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

• 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Health Sciences (hsv//eng)

Keyword

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

Sweden

Caucasian

genetic predisposition

genetics

genotype

middle aged

prostate tumor

risk

risk assessment

risk factor

tumor suppressor gene

African Americans

Case-Control Studies

European Continental Ancestry Group

Genes

Tumor Suppressor

Genetic Predisposition to Disease

Humans

Odds Ratio

Polymorphism

Single Nucleotide

Prostatic Neoplasms

ras GTPase-Activating Proteins

Risk Factors

Tumor Markers

Biological

Publication and Content Type

ref (subject category)

art (subject category)