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Wakle KS, Mokale SN, Sakle NS. Emerging perspectives: unraveling the anticancer potential of vitamin D 3. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:2877-2933. [PMID: 37994947 DOI: 10.1007/s00210-023-02819-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 10/26/2023] [Indexed: 11/24/2023]
Abstract
Vitamin D3, a fat-soluble vitamin known for its critical function in calcium homeostasis and bone health, is gaining interest for its anticancer properties. Observational studies have suggested a negative relationship between vitamin D levels and the incidence of some malignancies throughout the years, prompting substantial investigation to find its anticancer effects. The purpose of this comprehensive review is to investigate the diverse function of vitamin D3 in cancer prevention and therapy. We explored the molecular mechanism underlying its effects on cancer cells, which range from cell cycle control and death to angiogenesis and immune response modulation. Insights from in vitro and in vivo studies provide valuable evidence supporting its anticancer potential. Furthermore, we look at epidemiological and clinical studies that investigate the relationship between vitamin D3 levels and cancer risk or treatment results. Vitamin D3 supplementation's safety profile and cost-effectiveness increase its attractiveness as an adjuvant therapy in conjunction with traditional treatment regimens. Our critical review of the current literature provides an in-depth understanding of vitamin D3's anticancer effect, covering the obstacles and possibilities in realizing its promise for cancer prevention and therapy. The findings of this study might pave the way for the development of innovative treatment techniques that take use of the advantages of vitamin D3 to fight cancer and improve patient care. As research progresses, a better understanding of vitamin D3's anticancer processes will surely simplify its incorporation into personalized cancer care techniques, hence enhancing patient outcomes in the battle against cancer.
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Affiliation(s)
- Komal S Wakle
- Y. B. Chavan College of Pharmacy, Aurangabad, Maharashtra, 431001, India
| | - Santosh N Mokale
- Y. B. Chavan College of Pharmacy, Aurangabad, Maharashtra, 431001, India
| | - Nikhil S Sakle
- Y. B. Chavan College of Pharmacy, Aurangabad, Maharashtra, 431001, India.
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2
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Ismayilova N, Palamar M, Onay H, Ceylan EI, Atik T, Akalin T, Yagci A. Vitamin D receptor gene polymorphisms in ocular surface squamous cell neoplasms. Eur J Ophthalmol 2019; 30:901-907. [PMID: 31232112 DOI: 10.1177/1120672119858225] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
PURPOSE To investigate vitamin D receptor polymorphisms in ocular surface squamous cell neoplasm and to evaluate the relationship between the identified polymorphisms and susceptibility to ocular surface squamous cell neoplasm and the clinical course. MATERIALS AND METHODS A totala of 70 patients with ocular surface squamous cell neoplasm (study group) and 75 healthy age and gender-matched individuals (control group) were included in the study. Vitamin D receptor FokI and BsmI polymorphisms were examined. The relationships between histopathological diagnosis, recurrence rates, tumor stage, and identified polymorphisms were investigated. RESULTS Histopathologically, 43 of the cases were squamous cell carcinoma and 27 of the cases were conjunctival intraepithelial neoplasia. The frequency of FokI (FF, Ff, ff) and BsmI (BB, Bb, bb) polymorphism genotype of vitamin D receptor gene were similar in the groups. The frequency of polymorphism (heterozygous or homozygous) for BsmI (Bb and bb) was significantly higher (p = 0.046) in the study group, while no difference was found between the groups in terms of polymorphic carriers (heterozygous or homozygous) for FokI. There was no correlation between tumor stage, recurrence-polymorphism frequency, and patient age-polymorphism frequency. CONCLUSION It is known that active vitamin D inhibits the growth of cancer cells by binding to vitamin D receptor with regulation of genes responsible for cell proliferation. The presence of BsmI polymorphism in vitamin D receptor, in particular bb genotype and b allele, appears to be associated with the susceptibility of ocular surface squamous cell neoplasm. BsmI gene polymorphisms of vitamin D receptor might play an effective role in the formation, progression, and in the course of ocular surface squamous cell neoplasm.
