The results from these large prevention trials support the hypothesis that circulating levels of 25-OHD decrease the risk of clinically relevant prostate cancers. Cancer Epidemiol Biomarkers Prev; 23(8); 1447-9. ©2014 AACR.
... Unorthodoxly, the incidence of prostate cancer in our population seems to decrease after CM diagnosis, although this result should be cautiously interpreted, due to the relatively low number of this event in our patient cohort. The latter may be of particular interest, since several studies have connected CM and prostate cancer with common risk factors responsible for the pathogenesis of both cancer types, such as the UV exposure, with subsequently increased risk of prostate cancer diagnosis after melanoma diagnosis [12,16,[31][32][33][34]. On the other hand, the role of androgens and oestrogens in the melanoma development have been controversially discussed [35][36][37][38]; altogether, the assumption of an additional biological or hormonal relationship between CM, prostate cancer and breast cancer remains unclear. ...
Background: Recent progress in the diagnosis and treatment of primary and metastatic cutaneous melanoma (CM) has led to a significant increase in the patients` expectancy of life. The development of additional primary tumors (APT) other than CM represents an important survival issue. Results: Of a total of 1764 CM patients, 80 (4.5%) patients developed APT. For tumors diagnosed after CM, there was a 2.7 fold excess risk for APT compared to the swiss german population. A significantly increased risk was noted for female breast (SIR, 2.46), male larynx (SIR, 76.92), male multiple myeloma (SIR, 11.2), male oesophagus (SIR, 10.8) and thyroid on males (SIR, 58.8) and females (SIR, 38.1). All thyroid cancer cases had a common papillary histological subtype and a high rate of BRAFV600E mutation. Melanoma was the primary cause of death in the vast majority of patients. Methods: We used the cancer registry from the Comprehensive Cancer Center Zurich (CCCZ) and retrospectively analyzed patients with CM and APT between 2008 and 2018. We calculated the risk of APT compared to the swiss german population using the standardized incidence ratio (SIR). Conclusions: Patients with CM have an increased risk for hematologic and solid APT. Long-term follow-up is indicated.
... Similar studies have shown defi ciency of vitamin D in association with prostate and ovarian cancer risk. [16][17][18] However, hypopharyngeal carcinoma in association with LI and rickets is being reported for the fi rst time. Whether there is an underlying gene mutation responsible or due to vitamin D defi ciency per se for the underlying malignancy is still uncertain and at present literature too is unavailable for the same. ...
Lamellar ichthyosis (LI) is an autosomal recessive disorder rarely associated with systemic organ involvement and development of carcinoma. Rickets has occasionally been described with LI owing to impaired vitamin D synthesis following altered keratinization. There has also been a high association of cutaneous cancers in patients of LI. We as Dermatologists should therefore be very meticulous while doing a full work up of these patients. We report here a case of LI associated with rickets and carcinoma of the hypopharynx.
... However, we did not have information on environmental or secondhand tobacco smoke and could not account for such exposure. We also found that prostate and liver cancers were positively associated with current UVR exposure; these results are in contrast to those of previous studies that suggested an inverse relationship (11,29,30). Results for death from melanoma have been mixed (11,17,31), and in our study, we observed a positive association. ...
Geographic variations in mortality rate in the United States could be due to several hypothesized factors, one of which is exposure to solar ultraviolet radiation (UVR). Limited evidence from previous prospective studies has been inconclusive. The association between ambient residential UVR exposure and total and cause-specific mortality risks in a regionally diverse cohort (346,615 white, non-Hispanic subjects, 50-71 years of age, in the National Institutes of Health (NIH)-AARP Diet and Health Study) was assessed, with accounting for individual-level confounders. UVR exposure (averaged for 1978-1993 and 1996-2005) from NASA's Total Ozone Mapping Spectrometer was linked to the US Census Bureau 2000 census tract of participants' baseline residence. Multivariate-adjusted Cox proportional-hazards models were used to estimate hazard ratios and 95% confidence intervals. Over 12 years, UVR exposure was associated with total deaths (n = 41,425; hazard ratio for highest vs. lowest quartiles (HRQ4 vs. Q1) = 1.06, 95% confidence interval (CI): 1.03, 1.09; Ptrend < 0.001) and with deaths (all Ptrend < 0.05) due to cancer (HRQ4 vs. Q1 = 1.06, 95% CI: 1.02, 1.11), cardiovascular disease (HRQ4 vs. Q1 = 1.06, 95% CI: 1.00, 1.12), respiratory disease (HRQ4 vs. Q1 = 1.37, 95% CI: 1.21, 1.55), and stroke (HRQ4 vs. Q1 = 1.16, 95% CI: 1.01, 1.33) but not with deaths due to injury, diabetes, or infectious disease. These results suggest that UVR exposure might not be beneficial for longevity.
... It is well known that excessive exposure to ultraviolet radiation (UV) may lead to harmful 10 effects on humans [1,2,3,4,5,6] while moderate exposures are required to form vitamin D in 11 the skin desired for a healthy body [7,8,9]. The assessment of personal exposure to UV is, 12 therefore, a vital requirement as well as the development of UV measuring devices [10]. ...
The spectral response of solvent-cast polyvinyl chloride (PVC) thin film suitable for use as a long-term UV dosimeter has been determined by measuring the UV induced change in the 1064cm(-1) peak intensity of the PVC's infrared (IR) spectra as a function of the wavelength of the incident radiation. Measurements using cut-off filters, narrow band-pass filters and monochromatic radiation showed that the 16μm PVC film responds mainly to the UVB band. The maximum response was at 290nm and decreasing exponentially with wavelength up to about 340nm independent of temperature and exposure dose. The most suitable concentration (W/V%) of PVC/Tetrahydrofuran solution was found to be 10% and the best thickness for the dosimeter was determined as 16μm.
... Vitamin D deficiency and risk of PCa Research indicates that exposure to UV radiation is inversely correlated with PCa incidence and mortality [91][92][93] and that vitamin D protects against prostate cancer [94][95][96][97][98]. Although the underlying biological mechanisms between vitamin D and PCa may be complex, our dynamic model provides an explanation. ...
Background
Since the landmark study conducted by Huggins and Hodges in 1941, a failure to distinguish between the role of testosterone in prostate cancer development and progression has led to the prevailing opinion that high levels of testosterone increase the risk of prostate cancer. To date, this claim remains unproven.
Presentation of the hypothesis
We present a novel dynamic mode of the relationship between testosterone and prostate cancer by hypothesizing that the magnitude of age-related declines in testosterone, rather than a static level of testosterone measured at a single point, may trigger and promote the development of prostate cancer.
Testing the hypothesis
Although not easily testable currently, prospective cohort studies with population-representative samples and repeated measurements of testosterone or retrospective cohorts with stored blood samples from different ages are warranted in future to test the hypothesis.
Implications of the hypothesis
Our dynamic model can satisfactorily explain the observed age patterns of prostate cancer incidence, the apparent conflicts in epidemiological findings on testosterone and risk of prostate cancer, racial disparities in prostate cancer incidence, risk factors associated with prostate cancer, and the role of testosterone in prostate cancer progression. Our dynamic model may also have implications for testosterone replacement therapy.
... It might be more accurate to measure vitamin D metabolites rather than rely on calculations from diet, as vitamin D levels are influenced by numerous sources in addition to sunlight and diet [134]. The production of vitamin D 3 is reduced by about 50% in elderly people [135] and a significant inverse correlation has been found between UV radiation and PCa mortality in the USA [136]. ...
The field of personalized medicine is currently broadening in scope in at least three crucial dimensions. First, while genetics/genomics individual variability is an important aspect of personalized medicine, it is clear that environmental, nutritional, lifestyle and social risk factors play a crucial role for suboptimal therapeutics or disease susceptibility. Second, personalized medicine can inform not only drug therapy but also preventative medicine such that public health interventions that mitigate or prevent disease risks are also customized at an individual and subpopulation level. Third, personalized medicine is now truly global in scope demanding scholarship and innovation analysis beyond the developed countries. In this paper, we critically bring together these three emerging and broader strands of personalized medicine by focusing on prevention of prostate cancer in the developing world. Although prostate cancer prevalence used to be lower in developing countries in the past, this situation is beginning to change rapidly as people living in the developing world transition to a lifestyle more similar to that found in affluent countries. This transition to decreased physical activity, burgeoning overweight/obesity levels, changing nutritional habits, and greater consumption of tobacco, leads to an increased prevalence of non-communicable diseases. There are indications that these changes may also lead to an increase in prostate cancer in low and middle income countries (LMICs). We outline the risk factors associated with prostate cancer, some of the changes that are taking place in LMICs, the reasons behind these changes and the need for personalized or rationally targeted preventative interventions against prostate cancer in LMICs and globally.
... It might be more accurate to measure vitamin D metabolites rather than rely on calculations from diet, as vitamin D levels are influenced by numerous sources in addition to sunlight and diet [134]. The production of vitamin D 3 is reduced by about 50% in elderly people [135] and a significant inverse correlation has been found between UV radiation and PCa mortality in the USA [136]. A number of studies looked at the consumption of various fruits and vegetables [104]. ...
The field of personalized medicine is currently broadening in scope in at least three crucial dimensions. First, while genetics/genomics individual variability is an important aspect of personalized medicine, it is clear that environmental, nutritional, lifestyle and social risk factors play a crucial role for suboptimal therapeutics or disease susceptibility. Second, personalized medicine can inform not only drug therapy but also preventative medicine such that public health interventions that mitigate or prevent disease risks are also customized at an individual and subpopulation level. Third, personalized medicine is now truly global in scope demanding scholarship and innovation analysis beyond the developed countries. In this paper, we critically bring together these three emerging and broader strands of personalized medicine by focusing on prevention of prostate cancer in the developing world. Although prostate cancer prevalence used to be lower in developing countries in the past, this situation is beginning to change rapidly as people living in the developing world transition to a lifestyle more similar to that found in affluent countries. This transition to decreased physical activity, burgeoning overweight/obesity levels, changing nutritional habits, and greater consumption of tobacco, leads to an increased prevalence of non-communicable diseases. There are indications that these changes may also lead to an increase in prostate cancer in low and middle income countries (LMICs). We outline the risk factors associated with prostate cancer, some of the changes that are taking place in LMICs, the reasons behind these changes and the need for personalized or rationally targeted preventative interventions against prostate cancer in LMICs and globally.
... Hanchette and Schwartz's publication concerning a protective effect of vitamin D on mortality from prostate cancer [8,9] stimulated investigations into the possible protective effect of Vitamin D/sunlight in several cancers, including ovarian cancer [10][11][12][13][14]. Although an inverse correlation between ovarian cancer and ultraviolet radiation was reported in ecological studies, a systematic review of the analytic epidemiologic literature (i.e., case-control and cohort studies) does not support a protective effect of Vitamin D in ovarian cancer [15]. ...
Ovarian cancer is the fifth leading cause of female cancer mortality in the U.S. and accounts for five percent of all cancer deaths among women. No environmental risk factors for ovarian cancer have been confirmed. We previously reported that ovarian cancer incidence rates at the state level were significantly correlated with the extent of pulp and paper manufacturing. We evaluated that association using county-level data and advanced geospatial methods. Specifically, we investigated the relationship of spatial patterns of ovarian cancer incidence rates with toxic emissions from pulp and paper facilities using data from the Environmental Protection Agency's Toxic Release Inventory (TRI). Geospatial analysis identified clusters of counties with high ovarian cancer incidence rates in south-central Iowa, Wisconsin, New York, Pennsylvania, Alabama, and Georgia. A bivariate local indicator of spatial autocorrelation (LISA) analysis confirmed that counties with high ovarian cancer rates were associated with counties with large numbers of pulp and paper mills. Regression analysis of state level data indicated a positive correlation between ovarian cancer and water pollutant emissions. A similar relationship was identified from the analysis of county-level data. These data support a possible role of water-borne pollutants from pulp and paper mills in the etiology of ovarian cancer.
