Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer

AL Price

AM Barreto

AM Mondul

B Mikhak

BL Lokeshwar

C Bonilla

Carolina Bonilla

Chris Metcalfe

D Berry

David E. Neal

David M. Evans

DM Peehl

E Giovannucci

Freddie C. Hamdy

G Davey Smith

George Davey Smith

GG Schwartz

IM Shui

IM Thompson

J Ahn

J Ma

J. Athene Lane

JA Lane

JB Cheng

Jenny L. Donovan

John P. Kemp

KJM Janssen

L Chen

LV Stewart

M Epstein

M Ohori

M Speeckaert

MA Hernán

MA Rowlands

Mark Lathrop

MS Willis

P Royston

P Tuohimaa

R Gilbert

Rebecca Gilbert

RF Chun

Richard M. Martin

Sarah Lewis

SJ Lewis

SJ Weinstein

SK Holt

Smith G Davey

T Sakaki

TC Polek

TJ Wang

TM Palmer

WD Fraser

William D. Fraser

World Cancer Research Fund/American Institute for Cancer R

Y Xu

YR Lou

Z Guo

Cancer Causes & Control

English

PubMed

PURPOSE: Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer. METHODS: In a nested case-control study (within the ProtecT trial), we estimated odds ratios and 95 % confidence intervals (CIs) quantifying associations between SNPs and prostate cancer. Subgroup analyses investigated whether associations were stronger in men who had high/low sun exposure [a proxy for 25(OH)D]. We quantified associations of SNPs with stage (T1-T2/T3-T4) and grade (<7/≥7). Multiple variant scores included SNPs encoding proteins involved in 25(OH)D synthesis and metabolism. RESULTS: We included 1,275 prostate cancer cases (141 locally advanced, 385 high grades) and 2,062 healthy controls. Vitamin D-binding protein SNPs were associated with prostate cancer (rs4588-A: OR 1.20, CI 1.01, 1.41, p = 0.04; rs7041-T: OR 1.19, CI 1.02, 1.38, p = 0.03). Low 25(OH)D metabolism score was associated with high (vs low) grade (OR 0.76, CI 0.63, 0.93, p = 0.01); there was a similar association of its component variants: rs6013897-A in CYP24A1 (OR 0.78, CI 0.60, 1.01, p = 0.06) and rs10877012-T in CYP27B1 (OR 0.80, CI 0.63, 1.02, p = 0.07). There was no evidence that associations differed by level of sun exposure. CONCLUSION: We found some evidence that vitamin D pathway SNPs were associated with prostate cancer risk and grade, but not stage. There was no evidence of an association in men with deficient vitamin D (measured by having low sun exposure)

Gilbert, R

Bonilla, C

Metcalfe, C

Lewis, S

Evans, DM

Fraser, WD

Kemp, JP

Donovan, JL

Hamdy, FC

Neal, DE

Lane, JA

Smith, GD

Lathrop, M

Martin, RM

Spiral - Imperial College Digital Repository

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer: a nested case-control study

Gilbert, Rebecca

Bonilla, Carolina

Metcalfe, Chris

Lewis, Sarah

Evans, David M

Fraser, William D

Kemp, John P

Donovan, Jenny L

Hamdy, Freddie C

Neal, David E

Lane, J Athene

Smith, George Davey

Lathrop, Mark

Martin, Richard M

University of East Anglia digital repository

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case-control study

Springer - Publisher Connector

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer: a nested case–control study

