Cohort Consortium Vitamin Research Articles

Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974–2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50–<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (≥100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered.

Circulating 25-hydroxyvitamin D and risk of esophageal and gastric cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

Upper gastrointestinal (GI) cancers of the stomach and esophagus have high incidence and mortality worldwide, but they are uncommon in Western countries. Little information exists on the association between vitamin D and risk of upper GI cancers. This study examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and upper GI cancer risk in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 1,065 upper GI cancer cases and 1,066 age-, sex-, race-, and season-of blood draw–matched controls from 8 prospective cohort studies. In multivariate-adjusted models, circulating 25(OH)D concentration was not significantly associated with upper GI cancer risk. Subgroup analysis by race showed that among Asians, but not Caucasians, lower concentrations of 25(OH)D (<25 nmol/L) were associated with a statistically significant decreased risk of upper GI cancer (reference: 50–<75 nmol/L) (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91; P trend = 0.003). Never smokers with concentrations of <25 nmol/L showed a lower risk of upper GI cancers (odds ratio = 0.55, 95% confidence interval: 0.31, 0.96). Subgroup analyses by alcohol consumption produced opposing trends. Results do not support the hypothesis that interventions aimed at increasing vitamin D status would lead to a lower risk of these highly fatal cancers.

Circulating 25-hydroxyvitamin D and risk of kidney cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

Although the kidney is a major organ for vitamin D metabolism, activity, and calcium-related homeostasis, little is known about whether this nutrient plays a role in the development or the inhibition of kidney cancer. To address this gap in knowledge, the authors examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and kidney cancer within a large, nested case-control study developed as part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 775 kidney cancer cases and 775 age-, sex-, race-, and season-matched controls from 8 prospective cohort studies. Overall, neither low nor high concentrations of circulating 25(OH)D were significantly associated with kidney cancer risk. Although the data showed a statistically significant decreased risk for females (odds ratio = 0.31, 95% confidence interval: 0.12, 0.85) with 25(OH)D concentrations of ≥75 nmol/L, the linear trend was not statistically significant and the number of cases in this category was small (n = 14). The findings from this consortium-based study do not support the hypothesis that vitamin D is inversely associated with the risk of kidney cancer overall or with renal cell carcinoma specifically.

Overview of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) brought together 10 cohorts to conduct a prospective study of the association between vitamin D status, measured as serum concentrations of 25-hydroxyvitamin D (25(OH)D), and the development of 7 rarer cancer sites: endometrial, esophageal, gastric, kidney, non-Hodgkin lymphoma, ovarian, and pancreatic cancers. The cohorts come from 3 continents, with participants from a wide range of latitude who are racially diverse. Across each cancer site, there was no evidence of a protective association between higher concentrations of 25-hydroxyvitamin D (>75 nmol/L) and cancer outcome. An increased risk at very high levels (≥100 nmol/L) was noted for pancreatic cancer, confirming previous reports. The articles included in this issue detail the overall design and governance of the project, correlates of vitamin D status, and results from the cancer site-specific investigations. The Vitamin D Pooling Project realizes a major goal of consortium efforts, namely, to rigorously test hypotheses for rarer cancer outcomes that may not be adequately addressed in any one prospective cohort study. The results of this study have application for the planning and conduct of intervention trials, especially in determining potential risks.

Circulating 25-hydroxyvitamin D and risk of endometrial cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

