Association among an ornithine decarboxylase polymorphism, androgen receptor gene (CAG) repeat length and prostate cancer risk.
OBJECTIVE
A single nucleotide substitution of guanine to adenine (A) at base +316 in the ornithine decarboxylase (ODC) gene may be associated with greater ODC expression and increased tumor growth. ODC is induced by androgens in human prostatic epithelial cells, presumably via transcriptional activation of androgen receptor (AR) and also by nicotine. A nested case-control study was done to examine the association between this ODC genotype and prostate cancer risk, and whether it varies by AR gene CAG repeat length and smoking.


METHODS
A total of 164 cases were matched to 2 controls each from a community based cohort. ODC and AR genotyping was performed using a TaqMan (PE Applied Biosystems, Foster City, California) based assay and automated fragment analysis, respectively. Conditional logistic regression was used to estimate the OR and 95% CI.


RESULTS
The presence of the ODC A allele was not significantly associated with an increased risk of prostate cancer (OR 1.33, 95% CI 0.90 to 1.96). However, men who inherited at least 1 ODC A alleles and less than 22 AR CAG repeats were at twice the risk of prostate cancer compared with those with 2 guanine alleles and 22 or greater AR CAG repeats (OR 2.09, 95% CI 1.23 to 3.57). Smoking was associated with prostate cancer only in men carrying a least 1 ODC A allele (p interaction = 0.02).


CONCLUSIONS
The ODC A allele was not associated with a statistically significant increased risk of prostate cancer. However, this association may vary according to the number of CAG repeats in the AR receptor and smoking status.
Visvanathan
Kala
K
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. kvisvana@jhsph.edu
Helzlsouer
Kathy J
KJ
Boorman
David W
DW
Strickland
Paul T
PT
Hoffman
Sandy C
SC
Comstock
George W
GW
O'Brien
Thomas G
TG
Guo
Yongjun
Y
D000368:Aged; D016022:Case-Control Studies; D006801:Humans; D008297:Male; D009955:Ornithine Decarboxylase / Q000235:genetics*; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*; D020449:Repetitive Sequences, Amino Acid; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D011944:Receptors, Androgen; D009955:Ornithine Decarboxylase