... 5,6 Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated, in part, by vitamin D. 7 Many (but not all) epidemiologic studies have found an association between low levels of vitamin D and all-cause mortality, [8][9][10][11] cancer mortality, 12,13 and cancer survival. [14][15][16][17][18] Others have linked lower rates of prostate and ovarian cancer [19][20][21][22][23][24][25] to residency at lower latitudes. Some studies have shown that cancer patients who undergo treatment in summer have better survival rates than thosewho undergo treatment in winter, suggesting that variation in cancer survival may be associated with seasonal factors, including vitamin D levels. ...
Skin cancer is the most common cancer in the United States. Exposure to ultraviolet radiation is a known risk factor for skin cancer but is also the principal means by which the body obtains vitamin D. Several studies have suggested that vitamin D plays a protective role in a variety of internal malignancies. With regard to skin cancer, epidemiologic and laboratory studies suggest that vitamin D and its metabolites may have a similar protective effect. These noncalcemic actions of vitamin D have called into question whether the current recommended intake of vitamin D is too low for optimal health and cancer prevention. Part I will review the role of vitamin D in the epidermis; part II will review the role of vitamin D in keratinocyte-derived tumors to help frame the discussion on the possible role of vitamin D in the prevention of skin cancer.
... In this case study, at-risk locations were identified using simple processes like buffering on maps. Many other studies have been performed in this field and have considered the causative factors of diseases (MacKinnon et al. 2007;Schwartz and Hanchette 2006;Tian, Wilson, and Zhan 2011;Vieira et al. 2017;Wu, Huo, and Zhu 2008). The other type of study examines all or some known causative factors of a disease and the number of cases. ...
Almost all causative factors of diseases depend on location. The Digital Earth approach is suitable for studying diseases globally. Geospatial information systems integrated with statistical models can be used to model the relationship between a disease and its causative factors. Through modelling, the most important causative factors can be extracted and the epidemiology of the disease can be observed. In this paper, skin cancer (the most common type of cancer) has been modelled based on its causative factors, including climate factors, people's occupations, nutrition habits, socio-economic factors, and usage of chemical fertiliser. To fit the model, a data framework was first designed, and then data were gathered and processed. Finally, the disease was modelled using Generalised Linear Models (GLM), a statistical model based on the location of the factors. The results of this study identify the most important causative factors together with their relative priority. Furthermore, a model was used to predict the change in skin cancer occurrences caused by a change in one of its causative factors. This work illustrates the ability of the model to predict disease occurrence. Thus, by using this Digital Earth approach, skincancer can be studied in all the key countries around the world. © 2018
... Epidemiological data has shown an inverse correlation between lethal prostate cancer and geographical location, where the position of patient occupancy is indicative of sun light exposure and thus vitamin D (OHD) levels (Nair-Shalliker, et al. 2012; Schwartz and Hanchette 2006). Vitamin D deficiency has also been associated with increased risk of being diagnosed with prostate cancer (Murphy, et al. 2014). ...
Prostate cancer has, for decades, been treated by inhibiting androgen signalling. This is effective in the majority of patients, but inevitably resistance develops and patients progress to life-threatening metastatic disease – hence the quest for new effective therapies for ‘castrate-resistant’ prostate cancer (CRPC). Studies into what pathways can drive tumour recurrence under these conditions has identified several other nuclear receptor signalling pathways as potential drivers or modulators of CRPC.
The nuclear receptors constitute a large (48 members) superfamily of transcription factors sharing a common modular functional structure. Many of them are activated by the binding of small lipophilic molecules, making them potentially druggable. Even those for which no ligand exists or has yet been identified may be tractable to activity modulation by small molecules. Moreover, genomic studies have shown that in models of CRPC, other nuclear receptors can potentially drive similar transcriptional responses to the androgen receptor, while analysis of expression and sequencing databases shows disproportionately high mutation and copy number variation rates among the superfamily. Hence, the nuclear receptor superfamily is of intense interest in the drive to understand how prostate cancer recurs and how we may best treat such recurrent disease. This review aims to provide a snapshot of the current knowledge of the roles of different nuclear receptors in prostate cancer – a rapidly evolving field of research.
... Among the papers identifying cancer risk factors, we wish to highlight the following: i) the association between arsenic concentration in drinkable water and colon, lung and bladder cancer's incidence risk increase in Cordoba, Argentina (Aballay et al., 2012); ii) a relation between higher incidence and mortality rates by cervical cancer, and more poverty and/or higher distance to screening in USA (Horner et al., 2011); iii) the urban disadvantage in risk of breast, colorectal, lung and prostate cancers in Illinois (McLafferty and Wang, 2009); or iv) a relation between Vitamin D insufficiency and an increase of prostate cancer risk (Schwartz and Hanchette, 2006); v) a possible association among coal mining activities and cancer mortality in West Virginia (Hendryx et al., 2010). ...
Cancer is a major concern among chronic diseases today. Spatial epidemiology plays a relevant role in this matter and we present here a review of this subject, including a discussion of the literature in terms of the level of geographic data aggregation, risk factors and methods used to analyse the spatial distribution of patterns and spatial clusters. For this purpose, we performed a websearch in the Pubmed and Web of Science databases including studies published between 1979 and 2015. We found 180 papers from 63 journals and noted that spatial epidemiology of cancer has been addressed with more emphasis during the last decade with research based on data mostly extracted from cancer registries and official mortality statistics. In general, the research questions present in the reviewed papers can be classified into three different sets: i) analysis of spatial distribution of cancer and/or its temporal evolution; ii) risk factors; iii) development of data analysis methods and/or evaluation of results obtained from application of existing methods. This review is expected to help promote research in this area through the identification of relevant knowledge gaps. Cancer’s spatial epidemiology represents an important concern, mainly for public health policies design aimed to minimise the impact of chronic disease in specific populations.
... However, the epidemiological results investigating the link between sun exposure and prostate cancer risk have been inconclusive thus far. A number of studies have reported an inverse correlation between sun exposure levels and both prostate cancer incidence [37][38][39] and mortality [40,41]. On the other hand, ecological evidence from the U.S. has suggested that exposure to high levels of solar ultra-violet radiation is associated with an increased risk of PCa mortality [42]. ...
Prostate, bladder and kidney cancers remain the most common urological malignancies worldwide, and the prevention and treatment of these diseases pose a challenge to clinicians. In recent decades, many studies have been conducted to assess the association between supplementation with selected vitamins and elements and urinary tract tumour initiation and development. Here, we review the relationship between vitamins A, B, D, and E, in addition to calcium, selenium, and zinc, and the risk of developing prostate, kidney and bladder cancer. A relatively consistent body of evidence suggests that large daily doses of calcium (> 2,000 mg/day) increase the risk of prostate cancer. Similarly, supplementation with 400 IU/day of vitamin E carries a significant risk of prostate cancer. However, there have been many conflicting results regarding the effect of these nutrients on kidney and bladder neoplasms. Moreover, the role of other compounds in urinary tract carcinogenesis needs further clarification.
... 8 In addition to vitamin D, UVR exposure may affect health due to other mechanisms. 9 Existing evidence is derived mostly from ecologic studies, which lack individual-level covariates and have frequently relied on geographic location such as latitude 10,11 as surrogate for sunlight exposure. Estimated ground-level UVR exposure (erythemal dose) from the Total Ozone Mapping Spectrometer (TOMS) dataset of the National Aeronautics and Space Administration (NASA) has been widely used in recent studies 3,12 to better estimate potential UVR exposure. ...
Ecologic studies have reported that solar ultraviolet radiation (UVR) exposure is associated with cancer; however, little evidence is available from prospective studies. We aimed to assess the association between an objective measure of ambient UVR exposure and risk of total and site-specific cancer in a large, regionally diverse cohort [450,934 white, non-Hispanic subjects (50-71 years) in the prospective National Institutes of Health (NIH)-AARP Diet and Health Study] after accounting for individual-level confounding risk factors. Estimated erythemal UVR exposure from satellite Total Ozone Mapping Spectrometer (TOMS) data from NASA was linked to the US Census Bureau 2000 census tract (centroid) of baseline residence for each subject. We used Cox proportional hazards models adjusted for multiple potential confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for quartiles of UVR exposure. Restricted cubic splines examined nonlinear relationships. Over 9 years of follow-up, UVR exposure was inversely associated with total cancer risk (N = 75,917; highest versus lowest quartile; HR = 0.97, 95% CI = 0.95-0.99; p-trend < 0.001). In site-specific cancer analyses, UVR exposure was associated with increased melanoma risk (highest versus lowest quartile; HR = 1.22, 95% CI = 1.13-1.32; p-trend < 0.001) and decreased risk of non-Hodgkin's lymphoma (HR = 0.82, 95% CI = 0.74-0.92) and colon (HR = 0.88, 95% CI = 0.82-0.96), squamous cell lung (HR = 0.86, 95% CI = 0.75-0.98), pleural (HR = 0.57, 95% CI = 0.38-0.84), prostate (HR = 0.91, 95% CI = 0.88-0.95), kidney (HR = 0.83, 95% CI = 0.73-0.94) and bladder (HR = 0.88, 95% CI = 0.81-0.96) cancers (all p-trend < 0.05). We also found nonlinear associations for some cancer sites, including the thyroid and pancreas. Our results add to mounting evidence for the influential role of UVR exposure on cancer.
Evidence suggests early events might modify adult breast cancer risk and many adolescents learn of familial and genetic risks for breast cancer. Little is known about how adolescent girls understand and respond to breast cancer risk. Semi-structured interviews with 11-19 year-old girls at high-risk and population-risk for breast cancer evaluated knowledge and perceptions of breast cancer risk and risk modification. Framework analysis and descriptive statistics were utilized to analyze open-ended responses. Risk group and age differences were evaluated by Fisher's exact and McNemar's tests. Fifty-four girls (86 % of invited), 35 high-risk (65 %), and 19 population-risk (35 %) completed interviews. The most frequently reported risk for breast cancer was family history/hereditary predisposition (66 %). Only 17 % of girls were aware of BRCA1/2 genes. The majority (76 %) of high-risk girls perceive themselves to be at increased risk for breast cancer, compared to 22 % of population-risk girls (p = 0.001). Half of girls reported that women can get breast cancer before 20-years-old. The majority believe there are things women (70 %) and girls (67 %) can do to prevent breast cancer. Mother was the most frequently reported source of information for breast cancer among both high-risk (97 %) and population-risk (89 %) girls. In this study, many high-risk girls perceive themselves to be at increased risk for breast cancer, and many girls believe that breast cancer can occur in teens. Yet, most girls believe there are things women and girls can do to prevent breast cancer. Research evaluating the impact of awareness and perceptions of breast cancer risk on psychosocial, health, and risk behaviors is needed to develop strategies to optimize responses to cancer risk.
A new chemical UV dosimeter with a larger dose capacity than existing chemical dosimeters has been investigated for long-term UV measurements. Unstabilized polyvinyl chloride (PVC), cast in 40 µm thick film, has been found to respond to at least 745 SED (Standard Erythema Dose = 100 J m−2) of solar UV radiation, which is equivalent to about two to three summer weeks of exposure in subtropical sites. The UV-induced changes in the PVC dosimeter were quantified using a Fourier transform infrared spectrophotometer and the decrease in the absorption intensity of the 1064 cm−1 peak was employed to quantify these changes. Dose response curves have been established by relating the decrease in the PVC dosimeter's absorption intensity at 1064 cm−1 to the corresponding absolute and erythemal UV exposure dose.