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Affiliation(s)
- Nergiz Ismayilova
- Department of Ophthalmology, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Melis Palamar
- Department of Ophthalmology, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Huseyin Onay
- Department of Medical Genetics, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Emine Ipek Ceylan
- Department of Medical Genetics, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Tahir Atik
- Department of Paediatrics, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Taner Akalin
- Department of Pathology, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Ayse Yagci
- Department of Ophthalmology, Faculty of Medicine, Ege University, Izmir, Turkey
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Zhou T, Li H, Xie WJ, Zhong Z, Zhong H, Lin ZJ. Association of Methylenetetrahydrofolate Reductase, Vitamin D Receptor, and Interleukin-16 Gene Polymorphisms With Renal Cell Carcinoma Risk. Technol Cancer Res Treat 2019; 18:1533033819859413. [PMID: 31242814 PMCID: PMC6598331 DOI: 10.1177/1533033819859413] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 06/22/2018] [Accepted: 08/20/2018] [Indexed: 02/06/2023] Open
Abstract
In this meta-analysis, we investigated the association of methylenetetrahydrofolate reductase, vitamin D receptor, and interleukin-16 gene polymorphisms with the risk of renal cell carcinoma. We searched the PubMed and Cochrane Library databases up to July 1, 2017, and included 12 eligible case-control studies in our analysis. The vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype were all associated with the risk of renal cell carcinoma in Asian populations. However, methylenetetrahydrofolate reductase (rs1801133 and rs1801131), vitamin D receptor (TaqI and Fok1), and interleukin-16 (rs4778889 and rs11556218) gene polymorphisms were not associated with the risk of renal cell carcinoma. Our study indicates that the vitamin D receptor ApaI A allele, ApaI AA and aa genotypes, BsmI B allele, and Fok1 FF genotype are associated with renal cell carcinoma risk.
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Affiliation(s)
- Tianbiao Zhou
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Hongyan Li
- Department of Nephrology, Huadu District People's Hospital of Guangzhou, Southern Medical University, Guangzhou, China
| | - Wei-Ji Xie
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Zhiqing Zhong
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Hongzhen Zhong
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Zhi-Jun Lin
- Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, China
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Pośpiech E, Ligęza J, Wilk W, Gołas A, Jaszczyński J, Stelmach A, Ryś J, Blecharczyk A, Wojas-Pelc A, Jura J, Branicki W. Variants of SCARB1 and VDR Involved in Complex Genetic Interactions May Be Implicated in the Genetic Susceptibility to Clear Cell Renal Cell Carcinoma. BIOMED RESEARCH INTERNATIONAL 2015; 2015:860405. [PMID: 25945350 PMCID: PMC4402472 DOI: 10.1155/2015/860405] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Revised: 02/21/2015] [Accepted: 03/15/2015] [Indexed: 11/17/2022]
Abstract
The current data are still inconclusive in terms of a genetic component involved in the susceptibility to renal cell carcinoma. Our aim was to evaluate 40 selected candidate polymorphisms for potential association with clear cell renal cell carcinoma (ccRCC) based on independent group of 167 patients and 200 healthy controls. The obtained data were searched for independent effects of particular polymorphisms as well as haplotypes and genetic interactions. Association testing implied position rs4765623 in the SCARB1 gene (OR = 1.688, 95% CI: 1.104-2.582, P = 0.016) and a haplotype in VDR comprising positions rs739837, rs731236, rs7975232, and rs1544410 (P = 0.012) to be the risk factors in the studied population. The study detected several epistatic effects contributing to the genetic susceptibility to ccRCC. Variation in GNAS1 was implicated in a strong synergistic interaction with BIRC5. This effect was part of a model suggested by multifactor dimensionality reduction method including also a synergy between GNAS1 and SCARB1 (P = 0.036). Significance of GNAS1-SCARB1 interaction was further confirmed by logistic regression (P = 0.041), which also indicated involvement of SCARB1 in additional interaction with EPAS1 (P = 0.008) as well as revealing interactions between GNAS1 and EPAS1 (P = 0.016), GNAS1 and MC1R (P = 0.031), GNAS1 and VDR (P = 0.032), and MC1R and VDR (P = 0.035).
