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Validation of association of genetic variants at 10q with prostate-specific antigen (PSA) levels in men at high risk for prostate cancer.


ABSTRACT:

Objective

To validate six previously identified markers among men at increased risk of prostate cancer (African-American men and those with a family history of prostate cancer) enrolled in the Prostate Cancer Risk Assessment Program (PRAP), a prostate cancer screening study.

Patients and methods

Eligibility criteria for PRAP include age 35-69 years with a family history of prostate cancer, African-American ethnicity regardless of family history, and known BRCA gene mutations. The genome-wide association study markers assessed included rs2736098 (5p15.33), rs10993994 (10q11), rs10788160 (10q26), rs11067228 (12q24), rs4430796 (17q12) and rs17632542 (19q13.33). Genotyping methods included either the Taqman(®) single nucleotide polymorphism (SNP) genotyping assay (Applied Biosystems, Foster City, CA, USA) or pyrosequencing. Linear regression models were used to evaluate the association between individual markers and log-transformed baseline PSA levels, while adjusting for potential confounders.

Results

A total of 707 participants (37% Caucasian, 63% African-American) with clinical and genotype data were included in the analysis. Rs10788160 (10q26) was strongly associated with PSA levels among Caucasian participants in the high-risk group (P < 0.01), with a 33.2% increase in PSA level with each A-allele carried. Furthermore, rs10993994 (10q11) was found to be associated with PSA level (P = 0.03) in Caucasian men in the high-risk group, with a 15% increase in PSA level with each T-allele carried. A PSA adjustment model based on allele carrier status at rs10788160 and rs10993994 was proposed, specific to high-risk Caucasian men.

Conclusions

Genetic variation at 10q may be particularly important in personalizing the interpretation of PSA level for Caucasian men in the high-risk group. Such information may have clinical relevance in shared decision-making and individualized prostate cancer screening strategies for Caucasian men in the high-risk group, although further study is warranted.

SUBMITTER: Chang BL 

PROVIDER: S-EPMC3830710 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Publications

Validation of association of genetic variants at 10q with prostate-specific antigen (PSA) levels in men at high risk for prostate cancer.

Chang Bao-Li BL   Hughes Lucinda L   Chen David Y T DY   Gross Laura L   Ruth Karen K   Giri Veda N VN  

BJU international 20130813 5b


<h4>Objective</h4>To validate six previously identified markers among men at increased risk of prostate cancer (African-American men and those with a family history of prostate cancer) enrolled in the Prostate Cancer Risk Assessment Program (PRAP), a prostate cancer screening study.<h4>Patients and methods</h4>Eligibility criteria for PRAP include age 35-69 years with a family history of prostate cancer, African-American ethnicity regardless of family history, and known BRCA gene mutations. The  ...[more]

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