Heliotherapien durch die selektive Ausschaltung riskanter UV-A-/UV-B-Strahlungsbereiche sowie die Reduktion von IR-Strahlung bieten neue Möglichkeiten in der phototherapeutischen Behandlung vieler Hautkrankheiten. Zugleich können sie begleitend bei diversen Allgemeinerkrankungen mit Konnex zu Vitamin-D-Mangel und/oder Sonnenlichtmangel eingesetzt werden. Der Artikel schildert ein aktuelles Klinik-Projekt zum Thema in Dubai.
Het advies van de Gezondheidsraad over optimale inname van vitamine D zal de gezondheidsproblemen die ontstaan door vitamine-D-gebrek
onvoldoende verlichten. De redenen daarvoor zijn ongegronde angst voor overdosering en onderwaardering van de wetenschappelijke
aanwijzingen voor het heilzaam effect van hogere calcidiolspiegels.
commentaar-gezondheidsraad-vitaminen
Background:
The study assessed the impact of prostate-specific antigen (PSA) testing in the United States by comparing the rates of PSA testing in U.S. counties to the rates of prostate biopsies and newly treated prostate cancer and to deaths from prostate cancer.
Methods:
We examined the association between the percentage of men aged 66-74 from a nationally representative 5% Medicare sample who received PSA testing in each U.S. county in 1997 and the percent of men who received prostate biopsies or treatment for newly diagnosed prostate cancer in 1997 as well as mortality from prostate cancer and from all other causes from 1998 to 2007.
Results:
Analyses of 1,067 U.S. counties showed a significant relationship between the rate of PSA testing and both the rate of men undergoing treatment for prostate cancer and prostate cancer mortality (both p < .001) but no relationship with mortality from other causes. For every 100,000 men receiving a PSA test in 1997, an additional 4,894 men underwent prostate biopsy and 1,597 additional men underwent prostate cancer treatment in 1997, and 61 fewer men died from prostate cancer during 1998-2006. Analyses stratified by age and race produced similar results.
Conclusions:
PSA testing was associated with modest reductions in prostate cancer mortality and large increases in the number of men overdiagnosed with and overtreated for prostate cancer. The results are similar to those obtained by the large European randomized prospective trial of PSA testing.
Vitamin D status and cancer risk has been investigated in a number of epidemiologic studies. The methods to estimate vitamin
D status have included direct measures of circulating 25(OH)vitamin D (25(OH)D) levels, surrogates or determinants of 25(OH)D,
including region of residence, intake, and sun exposure estimates. For colorectal cancer, the evidence for an inverse association
between vitamin D status and risk is quite consistent. Evidence for breast cancer is intriguing, but prospective studies of
25(OH)D are sparse and conflicting. For prostate cancer, the data on circulating 25(OH)D have suggested no association or
a weak inverse association, but studies of sun exposure on prostate cancer risk are more suggestive. It is plausible that
for prostate cancer, vitamin D level, much longer before the time of diagnosis, is the most relevant exposure. Most of the
epidemiologic studies to date have examined vitamin D status in relation to risk of cancer, but emerging evidence suggests
that vitamin D may also be an important factor for cancer progression and mortality. Further study is needed to establish
when in the life span and on what stages of carcinogenesis vitamin D is relevant, the precise intakes and levels required
for benefit, and which cancer sites are most affected.
KeywordsEpidemiology-Cancer risks-Vitamin D level-Vitamin D intake-Colorectal cancer-Prostate cancer-Breast cancer-Pancreatic cancer-Ovarian cancer-Esophageal cancer-Gastric cancer-Non-Hodgkin lymphoma-25(OH)-vitamin D-UV radiation
An inadequate vitamin D supply per se does not fully explain the role of vitamin D in the prevention of cancer. The paradigm
for the vitamin D system differs from the rest of endocrinology because the enzymes that metabolize 25-hydroxyvitamin D [25(OH)D]
behave according to first-order reaction kinetics in vivo. Perpetually fluctuating 25(OH)D in the circulation forces perpetually
adaptive adjustments to the enzymes, CYP27B1 and CYP24, that respectively synthesize and catabolize 1,25-dihydroxyvitamin
D [1,25(OH)2D] in various tissues. Low levels of 1,25(OH)2D within tissues such as breast and prostate are thought to increase
propensity toward cancer. This chapter details the hypothesis that during the times when 25(OH)D levels are declining, such
as during fall and winter, concentrations of 1,25(OH)2D within tissues cannot be maintained at any cellular set point for
optimal cellular biology. If higher latitude increases the risk of cancer, then vitamin D supplementation will raise and stabilize
serum 25(OH)D concentrations, and this will lessen the adverse effects of seasonal fluctuations in serum 25(OH)D.
KeywordsLatitude-Seasonality-Enzyme kinetics-Pharmacokinetics-Feedback control-Regulation-Dosage interval-Cholecalciferol-Paracrine
Increasing evidence suggests that diet influences the initiation and progression of prostate cancer. Herein, we review associations of specific foods and nutrients with prostate cancer, summarizing important and clinically relevant emerging data on this complex topic. Foods and nutrients associated with a decreased risk of prostate cancer include lycopene, soy, cruciferous vegetables, vitamin E and selenium. Although prospective clinical trials of dietary supplements and dietary modification to prevent or control prostate cancer are underway, definitive clinical evidence is currently lacking.
Following epidemiological observations that suggested links between low vitamin D exposure and increased risk of prostate cancer, interest in clarifying a potential role of this steroid hormone in prostate cancer has grown. While the results have been mixed, epidemiologic studies have suggested that severe vitamin D deficiency may increase the risk of clinically important prostate cancer. Laboratory investigation provides clear evidence of the potential of vitamin D receptor (VDR) ligands to induce growth arrest and promote apoptosis in a variety of cancer models. Because there are hundreds of vitamin D responsive genes, multiple mechanisms for these observations have been proposed.
Prompted by clear evidence of dose-dependent antitumor effects, efforts to harness this knowledge to improve patient outcomes has focused primarily on the development of high dose calcitriol, often in combination with other anti-neoplastic agents. After encouraging phase II results, the phase III effort failed when excess deaths were reported in the experimental arm of a trial that compared calcitriol with docetaxel to prednisone with docetaxel. In addition to targeting the vitamin D receptor, the two arms of this study differed with respect to the dose, schedule, and dose intensity of the chemotherapy agent and steroids, making definitive conclusions about the potential of vitamin D receptor targeted therapy difficult. No prospective randomized studies aimed at prostate cancer prevention have been reported.
Continued efforts to target vitamin D signaling for prostate cancer prevention and treatment are needed in light of the strong preclinical evidence supporting the importance of this signaling pathway. Better understanding of the human prostate cancer’s biologic heterogeneity in vitamin D sensitivity may allow for more robust identification of ways in which vitamin D can be harnessed to help men who suffer from this disease.
Background:
Studies suggest that low levels of vitamin D may be associated with prostate cancer, and darker skin reduces the body's ability to generate vitamin D from sunshine. The impact of sunshine on racial disparities in prostate cancer incidence and mortality is unknown.
Methods:
Using the Surveillance, Epidemiology, and End Results program database, the authors calculated age-adjusted prostate cancer incidence rates among black and white men aged ≥ 45 years by race and county between 2000 and 2009 (N = 906,381 men). Similarly, county-level prostate cancer mortality rates were calculated from the National Vital Statistics System (N = 288,874). These data were linked with the average monthly solar ultraviolet (UV) radiation index by county and data regarding health, wellness, and demographics. Multivariable regression analysis was used to assess whether increases in the UV index (in deciles) moderated the association between black race and the incidence and mortality of prostate cancer.
Results:
Compared with counties in the lowest UV index decile, prostate cancer incidence rates for white and black men were lower in counties with a higher UV index (all Ps ≤ 0.051). Incidence rates were higher for black men versus white men, but the difference by race was less for counties in the fourth to fifth UV index deciles versus those in the first decile (Ps ≤ 0.02). Mortality rates also were found to decrease with increasing UV index for white men (Ps ≤ 0.003), but increase for black men, and an unexplained increase in racial differences in mortality rates was observed with an increasing UV index.
Conclusions:
Racial disparities in the incidence of prostate cancer were larger in some areas with less sunshine. Additional research should confirm the findings of the current study and assess whether optimizing vitamin D levels among black men can reduce disparities.
Objective:
Black and Hispanic individuals synthesize less vitamin D per unit of sun exposure than white individuals. The relationship between UV radiation and vitamin D insufficiency in minorities has not been well explored.
Design:
Prospective cohort study.
Setting:
Using the National Health and Nutrition Examination Survey, we obtained serum vitamin D levels for non-Hispanic Whites, Hispanics and non-Hispanic Blacks aged ≥18 years from 2000-2006. We linked these data with the average monthly solar UV index by census tract and data on sun exposure, vitamin D supplementation, health and demographics. We used multivariable regression analyses to assess vitamin D deficiency (<15 ng/ml) and insufficiency (<20 ng/ml) in January (when the UV index was lowest) by race/ethnicity and geography.
Subjects:
Adults (n 14,319) aged ≥18 years.
Results:
A 1-point increase in the UV index was associated with a 0·51 ng/ml increase in vitamin D (95% CI 0·35, 0·67 ng/ml; P<0·001). Non-Hispanic Black race and Hispanic ethnicity were associated with a 7·47 and 3·41 ng/ml decrease in vitamin D, respectively (both P<0·001). In January, an estimated 65·4% of non-Hispanic Blacks were deficient in vitamin D, compared with 28·9% of Hispanics and 14·0% of non-Hispanic Whites. An estimated 84·2% of non-Hispanic Blacks were insufficient in vitamin D v. 56·3% of Hispanics and 34·8% of non-Hispanic Whites. More non-Hispanic Blacks were estimated to be deficient in vitamin D in January in the highest UV index quartile than were non-Hispanic Whites in the lowest UV index quartile (60·2% v. 25·7%).
Conclusions:
Wintertime vitamin D insufficiency is pervasive among minority populations, and not uncommon among non-Hispanic Whites.
Benign prostatic hyperplasia (BPH) is a more common form of lower urinary tract symptoms (LUTS). BPH is due to the excessive growth of both stromal and epithelial cells of the prostate. Fifty percent of men over the age of 50 will have this disease, along with the probability that 90% of men at the age of 80 will have an enlarged prostate. The prevalence of vitamin D deficiency in the male urological population may represent a connection between BPH and vitamin D.
This review is geared to provide the most relevant data on the correlation between vitamin D and BPH. A comprehensive review was conducted on all studies on the specific topic and compiled into a complete article.
Data suggests that vitamin D has an inhibitory effect on the RhoA/ROCK pathway, along with cyclooxygenase-2 expression and prostaglandin E2 production in BPH stromal cells. Increasing intake of vitamin D from diet and supplements has shown a correlation with decreased BPH prevalence. Vitamin D analogues of up to 6000 IU/day have shown to decrease prostate volume in BPH patients. Pre-clinical trials have shown vitamin D to not only decrease BPH cell and prostate cell proliferation alone, but also when induced by known growth promoting molecules such as IL-8, Des (1-3) IGF-1, testosterone and dihydrotestosterone. Among all the studies there has not been any side effects or negative implications with increased vitamin D intake.
The impact of vitamin D on prostate volume and BPH has shown promising results, thus proposing further studies on vitamin D and BPH be conducted.
