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

Authors


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.

Ancillary