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Affiliation(s)
- Ewelina Pośpiech
- Institute of Zoology, Faculty of Biology and Earth Sciences, Jagiellonian University, Gronostajowa 9, 30-387 Cracow, Poland
| | - Janusz Ligęza
- Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, Poland
| | - Wacław Wilk
- Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Garncarska 11, 31-115 Cracow, Poland
| | - Aniela Gołas
- Institute of Zoology, Faculty of Biology and Earth Sciences, Jagiellonian University, Gronostajowa 9, 30-387 Cracow, Poland
| | - Janusz Jaszczyński
- Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Garncarska 11, 31-115 Cracow, Poland
| | - Andrzej Stelmach
- Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Garncarska 11, 31-115 Cracow, Poland
| | - Janusz Ryś
- Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Garncarska 11, 31-115 Cracow, Poland
| | - Aleksandra Blecharczyk
- Institute of Zoology, Faculty of Biology and Earth Sciences, Jagiellonian University, Gronostajowa 9, 30-387 Cracow, Poland
| | - Anna Wojas-Pelc
- Department of Dermatology, Collegium Medicum of the Jagiellonian University, Skawińska 8, 31-066 Cracow, Poland
| | - Jolanta Jura
- Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, Poland
| | - Wojciech Branicki
- Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, Poland
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Ou C, Zhao HL, Zhu B, Huang LS, Li PZ, Lao M. Association of vitamin D receptor gene polymorphism with the risk of renal cell carcinoma: a meta-analysis. J Recept Signal Transduct Res 2014; 34:463-8. [DOI: 10.3109/10799893.2014.919593] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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The association between VDR polymorphisms and renal cell carcinoma susceptibility: a meta-analysis. Tumour Biol 2014; 35:6065-72. [DOI: 10.1007/s13277-014-1803-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2013] [Accepted: 02/26/2014] [Indexed: 10/25/2022] Open
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Khan MI, Bielecka ZF, Najm MZ, Bartnik E, Czarnecki JS, Czarnecka AM, Szczylik C. Vitamin D receptor gene polymorphisms in breast and renal cancer: current state and future approaches (review). Int J Oncol 2013; 44:349-63. [PMID: 24297042 PMCID: PMC3898813 DOI: 10.3892/ijo.2013.2204] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Accepted: 10/29/2013] [Indexed: 12/28/2022] Open
Abstract
Cancer is a major health problem and cause of death worldwide that accounted for 7.6 million deaths in 2008, which is projected to continue rising with an estimated 13.1 million deaths in 2030 according to WHO. Breast cancer is the leading cause of cancer-based death among women around the world and its incidence is increasing annually with a similar tendency. In contrast, renal cell carcinoma accounts for only 3% of total human malignancies but it is still the most common type of urological cancer with a high prevalence in elderly men (>60 years of age). There are several factors linked with the development of renal cell cancer only, while others are connected only with breast cancer. Genetic risk factors and smoking are the factors which contribute to carcinogenesis in general. Some evidence exists indicating that vitamin D receptor (VDR) gene polymorphisms are associated with both breast and renal cancer; therefore, we put forward the hypothesis that polymorphisms in the VDR gene may influence both the occurrence risks of these cancers and their prognosis. However, the relationship between VDR polymorphisms and these two specific cancers remains a controversial hypothesis, and consequently needs further confirmation via clinical research together with genetic investigations. Here, we aimed to assess the correlation between the different alleles of VDR gene polymorphisms and renal cell cancer and breast cancer risks separately through a systematic review of the present literature. In contrast, this analysis has revealed that some VDR gene polymorphisms, such as: Bsm1, poly(A), Taq1, Apa1, are to some extent associated with breast cancer risk. Other polymorphisms were found to be significantly associated with renal cell cancer. Namely, they were Fok1, Bsm1, Taq1 and Apa1, which encode proteins participating mainly in proliferation, apoptosis and cell cycle regulation. However, data concerning renal cancer are not sufficient to firmly establish the VDR gene polymorphism association.