PurposeStudies found an association between decreased 25-OH vitamin D blood level and prostate cancer progression. Vitamin D supplementation is controversial and dosage recommendations inconsistent. This study identified factors associated with 25-OH vitamin D levels and whether vitamin D supplementation with 800 IU/day raised vitamin D levels in prostate cancer patients receiving androgen deprivation therapy (ADT).Data sourcesWe recruited 108 men treated with ADT for ≥9 months from eight cancer and urology practices. Sections of the NHANES 2005–2006 questionnaire and Canadian Fitness Survey were completed identifying age, ethnicity, length of ADT use, calcium supplementation ≥1000 IU mg/day, body mass index, exercise, alcohol and tobacco use, and vitamin D supplementation ≥800 IU/daily. Blood was collected for 25-OH vitamin D analysis.Conclusions
The majority of men (66%) had blood levels of 25-OH vitamin D <32 ng/mL. Regression analysis showed vitamin D supplementation (β = 6.556, CI 1.463, 11.650; p = .012) and African American ethnicity (β = −7.816, CI −12.996, −2.635; p = .003) is associated with 25-OH vitamin D level after controlling age and tobacco use.Practice implicationsFindings support current recommendations for supplementation with ≥800 IU vitamin D/day for men receiving ADT. Nurse practitioners caring for prostate cancer patients receiving ADT should include vitamin D monitoring and supplementation.
The hypothesis that vitamin D deficiency increases the risk of clinical prostate cancer has stimulated an extensive body of research. Ecologic studies have shown that mortality rates from prostate cancer are inversely correlated with levels of ultraviolet radiation, the principal source of vitamin D. Human prostate cells express receptors for 1,25-Dihydroxyvitamin D which exerts pleitropic anticancer effects on these cells in vitro and in animal models. Moreover, normal prostate cells synthesize 1,25-Dihydroxyvitamin D from circulating levels of 25-OHD, whose levels are dependent on exposure to ultraviolet light.
Analytic epidemiologic studies of vitamin D and prostate cancer have focused on polymorphisms in the vitamin D receptor (VDR), on serum vitamin D levels, and on solar exposure. A role for VDR polymorphisms in prostate cancer risk and progression is established. Prospective studies of serum 25(OH)D do not support a protective role for higher levels of 25(OH)D on prostate cancer risk overall, but a role for vitamin D deficiency is supported by several studies. Conversely, a growing body of evidence implicates low levels of 25-OHD with an increased risk of fatal prostate cancer. The results of most epidemiologic studies of sunlight exposure are consistent with a protective effect of exposure to ultraviolet radiation. The discrepancy between the results of studies of solar exposure and studies of serum 25-OHD may be related to methodological differences and to uncertainties regarding the critical period for vitamin D exposure. Additionally, both high dietary intake of calcium and high levels of calcium in serum are positively associated with prostate cancer risk. The relationship between serum 25(OH)D levels and risk of prostate cancer may differ by calcium intake.
There is substantial interest in whether vitamin D signaling plays a role in reducing risk for prostate cancer and in its use as a therapeutic target in prostate cancer. Vitamin D is synthesized in the skin through a UVB-mediated reaction and subsequently hydroxylated to form 1,25-dihydroxyvitamin D3, the ligand for the vitamin D receptor (VDR), a hormone activated transcription factor. Epidemiological studies correlating prostate cancer risk with reduced exposure to sunlight have suggested that vitamin D reduces risk, but the conclusions from studies of vitamin D metabolites have been variable. Similarly, despite promising results in preclinical studies, attempts to target VDR clinically have been less successful. This chapter reviews what is known regarding the actions of VDR in prostate and in prostate cancers and the evidence for activation of VDR as a strategy to reduce risk and/or treat prostate cancer. The chapter summarizes the evidence for a role in reducing prostate cancer risk and discusses the possibility that aberrant vitamin D metabolism contributes to the difficulties in correlating serum vitamin D metabolites with the level of VDR activation in cells. Also discussed are other mechanisms for resistance to the beneficial actions of VDR and strategies to optimize VDR activity.
Vitamin D is a steroid hormone that has traditionally been recognized for its role in calcium metabolism and skeletal homeostasis. However, there is growing recognition of its immunomodulatory and anti-tumorigenic effects both in vivo and in vitro. Vitamin D and its receptor form a nuclear receptor-ligand complex that exerts anti-proliferative effects via downstream intracellular signaling. While basic science data for the role of vitamin D in both treating and preventing malignancy have been promising, clinical and epidemiologic data in cancer patients have been mixed. In this paper, we will briefly review the basic science and clinical data for the role of vitamin D in cancer prevention and treatment for the four most common malignancies: breast, prostate, colorectal, and lung cancer.
Prostate cancer patients treated with androgen deprivation therapy (ADT) eventually develop castrate-resistant prostate cancer (CRPC). 1,25-dihydroxyvitamin D3 (1,25D3), is a potential adjuvant therapy that confers anti-proliferative and pro-differentiation effects in vitro, but has had mixed results in clinical trials. The impact of the tumor microenvironment on 1,25D3 therapy in CRPC patients has not been assessed. Transforming growth factor-β (TGF-β), which is associated with the development of tumorigenic “reactive stroma” in prostate cancer, induced VDR expression in the human WPMY-1 prostate stromal cell line. Similarly, TGF-β enhanced 1,25D3-induced upregulation of CYP24A1, which metabolizes of 1,25D3 and thereby limits VDR activity. Ablation of Hic-5, a TGF-β-inducible nuclear receptor co-regulator, inhibited basal VDR expression, 1,25D3-induced CYP24A1 expression and metabolism of 1,25D3 and TGF-β-enhanced CYP24A1 expression. Luciferase reporter mapping of the CYP24A1 promoter identified a Hic-5-responsive sequence 392-451 bp upstream of the transcription start site (TSS). Ectopic expression of Hic-5 sensitized LNCaP prostate tumor cells to growth-inhibitory effects of 1,25D3 at a lower concentration by a pathway independent of CYP24A1. The sensitivity of Hic-5-expressing LNCaP cells to 1,25D3-induced growth inhibition was accentuated in co-culture with Hic-5-ablated WPMY-1 cells. Therefore, my findings suggest that the search for mechanisms to sensitize prostate cancer cells to the anti-proliferative effects of VDR ligands needs to account for the impact of VDR activity in the tumor microenvironment. By acting as a co-regulator with distinct effects on VDR transactivation in prostate cancer and stromal cells, Hic-5 could exert diverse effects on adjuvant therapy designed to exploit VDR activity in prostate cancer.
Objectives:
Preventable risk factors for prostate cancer are poorly understood; sun exposure is a possible protective factor. The goal of this study was to investigate prostate cancer risk in outdoor workers, a population with high sun exposure.
Methods:
Prostate cancer cases and controls from a large study (conducted between 1994 and 1997) were used for this analysis. A job exposure matrix (JEM) was used to assign solar ultraviolet radiation (UVR) at work as moderate (2 to <6 hours outside/day) or high (≥6 hours). Average daily satellite UV-B measures were linked to the latitude/longitude of the residences of each participant. Several other exposure metrics were also examined, including ever/never exposed and standard erythemal dose by years (SED×years). Logistic regression was used to evaluate the association between solar UVR exposure and the odds of prostate cancer.
Results:
A total of 1638 cases and 1697 controls were included. Men of Indian and Asian descent had reduced odds of prostate cancer (ORs 0.17 (0.08 to 0.35) and 0.25 (0.15 to 0.41), respectively) compared with Caucasian men, as did single men (OR 0.76 (0.58 to 0.98)) compared with married men. Overall, no statistically significant associations were observed between sun exposure and prostate cancer with 1 exception. In the satellite-enhanced JEM that considered exposure in high category jobs only, prostate cancer odds in the highest quartile of cumulative exposure was decreased compared with unexposed men (OR 0.68 (0.51 to 0.92)).
Conclusions:
This study found limited evidence for an association with prostate cancer, with the exception of 1 statistically significant finding of a decreased risk among workers with the longest term and highest sun exposure.
Emerging evidence suggests that a diagnosis of cutaneous melanoma (CM) may be associated with prostate cancer (PC) incidence. We examined if the incidence of CM was associated with an increased subsequent risk of PC. We used data from the New South Wales Cancer Registry for all CM and PC cases diagnosed between January 1972 and December 2008. We calculated the age standardized incidence ratio (SIR) and 95% confidence intervals (95% CI) for PC incidence following a CM diagnosis, applying age- and calendar- specific rates to the appropriate person years at risk. We determined rate ratio (RR) and 95% CI of PC incidence according to specified socio-demographic categories and disease related characteristics, using a negative binomial model. There were 143,594 men diagnosed with PC or CM in the study period and of these 101,198 and 42,396 were diagnosed with PC and CM, respectively, as first primary cancers. Risk of PC incidence increased following CM diagnosis (n = 2,114; SIR = 1.25; 95% CI:1.20.8-1.31: p < 0.0001), with the increased risk apparent in men diagnosed with localised CM (n = 1,862;SIR = 1.26; 95% CI:1.20-1.32). CM diagnosis increased the subsequent risk of PC incidence. This raises the potential for future PC risk to be discussed with newly diagnosed males with CM.
Evidence supports the role of vitamin D in various conditions of development and ageing. Serum 25-hydroxyvitamin D (25(OH)D) is the best indicator for current vitamin D status. However, the cost of its measurement can be prohibitive in epidemiological research. We developed and validated multivariable regression models that quantified the relationships between vitamin D determinants, measured through an in-person interview, and serum 25(OH)D concentrations. A total of 200 controls participating in a population-based case–control study in Montreal, Canada, provided a blood specimen and completed an in-person interview on socio-demographic, reproductive, medical and lifestyle characteristics and personal attributes. Serum 25(OH)D concentrations were quantified by liquid chromatography–tandem MS. Multivariable least squares regression was used to build models that predict 25(OH)D concentrations from interview responses. We assessed high-order effects, performed sensitivity analysis using the lasso method and conducted cross-validation of the prediction models. Prediction models were built for users and non-users of vitamin D supplements separately. Among users, alcohol intake, outdoor time, sun protection, dose of supplement use, menopausal status and recent vacation were predictive of 25(OH)D concentrations. Among non-users, BMI, sun sensitivity, season and recent vacation were predictive of 25(OH)D concentrations. In cross-validation, 46–47 % of the variation in 25(OH)D concentrations were explained by these predictors. In the absence of 25(OH)D measures, our study supports that predicted 25(OH)D scores may be used to assign exposure in epidemiological studies that examine vitamin D exposure.
Survivors of invasive melanoma have an increased risk of developing second primary cancers; however, similar risks associated with in situ melanoma have not been established. We evaluated 39,872 survivors of first primary in situ melanoma diagnosed from 1982 through 2012 in Queensland, Australia. Relative risk of second nonmelanoma primary cancers was estimated from standardized incidence ratios with 95% confidence intervals. A total of 4,823 (12%) in situ melanoma survivors developed a second primary cancer. A small increased risk (6%) compared with the general population was found. In those younger than 50 years, risk was increased by 14% for all cancers combined. In situ melanoma survivors had significantly increased risks of developing lip, thyroid, pancreatic, and brain cancers and decreased risks of head and neck, and lung cancers. Male in situ melanoma survivors had a significantly increased risk of prostate cancer; female survivors had an increased risk of thyroid cancer and lymphoid leukemia. Findings indicate that in situ melanoma may predict the diagnosis of certain second primary cancers. This altered risk may be due to biological, behavioral, or genetic factors or increased medical surveillance, and it requires further investigation, particularly among people younger than 50 years.
