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Grant Details

Grant Number: 5R01CA105055-05 Interpret this number
Primary Investigator: Xu, Jianfeng
Organization: Wake Forest University Health Sciences
Project Title: Association of Inflammatory Genes and Prostate Cancer
Fiscal Year: 2008
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Abstract

DESCRIPTION (provided by applicant): Prostate cancer is of significant public health importance because it is the most common cancer and the second leading cause of cancer death among men in the United States. Although the etiology of prostate cancer remains unknown, epidemiologic studies have consistently demonstrated genetic susceptibility to this disease. To date, efforts to identify susceptibility genes have primarily focused on genes involved in androgen biosynthesis and growth factors. However, there remain several candidate pathways that have yet to be adequately studied. Chronic or recurrent inflammation is known to play a causative role in the development of many human cancers. Inflammatory changes have been recognized in prostate tissues for many years, leading to speculation that inflammation might contribute to prostate cancer development. The exact mechanism by which inflammation might act in tumor development and progression remains to be elucidated and is likely to be complex. Inflammation-associated DNA damage, decreased apoptosis (bypassing p53), growth and survival factors, angiogenesis, invasion and metastasis may all play a role in the development and progression of prostate cancer. We hypothesize that sequence variants in a number of inflammatory genes are associated with prostate cancer risk. To test this hypothesis, we propose to 1) perform exploratory tests for association of Prostate cancer risk with inflammatory gene sequence variants in an established Prostate cancer case-control population that was collected in Sweden, 2) perform confirmatory tests for association of Prostate cancer risk with a subset of inflammatory gene sequence variants that have been implicated in the first population in a second newly collected Swedish Prostate cancer case-control population and 3) explore the functional impact of htSNPs and htSNP-haplotypes on the corresponding protein levels in serum and/or prostate tissue for a subset of inflammatory genes that have been implicated in both study populations. Answers to these questions will significantly improve our knowledge of the role of inflammation in prostate cancer and will guide our efforts in identifying additional prostate cancer genes.

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Publications

Genetic markers associated with early cancer-specific mortality following prostatectomy.
Authors: Liu W, Xie CC, Thomas CY, Kim ST, Lindberg J, Egevad L, Wang Z, Zhang Z, Sun J, Sun J, Koty PP, Kader AK, Cramer SD, Bova GS, Zheng SL, Grönberg H, Isaacs WB, Xu J
Source: Cancer, 2013 Jul 1;119(13), p. 2405-12.
EPub date: 2013 Apr 22.
PMID: 23609948
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Identification of new differentially methylated genes that have potential functional consequences in prostate cancer.
Authors: Kim JW, Kim ST, Turner AR, Young T, Smith S, Liu W, Lindberg J, Egevad L, Gronberg H, Isaacs WB, Xu J
Source: PLoS One, 2012;7(10), p. e48455.
EPub date: 2012 Oct 31.
PMID: 23119026
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Pathway-based analysis of genetic susceptibility to cervical cancer in situ: HLA-DPB1 affects risk in Swedish women.
Authors: Ivansson EL, Juko-Pecirep I, Erlich HA, Gyllensten UB
Source: Genes Immun, 2011 Dec;12(8), p. 605-14.
EPub date: 2011 Jun 30.
PMID: 21716314
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Macrophage inhibitory cytokine-1 (MIC-1/GDF15): a new marker of all-cause mortality.
Authors: Wiklund FE, Bennet AM, Magnusson PK, Eriksson UK, Lindmark F, Wu L, Yaghoutyfam N, Marquis CP, Stattin P, Pedersen NL, Adami HO, Grönberg H, Breit SN, Brown DA
Source: Aging Cell, 2010 Dec;9(6), p. 1057-64.
EPub date: 2010 Oct 21.
PMID: 20854422
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Comparison of two methods for estimating absolute risk of prostate cancer based on single nucleotide polymorphisms and family history.
Authors: Hsu FC, Sun J, Zhu Y, Kim ST, Jin T, Zhang Z, Wiklund F, Kader AK, Zheng SL, Isaacs W, Grönberg H, Xu J
Source: Cancer Epidemiol Biomarkers Prev, 2010 Apr;19(4), p. 1083-8.
EPub date: 2010 Mar 23.
PMID: 20332264
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Inherited genetic variant predisposes to aggressive but not indolent prostate cancer.