A nested case-control study, including 830 cases and 992 controls from 7 cohorts, was conducted to evaluate the association of circulating 25-hydroxyvitamin D (25(OH)D), the best indicator of vitamin D status, with risk of endometrial cancer. Matching factors included age at blood donation, date of blood donation, and race. Conditional logistic regression was used in the main analysis. The median concentration of 25(OH)D was slightly lower in cases (49.4 nmol/L) than in controls (50.8 nmol/L) (P = 0.08). However, there was no association between 25(OH)D concentration and disease risk, after adjustment for body mass index. Compared with the 50–<75 nmol/L 25(OH)D category, the body mass index-adjusted odds ratios and 95% confidence intervals were 1.08 (95% confidence interval: 0.73, 1.57) for the <25 nmol/L category and 0.90 (95% confidence interval: 0.51, 1.58) for the ≥100 nmol/L category (Ptrend = 0.99). Similarly null results were observed after further adjustment for other known risk factors and in stratified analyses. Although an effect of circulating 25(OH)D at high concentrations cannot be ruled out (the highest category of 25(OH)D was ≥100 nmol/L, and for stratified analyses, ≥75 nmol/L), these results do not support a protective role of vitamin D against endometrial cancer.

Correlates of circulating 25-hydroxyvitamin D: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes.

Circulating 25-hydroxyvitamin D and the risk of rarer cancers: Design and methods of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP), a consortium of 10 prospective cohort studies from the United States, Finland, and China, was formed to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of rarer cancers. Cases (total n = 5,491) included incident primary endometrial (n = 830), kidney (n = 775), ovarian (n = 516), pancreatic (n = 952), and upper gastrointestinal tract (n = 1,065) cancers and non-Hodgkin lymphoma (n = 1,353) diagnosed in the participating cohorts. At least 1 control was matched to each case on age, date of blood collection (1974–2006), sex, and race/ethnicity (n = 6,714). Covariate data were obtained from each cohort in a standardized manner. The majority of the serum or plasma samples were assayed in a central laboratory using a direct, competitive chemiluminescence immunoassay on the DiaSorin LIAISON platform (DiaSorin, Inc., Stillwater, Minnesota). Masked quality control samples included serum standards from the US National Institute of Standards and Technology. Conditional logistic regression analyses were conducted using clinically defined cutpoints, with 50–<75 nmol/L as the reference category. Meta-analyses were also conducted using inverse-variance weights in random-effects models. This consortium approach permits estimation of the association between 25(OH)D and several rarer cancers with high accuracy and precision across a wide range of 25(OH)D concentrations.

Circulating 25-hydroxyvitamin D and risk of non-hodgkin lymphoma: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

Case-control studies generally suggesting an inverse association between sun exposure and non-Hodgkin lymphoma (NHL) have led to speculation that vitamin D may protect against lymphomagenesis. To examine this hypothesis, the authors conducted a pooled investigation of circulating 25-hydroxyvitamin D (25(OH)D) and subsequent NHL risk within 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. The authors analyzed measurements from 1,353 cases and 1,778 controls using conditional logistic regression and other methods to estimate the association of 25(OH)D with NHL. No clear evidence of association between categories of 25(OH)D concentration and NHL was observed overall (Ptrend = 0.68) or by sex (men, Ptrend = 0.50; women, Ptrend = 0.16). Findings for other measures (continuous log(25(OH)D), categories of 25(OH)D using sex-/cohort-/season-specific quartiles as cutpoints, categories of season-adjusted residuals of predicted 25(OH)D using quartiles as cutpoints) were generally null, although some measures of increasing 25(OH)D were suggestive of an increased risk for women. Results from stratified analyses and investigations of histologic subtypes of NHL were also null. These findings do not support the hypothesis that elevated circulating 25(OH)D concentration is associated with a reduced risk of NHL. Future research investigating the biologic basis for the sunlight–NHL association should consider alternative mechanisms, such as immunologic effects.