The mitochondrial enzyme 25-hydroxyvitamin D3-1a-hydroxylase (1a-hydroxylase) plays an important role in calcium homeostasis by catalyzing synthesis of the active form of vitamin D, 1,25-dihydroxyvi- tamin D3, in the kidney. However, enzyme activity assays indicate that 1a-hydroxylase is also expressed in a variety of extrarenal tis- sues; recent cloning of cDNAs for 1a-hydroxylase in different species suggests that a similar gene product is found at both renal and ex- trarenal sites. Using specific complementary ribonucleic acid probes and antisera to 1a-hydroxylase, we have previously reported the distribution of messenger ribonucleic acid and protein for the enzyme along the mouse and human nephron. Here we describe further im- munohistochemical and Western blot analyses that detail for the first time the extrarenal distribution of 1a-hydroxylase in both normal and diseased tissues. Specific staining for 1a-hydroxylase was detected in skin (basal keratinocytes, hair follicles), lymph nodes (granulomata), colon (epithelial cells and parasympathetic ganglia), pancreas (islets), adrenal medulla, brain (cerebellum and cerebral cortex), and placenta (decidual and trophoblastic cells). Further studies using psoriatic skin highlighted overexpression of 1a-hydroxylase throughout the dys- regulated stratum spinosum. Increased expression of skin 1a-hydrox- ylase was also associated with sarcoidosis. In lymph nodes and skin from these patients 1a-hydroxylase expression was observed in cells positive for the surface antigen CD68 (macrophages). The data pre- sented here confirm the presence of protein for 1a-hydroxylase in several extrarenal tissues, such as skin, placenta, and lymph nodes. The function of this enzyme at novel extrarenal sites, such as adrenal medulla, brain, pancreas, and colon, remains to be determined. How- ever, the discrete patterns of staining in these tissues emphasizes a possible role for 1a-hydroxylase as an intracrine modulator of vitamin D function in peripheral tissues. (J Clin Endocrinol Metab 86: 888 - 894, 2001)
Prostate cancer is a major cause of cancer death among males, yet little is known about its etiology. We hypothesize that Vitamin (Hormone) D deficiency may underlie the major risks for prostate cancer, including age, Black race, and northern latitudes. These factors all are associated with decreased synthesis of Vitamin D. Mortality rates from prostate cancer in the U.S. are inversely correlated with ultraviolet radiation, the principal source of Vitamin D. This hypothesis is consistent with known antitumor properties of Vitamin D, and may suggest new avenues for research in prostate cancer.
Epidemiological and laboratory data support a role for vitamin D in the growth and differentiation of human prostatic cells. These findings prompted us to ask whether prostatic cells could convert 25-hydroxyvitamin D3 (25-OH-D3), the major circulating metabolite of vitamin D3, to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the hormonally active metabolite, in a manner similar to cultured human keratinocytes. Therefore, we investigated three well-characterized human prostate cancer cell lines, LNCaP, DU 145, and PC-3; two primary cultures of cells derived from noncancerous human prostates (one normal and one benign prostatic hyperplasia); and primary cultures of normal human keratinocytes for their ability to synthesize 1,25(OH)2D3. Assays were performed in the presence of 25-OH-D3 as the enzyme substrate and 1,2-dianilinoethane, an antioxidant and free radical scavenger, and in the presence and absence of clotrimazole, a cytochrome P450 inhibitor. DU 145 and PC-3 cells produced 0.31 +/- 0.06 and 0.07 +/- 0.01 pmol of 1,25(OH)2D3/mg protein/h, respectively. No measurable 1,25(OH)2D3 was detected in LNCaP cells. The normal and benign prostatic hyperplasia primary cultures and keratinocyte cultures produced 3.08 +/- 1.56, 1.05 +/- 0.31, and 2.1 +/- 0.1 pmol of 1,25(OH)2D3/mg protein/h, respectively, using a calf thymus receptor binding assay to measure 1,25(OH)2D3 in the presence of 1,2-dianilinoethane. The identity of the analyte as 1,25(OH)2D3 was supported by high performance liquid chromatography using [3H]25-OH-D3 as the enzyme substrate and a solvent system that is specific for 1,25(OH)2D3. The production of 1,25(OH)2D3 in the prostate cancer cell lines and in the primary cultures was completely inhibited in the presence of clotrimazole. This report demonstrates that two of three human prostate cancer cell lines, as well as primary cultures of noncancerous prostatic cells, possess 1alpha-hydroxylase activity and can synthesize 1,25(OH)2D3 from 25-OH-D3. Together with recent data indicating that 1,25(OH)2D3 inhibits the invasiveness of human prostate cancer cells (G. G. Schwartz et al., Cancer Epidemiol. Biomark. Prev., 6: 727-732, 1997), these data suggest a potential role for 25-OH-D3 in the chemoprevention of invasive prostate cancer.
Exposure to ultraviolet radiation may reduce prostate cancer risk, suggesting that polymorphism in genes that mediate host pigmentation will be associated with susceptibility to this cancer. We studied 210 prostate cancer cases and 155 controls to determine whether vitamin D receptor (VDR, Taql and Fokl variants), tyrosinase (TYR, codon 192 variant) and melanocortin-1 receptor (MC1R, Arg151Cys, Arg160Trp, Val92Met, Asp294His and Asp84Glu variants) genotypes are associated with risk. UV exposure was determined using a questionnaire. MC1R Arg(160)/Arg(160) homozygotes were at increased risk (P = 0.027, odds ratio = 1.94) while TYR A2/A2 homozygotes were at reduced risk of prostate cancer (P = 0.033, odds ratio = 0.48). These associations remained significant after correction for UV-exposure. Stratification of cases and controls by quartiles of exposure, showed that the protective effect of TYR A1A2 (P = 0.006, odds ratio 0.075) and A2A2 (P = 0.003, odds ratio 0.055) was particularly strong in subjects who had received the greatest exposure. Our data show for the first time, that allelism in genes linked with skin pigment synthesis is associated with prostate cancer risk possibly because it mediates the protective effects of UV. Importantly, susceptibility is associated with an interaction between host predisposition and exposure.
To explore whether mortality from female breast, ovarian, colon, and prostate cancer were negatively associated with exposure to sunlight.
A death certificate based case-control study of mortality was conducted into five cancers: female breast, ovarian, colon, prostate, and non-melanoma skin cancer (as a positive control) to examine associations with residential and occupational exposure to sunlight. Cases were all deaths from these cancers between 1984 and 1995 in 24 states of the United States. Controls, which were age frequency matched to a series of cases, excluded deaths from cancer and certain neurological diseases. Multiple logistic regression was used in a model that included age, sex, race, residential exposure to sunlight (based on region), and socioeconomic status, occupational exposure to sunlight, and physical activity (the last three based on usual occupation).
Residential exposure to sunlight was negatively and significantly associated with mortality from female breast, ovarian, prostate, and colon cancer. Only female breast and colon cancer, however, also showed significant negative associations with jobs with the highest occupational exposure to sunlight (odds ratio (OR) 0.82 (95% confidence interval (95% CI) 0.70 to 0.97) for female breast cancer; OR 0.90 (95% CI 0.86 to 0.94) for colon cancer). For both cancers, the negative association with occupational sunlight was greatest in the geographical region of highest exposure to sunlight and was independent of physical activity on the job. Non-melanoma skin cancer, as expected, was positively associated with both residential and occupational sunlight.
In this exploratory study, unlike mortality from non-melanoma skin cancer, mortality from female breast cancer and colon cancer were negatively associated with both residential and occupational sunlight.
We discuss the move from reporting damaging UV radiation in terms of UVB to the now widely accepted erythemally weighted UV radiation (UV(Ery)) and the UV Index (UVI). The relationship between these quantities is given: to a good approximation, it is found that UVB(280-315 nm)= 7.55 [times] UV(Ery). In terms of the UV Index, the estimated UVB(280-315 nm) in units of W m(-2) is 18.9 times the UVI. These approximations generally hold to within approximately 10% for all solar zenith angles (sza) less than 70 degrees. For most practical purposes, this is a sufficient range, since for larger sza, the intensity of UVB is less than 10% of that for overhead sun conditions. The simple relationship above is verified using spectral measurements. However, tables are provided to enable calculation of the conversion with greater accuracy under such conditions. Similar model calculations are provided to estimate UVB(280-320 nm). Correction tables to convert erythemally weighted UV to other biological weightings are also presented.
Striking geographic variation in prostate cancer death rates have been observed in the United States since at least the 1950s; reasons for these variations are unknown. Here we examine the association between geographic variations in prostate cancer mortality and regional variations in access to medical care, as reflected by the incidence of late-stage disease, prostate-specific antigen (PSA) utilization, and residence in rural counties.
We analyzed mortality data from the National Center for Health Statistics, 1996 to 2000, and incidence data from 30 population-based central cancer registries from the North American Association of Central Cancer Registries, 1995 to 2000. Ecological data on the rate of PSA screening by registry area were obtained from the 2001 Behavioral Risk Factor Surveillance System. Counties were grouped into metro and nonmetro areas according to Beale codes from the Department of Agriculture. Pearson correlation analyses were used to examine associations.
Significant correlations were observed between the incidence of late-stage prostate cancer and death rates for Whites (r = 0.38, P = 0.04) and Blacks (r = 0.53, P = 0.03). The variation in late-stage disease corresponded to about 14% of the variation in prostate cancer death rates in White men and 28% in Black men. PSA screening rate was positively associated with total prostate cancer incidence (r = 0.42, P = 0.02) but inversely associated with the incidence of late-stage disease (r = -0.58, P = 0.009) among White men. Nonmetro counties generally had higher death rates and incidence of late-stage disease and lower prevalence of PSA screening (53%) than metro areas (58%), despite lower overall incidence rates.
These ecological data suggest that 10% to 30% of the geographic variation in mortality rates may relate to variations in access to medical care.
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.
Vitamin D has potent anticancer properties, especially against digestive-system cancers. Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure. Here, we considered multiple determinants of vitamin D exposure (dietary and supplementary vitamin D, skin pigmentation, adiposity, geographic residence, and leisure-time physical activity-to estimate sunlight exposure) in relation to cancer risk in the Health Professionals Follow-Up Study.
Among 1095 men of this cohort, we quantified the relation of these six determinants to plasma 25-hydroxy-vitamin D [25(OH)D] level by use of a multiple linear regression model. We used results from the model to compute a predicted 25(OH)D level for each of 47,800 men in the cohort based on these characteristics. We then prospectively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models.
From 1986 through January 31, 2000, we documented 4286 incident cancers (excluding organ-confined prostate cancer and nonmelanoma skin cancer) and 2025 deaths from cancer. From multivariable models, an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17% reduction in total cancer incidence (multivariable relative risk [RR] = 0.83, 95% confidence interval [CI] = 0.74 to 0.92), a 29% reduction in total cancer mortality (RR = 0.71, 95% CI = 0.60 to 0.83), and a 45% reduction in digestive-system cancer mortality (RR = 0.55, 95% CI = 0.41 to 0.74). The absolute annual rate of total cancer was 758 per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men for the top decile; these respective rates were 326 per 100,000 and 277 per 100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for digestive-system cancer mortality. Results were similar when we controlled further for body mass index or physical activity level.
Low levels of vitamin D may be associated with increased cancer incidence and mortality in men, particularly for digestive-system cancers. The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day.
Background. Prostate cancer is the most prevalent nonskin cancer among men in the United States and is the second leading cause of cancer deaths in men, The cause of prostate cancer remains obscure. Recently it was hypothesized that low levels of vitamin D, a hormone with potent antitumor properties, may increase the risk for clinical prostate cancer.
