Dataset Information

Association of reported prostate cancer risk alleles with PSA levels among men without a diagnosis of prostate cancer.

ABSTRACT: Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels.We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer.Of the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P < or = 0.05) were found for six SNPs. These six SNPs had a cumulative effect on PSA levels; the mean PSA levels in men were almost twofold increased across increasing quintile of number of PSA associated alleles, P-trend = 3.4 x 10(-14). In this Swedish study population risk allele frequencies were similar among T1c case patients (cancer detected by elevated PSA levels alone) as compared to T2 and above prostate cancer case patients.Results from this study may have two important clinical implications. The cumulative effect of six SNPs on PSA levels suggests genetic-specific PSA cutoff values may be used to improve the discriminatory performance of this test for prostate cancer; and the dual associations of these SNPs with PSA levels and prostate cancer risk raise a concern that some of reported prostate cancer risk-associated SNPs may be confounded by the prevalent use of PSA screening.

SUBMITTER: Wiklund F

PROVIDER: S-EPMC3348520 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Association of reported prostate cancer risk alleles with PSA levels among men without a diagnosis of prostate cancer.

Wiklund Fredrik F Zheng S Lilly SL Sun Jielin J Adami Hans-Olov HO Lilja Hans H Hsu Fang-Chi FC Stattin Pär P Adolfsson Jan J Cramer Scott D SD Duggan David D Carpten John D JD Chang Bao-Li BL Isaacs William B WB Grönberg Henrik H Xu Jianfeng J

The Prostate 20090301 4

<h4>Background</h4>Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels.<h4>Methods</h4>We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a di ...[more]

PMID: 19116992

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Project description:ObjectiveTo 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 methodsEligibility 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.ResultsA 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.ConclusionsGenetic 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.

Dataset Information

Association of reported prostate cancer risk alleles with PSA levels among men without a diagnosis of prostate cancer.

Publications

Association of reported prostate cancer risk alleles with PSA levels among men without a diagnosis of prostate cancer.

Similar Datasets

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