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Affiliation(s)
- Mohammed I Khan
- Molecular Oncology Laboratory, Clinic of Oncology, Military Institute of Medicine, 04-141 Warsaw, Poland
| | - Zofia F Bielecka
- Molecular Oncology Laboratory, Clinic of Oncology, Military Institute of Medicine, 04-141 Warsaw, Poland
| | - Mohammad Z Najm
- Department of Biochemistry, Jamia Hamdard University, New Delhi 110 062, India
| | - Ewa Bartnik
- Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, 02-106 Warsaw, Poland
| | - Jerzy S Czarnecki
- Department of Knowledge Management, Faculty of Management, University of Lodz, 90-237 Lodz, Poland
| | - Anna M Czarnecka
- Molecular Oncology Laboratory, Clinic of Oncology, Military Institute of Medicine, 04-141 Warsaw, Poland
| | - Cezary Szczylik
- Molecular Oncology Laboratory, Clinic of Oncology, Military Institute of Medicine, 04-141 Warsaw, Poland
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Fujimoto N, Kubo T, Inatomi H, Bui HTT, Shiota M, Sho T, Matsumoto T. Polymorphisms of the androgen transporting gene SLCO2B1 may influence the castration resistance of prostate cancer and the racial differences in response to androgen deprivation. Prostate Cancer Prostatic Dis 2013; 16:336-40. [PMID: 23896625 DOI: 10.1038/pcan.2013.23] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2013] [Revised: 06/01/2013] [Accepted: 06/26/2013] [Indexed: 02/02/2023]
Abstract
BACKGROUND Organic anion-transporting polypeptides (OATPs) encoded by SLCO mediate the cellular uptake of many compounds, including androgens. SLCO1B3 and SLCO2B1 are polymorphic, and single-nucleotide polymorphisms of those genes alter androgen transport efficiency. We aimed to investigate the association between genetic variations in SLCOs and the progression to castration-resistant prostate cancer (CRPC). METHODS We studied the progression to CRPC for the SLCO1B3 rs4149117 and SLCO2B1 rs12422149 genotypes in 87 prostate cancer patients who received androgen deprivation therapy (ADT). Data were analyzed using the χ(2) test, Kaplan-Meier survival analysis and Cox proportional hazard model. RESULTS SLCO3B1 genotypes were not significantly associated with the time to progression (TTP); however, patients carrying the active androgen transport SLCO2B1 genotype (GG allele) exhibited a median TTP that was 7 months shorter than that of patients with impaired androgen-transporting activity SLCO2B1 polymorphisms (GA/AA alleles) (10.0 vs 17.0 months, P=0.004). Active androgen transport genotypes of SLCO2B1 (GG allele) occurred more frequently in African and Caucasian populations than in Japanese and Han Chinese populations (P<0.001). CONCLUSIONS These data suggest that SLCO2B1 rs12422149 variants could provide prognostic value for prostate cancer patients treated with ADT and influence ethnic differences in response to ADT. Active androgen import may be one of the underlying mechanisms of resistance to ADT, and androgen-transporting systems could provide novel biomarkers and targets for CRPC treatment.
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Affiliation(s)
- N Fujimoto
- Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
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9
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Vitamin D receptor FokI and BsmI gene polymorphism and its association with grade and stage of renal cell carcinoma in North Indian population. Tumour Biol 2011; 33:23-31. [DOI: 10.1007/s13277-011-0236-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2011] [Accepted: 08/30/2011] [Indexed: 12/18/2022] Open
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10
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Karami S, Brennan P, Navratilova M, Mates D, Zaridze D, Janout V, Kollarova H, Bencko V, Matveev V, Szesznia-Dabrowska N, Holcatova I, Yeager M, Chanock S, Rothman N, Boffetta P, Chow WH, Moore LE. Vitamin d pathway genes, diet, and risk of renal cell carcinoma. Int J Endocrinol 2010; 2010:879362. [PMID: 20049159 PMCID: PMC2798114 DOI: 10.1155/2010/879362] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2009] [Accepted: 08/06/2009] [Indexed: 11/17/2022] Open
Abstract
Mediated by binding to the high-affinity vitamin D receptor (VDR), vitamin D forms a heterodimer complex with the retinoid-X-receptor (RXR). Variation in both genes has been shown to modify renal cell carcinoma (RCC) risk. Therefore, we investigated whether VDR and RXRA polymorphisms modify associations between RCC risk and frequency of dietary intake of vitamin D and calcium rich foods, and occupational ultraviolet exposure among 777 RCC case and 1035 controls from Central and Eastern Europe. A positive association was observed in this population between increasing dietary intake frequency of yogurt, while an inverse association was observed with egg intake frequency. RXRA polymorphisms, located 3' of the coding sequence, modified associations between specific vitamin D rich foods and RCC risk, while RXRA polymorphisms, located in introns 1 and 4, modified associations with specific calcium rich foods. Results suggest that variants in the RXRA gene modified the associations observed between RCC risk and calcium and vitamin D intake.