Mortality rates from prostate cancer are significantly higher among African Americans than Caucasian Americans and are inversely related to the availability of ultraviolet (UV) radiation. These findings support the hypothesis, originally proposed in 1990, that prostate cancer may be caused by vitamin D deficiency. In 1992, specific receptors for 1,25-dihydroxyvitamin D [1,25(OH)2D] were demonstrated in human prostate cells. We and others have shown that 1,25(OH)2D exerts prodifferentiating, antiproliferative, and antimetastatic effects on these cells. In 1998 we demonstrated that normal prostate cells express 1α-hydroxylase and synthesize their own 1,25(OH)2D. Thus, 1,25(OH)2D is an autocrine hormone in the prostate. The consensus emerging from analytic epidemiologic studies is that low levels of UV radiation/vitamin D are indeed associated with an increased risk of prostate cancer in individual men. The evolution of our understanding of the role of vitamin D in the epidemiology of prostate cancer parallels our understanding of the role of vitamin D in the epidemiology of rickets. In both diseases, ecologic observations about UV radiation preceded experimental observations and were subsequently validated by them.
This research is grounded in notions of differential economic restructuring across employment sectors and geographic space, as well as migration selectivity by occupation. A series of unconstrained competing-destinations models were employed to analyze the response by workers in thirteen occupational categories to sectoral employment change, average wages, and distance. As was hypothesized, workers in occupations that require high levels of education and skills are more responsive, in terms of migration, to economic opportunities in alternative labor-market areas. However, the results do not support the hypothesis that highly educated and skilled workers migrate longer distances. Further investigation suggests that opportunities for highly educated and skilled workers may be clustering in relatively few areas that are in relatively close proximity.
Background:
Prostate cancer is the most prevalent nonskin cancer among men in the United States and is the second leading cause of cancer deaths in men. The cause of prostate cancer remains obscure. Recently it was hypothesized that low levels of vitamin D, a hormone with potent antitumor properties, may increase the risk for clinical prostate cancer.
Methods:
Because the major source of vitamin D is casual exposure to ultraviolet (UV) radiation, the authors examined the geographic distributions of UV radiation and prostate cancer mortality in 3073 counties of the contiguous United States using linear regression and trend surface analyses.
Results:
The geographic distributions of UV radiation and prostate cancer mortality are correlated inversely (P < 0.0001). Prostate cancer mortality exhibits a significant north-south trend, with lower rates in the South. These geographic patterns are not readily explicable by other known risk factors for prostate cancer.
Conclusions:
These data lend support to the hypothesis that UV radiation may protect against clinical prostate cancer. Viewed in conjunction with other recent data, including those demonstrating a differentiating effect of vitamin D on human prostate cancer cells, these findings suggest that vitamin D may have an important role in the natural history of prostate cancer.
Epidemiologic and geographic research on cancer relationships has generally ignored the geographic scales at which the studies are conducted. Scales effects include the effects of the study population and level of data aggregation on the analysis. It is argued that the analysis of scale effects are critical to the interpretation of research results and to the synthesis of results obtained at different scales. The consideration of variance and its relation to scale is essential in understanding both the simple and the complex cancer relationships likely to appear in multivariate models. Examples of several scales are presented, including Wisconsin county-level data.
Clear, up-to-date coverage of methods for analyzing geographical information in a GIS context. Geographic Information Analysis, Second Edition is fully updated to keep pace with the most recent developments of spatial analysis in a geographic information systems (GIS) environment. Still focusing on the universal aspects of this science, this revised edition includes new coverage on geovisualization and mapping as well as recent developments using local statistics. Building on the fundamentals, this book explores such key concepts as spatial processes, point patterns, and autocorrelation in area data, as well as in continuous fields. Also addressed are methods for combining maps and performing computationally intensive analysis. New chapters tackle mapping, geovisualization, and local statistics, including the Moran Scatterplot and Geographically Weighted Regression (GWR). An appendix provides a primer on linear algebra using matrices. Complete with chapter objectives, summaries, "thought exercises," explanatory diagrams, and a chapter-by-chapter bibliography, Geographic Information Analysis is a practical book for students, as well as a valuable resource for researchers and professionals in the industry.
That sunlight leads to skin cancer has been generally accepted for nearly a century. Physical data are, for the first time, available which support this hypothesis. The authors have found that a simple power relationship can be used to describe the data and that the form of this power function suggests that the risk of nonmelanoma skin cancer is related to cumulative lifetime ultraviolet (UV) exposure and that the risk of melanoma skin cancer is related to annual UV exposure. The authors emphasize that skin cancer risk also depends on location-specific demographic variables other than ultraviolet radiation.
Prostate cancer is the most prevalent nonskin cancer among men in the United States and is the second leading cause of cancer deaths in men. The cause of prostate cancer remains obscure. Recently it was hypothesized that low levels of vitamin D, a hormone with potent antitumor properties, may increase the risk for clinical prostate cancer.
Because the major source of vitamin D is casual exposure to ultraviolet (UV) radiation, the authors examined the geographic distributions of UV radiation and prostate cancer mortality in 3073 counties of the contiguous United States using linear regression and trend surface analyses.
The geographic distributions of UV radiation and prostate cancer mortality are correlated inversely (P < 0.0001). Prostate cancer mortality exhibits a significant north-south trend, with lower rates in the South. These geographic patterns are not readily explicable by other known risk factors for prostate cancer.
These data lend support to the hypothesis that UV radiation may protect against clinical prostate cancer. Viewed in conjunction with other recent data, including those demonstrating a differentiating effect of vitamin D on human prostate cancer cells, these findings suggest that vitamin D may have an important role in the natural history of prostate cancer.
The potential protective effect of selenium status on the risk of developing cancer has been examined in animal and epidemiologic studies. This ecological study investigated the association between U.S. county forage selenium status and site- and sex-specific county cancer mortality rates (1950-1969) using weighted least squares regression. Consistent, significant (p less than .01) inverse associations were observed for cancers of the lung, rectum, bladder, esophagus, and cervix in a model limited to rural counties and for cancers of the lung, breast, rectum, bladder, esophagus, and corpus uteri in a model of all counties. No consistent significant positive associations were observed in the rural county models. This remarkable degree of consistency for the inverse associations strengthens the likelihood of a causal relationship between low selenium status and an increased risk of cancer mortality.
Cutaneous vitamin D3 synthesis and release into the circulation is promoted by skin exposure to ultraviolet B radiation (UVB, spectrum 290 to 320 nm). To determine the relation between UVB energy level and cutaneous vitamin D synthetic response, we delivered graded increases of UVB suberythemic radiant energy (3 to 27 millijoules/cm2 [mJ/cm2]) to 32 untanned young white subjects with skin type III (Fitzpatrick-Pathak classification). Serum vitamin D3 was determined 1 hour before (basal value) and 24 hours after a single whole body exposure to UVB in a phototherapy unit. The basal vitamin D3 concentration was similar in all individuals (mean +/- SEM for whole group, 1.6 +/- 0.2 ng/ml). UVB irradiances were followed by proportional rises in serum vitamin D3 (at 27 mJ/cm2, 14.3 +/- 3.7 ng/ml), and the overall correlation between UVB radiation and consequent serum vitamin D3 response (r = 0.81; p less than 0.02) was best described by an exponential function. The minimal UVB radiation level that produced a significant increase in serum vitamin D3 was 18 mJ/cm2, a value similar to the lowest solar broadband UVB irradiance that generates previtamin D3 in vitro from the precursor 7-dehydrocholesterol (20 mJ/cm2). Because in the northern United States winter UVB irradiance does not generally reach this threshold level, we conclude that individuals living at extreme northern (or southern) latitudes may have higher dependence on body stores and dietary supply to meet their vitamin D requirements during winter.
Sunlight has long been recognized as a major provider of vitamin D for humans; radiation in the UVB (290-315 nm) portion of the solar spectrum photolyzes 7-dehydrocholesterol in the skin to previtamin D3, which, in turn, is converted by a thermal process to vitamin D3. Latitude and season affect both the quantity and quality of solar radiation reaching the earth's surface, especially in the UVB region of the spectrum, but little is known about how these influence the ability of sunlight to synthesize vitamin D3 in skin. A model has been developed to evaluate the effect of seasonal and latitudinal changes on the potential of sunlight to initiate cutaneous production of vitamin D3. Human skin or [3 alpha-3H]7-dehydrocholesterol exposed to sunlight on cloudless days in Boston (42.2 degrees N) from November through February produced no previtamin D3. In Edmonton (52 degrees N) this ineffective winter period extended from October through March. Further south (34 degrees N and 18 degrees N), sunlight effectively photoconverted 7-dehydrocholesterol to previtamin D3 in the middle of winter. These results quantify the dramatic influence of changes in solar UVB radiation on cutaneous vitamin D3 synthesis and indicate the latitudinal increase in the length of the "vitamin D winter" during which dietary supplementation of the vitamin may be advisable.
THE antiricketic sterols are both assimilated from the diet and
endogenously produced by ultraviolet irradiation of cutaneous
7-dehydrocholesterol1-3. Before the modern practice of
supplementing foods with irradiated ergosterol (ergocalciferol, vitamin
D2), deficiency states were frequently observed in subjects
whose dark skin colour and/or minimal exposure to sunlight minimized the
natural endogenous production of cholecalciferol (vitamin
D3)4. It has been generally accepted that casual
exposure to sunlight and average diets provide enough antiricketic
sterol to prevent osteomalacia in the adult (American Academy of
Pediatrics, 1963). Infants, however, are recognized to require vitamin D
supplementation, for their maternally derived stores wane at a time when
their natural foods are a poor source and their exposure to ultraviolet
radiation unreliable. Supplementation of foods with vitamin
D2 has thus become a widespread and successful practice which
has subsequently undergone quantitative revisions in several countries.
Prostate cancer mortality among whites and nonwhites in U.S. counties are analyzed for geographic effects. To better visualize geographical effects, the data are smoothed with a bivariate smoother using age-specific rates. Among nonwhites, an important explanatory variable is the proportion of African Americans. A relationship between the mortality rate and this variable is derived, and the data are adjusted for this variable using this relationship. When the rates are adjusted for age only, among whites there is a north-south gradient: rates are higher in the north, lower in the south. Among nonwhites, the gradient runs east to west: higher in the east, lower in the west. The latter gradient disappears when the rates are further adjusted for African Americans. The study reveals the importance of both smoothing the data to visualize patterns in geography and adjusting the data for an important variable to identify underlying patterns. The additional adjustment permits the identification of other areas of the country with elevated or depressed rates.
We determined the quantitative relationships between graded oral dosing with vitamin D3, 25(OH)D3, and 1,25(OH)2D3 for short treatment periods and changes in circulating levels of these substances. The subjects were 116 healthy men (mean age, 28 +/- 4 years, with usual milk consumption of < or = 0.47 l/day and mean serum 25(OH)D of 67 +/- 25 nmol/l). They were distributed among nine open-label treatment groups: vitamin D3 (25, 250 or 1250 micrograms/day for 8 weeks), 25(OH)D3 (10, 20 or 50 micrograms/day for 4 weeks) and 1,25(OH)2D3 (0.5, 1.0 or 1.0 microgram/day for 2 weeks). All treatment occurred between January 3 and April 3. We measured fasting serum, calcium, parathyroid hormone, vitamin D3, 25(OH)D and 1,25(OH)2D immediately before and after treatment. In the three groups treated with vitamin D3, mean values for circulating vitamin D3 increased by 13, 137 and 883 nmol/l and serum 25(OH)D increased by 29, 146 and 643 nmol/l for the three dosage groups, respectively. Treatment with 25(OH)D3 increased circulating 25(OH)D by 40, 76 and 206 nmol/l, respectively. Neither compound changed serum 1,25(OH)2D levels. However, treatment with 1,25(OH)2D3 increased circulating 1,25(OH)2D by 10, 46 and 60 pmol/l, respectively. Slopes calculated from these data allow the following estimates of mean treatment effects for typical dosage units in healthy 70-kg adults: an 8-week course of vitamin D3 at 10 micrograms/day (400 IU/day) would raise serum vitamin D by 9 nmol/l and serum 25(OH)D by 11 nmol/l; a 4-week course of 25(OH)D3 at 20 micrograms/day would raise serum 25(OH)D by 94 nmol/l; and a 2-week course of 1,25(OH)2D3 at 0.5 microgram/day would raise serum 1,25(OH)2D by 17 pmol/l.