Crossref

PURPOSE: Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer.METHODS: In a nested case-control study (within the ProtecT trial), we estimated odds ratios and 95 % confidence intervals (CIs) quantifying associations between SNPs and prostate cancer. Subgroup analyses investigated whether associations were stronger in men who had high/low sun exposure [a proxy for 25(OH)D]. We quantified associations of SNPs with stage (T1-T2/T3-T4) and grade (&lt;7/≥7). Multiple variant scores included SNPs encoding proteins involved in 25(OH)D synthesis and metabolism.RESULTS: We included 1,275 prostate cancer cases (141 locally advanced, 385 high grades) and 2,062 healthy controls. Vitamin D-binding protein SNPs were associated with prostate cancer (rs4588-A: OR 1.20, CI 1.01, 1.41, p = 0.04; rs7041-T: OR 1.19, CI 1.02, 1.38, p = 0.03). Low 25(OH)D metabolism score was associated with high (vs low) grade (OR 0.76, CI 0.63, 0.93, p = 0.01); there was a similar association of its component variants: rs6013897-A in CYP24A1 (OR 0.78, CI 0.60, 1.01, p = 0.06) and rs10877012-T in CYP27B1 (OR 0.80, CI 0.63, 1.02, p = 0.07). There was no evidence that associations differed by level of sun exposure.CONCLUSION: We found some evidence that vitamin D pathway SNPs were associated with prostate cancer risk and grade, but not stage. There was no evidence of an association in men with deficient vitamin D (measured by having low sun exposure).</p

Evans, David M.

Fraser, William D.

Kemp, John P.

Donovan, Jenny L.

Hamdy, Freddie C.

Neal, David E.

Lane, J. Athene

Martin, Richard M.