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Affiliation(s)
- S. Karami
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
- *S. Karami:
| | - P. Brennan
- International Agency for Research on Cancer, Lyon, France
| | - M. Navratilova
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - D. Mates
- Institue of Public Health, Bucharest, Romania
| | - D. Zaridze
- Institute of Carcinogenesis, Cancer Research Centre, Moscow, Russia
| | - V. Janout
- Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic
| | - H. Kollarova
- Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic
| | - V. Bencko
- Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, Czech Republic
| | - V. Matveev
- Institute of Carcinogenesis, Cancer Research Centre, Moscow, Russia
| | | | - I. Holcatova
- Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, Czech Republic
| | - M. Yeager
- Core Genotyping Facility, Advanced Technology Center, Bethseda National Cancer Institute, NIH, Department of Health and Human Services, MD, USA
| | - S. Chanock
- Core Genotyping Facility, Advanced Technology Center, Bethseda National Cancer Institute, NIH, Department of Health and Human Services, MD, USA
| | - N. Rothman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
| | - P. Boffetta
- International Agency for Research on Cancer, Lyon, France
| | - W-H. Chow
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
| | - L. E. Moore
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
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Karami S, Brennan P, Rosenberg PS, Navratilova M, Mates D, Zaridze D, Janout V, Kollarova H, Bencko V, Matveev V, Szeszenia-Dabrowska N, Holcatova I, Yeager M, Chanock S, Menashe I, Rothman N, Chow WH, Boffetta P, Moore LE. Analysis of SNPs and haplotypes in vitamin D pathway genes and renal cancer risk. PLoS One 2009; 4:e7013. [PMID: 19753122 PMCID: PMC2737618 DOI: 10.1371/journal.pone.0007013] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2009] [Accepted: 07/14/2009] [Indexed: 11/25/2022] Open
Abstract
In the kidney vitamin D is converted to its active form. Since vitamin D exerts its activity through binding to the nuclear vitamin D receptor (VDR), most genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR and other vitamin D pathway genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC) etiology. RCC cases (N = 777) and controls (N = 1,035) were genotyped to investigate the relationship between RCC risk and variation in eight target genes. Minimum-p-value permutation (Min-P) tests were used to identify genes associated with risk. A three single nucleotide polymorphism (SNP) sliding window was used to identify chromosomal regions with a False Discovery Rate of <10%, where subsequently, haplotype relative risks were computed in Haplostats. Min-P values showed that VDR (p-value = 0.02) and retinoid-X-receptor-alpha (RXRA) (p-value = 0.10) were associated with RCC risk. Within VDR, three haplotypes across two chromosomal regions of interest were identified. The first region, located within intron 2, contained two haplotypes that increased RCC risk by approximately 25%. The second region included a haplotype (rs2239179, rs12717991) across intron 4 that increased risk among participants with the TC (OR = 1.31, 95% CI = 1.09-1.57) haplotype compared to participants with the common haplotype, TT. Across RXRA, one haplotype located 3' of the coding sequence (rs748964, rs3118523), increased RCC risk 35% among individuals with the variant haplotype compared to those with the most common haplotype. This study comprehensively evaluated genetic variation across eight vitamin D pathway genes in relation to RCC risk. We found increased risk associated with VDR and RXRA. Replication studies are warranted to confirm these findings.
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Affiliation(s)
- Sara Karami
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Bethesda, Maryland, USA.
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Luong KVQ, Nguyen LTH. The beneficial role of vitamin D and its analogs in cancer treatment and prevention. Crit Rev Oncol Hematol 2009; 73:192-201. [PMID: 19446468 DOI: 10.1016/j.critrevonc.2009.04.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2008] [Revised: 03/31/2009] [Accepted: 04/17/2009] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Cancer is the leading cause of death in the United States, and the probability of developing cancer increases dramatically with age. Interestingly, vitamin D deficiency is also recognized more often in people of advanced ages. A potential relationship between vitamin D deficiency and cancer has been reported in the literature. METHOD Review Medline database literature and discuss the relationship between vitamin D status and cancer. RESULTS Environmental (including seasonal and geographic) and genetic factors contribute to the development of both vitamin D deficiency and cancer. The vitamin D receptor is present in many tissues, especially in malignant cells, and may contribute to the successful use of vitamin D and its analogs in the treatment of some cancer patients. CONCLUSION Further investigation of the role of vitamin D in the treatment of cancer is warranted.
