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Sökning: onr:"swepub:oai:gup.ub.gu.se/130910" > Inherited genetic v...

Inherited genetic variant predisposes to aggressive but not indolent prostate cancer.

Xu, Jianfeng (författare)
Zheng, Siqun Lilly (författare)
Isaacs, Sarah D (författare)
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Wiley, Kathleen E (författare)
Wiklund, Fredrik (författare)
Sun, Jielin (författare)
Kader, A Karim (författare)
Li, Ge (författare)
Purcell, Lina D (författare)
Kim, Seong-Tae (författare)
Hsu, Fang-Chi (författare)
Stattin, Pär, (författare)
Umeå universitet, Urologi och andrologi
Hugosson, Jonas (författare)
Adolfsson, Jan (författare)
Walsh, Patrick C (författare)
Trent, Jeffrey M (författare)
Duggan, David (författare)
Carpten, John (författare)
Grönberg, Henrik (författare)
Isaacs, William B (författare)
Gronberg, H, (författare)
Karolinska Institutet
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Umeå universitet Medicinska fakulteten. Institutionen för kirurgisk och perioperativ vetenskap. Urologi och andrologi. (creator_code:org_t)
Göteborgs universitet Sahlgrenska akademin. Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för urologi. 
2010
Engelska.
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 1091-6490. ; 107:5, s. 2136-40
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  (hsv//swe)
MEDICAL AND HEALTH SCIENCES  (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Urology and Nephrology (hsv//eng)

Nyckelord

MEDICINE
MEDICIN
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

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