Authors: Xu J, Zheng SL, Isaacs SD, Wiley KE, Wiklund F, Sun J, Kader AK, Li G, Purcell LD, Kim ST, Hsu FC, Stattin P, Hugosson J, Adolfsson J, Walsh PC, Trent JM, Duggan D, Carpten J, Grönberg H, Isaacs WB
Source: Proc Natl Acad Sci U S A, 2010 Feb 2;107(5), p. 2136-40.
EPub date: 2010 Jan 11.
PMID: 20080650
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Association of 17 prostate cancer susceptibility loci with prostate cancer risk in Chinese men.
Authors: Zheng SL, Hsing AW, Sun J, Chu LW, Yu K, Li G, Gao Z, Kim ST, Isaacs WB, Shen MC, Gao YT, Hoover RN, Xu J
Source: Prostate, 2010 Mar 1;70(4), p. 425-32.
PMID: 19866473
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Macrophage inhibitory cytokine 1: a new prognostic marker in prostate cancer.
Authors: Brown DA, Lindmark F, Stattin P, Bälter K, Adami HO, Zheng SL, Xu J, Isaacs WB, Grönberg H, Breit SN, Wiklund FE
Source: Clin Cancer Res, 2009 Nov 1;15(21), p. 6658-64.
EPub date: 2009 Oct 20.
PMID: 19843661
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Estimation of absolute risk for prostate cancer using genetic markers and family history.
Authors: Xu J, Sun J, Kader AK, Lindström S, Wiklund F, Hsu FC, Johansson JE, Zheng SL, Thomas G, Hayes RB, Kraft P, Hunter DJ, Chanock SJ, Isaacs WB, Grönberg H
Source: Prostate, 2009 Oct 1;69(14), p. 1565-72.
PMID: 19562736
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Prostate cancer risk associated loci in African Americans.
Authors: Xu J, Kibel AS, Hu JJ, Turner AR, Pruett K, Zheng SL, Sun J, Isaacs SD, Wiley KE, Kim ST, Hsu FC, Wu W, Torti FM, Walsh PC, Chang BL, Isaacs WB
Source: Cancer Epidemiol Biomarkers Prev, 2009 Jul;18(7), p. 2145-9.
EPub date: 2009 Jun 23.
PMID: 19549807
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Two independent prostate cancer risk-associated Loci at 11q13.
Authors: Zheng SL, Stevens VL, Wiklund F, Isaacs SD, Sun J, Smith S, Pruett K, Wiley KE, Kim ST, Zhu Y, Zhang Z, Hsu FC, Turner AR, Johansson JE, Liu W, Kim JW, Chang BL, Duggan D, Carpten J, Rodriguez C, Isaacs W, Grönberg H, Xu J
Source: Cancer Epidemiol Biomarkers Prev, 2009 Jun;18(6), p. 1815-20.
PMID: 19505914
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Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients.
Authors: Kader AK, Sun J, Isaacs SD, Wiley KE, Yan G, Kim ST, Fedor H, DeMarzo AM, Epstein JI, Walsh PC, Partin AW, Trock B, Zheng SL, Xu J, Isaacs W
Source: Prostate, 2009 Aug 1;69(11), p. 1195-205.
PMID: 19434657
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Established prostate cancer susceptibility variants are not associated with disease outcome.
Authors: Wiklund FE, Adami HO, Zheng SL, Stattin P, Isaacs WB, Grönberg H, Xu J
Source: Cancer Epidemiol Biomarkers Prev, 2009 May;18(5), p. 1659-62.
PMID: 19423541
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A novel prostate cancer susceptibility locus at 19q13.
Authors: Hsu FC, Sun J, Wiklund F, Isaacs SD, Wiley KE, Purcell LD, Gao Z, Stattin P, Zhu Y, Kim ST, Zhang Z, Liu W, Chang BL, Walsh PC, Duggan D, Carpten JD, Isaacs WB, Grönberg H, Xu J, Zheng SL
Source: Cancer Res, 2009 Apr 1;69(7), p. 2720-3.
EPub date: 2009 Mar 24.
PMID: 19318570
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Association of a germ-line copy number variation at 2p24.3 and risk for aggressive prostate cancer.
