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  • 1.
    Brown, David A.
    et al.
    St Vincents Hosp, Ctr Appl Med Res, Sydney, NSW 2010, Australia.;Univ New S Wales, Sydney, NSW, Australia..
    Lindmark, Fredrik
    Umea Univ, Dept Radiat Sci, Umea, Sweden..
    Stattin, Par
    Umea Univ, Dept Surg & Preoperat Sci, Umea, Sweden..
    Bälter, Katarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden..
    Adami, Hans-Olov
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.;Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA..
    Zheng, Sigun L.
    Wake Forest Univ, Ctr Human Genom, Winston Salem, NC 27109 USA..
    Xu, Jianfeng
    Wake Forest Univ, Ctr Human Genom, Winston Salem, NC 27109 USA..
    Isaacs, William B.
    Johns Hopkins Univ, Dept Urol, Baltimore, MD USA..
    Gronberg, Henrik
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden..
    Breit, Samuel N.
    St Vincents Hosp, Ctr Appl Med Res, Sydney, NSW 2010, Australia.;Univ New S Wales, Sydney, NSW, Australia..
    Wiklund, Fredrik E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden..
    Macrophage Inhibitory Cytokine 1: A New Prognostic Marker in Prostate Cancer2009In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 15, no 21, p. 6658-6664Article in journal (Refereed)
    Abstract [en]

    Purpose: High serum levels of macrophage inhibitory cytokine 1 (MIC-1) are strongly associated with metastatic prostate cancer, suggesting MIC-1 is a biomarker for prostate cancer prognosis. Experimental Design: We conducted a prospective cohort study of 1,442 Swedish men with a pathologically verified diagnosis of prostate cancer between 2001 and 2003. Blood was drawn either pretreatment (n = 431) or posttreatment (n = 1,011) and cases were followed for a mean time of 4.9 years (range, 0.1-6.8 years). Results: MIC-1 serum levels independently predicted poor cancer-specific survival with an almost 3-fold higher cancer death rate in patients with serum levels in the highest quartile compared with men with serum levels in the lowest quartile (adjusted hazard ratio, 2.98; 95% confidence interval, 1.82-4.68). Pretreatment MIC-1 levels revealed an even stronger association with disease outcome with an 8-fold higher death rate in the highest compared with the lowest category (adjusted hazard ratio, 7.98; 95% confidence interval, 1.73-36.86). Among patients considered to have localized disease, MIC-1 significantly increased the discriminative capacity between indolent and lethal prostate cancer compared with the established prognostic markers clinical stage, pathologic grade, and prostate-specific antigen level (P = 0.016). A sequence variant in the MIC-1 gene was associated with decreased MIC-1 serum levels (P = 0.002) and decreased prostate cancer mortality (P = 0.003), suggesting a causative role of MIC-1 in prostate cancer prognosis. Conclusions: Serum MIC-1 concentration is a novel biomarker capable of predicting prostate cancer prognosis. (Clin Cancer Res 2009;15(21):6658-64)

  • 2. Lindstrom, Sara
    et al.
    Adami, Hans-Olov
    Bälter, Katarina Augustsson
    Xu, Jianfeng
    Zheng, S. Lilly
    Stattin, Paer
    Gronberg, Henrik
    Wiklund, Fredrik
    Inherited variation in hormone-regulating genes and prostate cancer survival2007In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 13, no 17, p. 5156-5161Article in journal (Refereed)
    Abstract [en]

    Purpose: Hormonal manipulation is the mainstay treatment of prostate cancer, notably in advanced stages. Despite initial favorably response, the cancer eventually develops hormone resistance resulting in disease progression and death. However, little is known about genetic determinants of disease progression and prostate cancer-specific death. Experimental Design: We analyzed a population-based cohort comprising 2,761 men diagnosed with prostate cancer from March 2001 to October 2003 and with complete follow-up through July 2006. During a median follow-up time of 3.8 years, a total of 300 men had died from prostate cancer. We genotyped 23 haplotype tagging single nucleoticle polymorphisms in the genes AR, CYP17, and SRD5A2 and used Cox proportional hazards analyses to quantify associations between genotype and risk of dying from prostate cancer. Results: The variant 'A': allele of an AR promoter single nucleoticle polymorphism, rs17302090, was borderline associated with a 50% increased risk of dying from prostate cancer (95% confidence interval, 1.0-2.3; P = 0.07). This finding was more pronounced in patients who received hormonal therapy as primary treatment at diagnosis (hazard ratio, 19; 95% confidence interval, 1.3-2.9; P = 0.007). We did not identify any associations between CYP17 or SRD5A2 variation and prostate cancer-specific death. Conclusions: Our results suggest that inherited genetic variation in the androgen receptor gene affects hormonal treatment response and ultimately prostate cancer death.

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