Circulating 25-hydroxyvitamin D and risk of epithelial ovarian cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

A role for vitamin D in ovarian cancer etiology is supported by ecologic studies of sunlight exposure, experimental mechanism studies, and some studies of dietary vitamin D intake and genetic polymorphisms in the vitamin D receptor. However, few studies have examined the association of circulating 25-hydroxyvitamin D (25(OH)D), an integrated measure of vitamin D status, with ovarian cancer risk. A nested case-control study was conducted among 7 prospective studies to evaluate the circulating 25(OH)D concentration in relation to epithelial ovarian cancer risk. Logistic regression models were used to estimate odds ratios and 95% confidence intervals among 516 cases and 770 matched controls. Compared with 25(OH)D concentrations of 50–<75 nmol/L, no statistically significant associations were observed for <37.5 (odds ratio (OR) = 1.21, 95% confidence interval (CI): 0.87, 1.70), 37.5–<50 (OR = 1.03, 95% CI: 0.75, 1.41), or ≥75 (OR = 1.11, 95% CI: 0.79, 1.55) nmol/L. Analyses stratified by tumor subtype, age, body mass index, and other variables were generally null but suggested an inverse association between 25(OH)D and ovarian cancer risk among women with a body mass index of ≥25 kg/m2 (Pinteraction < 0.01). In conclusion, this large pooled analysis did not support an overall association between circulating 25(OH)D and ovarian cancer risk, except possibly among overweight women.

Abstract 2776: Correlates of circulating 25-hydroxyvitamin D among cancer free adults in the Cohort Consortium Vitamin D Pooling Project

Abstract Objective: Vitamin D deficiency and insufficiency are common globally. Because low circulating 25-hydroxyvitamin D [25(OH)D] concentrations measured during adulthood have been associated with several disease outcomes, it is important to understand correlates of circulating 25(OH)D, especially in certain at-risk populations. Methods: Circulating 25(OH)D was assayed in 4,723 adult men and women with no diagnosed cancer from ten cohorts in the United States, Finland and China participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Data on potential correlates were obtained and harmonized by a central data coordinating center. Serum/plasma samples were assayed for 25(OH)D at Heartland Assays, Inc. using the DiaSorin LIAISON 25(OH)D TOTAL assay, a direct, competitive chemiluminescence immunoassay. We used stepwise linear regression and polytomous logistic regression to identify demographic and lifestyle correlates of circulating 25(OH)D. Results: Vitamin D deficiency (defined as &amp;lt;25 nmol/L) ranged from 3-36% (overall 14.4%) and insufficiency (defined as &amp;lt;50 nmol/L) ranged from 29-82% (overall 54.1%) across cohorts. Whites living in northern latitudes exhibited the largest seasonal differences in circulating 25(OH)D. Positive correlates of 25(OH)D in the overall population, controlled for cohort and age, included male sex, blood collection in the summer and fall season, greater levels of physical activity, alcohol consumption, greater dietary vitamin D intake, greater fish intake, and use of calcium and multivitamin supplements, whereas inverse correlates were black race, greater body mass index, history of diabetes, and cigarette smoking. Correlates varied within sex, season and racial strata. Female sex, black race, low dietary vitamin D intake, a body mass index of &amp;gt;25 kg/m2, and low physical activity were associated with greater risk of vitamin D deficiency (&amp;lt;25 nmol/L), whereas current multivitamin and calcium supplement use, and Asian race were associated with lower risk of deficiency. Conclusions: Vitamin D deficiency and insufficiency were common in this population. Multiple modifiable and non-modifiable factors were correlated with circulating 25(OH)D. These findings help identify individuals at risk for low vitamin D status, which may be useful for both clinical and research purposes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2776.