Authors: Liu W, Sun J, Li G, Zhu Y, Zhang S, Kim ST, Sun J, Wiklund F, Wiley K, Isaacs SD, Stattin P, Xu J, Duggan D, Carpten JD, Isaacs WB, Grönberg H, Zheng SL, Chang BL
Source: Cancer Res, 2009 Mar 15;69(6), p. 2176-9.
EPub date: 2009 Mar 3.
PMID: 19258504
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Genetic variation in the upstream region of ERG and prostate cancer.
Authors: Lindström S, Adami HO, Bälter K, Xu J, Zheng SL, Sun J, Stattin P, Grönberg H, Wiklund F
Source: Cancer Causes Control, 2009 Sep;20(7), p. 1173-80.
EPub date: 2009 Feb 10.
PMID: 19205910
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Genetic variants and family history predict prostate cancer similar to prostate-specific antigen.
Authors: Zheng SL, Sun J, Wiklund F, Gao Z, Stattin P, Purcell LD, Adami HO, Hsu FC, Zhu Y, Adolfsson J, Johansson JE, Turner AR, Adams TS, Liu W, Duggan D, Carpten JD, Chang BL, Isaacs WB, Xu J, Grönberg H
Source: Clin Cancer Res, 2009 Feb 1;15(3), p. 1105-11.
PMID: 19188186
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Fine mapping association study and functional analysis implicate a SNP in MSMB at 10q11 as a causal variant for prostate cancer risk.
Authors: Chang BL, Cramer SD, Wiklund F, Isaacs SD, Stevens VL, Sun J, Smith S, Pruett K, Romero LM, Wiley KE, Kim ST, Zhu Y, Zhang Z, Hsu FC, Turner AR, Adolfsson J, Liu W, Kim JW, Duggan D, Carpten J, Zheng SL, Rodriguez C, Isaacs WB, Grönberg H, Xu J
Source: Hum Mol Genet, 2009 Apr 1;18(7), p. 1368-75.
EPub date: 2009 Jan 19.
PMID: 19153072
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Sequence variants at 22q13 are associated with prostate cancer risk.
Authors: Sun J, Zheng SL, Wiklund F, Isaacs SD, Li G, Wiley KE, Kim ST, Zhu Y, Zhang Z, Hsu FC, Turner AR, Stattin P, Liu W, Kim JW, Duggan D, Carpten J, Isaacs W, Grönberg H, Xu J, Chang BL
Source: Cancer Res, 2009 Jan 1;69(1), p. 10-5.
PMID: 19117981
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Association of reported prostate cancer risk alleles with PSA levels among men without a diagnosis of prostate cancer.
Authors: Wiklund F, Zheng SL, Sun J, Adami HO, Lilja H, Hsu FC, Stattin P, Adolfsson J, Cramer SD, Duggan D, Carpten JD, Chang BL, Isaacs WB, Grönberg H, Xu J
Source: Prostate, 2009 Mar 1;69(4), p. 419-27.
PMID: 19116992
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Family-based samples can play an important role in genetic association studies.
Authors: Lange EM, Sun J, Lange LA, Zheng SL, Duggan D, Carpten JD, Gronberg H, Isaacs WB, Xu J, Chang BL
Source: Cancer Epidemiol Biomarkers Prev, 2008 Sep;17(9), p. 2208-14.
PMID: 18768484
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Homozygous deletions and recurrent amplifications implicate new genes involved in prostate cancer.
Authors: Liu W, Xie CC, Zhu Y, Li T, Sun J, Cheng Y, Ewing CM, Dalrymple S, Turner AR, Sun J, Isaacs JT, Chang BL, Zheng SL, Isaacs WB, Xu J
Source: Neoplasia, 2008 Aug;10(8), p. 897-907.
PMID: 18670647
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A multigenic approach to evaluating prostate cancer risk in a systematic replication study.
Authors: Hsu FC, Lindström S, Sun J, Wiklund F, Chen SH, Adami HO, Turner AR, Liu W, Bälter K, Kim JW, Stattin P, Chang BL, Isaacs WB, Xu J, Grönberg H, Zheng SL
Source: Cancer Genet Cytogenet, 2008 Jun;183(2), p. 94-8.
PMID: 18503826
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Cumulative effect of five genetic variants on prostate cancer risk in multiple study populations.
