A polymorphism of the 5 alpha-reductase gene and its association with prostate cancer: a case-control analysis.
Prostate cancer (CaP) is the most commonly diagnosed, nondermatological cancer in the United States. The development and progression of CaP is influenced by androgens. 5 alpha-Reductase, type II, converts testosterone to dihydrotestosterone and is critical to the development of the prostate. A TA dinucleotide repeat polymorphism exists in the 3' untranslated region of the 5 alpha-reductase type II gene. 5 alpha-Reductase alleles with longer TA repeats are more common in African-Americans, the group with the highest incidence of CaP. It has been hypothesized that the longer TA repeat alleles might be associated with increased risk of CaP. We studied this potential association within the Physician's Health Study, a predominantly Caucasian cohort study. Using PCR we identified the TA genotype in 590 men with CaP and 802 age-matched controls. The frequency of each allele in the controls was TA(0), 0.87, TA(9), 0.13, and TA(18), 0.01. Homozygotes for the longer TA alleles, TA(9) and TA(18), were underrepresented among cases with an odds ratio of 0.47 (confidence interval, 0.20-1.12), but this was not statistically significant (P = 0.08, two tailed). Our analysis does not support the prior hypothesis that longer TA alleles confer an increased risk of CaP in a predominantly Caucasian population; in fact, longer TA alleles are more prevalent in men without CaP.
Kantoff
P W
PW
Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Febbo
P G
PG
Giovannucci
E
E
Krithivas
K
K
Dahl
D M
DM
Chang
G
G
Hennekens
C H
CH
Brown
M
M
Stampfer
M J
MJ
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000728:Androgens / Q000502:physiology; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D013196:Dihydrotestosterone / Q000378:metabolism; D018450:Disease Progression; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D005838:Genotype; D006720:Homozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D011467:Prostate / Q000254:growth & development; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors; D013739:Testosterone / Q000378:metabolism; D044465:White People / Q000235:genetics; D001741:Black or African American
D000728:Androgens; D013196:Dihydrotestosterone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase