Single nucleotide polymorphisms and the likelihood of prostate cancer at a given prostate specific antigen level.
OBJECTIVE
Prostate specific antigen is used for prostate cancer screening but its specificity is limited. Specificity might be increased by considering genotype associated prostate specific antigen levels.


METHODS
We examined associations between single nucleotide polymorphisms on chromosomes 10 and 19 (previously shown to be associated with prostate specific antigen) with prostate specific antigen and prostate cancer in 505 men from the Baltimore Longitudinal Study of Aging.


RESULTS
In a model with age and date the risk ratio for prostate cancer was 1.18 (95% CI 1.13-1.23) per unit increase in prostate specific antigen. Including the interaction between alleles and prostate specific antigen significantly altered the risk ratio for prostate cancer (Cox proportional hazards p <0.001). Specifically prostate cancer risk per unit increase in prostate specific antigen was significantly different in carriers than in noncarriers of a minor allele (1.28 vs 1.10, respectively, Cox proportional hazards p <0.001), whereas men with a minor allele had a significantly higher risk of prostate cancer at prostate specific antigen levels greater than 6 ng/ml.


CONCLUSIONS
Our data suggest that genotype influences the risk of prostate cancer per unit increase in prostate specific antigen. Prostate cancer risk stratification using prostate specific antigen and genotype could improve prostate specific antigen test performance.
Loeb
Stacy
S
James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. stacyloeb@gmail.com
Carter
H Ballentine
HB
Walsh
Patrick C
PC
Isaacs
William B
WB
Kettermann
Anna
A
Tanaka
Toshiko
T
Ferrucci
Luigi
L
Metter
E Jeffrey
EJ
D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics / Q000502:physiology; D001707:Biopsy, Needle; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D017430:Prostate-Specific Antigen