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  • br Fig PCR product of CYP

    2020-08-18


    Fig. 2. PCR product of CYP19 gene fragment in patients and control samples on agarose gel electrophoresis. L = DNA Ladder 100 bp.
    while some studies failed to show an association with TTTA repeats polymorphism and the risk of breast cancer (Healey et al., 2000; Probst-Hensch et al., 1999; Young et al., 2000).
    The distribution of TTTA repeat polymorphism of the CYP19 gene among the controls and EC patients, showed the risk factor increased about two-fold with (TTTA)9, (TTTA)11 and (TTTA)12 repeats (Table 1).While the risk factor increased in OC patients about two-fold with (TTTA)11, and about four fold with (TTTA) 12, (Table 2).
    The present study examined the polymorphisms in intron 4 of CYP19 gene: the TTTA repeat, and found the risk factor to EC increased about eleven fold with (7–11) allele (Table 3). While the results showed there was a significant effect in (7–10), (7–12) and (11–11) hetero-zygote allele between control and OC patients the risk increased about two-fold, and about six-fold in (7–11) heterozygote allele (Table 4). The long allele enhanced the aromatase activity (Stratakis et al., 1998).
    Tworoger et al. suggested that the CYP19 polymorphisms may alter sex hormone concentrations in some postmenopausal women. This in-formation may help elucidate pathways through which variations in this gene may influence breast cancer etiology (Tworoger et al., 2004). Previous studies had shown that CYP19 might be involved in breast cancer susceptibility (Kristensen et al., 2000; Miyoshi et al., 2000; Siegelmann-Danieli and Buetow, 1999), probably due to its role in the 
    conversion of C19 steroids into estrogens.
    Wang et al. shows that CYP19 gene polymorphisms are not asso-ciated with endometriosis or endometriosis-related chocolate cysts in Chinese women (Wang et al.). Also the studies from Korean (Hur et al.), Japanese (Kado et al.) and Caucasian populations (Trabert et al., 2011) reported no significant association of CYP19 gene polymorphisms with the risk of endometriosis or chocolate cysts (Kado et al., 2002; Hur et al., 2007; Trabert et al., 2011).
    Hur et al. found frequency of the higher risk G 418 of the CYP19 gene was not higher in endometriosis if compared with the control group. Furthermore, found that endometriosis risk did not increase with the number of higher risk alleles. The association between the CYP19 (TTTA) and endometriosis risk may be back to differences of allele frequencies between different environmental factors, genetic hetero-geneity and ethnic groups (Hur et al., 2007).
    In conclusion, this study showed A strong association between CYP19 polymorphisms, with Endometrial and Ovarian Cancer espe-cially the long Alleles and the haplotype and genotypes frequencies of CYP19 maybe an indicator for susceptibility for Endometrial and Ovarian Cancer.
    Table 1
    The distribution of TTTA repeats polymorphism of the CYP19 gene with EC.
    Number Of TTTA Controls Patients (EC) OR 95% CI
    Table 2
    The distribution of TTTA repeats polymorphism of the CYP19 gene with OC.
    Number Of TTTA Controls Patients (OC) OR 95% CI 
    Table 4
    The distribution of the CYP19 gene between OC patients and controls.
    Genotype Controls Patients OR 95% CI
    Table 3
    The distribution of the CYP19 gene between EC patients and controls.
    Genotype Controls Patients OR 95% CI  Table 5
    Frequency of CYP19 (TTTA)n alleles and genotypes in EC.
    Genotype Controls allele Patients allele OR 95% CI
    frequency frequency
    Frequency of CYP19 (TTTA)n alleles and genotypes in OC.
    Genotype Controls allele Patients allele OR 95% CI
    frequency frequency
    References
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    Aromatase in endometriosis and uterine leiomyomata. J. Steroid Biochem. Mol. Biol.
    and haplotypes of the gene encoding the estrogen-metabolizing CYP19 gene in Korean women: no association with advanced-stage endometriosis. J. Hum. Genet. 52 (9), 703–711.
    Sebastian, S., Bulun, S.E., 2001. A highly complex organization of the regulatory region of the human CYP19 (aromatase) gene revealed by the Human Genome Project. J. Clin. Endocrinol. Metab. 86 (10), 4600–4602. Sheskin, D.J., 2004. Handbook of Parametric and Nonparametric Statistical Procedures.
    CRC Press, Boca Raton, FL.
    Shimada, T., Yamazaki, H., Mimura, M., Inui, Y., Guengerich, F.P., 1994. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J. Pharmacol. Exp. Ther. 270 (1), 414–423.
    R. Stapleton, J. W. Lampe, F, M. Farin, & F. Z. Stanczyk. Association of CYP17, CYP19, CYP1B1, and COMT polymorphisms with serum and urinary sex hormone concentrations in postmenopausal women. Cancer Epidemiol. Prev. Biomark.