Confirmation of a positive association between prostate cancer risk and a locus at chromosome 8q24.
BACKGROUND
Family-based linkage studies, association studies, and studies of tumors have highlighted human chromosome 8q as a genomic region of interest for prostate cancer susceptibility loci. Recently, a locus at 8q24, characterized by both a single nucleotide polymorphism (SNP) and a microsatellite marker, was shown to be associated with prostate cancer risk in Icelandic, Swedish, and U.S. samples. Although the data were provocative, the U.S. samples were not population based, which precludes assessment of the potential contribution of this locus to prostate cancer incidence in the United States.


METHODS
We analyzed both markers in a population-based, case-control study of middle-aged men from King County, Washington.


RESULTS
Overall, there was a significant positive association between the A allele of the SNP rs1447295 and prostate cancer risk [odds ratio, 1.4; 95% confidence interval (95% CI), 1.1-2.0] but no significant association with the microsatellite DG8S737. However, significant associations were observed for both markers in men with high Gleason scores. Adjusting for age, first-degree family history of prostate cancer, and prostate cancer screening history, the adjusted odds ratios were 1.4 (95% CI, 1.1-1.8) for the A allele of the SNP and 1.9 (95% CI, 1.2-2.8) for the -10 allele of the microsatellite.


CONCLUSIONS
These data suggest that the locus on chromosome 8q24 harbors a genetic variant associated with prostate cancer and that the microsatellite marker is a stronger risk factor for aggressive prostate cancers defined by poorly differentiated tumor morphology.
Suuriniemi
Miia
M
Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
Agalliu
Ilir
I
Schaid
Daniel J
DJ
Johanneson
Bo
B
McDonnell
Shannon K
SK
Iwasaki
Lori
L
Stanford
Janet L
JL
Ostrander
Elaine A
EA
D000328:Adult; D000483:Alleles; D016009:Chi-Square Distribution; D002898:Chromosomes, Human, Pair 8; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D014861:Washington / Q000453:epidemiology