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Inherited genetic v...
Inherited genetic variant predisposes to aggressive but not indolent prostate cancer.
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Xu, Jianfeng (author)
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Zheng, Siqun Lilly (author)
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Isaacs, Sarah D (author)
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show more...
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Wiley, Kathleen E (author)
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- Wiklund, Fredrik (author)
- Karolinska Institutet
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Sun, Jielin (author)
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Kader, A Karim (author)
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Li, Ge (author)
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Purcell, Lina D (author)
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Kim, Seong-Tae (author)
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Hsu, Fang-Chi (author)
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- Stattin, Pär (author)
- Umeå universitet,Urologi och andrologi
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- Hugosson, Jonas, 1955 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för urologi,Institute of Clinical Sciences, Department of Urology
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- Adolfsson, Jan (author)
- Karolinska Institutet
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Walsh, Patrick C (author)
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Trent, Jeffrey M (author)
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Duggan, David (author)
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Carpten, John (author)
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- Grönberg, Henrik (author)
- Karolinska Institutet
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Isaacs, William B (author)
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(creator_code:org_t)
- 2010-01-11
- 2010
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 107:5, s. 2136-40
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Abstract
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- Autopsy studies suggest that most aging men will develop lesions that, if detected clinically, would be diagnosed as prostate cancer (PCa). Most of these cancers are indolent and remain localized; however, a subset of PCa is aggressive and accounts for more than 27,000 deaths in the United States annually. Identification of factors specifically associated with risk for more aggressive PCa is urgently needed to reduce overdiagnosis and overtreatment of this common disease. To search for such factors, we compared the frequencies of SNPs among PCa patients who were defined as having either more aggressive or less aggressive disease in four populations examined in the Genetic Markers of Susceptibility (CGEMS) study performed by the National Cancer Institute. SNPs showing possible associations with disease severity were further evaluated in an additional three independent study populations from the United States and Sweden. In total, we studied 4,829 and 12,205 patients with more and less aggressive disease, respectively. We found that the frequency of the TT genotype of SNP rs4054823 at 17p12 was consistently higher among patients with more aggressive compared with less aggressive disease in each of the seven populations studied, with an overall P value of 2.1 x 10(-8) under a recessive model, exceeding the conservative genome-wide significance level. The difference in frequency was largest between patients with high-grade, non-organ-confined disease compared with those with low-grade, organ-confined disease. This study demonstrates that inherited variants predisposing to aggressive but not indolent PCa exist in the genome, and suggests that the clinical potential of such variants as potential early markers for risk of aggressive PCa should be evaluated.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
Keyword
- Gene Frequency
- Genetic Predisposition to Disease
- Genetic Variation
- Genotype
- Humans
- Male
- Neoplasm Invasiveness
- genetics
- Polymorphism
- Single Nucleotide
- Prostatic Neoplasms
- genetics
- pathology
- Registries
- Sweden
- Tumor Markers
- Biological
- genetics
- United States
- MEDICINE
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Xu, Jianfeng
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Zheng, Siqun Lil ...
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Isaacs, Sarah D
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Wiley, Kathleen ...
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Wiklund, Fredrik
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Sun, Jielin
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show more...
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Kader, A Karim
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Li, Ge
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Purcell, Lina D
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Kim, Seong-Tae
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Hsu, Fang-Chi
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Stattin, Pär
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Hugosson, Jonas, ...
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Adolfsson, Jan
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Walsh, Patrick C
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Trent, Jeffrey M
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Duggan, David
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Carpten, John
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Grönberg, Henrik
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Isaacs, William ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Urology and Neph ...
- Articles in the publication
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Proceedings of t ...
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Proceedings of t ...
- By the university
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University of Gothenburg
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Umeå University
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Karolinska Institutet