Abstract 2787: Circulating 25-hydroxyvitamin D and risk of endometrial cancer: Results from the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Abstract Objective: Experimental evidence suggests that vitamin D, a modifiable factor, protects against cancer. Ecological studies have reported an inverse association between ultraviolet B irradiation and endometrial cancer incidence rates, suggesting a protective role of vitamin D against endometrial cancer. The purpose of this study was to examine the association between circulating 25-hydroxyvitamin D (25(OH)D), the best indicator of vitamin D status, and risk of endometrial cancer within a large nested case-control study in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP). Methods: The study included 830 cases and 992 matched controls from seven cohorts: CLUE, the Cancer Prevention Study II Nutrition Cohort (CPS-II), the Multiethnic Cohort Study (MEC), the Nurses’ Health Study (NHS), the New York University Women's Health Study (NYUWHS), the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Study, and the Shanghai Women's Health Study (SWHS). Matching factors included cohort, age at blood donation, date of blood donation and race. Serum/plasma samples were assayed for 25(OH)D using the DiaSorin LIAISON 25(OH)D TOTAL assay, a direct, competitive chemiluminescence immunoassay. Conditional logistic regression was used in the main analysis using clinically-defined cutpoints corresponding to deficient, insufficient, and sufficient 25(OH)D concentrations with 50 to &amp;lt;75nmol/L as the reference category, as well as using season-specific cutpoints to take into account seasonal changes in 25(OH)D levels. Results: The median concentration of 25(OH)D was slightly lower in cases (49.4 nmol/L) than in controls (50.8 nmol/L, P = 0.08). In the crude analysis, there was some suggestion (P for trend = 0.12) that lower concentrations (&amp;lt;25 nmol/L) were associated with a small increased risk of endometrial cancer compared to the referent category of 50-&amp;lt;75 nmol/L (odds ratio (OR): 1.20; 95% confidence interval (CI): 0.83, 1.72) and higher concentrations (≥100 nmol/L) were associated with a lower risk (OR: 0.78; 95% CI: 0.45, 1.34). However, there was no association between 25(OH)D concentration and disease risk after adjusting for body mass index (BMI), which was strongly associated with both endometrial cancer risk and circulating 25(OH)D. Compared to the 50-&amp;lt;75 nmol/L 25(OH)D category, the BMI-adjusted OR and 95% CI were 1.08 (95% CI: 0.73, 1.57) for the &amp;lt;25 nmol/L category and 0.90 (95% CI: 0.51, 1.58) for the ≥100 nmol/L category (P for trend = 0.99). Null results were also observed after further adjustment for other risk factors, in stratified analyses and in analyses limited to women who did not use calcium supplements, white women, or women with endometrioid tumors. Conclusion: Although an effect of circulating 25(OH)D at high concentrations cannot be ruled out, these results do not support a protective role of vitamin D against endometrial cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2787.

Abstract 2805: A pooled investigation of circulating 25-hydroxyvitamin D and non-Hodgkin lymphoma: The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Abstract Findings from several epidemiologic studies suggest that exposure to solar ultraviolet radiation may be associated with a reduced risk of non-Hodgkin lymphoma (NHL). These observations have led to speculation that vitamin D may protect against lymphomagenesis. To investigate this hypothesis, the authors conducted a pooled investigation of circulating 25-hydroxyvitamin D [25(OH)D] and subsequent NHL risk within ten cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Prediagnostic samples of serum or plasma from 1,353 cases and 1,778 controls were assayed for 25(OH)D by immunoassay at a single laboratory. Odds ratios (ORs) and 95% confidence intervals (CIs) relating categories of 25(OH)D concentration with NHL risk were calculated using conditional logistic regression models, with 50-&amp;lt;75 nmol/L used as the reference category. Analyses of common NHL histologic subtypes were performed using polytomous regression modeling. Overall, no evidence of association with NHL risk was observed for either low 25(OH)D concentration (&amp;lt;25 nmol/L: OR 1.08, 95% CI 0.78-1.50) or high concentration (≥100 nmol/L: OR 0.86, 95% CI 0.57-1.27), and a test for trend was not statistically significant (P = 0.68). Analyses of other measures of 25(OH)D {continuous log[25(OH)D], categories of 25(OH)D using sex/cohort/season-specific cutpoints, categories of season-adjusted residuals of predicted 25(OH)D} were similarly null, as were results from stratified analyses and investigations of histologic subtypes of NHL. These findings do not support the hypothesis that elevated circulating 25(OH)D levels are associated with reduced NHL risk. Future research investigating the biologic basis for the sunlight-NHL association should consider alternative mechanisms, such as immunologic effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2805.