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Abstract
We analyzed renal cell cancer incidence patterns in the United States and reviewed recent epidemiologic evidence with regard to environmental and host genetic determinants of renal cell cancer risk. Renal cell cancer incidence rates continued to rise among all racial/ethnic groups in the United States, across all age groups, and for all tumor sizes, with the most rapid increases for localized stage disease and small tumors. Recent cohort studies confirmed the association of smoking, excess body weight, and hypertension with an elevated risk of renal cell cancer, and suggested that these factors can be modified to reduce the risk. There is increasing evidence for an inverse association between renal cell cancer risk and physical activity and moderate intake of alcohol. Occupational exposure to trichloroethylene has been positively associated with renal cell cancer risk in several recent studies, but its link with somatic mutations of the von Hippel-Lindau gene has not been confirmed. Studies of genetic polymorphisms in relation to renal cell cancer risk have produced mixed results, but genome-wide association studies with larger sample size and a more comprehensive approach are underway. Few epidemiologic studies have evaluated risk factors by subtypes of renal cell cancer defined by somatic mutations and other tumor markers.
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Naderi N, Farnood A, Habibi M, Derakhshan F, Balaii H, Motahari Z, Agah MR, Firouzi F, Rad MG, Aghazadeh R, Zojaji H, Zali MR. Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease. J Gastroenterol Hepatol 2008; 23:1816-22. [PMID: 18752562 DOI: 10.1111/j.1440-1746.2008.05525.x] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be linked to inflammatory bowel disease (IBD). Many studies have recognized the relation of VDR gene polymorphisms with inflammatory and autoimmune disorders. Determining the frequency of these polymorphisms and their possible relation with IBD can improve understandings about the genetic background of these diseases. The objective of this study was to assess the association of VDR gene polymorphisms (Apa I, Taq I, Bsm I, Fok I) with IBD in Iran. METHODS In this case control designed study 150 patients with ulcerative colitis, 80 patients with Crohn's disease and 150 Age and Sex matched healthy controls from Iranian origin were enrolled. These patients were referred to a tertiary center during a two-year period (2004-2006). Assessment of VDR gene polymorphisms was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype-phenotype association for these polymorphisms was analyzed. RESULTS Only the frequency of the Fok I polymorphism was significantly higher in ulcerative colitis and Crohn's groups. The frequency of the polymorphic allele f was higher in ulcerative colitis and Crohn's patients comparing with controls (P = 0.011 and P < 0.001, respectively). The f/f genotype was also significantly more frequent (P < 0.001), while the F/F genotype was less presented in Crohn's patients compared to controls (P < 0.001). No genotype-phenotype association was observed with any mutations. CONCLUSIONS This study suggests a probable association of the Fok I polymorphism in VDR receptor gene and Crohn's susceptibility in Iranian population.
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Affiliation(s)
- Nosratollah Naderi
- Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University, MC, Tehran, Iran
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Karami S, Brennan P, Hung RJ, Boffetta P, Toro J, Wilson RT, Zaridze D, Navratilova M, Chatterjee N, Mates D, Janout V, Kollarova H, Bencko V, Szeszenia-Dabrowska N, Holcatova I, Moukeria A, Welch R, Chanock S, Rothman N, Chow WH, Moore LE. Vitamin D receptor polymorphisms and renal cancer risk in Central and Eastern Europe. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2008; 71:367-72. [PMID: 18246496 PMCID: PMC2799224 DOI: 10.1080/15287390701798685] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/07/2023]
Abstract
Previous studies investigated the role of vitamin D intake and cancer risk. The kidney is a major organ for vitamin D metabolism, activity, and calcium homeostasis; therefore, it was hypothesized that dietary vitamin D intake and polymorphisms in the vitamin D receptor (VDR) gene may modify renal cell carcinoma (RCC) risk. Three common VDR gene polymorphisms (BsmI, FokI, TaqI) were evaluated among 925 RCC cases and 1192 controls enrolled in a hospital-based case-control study conducted in Central and Eastern Europe. Overall associations with RCC risk were not observed; however, subgroup analyses revealed associations after stratification by median age of diagnosis and family history of cancer. Among subjects over 60 yr, reduced risks were observed among carriers of the f alleles in the FokI single-nucleotide polymorphism (SNP) (odds ratio [OR] = 0.61 for Ff and OR = 0.74 for ff genotypes) compared to subjects with the FF genotype (P trend = 0.04; P interaction = 0.004). Subjects with the BB BsmI genotype and a positive family history of cancer had lower risk compared to subjects with the bb allele (OR = 0.60; 95% CI: 0.33-1.1; P trend = 0.05). Genotype associations with these subgroups were not modified when dietary sources of vitamin D or calcium were considered. Additional studies of genetic variation in the VDR gene are warranted.
