A Prospective Study of Total and Ionized Serum Calcium and Time to Fatal Prostate Cancer

Schwartz, Gary G.; Skinner, Halcyon G.

doi:10.1158/1055-9965.epi-12-0585

Cited by 28 publications

(15 citation statements)

References 45 publications

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“…Recently, the World Cancer Research Fund International concluded that evidence linking high calcium intake to PCa risk is limited [23], but the results of the current work are consistent with many other studies that demonstrated that high calcium intake increases risk of PCa [3, 5, 6, 13] as well as reports showing associations between high serum calcium levels and increasing PCa risk and risk of fatal PCa [24, 25]. Epidemiologic evidence also does not provide definitive support for an inverse association between vitamin D and PCa [26–28], and other studies that explored the relationship between vitamin D intake and PCa did not find significant associations [5, 7].…”

Section: Discussionsupporting

confidence: 89%

Race and BMI modify associations of calcium and vitamin D intake with prostate cancer

et al. 2017

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BackgroundAfrican Americans have disproportionately higher burden of prostate cancer compared to European Americans. However, the cause of prostate cancer disparities is still unclear. Several roles have been proposed for calcium and vitamin D in prostate cancer pathogenesis and progression, but epidemiologic studies have been conducted mainly in European descent populations. Here we investigated the association of calcium and vitamin D intake with prostate cancer in multiethnic samples.MethodsA total of 1,657 prostate cancer patients who underwent screening and healthy controls (888 African Americans, 620 European Americans, 111 Hispanic Americans, and 38 others) from Chicago, IL and Washington, D.C. were included in this study. Calcium and vitamin D intake were evaluated using food frequency questionnaire. We performed unconditional logistic regression analyses adjusting for relevant variables.ResultsIn the pooled data set, high calcium intake was significantly associated with higher odds for aggressive prostate cancer (ORQuartile 1 vs. Quartile 4 = 1.98, 95% C.I.: 1.01–3.91), while high vitamin D intake was associated with lower odds of aggressive prostate cancer (ORQuartile 1 vs. Quartile 4 = 0.38, 95% C.I.: 0.18–0.79). In African Americans, the association between high calcium intake and aggressive prostate cancer was statistically significant (ORQuartile 1 vs. Quartile 4 = 4.28, 95% C.I.: 1.70–10.80). We also observed a strong inverse association between total vitamin D intake and prostate cancer in African Americans (ORQuartile 1 vs. Quartile 4 = 0.06, 95% C.I.: 0.02–0.54). In European Americas, we did not observe any significant associations between either calcium or vitamin D intake and prostate cancer. In analyses stratifying participants based on Body Mass Index (BMI), we observed a strong positive association between calcium and aggressive prostate cancer and a strong inverse association between vitamin D intake and aggressive prostate cancer among men with low BMI (<27.8 kg/m2), but not among men with high BMI (≥27.8 kg/m2). Interactions of race and BMI with vitamin D intake were significant (P Interaction < 0.05).ConclusionCalcium intake was positively associated with aggressive prostate cancer, while vitamin D intake exhibited an inverse relationship. However, these associations varied by race/ethnicity and BMI. The findings from this study may help develop better prostate cancer prevention and management strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3060-8) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 89%

Race and BMI modify associations of calcium and vitamin D intake with prostate cancer

et al. 2017

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“…For example, Nox5 activity is strongly enhanced by binding of Ca 2+ to the N‐terminal region of Nox5 . In this respect it may be noted that a large body of evidence suggests that increased calcium intake is associated with enhanced PCa risk . Moreover, the Ca 2+ channel TRPV6, which is overexpressed in PCa and correlates with tumor progression and poor prognosis, is also expressed at higher levels in the Nox5‐positive PCa cell lines PC‐3 and LNCaP compared to normal and benign epithelial cells .…”

