Arginine-cysteine polymorphism at codon 264 of the human CYP19 gene does not affect aromatase activity

Genetic polymorphisms of cytochrome P450 19 and 1B1, alcohol use, and breast cancer risk in Korean women

“…The contrasting findings with previous studies (Watanabe et al, 1997;Siegelmann-Danieli and Buetow, 1999;Healey et al, 2000;Miyoshi et al, 2000) may be because of the differences in subject selection (noncomparable controls in the above studies), sample size (less than 200 in both cases and controls), and inadequate statistical power, marked differences in frequency of Cys allele (52 -54% for Japanese women, 39% for Korean women, and less than 10% for Caucasian), and different genotyping methods (single-strand conformation polymorphism, sequencing, and dynamic allele-specific hybridisation). The Arg 264 Cys polymorphism is located in or near recognition site of CYP19 aromatase and thus, it might enhance the oestrogen synthesis and exposure to endogenous oestrogen.…”

“…The genotype distributions in the control subjects agreed with those predicted by the Hardy -Weinberg equilibrium. The frequency of CYP19 Cys allele-containing genotypes (39%) was somewhat lower than that previously found in Japanese women (52 -54%) (Watanabe et al, 1997;Miyoshi et al, 2000), whereas the frequency of CYP19 Cys allele-containing genotypes was very low, less than 10% for Caucasians (Siegelmann-Danieli and Buetow, 1999;Healey et al, 2000). The frequency of CYP1B1 Val allele-containing genotype (21%), on the other hand, was similar to that (29%) found in Japanese women (Watanabe et al, 2000).…”

“…However, it is also be possible that CYP19 Arg 264 Cys polymorphism is in linkage disequilibrium with other important polymorphic site such as TTTA repeat polymorphism (Kristensen et al, 1998;Haiman et al, 2000;Baxter et al, 2001). Watanabe et al (1997) reported, however, that Arg 264 Cys genotype did not affect the aromatase activity in vitro test so further studies on the potential role of this polymorphism in breast cancer aetiology are required.…”

“…Polymeropulous et al, 1991;Sourdaine et al, 1994;Siegelmann-Danieli and Buetow, 1999;Healey et al, 2000;Miyoshi et al, 2000). One of these, a C-to-T variation in exon 7 resulting in an Arg 264 Cys amino-acid exchange, has been shown to be very common in Asians (Watanabe et al, 1997;Miyoshi et al, 2000) and could thus be an important modifier of breast cancer risk in this ethnic group.The CYP1B1 enzyme is known to be involved in the formation of 4-hydroxyoestradiol, which is a catechol metabolite of oestrogen (Hayes et al, 1996). A C-to-G variation in exon 3 of the CYP1B1 gene results in a Leu 432 Val amino-acid exchange.…”

Functional Genetic Polymorphisms in the Aromatase Gene CYP19 Vary the Response of Breast Cancer Patients to Neoadjuvant Therapy with Aromatase Inhibitors

“…Selected CYP19 polymorphisms have been investigated for their possible association with the therapeutic efficacy of aromatase inhibitors and with sex hormone levels or risk for estrogendependent diseases (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Although the results of those studies are controversial, they suggest an important role for genetic variation in aromatase function and, as a result, in estrogen production.…”