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Affiliation(s)
- S Karami
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. karamis@ mail.nih.gov
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Renal cell carcinoma in a child presented as bilateral femur neck fractures caused by severe vitamin D deficiency. J Pediatr Hematol Oncol 2007; 29:848-50. [PMID: 18090936 DOI: 10.1097/mph.0b013e3181581587] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
An Ethiopian girl 14 years and 11 months of age presented with bilateral transcervical hip fractures. Workup revealed severe vitamins D and C deficiencies with secondary hyperparathyroidism. Imaging studies showed bilateral radiolucent metaphyseal bands with multiple lytic lesions in long bones. A mass in the right flank was found to be renal cell carcinoma (RCC). Currently, 9 months postsurgery and supplemental therapy, the patient is fully ambulatory and free of pain. This first report of asymptomatic RCC in severely vitamin D deficient child highlights the relation of RCC to vitamin D deficiency and emphasizes the importance of careful evaluation of these children.
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18
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Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta 2006; 371:1-12. [PMID: 16563362 DOI: 10.1016/j.cca.2006.02.016] [Citation(s) in RCA: 360] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2005] [Revised: 01/09/2006] [Accepted: 02/09/2006] [Indexed: 12/31/2022]
Abstract
The vitamin D endocrine system is central to the control of bone and calcium homeostasis. Thus, alterations in the vitamin D pathway lead to disturbances in mineral metabolism. Furthermore, a role for vitamin D has been suggested in other diseases, like cancer, diabetes and cardiovascular disease. Expression and nuclear activation of the vitamin D receptor (VDR) are necessary for the effects of vitamin D. Several genetic variations have been identified in the VDR. DNA sequence variations, which occur frequently in the population, are referred to as "polymorphisms" and can have biological effects. To test whether there is a linkage between VDR polymorphisms and diseases, epidemiological studies are performed. In these studies, the presence of a variation of the gene is studied in a population of patients, and then compared to a control group. Thus, association studies are performed, and a link among gene polymorphisms and diseases can be established. Since the discovery of VDR polymorphisms a number of papers have been published studying its role in bone biology, renal diseases, diabetes, etc. The purpose of this review is to summarize the vast amount of information regarding vitamin D receptor polymorphisms and human diseases, and discuss its possible role as diagnostic tools.
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Affiliation(s)
- Jose M Valdivielso
- Laboratorio de Investigación HUAV-UDL, Hospital Universitario Arnau de Vilanova, Rovira Roure 80, 25198, Lleida, Spain.
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Jacobs ET, Haussler MR, Martínez ME. Vitamin D activity and colorectal neoplasia: a pathway approach to epidemiologic studies. Cancer Epidemiol Biomarkers Prev 2005; 14:2061-3. [PMID: 16172209 DOI: 10.1158/1055-9965.epi-05-0472] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Gong YL, Xie DW, Deng ZL, Bostick RM, Miao XJ, Zhang JH, Gong ZH. Vitamin D receptor gene Tru9I polymorphism and risk for incidental sporadic colorectal adenomas. World J Gastroenterol 2005; 11:4794-9. [PMID: 16097046 PMCID: PMC4398724 DOI: 10.3748/wjg.v11.i31.4794] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: Recent laboratory and epidemiological studies suggest that vitamin D is a potential agent for colorectal cancer prevention. Its function is partially mediated by the vitamin D receptor (VDR). The aim of this study was to investigate whether a novel G (allele ‘U’)>A (allele ‘u’) polymorphism (Tru9I) in the VDR intron 8 region is associated with risk for colorectal adenoma in a colonoscopy-based case-control study.
METHODS: Genotyping for a total of 391 subjects was carried out through PCR and restriction fragment length polymorphism.
RESULTS: The frequencies of ‘U’ and ‘u’ alleles were 89.3% and 10.7%, respectively. The ‘Uu’ and ‘uu’ genotypes were associated with decreased risk for adenoma (OR, 0.71; 95%CI, 0.40-1.25). The inverse association was more pronounced for multiple adenomas and adenomas that were larger had moderate or greater dysplasia, or were sessile: the odds ratios (ORs) were, 0.51 (95%CI, 0.21-1.24), 0.37 (95%CI, 0.11-1.28), 0.68 (95%CI, 0.33-1.41), and 0.36 (95%CI, 0.13-0.97) respectively. In joint/combined analyses, inverse associations were more obvious among those who had at least one ‘u’ allele and also were younger (OR, 0.60; 95%CI, 0.26-1.37), women (OR, 0.38; 95%CI, 0.17-0.88), did not smoke (OR, 0.39; 95%CI, 0.13-1.23), or took NSAID (OR, 0.38; 95%CI, 0.12-1.25), but no evidence existed for interactions with calcium or vitamin D intake.
