Association Among an Ornithine Decarboxylase Polymorphism, Androgen Receptor Gene (CAG) Repeat Length and Prostate Cancer Risk

Abstract

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. 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. 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). 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.