The relationship of uterine leiomyomata and genetic polymorphisms of Cytochrome P-450 1A1, Cytochrome P-450 1B1, and Catechol-O-Methyltransferase Public Deposited

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  • March 22, 2019
  • Gooden, Kyna McCullough
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Uterine leiomyomata, or fibroids, are one of the most common neoplasms in women of reproductive age. They occur more often and are larger in African American women compared to White women. Although benign, the etiology of fibroids is largely unknown, however they are hormonally dependent. The biologic effect of estrogen is influenced by estrogen metabolism; therefore estrogen metabolism enzymes may influence fibroid development. Cytochrome P-450 1A1 (CYP1A1), Cytochrome P-450 1B1 (CYP1B1), and Catechol-O-Methyltransferase (COMT) are polymorphic genes that encode key enzymes in the estrogen metabolism pathway. Four single nucleotide polymorphisms (SNP) of CYP1A1, 2 SNPs of CYP1B1, and 1 SNP of COMT were evaluated for associations with fibroid prevalence and size in a cross-sectional sample of premenopausal African American (n=583) and White (n=404) women from the National Institute of Environmental Health Sciences Uterine Fibroid Study. Participants provided DNA samples and completed telephone interviews and questionnaires. Race-specific prevalence ratios (PR) and 95% confidence intervals (CI) were estimated from log-risk regression models; prevalence differences (PD) and 95% CI were estimated from linear-risk regression models. Haplotypes and diplotypes were inferred for CYP1A1 and CYP1B1. Genotype distributions varied by race. African Americans were more likely to have fibroids (72% vs 50%) and to have large fibroids (24% vs 11%) than Whites. The CYP1A1*3allele was associated with fibroids among African Americans (PR=1.14; 95%CI: 1.02, 1.28; PD=0.10; 95%CI: 0.01, 0.19). The CYP1A1*4 allele was positively associated with fibroids among both Whites (PR=1.20; 95%CI: 0.90, 1.61; iv PD=0.10; 95%CI: -0.07, 0.27) and African Americans (PR=1.16; 95%CI: 0.92, 1.48; PD=0.12; 95%CI: -0.08, 0.32). Haplotypes and diplotypes that included CYP1A1*3 and CYP1A1*4 showed similar results. Estimates for CYP1B1 and COMT alleles were close to the null. Analyses of effect measure modification by age, body mass index, smoking status, alcohol use, oral contraceptive use, and number of fullterm births did not show deviations from additive or multiplicative expectations. Our results reveal possible relationships between CYP1A1*3 and *4 polymorphisms and fibroid prevalence. These results must be confirmed in other populations, and consider additional genes and variants within the estrogen metabolism pathway.
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  • Schroeder, Jane C.
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  • University of North Carolina at Chapel Hill
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