|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|
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.