CONCLUSION: Our findings suggest that the VDR Tru9I polymorphism may be associated with lower risk for colorectal adenoma, particularly in interaction with various risk factors, but not with calcium or vitamin D.
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Affiliation(s)
- You-Ling Gong
- Tumor Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Lowe LC, Guy M, Mansi JL, Peckitt C, Bliss J, Wilson RG, Colston KW. Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. Eur J Cancer 2005; 41:1164-9. [PMID: 15911240 DOI: 10.1016/j.ejca.2005.01.017] [Citation(s) in RCA: 181] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2004] [Revised: 01/05/2005] [Accepted: 01/31/2005] [Indexed: 01/08/2023]
Abstract
Low levels of 25-hydroxy vitamin D (25(OH)D) and polymorphisms in the vitamin D receptor gene (VDR) have been found separately to increase risk of breast cancer. The aim of this study was to determine whether low 25(OH)D levels, alone and in combination with BsmI VDR genotype, increased breast cancer risk in a United Kingdom (UK) Caucasian population. Breast cancer patients (n=179) and control women (n=179) were recruited and 25(OH)D levels measured by enzyme-linked immunosorbent assay (ELISA). VDR genotype was determined by polymerase chain reaction (PCR) and restriction enzyme digest. Analysis showed that subjects with 25(OH)D levels <50 nM and the bb BsmI VDR genotype are 6.82 times more likely to have breast cancer than subjects with levels of 25(OH)D>50 nM and either the BB or Bb genotype (95% confidence interval (CI) 2.31-14.7, P<0.001). This study indicates that low levels of circulating 25(OH)D, both alone and in combination with BsmI VDR genotype, may increase risk of breast cancer in a UK Caucasian population.
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Affiliation(s)
- Lorraine C Lowe
- Department of Cellular and Molecular Medicine, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK
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Halsall JA, Osborne JE, Potter L, Pringle JH, Hutchinson PE. A novel polymorphism in the 1A promoter region of the vitamin D receptor is associated with altered susceptibilty and prognosis in malignant melanoma. Br J Cancer 2004; 91:765-70. [PMID: 15238985 PMCID: PMC2364794 DOI: 10.1038/sj.bjc.6602006] [Citation(s) in RCA: 81] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
The association of Taq 1 and Fok 1 restriction fragment length polymorphisms of the vitamin D receptor with occurrence and outcome of malignant melanoma (MM), as predicted by tumour (Breslow) thickness, has been reported previously. We now report a novel adenine–guanine substitution −1012 bp relative to the exon 1a transcription start site (A-1012G), found following screening by single-stranded conformational polymorphism of this promoter region. There was a total of 191 MM cases , which were stratified according to conventional Breslow thickness groups, cases being randomly selected from each group to form a distribution corresponding to the known distribution of Breslow thickness in our area, and this population (n=176) was compared to 80 controls. The A allele was over-represented in MM patients and, with GG as reference, odds ratio (OR) for AG was 2.5, 95% confidence interval (CI) 1.1–5.7, (P=0.03) and AA 3.3, CI 1.4–8.1, (P=0.007). The outcome was known in 171 of 191 patients and the A allele was related to the development of metastasis, the Kaplan–Meier estimates of the probability of metastasis at 5 years being: GG 0%; AG 9%, CI 4–16%; AA 21%, CI 12–36%; (P=0.008), and to thicker Breslow thickness groups (P=0.04). The effect on metastasis was independent of tumour thickness and A-1012G may have predictive potential, additional to Breslow thickness. Neither the Fok 1 nor Taq 1 variants (f and t) were significantly related to the development of metastasis, although there was a strong relationship of fftt with the thickest Breslow thickness group (P=0.005). There was an interaction between the A-1012G and Fok 1 polymorphisms (P=0.025) and the Fok 1 variant enhanced the effect of the A allele of the A-1012G polymorphism on metastasis, the probability of metastasis for AAff at 5 years follow-up being 57%, CI 24–92%.
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Affiliation(s)
- J A Halsall
- Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK.
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