Explore Bristol Research

                          Gilbert, R., Bonilla, C., Metcalfe, C., Lewis, S., Evans, D. M., Fraser, W. D.,... Martin, R. M. (2015). Associations of vitamin D pathway genes withcirculating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostatecancer: a nested case–control study. Cancer Causes and Control, 26(2), 205-218. DOI: 10.1007/s10552-014-0500-5Publisher's PDF, also known as Version of recordLicense (if available):CC BYLink to published version (if available):10.1007/s10552-014-0500-5Link to publication record in Explore Bristol ResearchPDF-documentThis is the final published version of the article (version of record). It first appeared online via Springer athttp://link.springer.com/article/10.1007%2Fs10552-014-0500-5. Please refer to any applicable terms of use ofthe publisherUniversity of Bristol - Explore Bristol ResearchGeneral rightsThis document is made available in accordance with publisher policies. Please cite only the publishedversion using the reference above. Full terms of use are available:http://www.bristol.ac.uk/pure/about/ebr-terms.html1  ASSOCIATIONS OF VITAMIN D-PATHWAY GENES WITH CIRCULATING 25-HYDROXYVITAMIN-D, 1,25-DIHYDROXYVITAMIN-D AND PROSTATE CANCER:  SUPPLEMENTARY TABLE  Rebecca Gilbert1, Carolina Bonilla1, Chris Metcalfe1, Sarah Lewis1,2, David M Evans2, William D Fraser3, John P Kemp1,2, Jenny Donovan1, Freddie Hamdy4, David E Neal5, J Athene Lane1, George Davey Smith1,2*, Mark Lathrop6,7*, Richard M Martin1,2,8*  1 School of Social and Community Medicine, University of Bristol, Bristol, UK. 2 MRC Centre for Causal Analysis in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK. 3 Norwich Medical School, University of East Anglia, Norwich, UK. 4 Nuffield Department of Surgery, University of Oxford, Oxford, UK. 5 Department of Oncology, University of Cambridge, Cambridge, UK. 6 Commissariat à l'Energie Atomique, Center National de Génotypage, Evry, France. 7McGill University-Génome Québec Innovation Centre, Montreal, Canada 8National Institute for Health Research, Bristol Biomedical Research Unit in Nutrition, Bristol, UK *Joint last authors – these authors contributed equally to this work.  Corresponding author: Rebecca Gilbert, School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK. Email: Becky.Gilbert@bristol.ac.uk   2  Supplementary Table 1: Associations between SNPs and the ten principal components (PCs) used to adjust all analyses for population stratification PCsa Effect of SNP on PCb 95% CI p-value Effect of SNP on PCb 95% CI p-value Effect of SNP on PCb 95% CI p-value  CYP2R1 rs10741657 CYP2R1 rs2060793 DHCR7 rs12785878 1 -0.00046 (-0.00137,0.00044) 0.314 -0.00046 (-0.00137,0.00044) 0.314 -0.00142 (-0.00252,-0.00032) 0.011 2 0.00036 (-0.00055,0.00127) 0.436 0.00036 (-0.00055,0.00127) 0.436 -0.00035 (-0.00145,0.00075) 0.535 3 -0.00079 (-0.00170,0.00011) 0.086 -0.00079 (-0.00170,0.00011) 0.086 -0.00027 (-0.00137,0.00083) 0.628 4 -0.00021 (-0.00112,0.00070) 0.651 -0.00021 (-0.00112,0.00070) 0.651 -0.0006 (-0.00171,0.00050) 0.285 5 0.00053 (-0.00037,0.00144) 0.248 0.00053 (-0.00037,0.00144) 0.248 -0.00033 (-0.00144,0.00077) 0.553 6 -0.00078 (-0.00169,0.00013) 0.095 -0.00078 (-0.00169,0.00013) 0.095 0.00102 (-0.00009,0.00212) 