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Sökning: onr:"swepub:oai:DiVA.org:mdh-40791" > Two genome-wide ass...

Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP

Duggan, David (författare)
Zheng, Siqun L (författare)
Knowlton, Michele (författare)
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Benitez, Debbie (författare)
Dimitrov, Latchezar (författare)
Wiklund, Fredrik (författare)
Robbins, Christiane (författare)
Isaacs, Sarah D (författare)
Cheng, Yu (författare)
Li, Ge (författare)
Sun, Jielin (författare)
Chang, Bao-Li (författare)
Marovich, Leslie (författare)
Wiley, Kathleen E (författare)
Bälter, Katarina (författare)
Stattin, Pär, (författare)
Umeå universitet, Urologi och andrologi
Adami, Hans-Olov (författare)
Gielzak, Marta (författare)
Yan, Guifang (författare)
Sauvageot, Jurga (författare)
Liu, Wennuan (författare)
Kim, Jin Woo (författare)
Bleecker, Eugene R (författare)
Meyers, Deborah A (författare)
Trock, Bruce J (författare)
Partin, Alan W (författare)
Walsh, Patrick C (författare)
Isaacs, William B (författare)
Grönberg, Henrik (författare)
Xu, Jianfeng (författare)
Carpten, John D (författare)
Baeter, K (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)
2007
Engelska.
Ingår i: Journal of the National Cancer Institute. - 0027-8874. ; 99:24, s. 1836-1844
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Background: The consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment. Methods: We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. Results: Among the approximately 60000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancer patients and 571 control subjects of European descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value =. 004). The association was also statistically significant in an African American study population that included 210 prostate cancer patients and 346 control subjects (one-sided P value =. 02). Conclusion: A genetic variant in DAB2IP may be associated with the risk of aggressive prostate cancer and should be evaluated further.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Health Sciences (hsv//eng)

Nyckelord

African Americans/genetics
Aged
Case-Control Studies
European Continental Ancestry Group/*genetics
Genes; Tumor Suppressor
Genetic Predisposition to Disease
Genotype
Humans
Male
Middle Aged
Odds Ratio
Polymorphism; Single Nucleotide
Prostatic Neoplasms/*genetics
Risk Assessment
Risk Factors
Sweden
Tumor Markers; Biological/*genetics
ras GTPase-Activating Proteins/*genetics
guanosine triphosphatase activating protein
DAB2IP protein
human
tumor marker
unclassified drug
adult
African American
aged
allele
article
cancer risk
case control study
controlled study
dab2ip gene
gene
gene location
genetic association
genetic code
genetic marker
genetic model
genetic susceptibility
genetic variability
human
major clinical study
male
population research
priority journal
prostate cancer
single nucleotide polymorphism
statistical significance
suppressor gene
Caucasian
genetic predisposition
genetics
genotype
middle aged
prostate tumor
risk
risk assessment
risk factor
tumor suppressor gene
African Americans
European Continental Ancestry Group
Genes
Tumor Suppressor
Polymorphism
Single Nucleotide
Prostatic Neoplasms
ras GTPase-Activating Proteins
Tumor Markers
Biological

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