Abstract 2785: A pooled analysis of circulating 25(OH)D and ovarian cancer risk

Abstract Although the pathogenesis of ovarian cancer is poorly understood, experimental mechanism studies suggest that vitamin D might reduce ovarian cancer through induction of apoptosis or growth inhibition. Epidemiologic studies of sunlight exposure, dietary vitamin D, and genetic variation in the vitamin D receptor also support a role for vitamin D in ovarian carcinogenesis. However, few prospective studies have examined associations between ovarian cancer and circulating 25-hydroxyvitamin D [25(OH)D], a biologically integrated measure of dietary and non-dietary vitamin D exposure. Therefore, we examined associations between 25(OH)D and ovarian cancer risk in a prospective study of 516 cases and 770 controls from seven cohort studies in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP): the CLUE Study (CLUE), the Cancer Prevention Study II Nutrition Cohort (CPS-II), the Multiethnic Cohort (MEC), the Nurses’ Health Study (NHS), the New York University Women's Health Study (NYU-WHS), the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), and the Shanghai Women's Health Study (SWHS). Cases and controls were matched on age at blood collection, race/ethnicity, and date of blood draw. Circulating vitamin D levels were measured using the DiaSorin LIAISON 25(OH)D TOTAL assay. Quality control samples consisted of cohort-specific samples and standard samples provided by the National Institute of Standards and Technology. Using data from all VDPP batches (including other cancer sites), the intrabatch CV by cohort ranged from 3.8% to 16.4% and interbatch CV ranged from 4.8% to 17%. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression for the main analyses and unconditional logistic regression for stratified analyses. Blood samples were obtained a median of 5.9 years prior to cancer diagnosis (range 2.7-10.2 years). Compared to the a priori reference category of 50 to &amp;lt;75 nmol/L, no statistically significant associations were observed for the following 25(OH)D categories: &amp;lt;25 nmol/L (OR=1.08, 95% CI: 0.64-1.81), 25 to &amp;lt;37.5 nmol/L (OR=1.27, 95% CI: 0.88-1.85), 37.5 to &amp;lt;50 nmol/L (OR=1.03, 95% CI: 0.75-1.40), 75 to &amp;lt;100 nmol/L (OR=1.10, 95% CI: 0.77-1.59), or &amp;gt;100 nmol/L (OR=1.11, 95% CI: 0.61-2.05) (p-trend=0.65). Results also were null for analyses stratified by tumor subtype and age at blood draw. In analyses stratified by body mass index (BMI), there was some suggestion of an inverse relationship between 25(OH)D and ovarian cancer risk among overweight women (p-trend=0.01 among women with a BMI &amp;gt; 25 kg/m2). Overall, results from the VDPP do not support an association between circulating 25(OH)D and ovarian cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2785.

Abstract 2800: The association between circulating 25-hydroxyvitamin D and the development of kidney cancer in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Abstract Objective. Ecological studies conducted in the United States and globally have shown an inverse association between levels of solar ultraviolet irradiance and kidney cancer incidence, suggesting that vitamin D, which is obtained from exposure to ultraviolet light (sunlight), may be associated with a reduced risk of kidney cancer. However, results from two prospective cohort and two case-control studies focusing on dietary vitamin D reported no statistically significant association with the development of kidney cancer. Thus, the purpose of this study was to examine the association between circulating 25-hydroxyvitamin D (25(OH)D), the accepted biomarker for vitamin D status, and the development of kidney cancer within a large pooled nested case-control study carried out as part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP). Methods. Kidney cancer cases (n = 775) and age-, sex-, race-, and season-matched controls (n = 775) were identified from eight prospective cohort studies participating in the VDPP. Data on potential confounders were obtained and harmonized by a central data coordinating center. Serum/plasma samples were assayed for 25(OH)D at Heartland Assays, Inc using the DiaSorin LIAISON 25(OH)D TOTAL assay, a direct, competitive chemiluminescence immunoassay. Clinically-defined cutpoints suggesting deficient, insufficient, and sufficient 25(OH)D concentrations were used to analyze the association between high and low circulating 25(OH)D and kidney cancer, with 50 to &amp;lt;75nmol/L chosen as the reference category. The main analyses were conducted using conditional logistic regression models adjusting for matching variables and potential confounders such as high blood pressure and body mass index. Results. Neither low nor high concentrations of circulating 25(OH)D were significantly associated with kidney cancer risk overall or the renal cell carcinoma subtype. Sex-specific analyses showed, however, that high concentrations of 25(OH)D (&amp;gt;75 nmol/l) were associated with a non-significant increased risk of kidney cancer among males (reference: 50 to &amp;lt;75 nmol/l) (OR=1.52, 95% CI: 0.95, 2.41) and a statistically significant decreased risk among females (OR=0.31, 95% CI: 0.12, 0.85) (interaction P-value = 0.42). Conclusions. The findings from this consortium-based study indicate that vitamin D is not associated with the risk of kidney cancer or the renal cell carcinoma subtype, although additional investigation of the possible modification of the association by sex is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2800.