0.072 7 0.00043 (-0.00047,0.00134) 0.348 0.00043 (-0.00047,0.00134) 0.348 -0.00034 (-0.00144,0.00076) 0.542 8 -0.00029 (-0.00120,0.00062) 0.531 -0.00029 (-0.00120,0.00062) 0.531 -0.0015 (-0.00260,-0.00039) 0.008 9 0.00081 (-0.00009,0.00172) 0.079 0.00081 (-0.00009,0.00172) 0.079 -0.00046 (-0.00156,0.00065) 0.419 10 0.00022 (-0.00070,0.00113) 0.642 0.00022 (-0.00070,0.00113) 0.642 -0.00072 (-0.00182,0.00039) 0.206            NADSYN1 rs3829251 Synthesis scorec VDBP rs2282679 1 -0.00164 (-0.00299,-0.00029) 0.017 -0.0003 (-0.00100,0.00040) 0.405 -0.00011 (-0.00109,0.00088) 0.831 2 -0.00026 (-0.00162,0.00109) 0.704 -0.00036 (-0.00106,0.00034) 0.318 0.0002 (-0.00079,0.00119) 0.698 3 -0.00068 (-0.00203,0.00067) 0.326 0.00036 (-0.00034,0.00107) 0.308 0.00079 (-0.00019,0.00178) 0.115 4 -0.0005 (-0.00186,0.00086) 0.469 -0.00012 (-0.00082,0.00059) 0.740 0.00009 (-0.00090,0.00108) 0.856 5 -0.00087 (-0.00223,0.00048) 0.206 -0.00046 (-0.00116,0.00025) 0.203 0.00043 (-0.00056,0.00141) 0.398 6 0.00126 (-0.00010,0.00262) 0.069 0.00088 (0.00017,0.00158) 0.015 -0.00032 (-0.00131,0.00068) 0.532 7 -0.00113 (-0.00248,0.00022) 0.101 -0.0004 (-0.00110,0.00030) 0.265 -0.00017 (-0.00115,0.00082) 0.741 8 -0.00177 (-0.00313,-0.00041) 0.011 -0.00043 (-0.00114,0.00027) 0.229 0.00002 (-0.00097,0.00102) 0.962 9 -0.00048 (-0.00184,0.00088) 0.487 -0.00067 (-0.00138,0.00003) 0.061 0.00074 (-0.00025,0.00173) 0.142 10 -0.00055 (-0.00191,0.00081) 0.430 -0.00042 (-0.00113,0.00029) 0.244 -0.00038 (-0.00137,0.00061) 0.451            VDBP rs4588  VDBP rs7041 VDBP rs1155563 1 -0.0003 (-0.00173,0.00112) 0.675 -0.00054 (-0.00184,0.00077) 0.422 -0.00029 (-0.00126,0.00069) 0.564 2 -0.00044 (-0.00184,0.00095) 0.532 -0.00036 (-0.00164,0.00091) 0.576 0.00046 (-0.00052,0.00144) 0.353 3 0.00095 (-0.00047,0.00236) 0.189 0.00001 (-0.00129,0.00130) 0.991 0.00097 (-0.00000,0.00195) 0.051 4 0.00043 (-0.00096,0.00182) 0.541 0.0001 (-0.00117,0.00138) 0.872 0.00014 (-0.00084,0.00113) 0.772 5 0.0003 (-0.00112,0.00171) 0.680 0.00068 (-0.00063,0.00198) 0.309 0.00025 (-0.00073,0.00123) 0.617 6 -0.00023 (-0.00167,0.00120) 0.752 -0.00127 (-0.00259,0.00005) 0.059 -0.00027 (-0.00126,0.00071) 0.587 7 0.00017 (-0.00124,0.00158) 0.812 0.00041 (-0.00088,0.00170) 0.531 -0.00023 (-0.00121,0.00074) 0.639 8 0.00081 (-0.00058,0.00220) 0.253 0.00005 (-0.00123,0.00132) 0.943 0.00003 (-0.00096,0.00101) 0.956 9 0.00102 (-0.00039,0.00242) 0.156 0.00036 (-0.00094,0.00165) 0.589 0.0008 (-0.00018,0.00178) 0.112 10 -0.00032 (-0.00173,0.00109) 0.658 0.00079 (-0.00050,0.00208) 0.231 -0.00092 (-0.00190,0.00006) 0.067            CYP24A1 rs6013897 CYP27B1 rs703842 CYP27B1 rs10877012 1 -0.00038 (-0.00154,0.00078) 0.519 0.00107 (0.00010,0.00204) 0.031 0.00072 (-0.00070,0.00213) 0.319 2 0.00049 (-0.00068,0.00165) 0.410 -0.00025 (-0.00122,0.00073) 0.618 0.00054 (-0.00083,0.00192) 0.439 3 0.0002 (-0.00096,0.00136) 0.733 -0.00027 (-0.00124,0.00070) 0.581 -0.00077 (-0.00216,0.00063) 0.281 4 -0.00003 (-0.00120,0.00113) 0.954 0.00001 (-0.00097,0.00098) 0.990 0.00008 (-0.00129,0.00145) 0.908 5 -0.00049 (-0.00165,0.00068) 0.412 0.00056 (-0.00042,0.00153) 0.264 0.00047 (-0.00092,0.00186) 0.505 3  6 0.00053 (-0.00063,0.00170) 0.370 -0.00115 (-0.00212,-0.00017) 0.022 -0.00156 (-0.00297,-0.00015) 0.031 7 -0.00056 (-0.00172,0.00060) 0.343 0.00153 (0.00056,0.00250) 0.002 0.00111 (-0.00028,0.00251) 0.116 8 -0.00004 (-0.00120,0.00113) 0.951 -0.00125 (-0.00222,-0.00027) 0.012 -0.00155 (-0.00291,-0.00018) 0.027 9 -0.00019 (-0.00136,0.00097) 0.747 0.00056 (-0.00042,0.00153) 0.264 0.00051 (-0.00088,0.00190) 0.469 10 -0.00081 (-0.00197,0.00036) 0.176 -0.00005 (-0.00103,0.00093) 0.918 0.00034 (-0.00105,0.00173) 0.629            Metabolism scored VDR ApaI VDR BsmI  1 0.00059 (-0.00051,0.00168) 0.294 -0.0018 (-0.00308,-0.00052) 0.006 0.00113 (-0.00020,0.00245) 0.095 2 0.00035 (-0.00072,0.00142) 0.519 0.00063 (-0.00063,0.00189) 0.326 -0.00026 (-0.00155,0.00104) 0.699 3 -0.00011 (-0.00119,0.00097) 0.843 0.00066 (-0.00062,0.00194) 0.310 -0.00081 (-0.00213,0.00050) 0.227 4 -0.00017 (-0.00123,0.00090) 0.760 -0.00103 (-0.00229,0.00022) 0.105 0.00129 (0.00000,0.00258) 0.050 5 0.00021 (-0.00087,0.00129) 0.699 -0.00133 (-0.00262,-0.00005) 0.042 0.00084 (-0.00048,0.00216) 0.214 6 -0.00088 (-0.00198,0.00022) 0.116 0.00002 (-0.00128,0.00132) 0.972 -0.00027 (-0.00161,0.00106) 0.689 7 0.00002 (-0.00106,0.00110) 0.969 -0.00007 (-0.00134,0.00120) 0.916 0.00028 (-0.00103,0.00159) 0.671 8 -0.00069 (-0.00175,0.00037) 0.203 0.00061 (-0.00065,0.00187) 0.341 0.00011 (-0.00118,0.00140) 0.870 9 0.00015 (-0.00093,0.00123) 0.787 0.00088 (-0.00040,0.00215) 0.177 -0.00089 (-0.00220,0.00042) 0.184 10 -0.00035 (-0.00143,0.00073) 0.526 0.00035 (-0.00092,0.00163) 0.587 -0.00023 (-0.00154,0.00108) 0.732            VDR FokI VDR TaqI VDR Cdx2 1 0.0004 (-0.00100,0.00180) 0.577 0.00114 (-0.00019,0.00248) 0.093 0.0021 (0.00053,0.00367) 0.009 2 0.00021 (-0.00116,0.00158) 0.766 -0.00027 (-0.00157,0.00104) 0.686 0.00008 (-0.00146,0.00162) 0.916 3 0.00043 (-0.00095,0.00182) 0.541 -0.00078 (-0.00210,0.00054) 0.247 -0.0006 (-0.00216,0.00096) 0.449 4 -0.00075 (-0.00210,0.00061) 0.279 0.00126 (-0.00003,0.00256) 0.056 0.00011 (-0.00141,0.00164) 0.884 5 -0.00031 (-0.00170,0.00108) 0.662 0.0008 (-0.00052,0.00213) 0.235 -0.00035 (-0.00191,0.00121) 0.661 6 0.00008 (-0.00133,0.00148) 0.913 0.00004 (-0.00130,0.00139) 0.952 -0.00026 (-0.00184,0.00132) 0.744 7 -0.00038 (-0.00176,0.00100) 0.586 0.00047 (-0.00084,0.00179) 0.482 0.00039 (-0.00116,0.00194) 0.622 8 -0.00045 (-0.00182,0.00091) 0.514 -0.00024 (-0.00154,0.00106) 0.715 -0.00069 (-0.00222,0.00084) 0.378 9 0.00023 (-0.00115,0.00161) 0.746 -0.00119 (-0.00251,0.00012) 0.075 0.00034 (-0.00121,0.00189) 0.666 10 0.00122 (-0.00016,0.00260) 0.084 -0.00047 (-0.00179,0.00085) 0.487 -0.00072 (-0.00227,0.00084) 0.365 a Principal components calculated with the program Eigenstrat  b Calculated using regression, unadjusted. c Synthesis score: rs10741657, rs12785878  d Metabolism score: rs6013897, rs10877012. CI=confidence interval.      

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case–control study

https://link.springer.com/content/pdf/10.1007%2Fs10552-014-0500-5.pdf

Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case-control study

Abstract

Similar works

Full text

Available Versions

Spiral - Imperial College Digital Repository

University of East Anglia digital repository

Springer - Publisher Connector

Crossref

Springer - Publisher Connector

Explore Bristol Research