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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
Author(s) -
Chang BaoLi,
Hughes Lucinda,
Chen David Y.T.,
Gross Laura,
Ruth Karen,
Giri Veda N.
Publication year - 2014
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.12264
Subject(s) - medicine , prostate cancer , prostate specific antigen , single nucleotide polymorphism , genotyping , oncology , genotype , family history , allele , snp , prostate , confounding , cancer , gynecology , genetics , gene , biology
Objective To validate six previously identified markers among men at increased risk of prostate cancer ( A frican‐ A merican men and those with a family history of prostate cancer) enrolled in the P rostate C ancer R isk A ssessment P rogram ( 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, A frican‐ A merican 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 T aqman ® single nucleotide polymorphism (SNP) genotyping assay ( A pplied B iosystems, F oster C ity, 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% C aucasian, 63% A frican‐ A merican) with clinical and genotype data were included in the analysis. R s10788160 (10q26) was strongly associated with PSA levels among C aucasian 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 C aucasian 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 C aucasian men.Conclusions Genetic variation at 10q may be particularly important in personalizing the interpretation of PSA level for C aucasian men in the high‐risk group. Such information may have clinical relevance in shared decision‐making and individualized prostate cancer screening strategies for C aucasian men in the high‐risk group, although further study is warranted.