Association of CD14 variant with prostate cancer in African American men.
BACKGROUND
African American men have the highest rates of prostate cancer worldwide, and immunogenetic studies suggest that people of African descent have increased susceptibility to diseases of inflammation. Since genetic susceptibility is an etiological factor in prostate cancer, we hypothesize that sequence variants in the promoter region of the CD14 gene that regulate inflammation may modify individual susceptibility to this disease.


METHODS
The CD14 promoter was screened for single-nucleotide polymorphisms (SNPs) using dHPLC. One variant, -260 C>T (rs2569190), was genotyped via restriction digest in all study participants (264 cases and 188 controls). The association of disease status and the polymorphism was analyzed by unconditional logistic regression. Odds ratios with 95% confidence intervals were calculated, stratifying by ethnicity and adjusting for age. Two-sided P-values of < or =0.05 were considered as statistically significant.


RESULTS
Eleven variants (four novel) were identified in the promoter region of CD14. A marginal association between the C genotypes (C/C + C/T) and prostate cancer was found (P = 0.07). When stratified by age, among men > or =55 years of age, the C genotypes were significantly associated with prostate cancer (P < 0.05). When stratified by self-reported ethnicity, African American males who had the C genotypes were at a higher risk for prostate cancer (P < 0.05).


CONCLUSIONS
This is the first study to show an association between the C genotypes of the CD14 (-260) variant and prostate cancer which supports the hypothesis that genetic variation in the inflammatory process can contribute to prostate cancer susceptibility in African American men.
Mason
Tshela E
TE
National Human Genome Center at Howard University, Washington, DC 20059, USA.
Ricks-Santi
Luisel
L
Chen
Weidong
W
Apprey
Victor
V
Joykutty
Jessy
J
Ahaghotu
Chiledum
C
Kittles
Rick
R
Bonney
George
G
Dunston
Georgia M
GM
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002908:Chronic Disease; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*
D018950:Lipopolysaccharide Receptors