The CYP3A4*1B variant is related to the onset of puberty, a known risk factor for the development of breast cancer.
Breast development, one of the first signs of puberty, is closely associated with age at menarche; and early menarche is in turn a well-established risk factor for female breast cancer. We examined the relationships between the onset of puberty and gene variants for certain enzymes that regulate hormone metabolism among 137 healthy nine-year-old girls from two pediatric clinics. High-activity CYP17 alleles, involved in estrogen formation, and high-activity CYP1A2 and CYP1B1 alleles, whose gene products metabolize estradiol, were not associated with pubertal stage. High activity CYP3A4, but not CYP3A5, which primarily metabolizes testosterone, showed a striking association with the onset of puberty (adjusted odds ratio, 3.21; 95% confidence interval, 1.62-6.89 for the genotype 0-1-2 rapid alleles). Of the homozygous CYP3A4*1B/1B girls, 90% had reached puberty; whereas, for the low-activity homozygous CYP3A4*1A/1A individuals, only 40% had done so. In heterozygotes, 56% had reached puberty. CYP1B1, CYP3A4, and CYP3A5 rapid variants were more common in African-American than in Hispanic or Caucasian girls.
Kadlubar
Fred F
FF
Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, Arkansas 72079, USA. fkadlubar@nctr.fda.gov
Berkowitz
Gertrud S
GS
Delongchamp
Robert R
RR
Wang
Charles
C
Green
Bridgett L
BL
Tang
George
G
Lamba
Jatinder
J
Schuetz
Erin
E
Wolff
Mary S
MS
D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000941:ethics / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D009518:New York; D011627:Puberty / Q000235:genetics*; D012307:Risk Factors; D013223:Statistics as Topic; D013997:Time Factors; D016387:Women's Health
D005819:Genetic Markers; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human