Estimation of absolute risk for prostate cancer using genetic markers and family history.
BACKGROUND
Multiple DNA sequence variants in the form of single-nucleotide polymorphisms (SNPs) have been found to be reproducibly associated with prostate cancer (PCa) risk.


METHODS
Absolute risk for PCa among men with various numbers of inherited risk alleles and family history of PCa was estimated in a population-based case-control study in Sweden (2,893 cases and 1,781 controls), and a nested case-control study from the Prostate, Lung, Colon and Ovarian (PLCO) Cancer Screening Trial in the U.S. (1,172 cases and 1,157 controls).


RESULTS
Increased number of risk alleles and positive family history were independently associated with PCa risk. Considering men with 11 risk alleles (mode) and negative family history as having baseline risk, men who had >or=14 risk alleles and positive family history had an odds ratio (OR) of 4.92 [95% confidence interval (CI): 3.64-6.64] in the Swedish study. These associations were confirmed in the U.S. population. Once a man's SNP genotypes and family history are known, his absolute risk for PCa can be readily calculated and easily interpreted. For example, 55-year-old men with a family history and >or=14 risk alleles have a 52% and 41% risk of being diagnosed with PCa in the next 20 years in the Swedish and U.S. populations, respectively. In comparison, without knowledge of genotype and family history, these men had an average population absolute risk of 13%.


CONCLUSIONS
This risk prediction model may be used to identify men at considerably elevated PCa risk who may be selected for chemoprevention.
Xu
Jianfeng
J
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. jxu@wfubmc.edu
Sun
Jielin
J
Kader
A Karim
AK
Lindström
Sara
S
Wiklund
Fredrik
F
Hsu
Fang-Chi
FC
Johansson
Jan-Erik
JE
Zheng
S Lilly
SL
Thomas
Gilles
G
Hayes
Richard B
RB
Kraft
Peter
P
Hunter
David J
DJ
Chanock
Stephen J
SJ
Isaacs
William B
WB
Grönberg
Henrik
H
D016022:Case-Control Studies; D005192:Family Health; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000517:prevention & control; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
D005819:Genetic Markers