The hormonal metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] is known to inhibit the proliferation of prostatic epithelial cells. This has stimulated interest in vitamin D compounds as therapeutic agents for prostate cancer. However, the therapeutic use of 1,25(OH)2D3 is limited because elevations in serum 1,25(OH)2D3 can cause dangerous elevations in serum calcium levels. We wondered whether the prohormone of 1,25(OH)2D3, 25-hydroxyvitamin D3 (25-OH-D3), which is much less calcemic, could also achieve antiproliferative effects in prostatic cells. 25-OH-D3 is converted to 1,25(OH)2D3 by the mitochondrial enzyme 1-alpha-hydroxylase. We have recently shown that human prostatic cells also possess significant 1-alpha-hydroxylase activity (Schwartz et al., Cancer Epidemiol. Biomark. Prev., 7: 391-395, 1998). We studied 1-alpha-hydroxylase gene expression in four strains of primary human prostatic epithelial cells by reverse transcription PCR amplification (RT-PCR) of 1-alpha-hydroxylase. Human prostatic stromal cells were negative for 1-alpha-hydroxylase by RT-PCR. This led us to hypothesize that 25-OH-D3 would inhibit the proliferation of prostatic epithelial cells because 25-OH-D3 would be converted to 1,25(OH)2D3 intracellularly. We studied the effects of 25-OH-D3 and 1,25(OH)2D3 on the proliferation of prostatic epithelial cells using high density growth and clonal growth assays on two different primary cell strains derived from normal human prostatic peripheral zone. 25-OH-D3 and 1,25(OH)2D3 each inhibited growth in a dose- and time-dependent manner. Growth inhibition was evident at 1 nM, and maximal inhibition was observed at 100 nM within 10-12 days of exposure. The potencies of 25-OH-D3 and 1,25(OH)2D3 were not significantly different. These data demonstrate that 25-OH-D3, which previously was thought to have little biological activity, can become a potent antiproliferative hormone for prostatic cells that express 1-alpha-hydroxylase. Because 25-OH-D3 exhibits similar potency to 1,25(OH)2D3 but is less calcemic, 25-OH-D3 may offer a safer option than 1,25(OH)2D3 for prostate cancer therapy. Moreover, because 25-OH-D3 is produced endogenously from vitamin D, these findings support a potential role for vitamin D in the chemoprevention of prostate cancer.
To examine whether the survival (both overall and disease-specific) of patients who underwent radical prostatectomy varies from region to region in the United States. Previous reports have documented a geographic variation in the use of radical prostatectomy.
This study was based on the data from nine geographic regions of the Surveillance, Epidemiology, and End Results Program (SEER) for 1983 through 1992. Patients with localized prostate cancer who underwent radical prostatectomy were included in the analysis. A proportional hazards model was used to investigate whether geographic variation is associated with both overall and disease-specific survival.
From 1983 through 1992, the SEER Program collected information from nine geographic regions on 66,293 patients with localized prostate cancer (mean age 71.8 +/- 8.4 years), who had SEER grade codes of 1, 2, or 3. Of these patients, 11,429 (mean age 65.3 +/- 6.5 years) underwent radical prostatectomy and lymph node dissection. Cox's proportional hazards analyses revealed that the impact of geographic location on both overall and disease-specific survival in patients who underwent radical prostatectomy was not statistically significant.
The results of this study indicate that the survival (both overall and disease-specific) of patients with localized prostate cancer who underwent radical prostatectomy is not influenced by geographic location, suggesting that their survival is relatively uniform across the geographic regions in the United States.
The recently published atlas of cancer mortality in the United States revealed that prostate cancer mortality rates were elevated among white men in the Northwest, the Rocky Mountain states, the north-central area, New England and the South Atlantic area, and among black men in the South Atlantic area. Here we determine whether the elevated regional rates were statistically different from rates in the rest of the country and whether the pattern can be explained by selected regional characteristics. A spatial scan statistic was applied to county-based mortality data from 1970 through 1989 to identify geographic clusters of the elevated rates for prostate cancer. Five clusters of elevated mortality were detected in white men (p < 0.005) and 3 in black men (p = 0.0001-0.056). For white men, the primary cluster was in the northwestern quadrant, followed by clusters in New England, the eastern part of the north-central area, the mid-Atlantic states and the South Atlantic area, whereas for black men the primary cluster was in the South Atlantic area, followed by clusters in Alabama and the eastern part of the north-central area. Further analyses of these clusters revealed several significant subclusters (p < 0.05). None of the selected demographic and socioeconomic factors, separately or collectively, accounted for the primary clusters in the U.S. white and black populations. The patterns observed could not be attributed to selected demographic or socioeconomic characteristics but should provide leads for further study into the risk factors and the medical or reporting practices that may contribute to geographic variation in mortality from prostate cancer.
Several recent studies have identified a surprisingly high prevalence of vitamin D insufficiency in otherwise healthy adults living in Canada and the United States. Most striking are the effects of latitude, season, and race. Also noteworthy is that dietary vitamin D is not reaching the population in greatest need, nor is it very protective against insufficiency. Fluid milk, as the predominant vehicle for vitamin D fortification, is apparently not very effective in staving off vitamin D insufficiency in adults in all populations at all times of the year.
We propose a technique for the display of results of Kulldorff's spatial scan statistic and related cluster detection methods that provides a greater degree of informational content. By simultaneously considering likelihood ratio and relative risk, it is possible to identify focused sub-clusters of higher (or lower) relative risk among broader regional excesses or deficits. The result is a map with a nested or contoured appearance. Here the technique is applied to prostate cancer mortality data in counties within the contiguous United States during the period 1970-1994. The resulting map shows both broad and localized patterns of excess and deficit, which complements a choropleth map of the same data.
Vitamin D inhibits the development and growth of prostate cancer cells. Epidemiologic results on serum vitamin D levels and prostate cancer risk have, however, been inconsistent. We conducted a longitudinal nested case-control study on Nordic men (Norway, Finland and Sweden) using serum banks of 200,000 samples. We studied serum 25(OH)-vitamin D levels of 622 prostate cancer cases and 1,451 matched controls and found that both low (</=19 nmol/l) and high (>/=80 nmol/l) 25(OH)-vitamin D serum concentrations are associated with higher prostate cancer risk. The normal average serum concentration of 25(OH)-vitamin D (40-60 nmol/l) comprises the lowest risk of prostate cancer. The U-shaped risk of prostate cancer might be due to similar 1,25-dihydroxyvitamin D(3) availability within the prostate: low vitamin D serum concentration apparently leads to a low tissue concentration and to weakened mitotic control of target cells, whereas a high vitamin D level might lead to vitamin D resistance through increased inactivation by enhanced expression of 24-hydroxylase. It is recommended that vitamin D deficiency be supplemented, but too high vitamin D serum level might also enhance cancer development.
The possibility that exposure to sunlight reduces the risk of clinical prostate cancer has been strongly suggested by ecologic data. However, data on prostate cancer risk in relation to sunlight exposure in individuals are sparse. We analyzed data from the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study in order to test the hypothesis that residential sunlight exposure reduces the risk of prostate cancer. We identified 153 men with incident prostate cancer from a cohort of 3414 white men who completed the baseline interview and dermatologic examination in 1971-1975 and were followed up to 1992. We used Cox proportional hazards modeling to estimate relative risks (RR) and 95% confidence intervals (CI) for measures of residential sunlight exposure, adjusting for age, family history of prostate cancer, and dietary intake of fat and calcium. Residence in the South at baseline (RR = 0.68, CI = 0.41-1.13), state of longest residence in the South (RR = 0.62, CI = 0.40-0.95), and high solar radiation in the state of birth (RR = 0.49, CI = 0.30-0.79) were associated with significant and substantial reductions in prostate cancer risk. These data support the hypothesis that sunlight exposure reduces the risk of prostate cancer and have important implications for prostate cancer prevention.
This review describes what is currently known about the genetics of prostate cancer. Traditionally, the genetics of a suspected inherited cancer predisposition have generally been thought of in terms of a single, high-risk gene with a dominant mode of inheritance. Such a gene might be observed in families, as has been documented in familial breast cancer (BRCA1/2), familial colorectal cancer (HNPCC), retinoblastoma (RB1), and Wilms tumor (WT1). This review investigates the evidence for the existence, first of familial prostate cancer, and second, for the presence of such a high-risk gene in those families by epidemiological and experimental approaches. Another current area of interest in prostate cancer is the investigation of the contribution of common lower penetrance genes to the disease. This alternative approach has become popular, as it raises the issue of frequently seen genetic variations such as single nucleotide polymorphisms (SNPs) having relevance to the risk of developing the disease. Finally, this article will explore the way forward, with emphasis on worldwide collaboration from teams attempting to find the genes responsible for the disease and investment in new technologies that will aid in their discovery.
To examine American beverage consumption trends and causes.
Nationally representative data from the 1977-1978 Nationwide Food Consumption Survey, the 1989-1991 and 1994-1996 (also for children aged 2 to 9 years in 1998) Continuing Surveys of Food Intake by Individuals (CSFII), and 1999-2001 National Health and Nutrition Examination Survey were used in this study. The sample consisted of 73,345 individuals, aged >or=2 years. For each survey year, the percentage of total energy intake from meals and snacks was calculated separately for respondents aged 2 to 18 years, 19 to 39, 40 to 59, and >or=60. The percentage of energy intake by location (at home consumption or preparation, vending, store eaten out, restaurant/fast food, and school), as well as for specific beverages was computed separately for all age groups. The proportion consumed, mean portion size, and number of servings were calculated.
For all age groups, sweetened beverage consumption increased and milk consumption decreased. Overall, energy intake from sweetened beverages increased 135% and was reduced by 38% from milk, with a 278 total calorie increase. These trends were associated with increased proportions of Americans consuming larger portions, more servings per day of sweetened beverage, and reductions in these same measures for milk.
There is little research that has focused on the beneficial impacts of reduced soft drink and fruit drink intake. This would seem to be one of the simpler ways to reduce obesity in the United States.
Obesity is a major public health problem in the United States. Data on measured heights and weights indicates that the prevalence of obesity has significantly increased among the US population over the past 30 years. Data collected from 1999 to 2002 estimates that nearly 1/3 of adults are obese (27.6% of men and 33.2% of women) and one in six children and adolescents is overweight. Increased prevalence of excessive weight is noted among all age, gender and racial/ethnic groups; however, disparities exist. There is a need for further research to better understand why these increases have occurred, why the observed disparities exist and how to reverse these trends.
In some studies, high calcium intake has been associated with an increased risk of prostate cancer, but no randomized studies have investigated this issue.
We randomly assigned 672 men to receive either 3 g of calcium carbonate (1,200 mg of calcium), or placebo, daily for 4 years in a colorectal adenoma chemoprevention trial. Participants were followed for up to 12 years and asked periodically to report new cancer diagnoses. Subject reports were verified by medical record review. Serum samples, collected at randomization and after 4 years, were analyzed for 1,25-(OH)2 vitamin D, 25-(OH) vitamin D, and prostate-specific antigen (PSA). We used life table and Cox proportional hazard models to compute rate ratios for prostate cancer incidence and generalized linear models to assess the relative risk of increases in PSA levels.