Authors: Sun J, Chang BL, Isaacs SD, Wiley KE, Wiklund F, Stattin P, Duggan D, Carpten JD, Trock BJ, Partin AW, Walsh PC, Grönberg H, Xu J, Isaacs WB, Zheng SL
Source: Prostate, 2008 Sep 1;68(12), p. 1257-62.
PMID: 18491292
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Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer.
Authors: Gudmundsson J, Sulem P, Rafnar T, Bergthorsson JT, Manolescu A, Gudbjartsson D, Agnarsson BA, Sigurdsson A, Benediktsdottir KR, Blondal T, Jakobsdottir M, Stacey SN, Kostic J, Kristinsson KT, Birgisdottir B, Ghosh S, Magnusdottir DN, Thorlacius S, Thorleifsson G, Zheng SL, Sun J, Chang BL, Elmore JB, Breyer JP, McReynolds KM, Bradley KM, Yaspan BL, Wiklund F, Stattin P, Lindström S, Adami HO, McDonnell SK, Schaid DJ, Cunningham JM, Wang L, Cerhan JR, St Sauver JL, Isaacs SD, Wiley KE, Partin AW, Walsh PC, Polo S, Ruiz-Echarri M, Navarrete S, Fuertes F, Saez B, Godino J, Weijerman PC, Swinkels DW, Aben KK, Witjes JA, Suarez BK, Helfand BT, Frigge ML, Kristjansson K, Ober C, Jonsson E, Einarsson GV, Xu J, Gronberg H, Smith JR, Thibodeau SN, Isaacs WB, Catalona WJ, Mayordomo JI, Kiemeney LA, Barkardottir RB, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K
Source: Nat Genet, 2008 Mar;40(3), p. 281-3.
EPub date: 2008 Feb 10.
PMID: 18264098
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Cumulative association of five genetic variants with prostate cancer.
Authors: Zheng SL, Sun J, Wiklund F, Smith S, Stattin P, Li G, Adami HO, Hsu FC, Zhu Y, Bälter K, Kader AK, Turner AR, Liu W, Bleecker ER, Meyers DA, Duggan D, Carpten JD, Chang BL, Isaacs WB, Xu J, Grönberg H
Source: N Engl J Med, 2008 Feb 28;358(9), p. 910-9.
EPub date: 2008 Jan 16.
PMID: 18199855
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Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP.
Authors: Duggan D, Zheng SL, Knowlton M, Benitez D, Dimitrov L, Wiklund F, Robbins C, Isaacs SD, Cheng Y, Li G, Sun J, Chang BL, Marovich L, Wiley KE, Bälter K, Stattin P, Adami HO, Gielzak M, Yan G, Sauvageot J, Liu W, Kim JW, Bleecker ER, Meyers DA, Trock BJ, Partin AW, Walsh PC, Isaacs WB, Grönberg H, Xu J, Carpten JD
Source: J Natl Cancer Inst, 2007 Dec 19;99(24), p. 1836-44.
EPub date: 2007 Dec 11.
PMID: 18073375
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A support vector machine approach for detecting gene-gene interaction.
Authors: Chen SH, Sun J, Dimitrov L, Turner AR, Adams TS, Meyers DA, Chang BL, Zheng SL, Grönberg H, Xu J, Hsu FC
Source: Genet Epidemiol, 2008 Feb;32(2), p. 152-67.
PMID: 17968988
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Assembly of inflammation-related genes for pathway-focused genetic analysis.
Authors: Loza MJ, McCall CE, Li L, Isaacs WB, Xu J, Chang BL
Source: PLoS One, 2007 Oct 17;2(10), p. e1035.
EPub date: 2007 Oct 17.
PMID: 17940599
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Inherited variation in hormone-regulating genes and prostate cancer survival.
Authors: Lindström S, Adami HO, Bälter KA, Xu J, Zheng SL, Stattin P, Grönberg H, Wiklund F
Source: Clin Cancer Res, 2007 Sep 1;13(17), p. 5156-61.
PMID: 17785571
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Deletion of a small consensus region at 6q15, including the MAP3K7 gene, is significantly associated with high-grade prostate cancers.
Authors: Liu W, Chang BL, Cramer S, Koty PP, Li T, Sun J, Turner AR, Von Kap-Herr C, Bobby P, Rao J, Zheng SL, Isaacs WB, Xu J
Source: Clin Cancer Res, 2007 Sep 1;13(17), p. 5028-33.