Abstract 2801: Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP)

Abstract Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D [25(OH) D] concentrations have been inconsistent. For most people, more than 90% of their vitamin D status is produced endogenously from exposure of the skin to solar ultra-violet B (UVB) light (280-320 nm) resulting in cutaneous production of precursors to 25(OH)D. 25(OH)D is the major circulating vitamin D metabolite in humans and is also considered the best indicator of vitamin D status from both sun exposure and diet. Therefore, we conducted a pooled nested case-control study of participants from 8 cohorts within the Vitamin D Pooling Project-Rarer Cancer Consortium (VDPP) to test whether pre-diagnostic circulating 25(OH)D concentrations were associated with the development of incident pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (average follow-up 6.5 years). Controls (n=1333) were matched to each case by cohort, age, sex, race, date of blood draw, and follow-up time. Circulating vitamin D levels were measured using the DiaSorin LIAISON 25(OH)D TOTAL assay or an older DiaSorin radioassay. We used conditional logistic regression to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios (OR) and 95% confidence intervals (CI) for pancreatic cancer. Clinically relevant cut-points were compared to adequate status (defined as 50 to &amp;lt;75nmol/L) as the reference. No significant associations were apparent for deficient or inadequate status. However, high 25(OH)D concentration (&amp;gt; 100 nmol/L) was associated with a significant 2-fold increase in pancreatic cancer risk overall (OR=2.12, 95% CI 1.23-3.71). No statistically significant associations were observed for deficient (&amp;lt;25.0 nmol/L) or inadequate (25.0 to &amp;lt;37.5 nmol/L) status overall or in stratified models. This association was observed in smokers and non-smokers, and both men and women, although it was slightly stronger in men. Given this result, recommendations to increase vitamin D concentrations in healthy individuals for the prevention of cancer should be carefully considered. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2801.

Abstract 2803: A pooled analysis of circulating 25(OH)D and upper gastrointestinal cancer risk in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Abstract Upper gastrointestinal (UGI) cancers of the stomach and esophagus have high incidence and mortality worldwide, but are uncommon in Western countries. While it is clear that vitamin D plays important roles in human health, only one prospective study has examined the association between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and risk of UGI cancers. This study examines the association in eight prospective cohort studies from China, Finland, and the USA that are part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. 25(OH)D concentrations in serum or plasma were measured from 1065 UGI cancer cases and 1066 age-, sex-, race-, and season of blood draw-matched controls. In controls, the median (interquartile range) of circulating 25(OH)D was 39.1 (25.8-56.7) nmol/L, while in cases it was 39.4 (26.3-56.1). 25(OH)D exposure was categorized as six clinically defined categories. A meta-analytic approach showed no significant heterogeneity of effect among the included studies. In multivariate-adjusted models, circulating 25(OH)D concentration was not significantly associated with UGI cancer risk. Compared to the referent group, 50 to &amp;lt;75 nmol/l, those in the lowest (&amp;lt;25 nmol/L) or highest (&amp;gt;=100 nmol/L) categories had odds ratios (95% confidence intervals (CI)) of 0.90 (0.65-1.24) and 0.81 (0.39-1.69), respectively. Subgroup analysis by race showed that among Asians, being in the lowest category was associated with a statistically significant decreased risk of UGI cancer with odds ratio (95% CI) = 0.53 (0.31-0.91) compared to the referent group, but no association in Caucasians, odds ratio (95% CI) = 0.98 (0.67-1.44). Never smokers with concentrations &amp;lt;25 nmol/L were also at lower risk of UGI cancers with odds ratio (95% CI) = 0.55 (0.31-0.96). These results do not support the hypothesis that interventions aimed at increasing vitamin D status would lead to lower risk of these highly fatal cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2803.