After a mean follow-up of 10.3 years, there were 33 prostate cancer cases in the calcium-treated group and 37 in the placebo-treated group [unadjusted rate ratio, 0.83; 95% confidence interval (95% CI), 0.52-1.32]. Most cases were not advanced; the mean Gleason's score was 6.2. During the first 6 years (until 2 years post-treatment), there were significantly fewer cases in the calcium group (unadjusted rate ratio, 0.52; 95% CI, 0.28-0.98). The calcium risk ratio for conversion to PSA >4.0 ng/mL was 0.63 (95% CI, 0.33-1.21). Baseline dietary calcium intake, plasma 1,25-(OH)2 vitamin D and 25-(OH) vitamin D levels were not materially associated with risk.
In this randomized controlled clinical trial, there was no increase in prostate cancer risk associated with calcium supplementation and some suggestion of a protective effect.
This review examines the relationship between obesity and prostate cancer, with an update of recent research in this field.
A recent report of the Cancer Prevention Study II showed a direct relationship between increasing body mass index and prostate cancer mortality. However, the US Health Professionals Followup Study reported an inverse association between obesity and the risk of developing prostate cancer in men under 60 years of age or in those with a family history of prostate cancer. These studies illustrate the contradictory evidence linking obesity to prostate cancer risk and mortality. Body mass does not appear to affect the performance of prostate-specific antigen as a diagnostic test, and on prostate biopsy a lower body mass is associated with a higher cancer detection rate and a higher cancer volume as measured by core length involvement. In two recent radical prostatectomy series, obesity was associated with worse pathological features and higher biochemical recurrence rates. The higher risk of recurrence persisted in patients with organ-confined disease and negative surgical margins, implying that this risk is not related to surgical technique. Several potential biological mechanisms have been proposed to explain this link including hormonal alterations, hyperinsulinemia, glucose intolerance, and elevated insulin-like growth factor and leptin levels.
Recent literature provides evidence that obesity may promote the development of a more aggressive form of prostate cancer, resulting in higher recurrence rates after primary therapy and higher cancer mortality rates overall. The mechanism to explain the association between obesity and prostate cancer is unclear.
Substantial experimental evidence indicates that the hormonal form of vitamin D promotes the differentiation and inhibits the proliferation, invasiveness, and metastasis of human prostatic cancer cells. Results from epidemiologic studies of vitamin D status and/or vitamin D receptor (VDR) polymorphisms and prostate cancer risk have been mixed. We conducted a population-based, case-control study of advanced prostate cancer among men ages 40 to 79 years from the San Francisco Bay area. Interview data on lifetime sun exposure and other risk factors were collected for 905 non-Hispanic White men (450 cases and 455 controls). Using a reflectometer, we measured constitutive skin pigmentation on the upper underarm (a sun-protected site) and facultative pigmentation on the forehead (a sun-exposed site) and calculated a sun exposure index from these measurements. Biospecimens were collected for 426 cases and 440 controls. Genotyping was done for VDR polymorphisms in the 5' regulatory region (Cdx-2), exon 2 (FokI), and the 3' region (TaqI and BglI). Reduced risk of advanced prostate cancer was associated with high sun exposure determined by reflectometry [odds ratio (OR), 0.51; 95% confidence interval (95% CI), 0.33-0.80] and high occupational outdoor activity (OR, 0.73; 95% CI, 0.48-1.11). Significant risk reductions with the high-activity alleles FokI FF or Ff, TaqI tt, and BglI BB genotypes and a nonsignificant reduction with Cdx-2 AG or AA genotype were observed in the presence of high sun exposure, with ORs ranging from 0.46 to 0.67. Our findings support the hypothesis that sun exposure and VDR polymorphisms together play important roles in the etiology of prostate cancer.
The Vitamin D-activating enzyme 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase) is now known to be expressed in a much wider range of tissues that previously thought, suggesting a role for 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), which is more in keeping with a cytokine than a hormone. In this capacity, the function of 1alpha-hydroxylase in tumors is far from clear. Studies from several groups including ours have shown altered expression of 1alpha-hydroxylase in different types of neoplasm including breast, prostate and colon cancers. However, functional analysis of Vitamin D metabolism in cancer is complicated by the heterogenous composition of tumors. Immunohistochemical analysis of breast tumors has shown that 1alpha-hydroxylase is expressed by both epithelial cells and by tumor-infiltrating macrophages, suggesting an immunomodulatory component to 1,25(OH)(2)D(3) production in some types of cancer. The demonstration of 1alpha-hydroxylase activity in tumors and their equivalent normal tissues has implications for both the treatment and prevention of cancers. For example, in tumors chemotherapy options may include the use of non-1alpha-hydroxylated Vitamin D analogs to increase local concentrations of active metabolites without systemic side-effects. The role of 1alpha-hydroxylase in protection against cancer is likely to be more complicated and may involve anti-tumor immune responses.
1alpha, 25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active form of vitamin D, is an important hormone that is critically required for the maintenance of mineral homeostasis and structural integrity of bones. 1,25-(OH)2D3 accomplishes this by facilitating calcium absorption from the gut and by a direct action on osteoblasts, the bone forming cells. Apart form its classical actions on the gut and bone, 1,25-(OH)2D3 and its synthetic analogs also possess potent anti-proliferative, differentiative and immunomodulatory activities. 1,25-(OH)2D3 exerts these effects through vitamin D receptor (VDR), a ligand-dependent transcription factor that belongs to the superfamily of steroid/thyroid hormone/retinoid nuclear receptors. The presence of VDR in various tissues other than gut and bone, along with their ability to exert differentiation, growth inhibitory and anti-inflammatory action, has set the stage for therapeutic exploitation of VDR ligands for the treatment of various inflammatory indications and cancer. However, the use of VDR ligands in clinic is limited by their major dose-related side effect, namely hypercalcemia/hypercalciuria. Efforts are being undertaken to develop vitamin D receptor modulators (VDRMs) that are tissue-selective and/or gene-selective in their action and these ligands may exhibit increased therapeutic indices. This review explores the recent advances in VDR biology, non-secosteroidal VDR ligands and the current and potential clinical applications of VDR ligands in inflammation and cancer.
Recent studies have suggested that selenium intake may prevent the risk of developing prostate cancer. Results from some of these studies have given conflicting results. Because of these discrepant results we sought to explore the association between selenium intake and prostate cancer by conducting a systematic review and meta-analysis of the literature.
We systematically searched MEDLINE, EMBASE and Cochrane Library between 1966 and May 2005 for articles that examined the association between intake of selenium and the risk of prostate cancer. We abstracted the data from relevant studies. A random effects model was used to estimate pooled relative risks for both cohort and case-control studies. Heterogeneity was assessed graphically using a Funnel Plot.
Sixteen studies (eleven cohort studies and five case-control studies) were included in the final analysis. The pooled relative risk of prostate cancer for any intake of selenium was 0.72 (0.61-0.84) for cohort studies and 0.74 (0.61-1.39) for case-control studies. The pooled relative risk of moderate intake was 0.74 (0.61-0.90) for cohort studies and 0.74 (0.39-1.39) for case-control studies. A dose-response trend was observed when we stratified the studies by disease severity.
The results of our systematic review suggest that selenium intake may reduce the risk of prostate cancer. The results confirm the need for large randomized controlled trials, which are ongoing, to answer this question.
Increasing evidence supports the important role of nutrition in cancer prevention, including prevention of prostate cancer. In this review, we summarize data for some of the most consistently observed dietary associations for prostate cancer incidence, briefly consider possible postdiagnostic effects of nutrition on prostate cancer progression/survival, discuss new but limited data on diet-gene interactions, and comment on current areas of controversy for future research focus. Potential protective dietary elements include tomatoes/lycopene, other carotenoids, cruciferous vegetables, vitamin E, selenium, fish/marine omega-3 fatty acids, soy, isoflavones and polyphenols; whereas milk, dairy, calcium, zinc at high doses, saturated fat, grilled meats, and heterocyclic amines may increase risk. It is important to note that randomized clinical trial data exist only for vitamin E, calcium, beta-carotene, and selenium (all of which suggest inverse or no association). Several genes, such as MnSOD, XRCC1, and GST, may modify the association of specific nutrients and foods with prostate cancer risk; and further research is warranted to confirm these initial observed relationships. Until further clinical trial data are available on specific supplements and prostate cancer prevention, it would be prudent to emphasize a diet consisting of a wide variety of plant-based foods and fish; this is similar to what is recommended (and what is more well established) for the primary prevention of heart disease.
Spatial-temporal trends in prostate cancer mortality are of interest because of the introduction and increasing use of the prostate-specific antigen (PSA) screening test after 1986. This article describes spatial-temporal changes in U.S. prostate cancer mortality from 1968 to 1998.
Prostate cancer mortality data were obtained from Compressed Mortality Files available from the National Center for Health Statistics. To minimize potential problems such as small numbers or missing data, the analysis was limited to white males aged 25 and over, and located in 2970 counties with complete data. Statistical analyses included the global distance between observed and expected multinomial probabilities, Hoover's Index of Concentration, and a retrospective test for change in spatial patterns.
Fairly steady declines were observed in prostate cancer mortality from 1968 until 1993, with an increasing tendency toward spatial uniformity. Spatial concentration increased from 1994 to 1998, and by 1998 the level of spatial concentration had returned to levels that prevailed during the early to mid-1980s. Comparing 1991-1998 to 1968-1990, the observed number of prostate deaths increased the most rapidly with respect to the expected number in western Appalachia and the south central U.S. Recent relative declines in mortality were observed in southern California and parts of Florida.
The observed results are generally consistent with prior evaluations of prostate cancer spatial-temporal patterns. However, the current study identified a heretofore unnoticed recent pattern of change in western Appalachia and the south central U.S. Recent declines in Florida and southern California may have contributed to recent increases in spatial concentration of prostate cancer mortality, and may possibly be associated with realized benefits from screening programs.
Sunlight is essential for the production of vitamin D in the body. Evidence exists to suggest that vitamin D metabolites may have a role in tumor growth suppression. In this large study, involving over a million cancer patients from the United Kingdom, we have analyzed the role of season of diagnosis and sunlight exposure in cancer survival for cancers of the breast, colorectum, lung, prostate and at all sites combined. We used population-based data from the Thames Cancer Registry to analyze cancer survival in periods 0-1 and 0-5 years after diagnosis. The analysis was performed using Cox proportional regression analysis adjusting for age and period at diagnosis and including season of diagnosis and sunlight exposure in the preceding months as factors in the analysis. We found evidence of substantial seasonality in cancer survival, with diagnosis in summer and autumn associated with improved survival compared with that in winter, especially in female breast cancer patients and both male and female lung cancer patients (hazard ratios 0.86 [95% CI 0.83-0.89], 0.95 [95% CI 0.92-0.97] and 0.95 [95% CI 0.93-0.98] respectively). Cumulative sunlight exposure in the months preceding diagnosis was also a predictor of subsequent survival, although season of diagnosis was a stronger predictor than cumulative sunlight exposure. We found seasonality in cancer survival to be stronger in women than in men. Our results add to a growing body of evidence that vitamin D metabolites play an important role in cancer survival.
A prospective study of predictors of vitamin D status and cancer incidence and mortality in men
- E Giovannucci
- Y Liu
- Eb
Giovannucci E, Liu Y, Rimm EB, et al (2006) A prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 98:451–459
The prostate: a guide for men
- Walsh Pc Worthington
- Jf
Walsh PC, Worthington JF (1995) The prostate: a guide for men. Johns Hopkins Uninversity Press, Baltimore, MD
DC: US Govt Print Off
- Washington
Washington, DC: US Govt Print Off;