The CYP3A41B 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 closelyassociated 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 horm...

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Published inCancer epidemiology, biomarkers & prevention Vol. 12; no. 4; pp. 327 - 331
Main Authors Kadlubar, Fred F, Berkowitz, Gertrud S, Delongchamp, Robert R, Wang, Charles, Green, Bridgett L, Tang, George, Lamba, Jatinder, Schuetz, Erin, Wolff, Mary S
Format Journal Article
LanguageEnglish
Published United States American Association for Cancer Research 01.04.2003
Subjects
Alleles
Breast Neoplasms - epidemiology
Breast Neoplasms - genetics
Child
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System - genetics
Female
Gene Frequency
Genetic Markers - ethics
Genetic Markers - genetics
Genetic Predisposition to Disease - epidemiology
Genetic Predisposition to Disease - genetics
Genetic Variation
Genotype
Humans
New York
Puberty - genetics
Risk Factors
Statistics as Topic
Time Factors
Women's Health
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Summary:Breast development, one of the first signs of puberty, is closelyassociated 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.
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ISSN:1055-9965
1538-7755