PMID: 17785553
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Germ-line genetic variation in the key androgen-regulating genes androgen receptor, cytochrome P450, and steroid-5-alpha-reductase type 2 is important for prostate cancer development.
Authors: Lindström S, Wiklund F, Adami HO, Bälter KA, Adolfsson J, Grönberg H
Source: Cancer Res, 2006 Nov 15;66(22), p. 11077-83.
PMID: 17108148
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Association of frequent consumption of fatty fish with prostate cancer risk is modified by COX-2 polymorphism.
Authors: Hedelin M, Chang ET, Wiklund F, Bellocco R, Klint A, Adolfsson J, Shahedi K, Xu J, Adami HO, Grönberg H, Bälter KA
Source: Int J Cancer, 2007 Jan 15;120(2), p. 398-405.
PMID: 17066444
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A common variant associated with prostate cancer in European and African populations.
Authors: Amundadottir LT, Sulem P, Gudmundsson J, Helgason A, Baker A, Agnarsson BA, Sigurdsson A, Benediktsdottir KR, Cazier JB, Sainz J, Jakobsdottir M, Kostic J, Magnusdottir DN, Ghosh S, Agnarsson K, Birgisdottir B, Le Roux L, Olafsdottir A, Blondal T, Andresdottir M, Gretarsdottir OS, Bergthorsson JT, Gudbjartsson D, Gylfason A, Thorleifsson G, Manolescu A, Kristjansson K, Geirsson G, Isaksson H, Douglas J, Johansson JE, Bälter K, Wiklund F, Montie JE, Yu X, Suarez BK, Ober C, Cooney KA, Gronberg H, Catalona WJ, Einarsson GV, Barkardottir RB, Gulcher JR, Kong A, Thorsteinsdottir U, Stefansson K
Source: Nat Genet, 2006 Jun;38(6), p. 652-8.
EPub date: 2006 May 7.
PMID: 16682969
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Interactions of sequence variants in interleukin-1 receptor-associated kinase4 and the toll-like receptor 6-1-10 gene cluster increase prostate cancer risk.
Authors: Sun J, Wiklund F, Hsu FC, Bälter K, Zheng SL, Johansson JE, Chang B, Liu W, Li T, Turner AR, Li L, Li G, Adami HO, Isaacs WB, Xu J, Grönberg H
Source: Cancer Epidemiol Biomarkers Prev, 2006 Mar;15(3), p. 480-5.
PMID: 16537705
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Genetic variation in the COX-2 gene and the association with prostate cancer risk.
Authors: Shahedi K, Lindström S, Zheng SL, Wiklund F, Adolfsson J, Sun J, Augustsson-Bälter K, Chang BL, Adami HO, Liu W, Grönberg H, Xu J
Source: Int J Cancer, 2006 Aug 1;119(3), p. 668-72.
PMID: 16506214
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Meta-analysis of association of rare mutations and common sequence variants in the MSR1 gene and prostate cancer risk.
Authors: Sun J, Hsu FC, Turner AR, Zheng SL, Chang BL, Liu W, Isaacs WB, Xu J
Source: Prostate, 2006 May 15;66(7), p. 728-37.
PMID: 16425212
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The interaction of four genes in the inflammation pathway significantly predicts prostate cancer risk.
Authors: Xu J, Lowey J, Wiklund F, Sun J, Lindmark F, Hsu FC, Dimitrov L, Chang B, Turner AR, Liu W, Adami HO, Suh E, Moore JH, Zheng SL, Isaacs WB, Trent JM, Grönberg H
Source: Cancer Epidemiol Biomarkers Prev, 2005 Nov;14(11 Pt 1), p. 2563-8.
PMID: 16284379
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Genome-wide screen for prostate cancer susceptibility genes in men with clinically significant disease.
Authors: Chang BL, Isaacs SD, Wiley KE, Gillanders EM, Zheng SL, Meyers DA, Walsh PC, Trent JM, Xu J, Isaacs WB
Source: Prostate, 2005 Sep 1;64(4), p. 356-61.
PMID: 15754351
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Serum levels of phytanic acid are associated with prostate cancer risk.
Authors: Xu J, Thornburg T, Turner AR, Vitolins M, Case D, Shadle J, Hinson L, Sun J, Liu W, Chang B, Adams TS, Zheng SL, Torti FM
Source: Prostate, 2005 May 15;63(3), p. 209-14.
PMID: 15712232
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