| 1. |
- Johansson, Mattias, et al.
(författare)
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Implications for prostate cancer of insulin-like growth factor-I (IGF-I) genetic variation and circulating IGF-I levels
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Umea Univ Hosp, Dept Surgical & Perioperative Sci, S-90185 Umea, Sweden. Umea Univ Hosp, Dept Urol Androl, S-90185 Umea, Sweden. Umea Univ Hosp, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden. Int Agcy Res Canc, F-69372 Lyon, France. Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden. Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-85500 Utrecht, Netherlands. Harvard Univ, Dept Epidemiol, Boston, MA 02215 USA. German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany. : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 92:12, s. 4820-4826
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated levels of circulating IGF-I have consistently been associated with increased prostate cancer risk. We recently found a haplotype in the 3 ' region of the IGF-I gene associated with increased risk of prostate cancer, and we hypothesized that the observed association is mediated by circulating IGF-I. Materials and Methods: We analyzed haplotypes and three haplotype-tagging single nucleotide polymorphisms (htSNPs) in the 3 ' region of the IGF-I gene in relation to circulating levels IGF-I in 698 control subjects from the CAncer Prostate in Sweden ( CAPS) study and 575 cases and controls from the prospective Northern Sweden Health and Disease Cohort ( NSHDC) study. We also performed a meta-analysis of these two and four other association studies on genetic variation in the 3 ' region of the IGF-I gene in relation to circulating IGF-I levels. Results: The IGF-I haplotype previously associated with prostate cancer risk, labeled "TCC," was associated with elevated levels of IGF-I in the CAPS study (P = 0.02), but not in the NSHDC study. In contrast, two of the three IGF-I htSNPs tagging this haplotype, rs6220 and rs7136446, were associated with elevated levels of IGF-I in the NSHDC ( P = 0.03 and P = 0.04, respectively), but not in the CAPS study. In the meta-analysis, the TCC haplotype and the rs6220 SNP were associated with elevated levels of circulating IGF-I ( P = 0.001 and P < 0.0001, respectively). Conclusions: Genetic variation in the 3 ' region of the IGF-I gene seems to influence circulating levels of IGF-I. This observation is consistent with the hypothesis that variation in the IGF-I gene plays a role in prostate cancer susceptibility by influencing circulating levels of IGF-I.
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| 2. |
- Lin, Daniel W., et al.
(författare)
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Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Philadelphia : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:9, s. 1928-1936
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate cancer is the second leading cause of cancer-related deaths in men, accounting for more than 30,000 deaths annually. The purpose of this study was to test whether variation in selected candidate genes in biological pathways of interest for prostate cancer progression could help distinguish patients at higher risk for fatal prostate cancer. Methods: In this hypothesis-driven study, we genotyped 937 single nucleotide polymorphisms (SNPs) in 156 candidate genes in a population-based cohort of 1,309 prostate cancer patients. We identified 22 top-ranking SNPs (P <= 0.01, FDR <= 0.70) associated with prostate cancer-specific mortality (PCSM). A subsequent validation study was completed in an independent population-based cohort of 2,875 prostate cancer patients. Results: Five SNPs were validated (P <= 0.05) as being significantly associated with PCSM, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes. Compared with patients with 0 to 2 of the at-risk genotypes those with 4 to 5 at-risk genotypes had a 50% (95% CI, 1.2-1.9) higher risk of PCSM and risk increased with the number of at-risk genotypes carried (P(trend) = 0.001), adjusting for clinicopathologic factors known to influence prognosis. Conclusion: Five genetic markers were validated to be associated with lethal prostate cancer. Impact: This is the first population-based study to show that germline genetic variants provide prognostic information for prostate cancer-specific survival. The clinical utility of this five-SNP panel to stratify patients at higher risk for adverse outcomes should be evaluated. Cancer Epidemiol Biomarkers Prev; 20(9); 1928-36. (C)2011 AACR.
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| 3. |
- Lindstrom, Sara, et al.
(författare)
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Inherited variation in hormone-regulating genes and prostate cancer survival
- 2007
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Ingår i: Clinical Cancer Research. - Umea Univ, Dept Radiat Sci Oncol, SE-90185 Umea, Sweden. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Wake Forest Univ, Sch Med, Ctr Human Genom, Winston Salem, NC 27109 USA. : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 13:17, s. 5156-5161
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Tidskriftsartikel (refereegranskat)abstract
- 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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