Section: Discussionmentioning

confidence: 99%

ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells

Höll

Kozieł

Schäfer

et al. 2015

Molecular Carcinogenesis

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Prostate cancer (PCa) is the most commonly diagnosed cancer and second leading cause of male cancer death in Western nations. Thus, new treatment modalities are urgently needed. Elevated production of reactive oxygen species (ROS) by NADPH oxidase (Nox) enzymes is implicated in tumorigenesis of the prostate and other tissues. However, the identity of the Nox enzyme(s) involved in prostate carcinogenesis remains largely unknown. Analysis of radical prostatectomy tissue samples and benign and malignant prostate epithelial cell lines identified Nox5 as an abundantly expressed Nox isoform. Consistently, immunohistochemical staining of a human PCa tissue microarray revealed distinct Nox5 expression in epithelial cells of benign and malignant prostatic glands. shRNA‐mediated knockdown of Nox5 impaired proliferation of Nox5‐expressing (PC‐3, LNCaP) but not Nox5‐negative (DU145) PCa cell lines. Similar effects were observed upon ROS ablation via the antioxidant N‐acetylcysteine confirming ROS as the mediators. In addition, Nox5 silencing increased apoptosis of PC‐3 cells. Concomitantly, protein kinase C zeta (PKCζ) protein levels and c‐Jun N‐terminal kinase (JNK) phosphorylation were reduced. Moreover, the effect of Nox5 knockdown on PC‐3 cell proliferation could be mimicked by pharmacological inhibition of JNK. Collectively, these data indicate that Nox5 is expressed at functionally relevant levels in the human prostate and clinical PCa. Moreover, findings herein suggest that Nox5‐derived ROS and subsequent depletion of PKCζ and JNK inactivation play a critical role in modulating intracellular signaling cascades involved in the proliferation and survival of PCa cells. © 2014 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.

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“…We found higher corrected serum calcium levels in our population to be significantly associated with better survival. Research has noted these variables to be inversely related, typically in the setting of hypercalcemia associated with bone metastases and more advanced disease [ 32 , 33 ]. Our mean corrected serum calcium was 9.2 mg/dl which is within the normal limits of 8.5 to 10.1 mg/dl.…”

Section: Discussionmentioning

confidence: 99%

The Association between Pre-Treatment Serum 25-Hydroxyvitamin D and Survival in Newly Diagnosed Stage IV Prostate Cancer

et al. 2015

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Background/AimsEmerging evidence in the literature suggests a positive association between serum 25-hydroxyvitamin D [25(OH)D], a standard indicator of vitamin D status, and survival in certain types of cancer. We investigated this relationship in newly diagnosed stage IV prostate cancer patients.MethodsA consecutive cohort of 125 newly diagnosed stage IV prostate cancer patients underwent a baseline serum 25(OH)D evaluation prior to receiving any treatment at our institution between January 2008 and December 2011. We used the vitamin D categories of “deficient (<20 ng/ml)”, “insufficient (20 to 32 ng/ml)”, and “sufficient (>32 ng/ml)”. Cox regression was used to evaluate the prognostic significance of serum 25(OH)D after adjusting for relevant confounders.ResultsMean age at diagnosis was 60 years. Of the 125 patients, 32 (25.6%) were deficient, 49 (39.2%) were insufficient and 44 (35.2%) were sufficient in vitamin D at the time of diagnosis. The median survival in deficient, insufficient and sufficient cohorts was 47.8, 44.0 and 52.6 months respectively (p = 0.60). On univariate analysis, four variables demonstrated a statistically significant association with survival: nutritional status, bone metastasis, corrected serum calcium and serum albumin (p<0.05 for all). On multivariate analysis, five variables demonstrated statistically significant associations with survival: hospital location, age, bone metastasis, serum albumin and corrected serum calcium (p<0.05 for all). Serum vitamin D status was not significant on either univariate or multivariate analysis.ConclusionContrary to previously published research, we found no significant association between pre-treatment serum 25(OH)D and survival in newly diagnosed stage IV prostate cancer patients. The lack of a significant association between serum vitamin D and survival in our study could perhaps be due to the fact that the disease was far too advanced in our patients for vitamin D levels to have any impact on prognosis.

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A Prospective Study of Total and Ionized Serum Calcium and Time to Fatal Prostate Cancer

Cited by 28 publications

References 45 publications

Race and BMI modify associations of calcium and vitamin D intake with prostate cancer

Race and BMI modify associations of calcium and vitamin D intake with prostate cancer

ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells

The Association between Pre-Treatment Serum 25-Hydroxyvitamin D and Survival in Newly Diagnosed Stage IV Prostate Cancer

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