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e demonstrated that, premenopausal women with homozygous for the minor allele of CYP19 rs4646 had significantly longer DFS than those carrying the major PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19764249 allele, however, the same homozygous variant was estimated to be associated with poorer DFS among the postmenopausal women. These differences were further confirmed by multivariate analysis. The findings are biologically plausible, given the crucial role of aromatase in estrogen synthesis, its identified impact on tumor growth and progression, and the potential functional significance of CYP19 genetic polymorphisms. Population-based studies of CYP19 polymorphisms have generated inconsistent results with regard to their potential association with clinical outcome. It has been suggested that rare T allele of rs4646 was correlated with prolonged TTP in postmenopausal MBC women with letrozole therapy. Additionally, the frequency of the variant allele was significantly higher in the responder group . Likewise, Liu et al estimated that this minor allele of rs4646 was significantly linked with longer TTP and OS when assessed in MBC women with anastrozole administration. The other study, conversely, the same variant was revealed to be in relation with shorter progression-free survival in the neoadjuvant setting. Besides, the genotypic variants of rs4646 were more frequently represented in the nonresponder cohort . Similarly, the data in 296 early breast cancer patients indicated that the combined high risk A/A + A/C alleles of CYP19 polymorphism rs4646 were significantly related to poorer distant disease-free survival and marginally associated with shorter DFS and OS. However, other studies did not observe any significant differences between the rs4646 polymorphisms with clinical outcome. Given the critical role of hormone in the pathogenesis and progression of breast cancer, the circulating estrogen levels may have negative impact on survival in women with breast cancer. Lnning et al. showed that circulating estrogen levels were significantly associated with poorer DFS in postmenopausal patients. In a casecontrol cohort study, Rock et al. indicated that total estradiol, bioavailable estradiol, and free estradiol circulating concentrations were correlated with risk of recurrence. Besides, it has been suggested that CYP19 polymorphisms were significantly associated with hormone levels. Haiman et al. demonstrated that patients with the 8-repeat allele of the TTTA polymorphism have higher estrogen levels than those carrying the 7-repeat allele. The analysis in five large prospective cohorts showed that rs727479 and rs749292 were significantly related to higher estradiol and estrone levels. More recently, some data indicated that the rs4646 may be linked with circulating 10 / 13 The CYP19 RS4646 Polymorphism and the Prognosis PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19763832 of Early Breast Cancer hormone levels in postmenopausal breast cancer. Interestingly, rs1065779 of CYP19 has been estimated to have impact on transcription or expression of aromatase. Elevated levels of aromatase expression have been observed in breast tumors relative to normal breast tissue. Meanwhile, some other analysis have indicated a significant association between aromatase and estrogen-related receptor mRNA expression in isolated tumor cells. A number of studies showed that CYP19 polymorphisms were DMXB-A relevant to greater aromatase activity. Kristensen et al showed that a higher number of TTTA repeats of CYP19 was associated with greater aromatase activity. Likewise, anoth

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Author: M2 ion channel