An ecological study of cancer mortality rates in the United States with respect to solar ultraviolet-B doses, smoking, alcohol consumption and urban/rural residence.

The Cohort Consortium Vitamin D Polling Project of Rarer Cancers (VDPP ) study failed to find a beneficial role of prediagnostic serum 25-hydroxyvitamin D [25(OH)D] levels on risk of seven types of rarer cancer: endometrial, esophageal, gastric, kidney, ovarian and pancreatic cancer and non-Hodgkin's lymphoma (NHL). However, ecological studies and studies of oral vitamin D intake have generally found solar ultraviolet B (UVB) and oral vitamin D inversely correlated with incidence and/or mortality rates of these cancers. To explore the discrepancy, I conducted an ecological study of cancer mortality rates for white Americans in the United States for 1950-1994 with data for 503 state economic areas in multiple linear regression analyses with respect to UVB for July, lung cancer, alcohol consumption and urban/rural residence. UVB was significantly inversely correlated with six types of cancer (not pancreatic cancer) in both periods. However, the adjusted R(2) values were much lower for cancers with lower mortality rates than those in an earlier ecological study that used state-averaged data. This finding suggests that the VDPP study may have had too few cases. Thus, the VDPP study should not be considered as providing strong evidence against the solar UVB-vitamin D-cancer hypothesis.

Abstract PL04-05: Vitamin D: Panacea or a Pandora's box for prevention?

Abstract Widespread interest in the possible preventive role of vitamin D against cancer emerged from ecological studies of the association between latitude and cancer mortality, in-vitro studies of the effects of vitamin D on proliferation and apoptosis, and presence of vitamin D receptors in many tissues. Observational studies of colorectal cancer provide the most promising data supporting a potential preventive benefit for vitamin D but this effect, so far, is not supported by results from randomized trials. Observational studies for other common cancers such as prostate and breast provide little support for a significant preventive effect of vitamin D. The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) is a consortial effort including 10 prospective cohorts from the United States, Finland and China to examine the association between concentrations of 25-hydroxyvitamin D (25(OH)D) and risk of seven types of rarer cancers: endometrial, esophageal, gastric, kidney, non-Hodgkin's lymphoma, pancreatic and ovarian. No associated benefit, and potential harms, were observed including confirmation of prior reports of an increased risk of pancreatic cancer with higher concentrations of 25(OH)D. The association between mortality and 25(OH)D concentrations was examined in the Third National Health and Nutrition Examination Survey (NHANES III). The mortality rate ratio was statistically significantly higher for those with vitamin D concentrations in the deficient range, defined as &amp;lt;45nmol/L. Among women, an increased rate of mortality was observed both for deficient concentrations and very high concentrations (&amp;gt;124nmol/L). Results suggest that caution should be exercised in using very high dose vitamin D supplementation in prevention trials that may result in high concentrations of vitamin D (&amp;gt;100nmol/L). Citation Information: Cancer Prev Res 2010;3(1 Suppl):PL04-05.