CYP19 gene polymorphism in endometrial cancer patients

Berstein, Lev M.; Imyanitov, Evgeny N.; Suspitsin, Evgeny N.; Grigoriev, M.; Sokolov, E.P.; Togo, Alexandr V.; Hanson, Kaido P.; Порошина, Т. Е.; Vasiljev, Dmitry A.; Kovalevskij, Anatolij Y.; Gamajunova, V. B.

doi:10.1007/s004320000200

Cited by 51 publications

(34 citation statements)

References 7 publications

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“…Previous population-based studies of common CYP19 polymorphisms have generated inconsistent results with regard to their possible association with either sex hormone levels or risk for estrogen-dependent diseases (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Selected CYP19 polymorphisms have also been investigated for their possible association with the therapeutic efficacy of aromatase inhibitors (25).…”

Section: Introductionmentioning

confidence: 99%

“…Selected CYP19 polymorphisms have also been investigated for their possible association with the therapeutic efficacy of aromatase inhibitors (25). The fact that past data with regard to the association of CYP19 polymorphisms with estrogen-dependent disease has been inconsistent (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), as well as the lack of functional studies of these polymorphisms, underscores the importance of applying a systematic approach to identify and functionally characterize CYP19 polymorphisms. In the present study, we have used gene resequencing to identify previously unreported genetic variation in this important gene.…”

Section: Introductionmentioning

confidence: 99%

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Human Aromatase: Gene Resequencing and Functional Genomics

Cynthia¹,

Adjei²,

et al. 2005

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Aromatase [cytochrome P450 19 (CYP19)] is a critical enzyme for estrogen biosynthesis, and aromatase inhibitors are of increasing importance in the treatment of breast cancer. We set out to identify and characterize genetic polymorphisms in the aromatase gene, CYP19, as a step toward pharmacogenomic studies of aromatase inhibitors. Specifically, we ''resequenced'' all coding exons, all upstream untranslated exons plus their presumed core promoter regions, all exonintron splice junctions, and a portion of the 3V-untranslated region of CYP19 using 240 DNA samples from four ethnic groups. Eighty-eight polymorphisms were identified, resulting in 44 haplotypes. Functional genomic studies were done with the four nonsynonymous coding single nucleotide polymorphisms (cSNP) that we observed, two of which were novel. ) displayed a significant change from the WT enzyme in inhibitor constant for the aromatase inhibitors exemestane and letrozole. These observations indicate that genetic variation in CYP19 might contribute to variation in the pathophysiology of estrogendependent disease. (Cancer Res 2005; 65(23): 11071-82)

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human Aromatase: Gene Resequencing and Functional Genomics

Cynthia¹,

Adjei²,

et al. 2005

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“…The multiple nontranslated exon I controls gene expression in a tissue-specific manner and under complex hormonal regulation (15). Polymorphisms in CYP19A1 have been evaluated for their association with breast cancer risk (16)(17)(18)(19)(20)(21)(22)(23) and, to a lesser extent, with endometrial (24,25) and prostate cancer (26,27) and endometriosis (28). The CYP19A1 gene is highly polymorphic (16).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the CYP19A1 (Aromatase) Gene and Endometrial Cancer Risk in Chinese Women

Tao

Cai

Zhang

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Aromatase, encoded by the CYP19A1 gene, is a key enzyme in estradiol biosynthesis, which catalyzes the conversion of androstenedione and testosterone to estrone and estradiol, respectively. Given the critical role of estrogen in the development of endometrial cancer risk, we evaluated genetic polymorphisms of the CYP19A1 gene, including rs1065779, rs700519, rs28566535, rs752760, and rs1870050, in association with endometrial cancer in a population-based case-control study conducted in Shanghai, China. Genotypes of 1,040 incident endometrial cancer cases and 1,031 frequencymatched controls were included in the study. We applied a logistic regression model to derive adjusted odds ratios (OR) and their 95% confidence intervals (95% CI). Six common haplotypes with a frequency z5% were estimated; the highest frequency haplotype was GCACA (27.8% in cases and 26.2% in controls). We observed an inverse association between CYP19A1 haplotype TCATC and endometrial cancer in our population (OR, 0.76; 95% CI,). An inverse association was found between endometrial cancer and single nucleotide polymorphism rs1870050 in the promoter region with ORs of 0.81 (95% CI, 0.68-0.97) and 0.58 (95% CI, 0.42-0.80) for the AC and CC genotypes, respectively. We observed a multiplicative interaction between single nucleotide polymorphism rs700519 and body mass index among postmenopausal women (P = 0.01), with stronger associations between rs700519 genotypes and endometrial cancer risk among heavier (body mass index, z25) postmenopausal women. In summary, our data show that polymorphisms in the CYP19A1 gene may contribute to endometrial carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2007;16(5):943 -9)

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Ma¹,

Ellis²

2010

Yearbook of Oncology

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Aromatase (CYP19) is a critical enzyme for estrogen biosynthesis, and aromatase inhibitors (AIs) are established endocrine therapy for post-menopausal women with breast cancer. DNA samples were obtained from 52 women pre-and post-AI treatment in the neoadjuvant setting. 82 breast cancer and 19 normal breast samples were resequenced to test the hypothesis that single nucleotide polymorphisms (SNPs) in the CYP19 gene might contribute to response to neoadjuvant AI therapy. There were no differences in CYP19 sequence between tumor and germline DNA in the same patient. Forty-eight CYP19 SNPs were identified, with four being novel when compared with previous resequencing data. Genotype-phenotype association studies performed with levels of aromatase activity, estrone, estradiol and tumor size pre-and post-AI treatment indicated that two tightly linked SNPs, rs6493497 and rs7176005 in the 5'-flanking region of CYP19 exon 1.1, were significantly associated with a greater change in aromatase activity after AI treatment. A follow-up study in 200 women with early breast cancer treated with adjuvant anastrozole showed that these same two SNPs were also associated with higher plasma estradiol levels pre-and post-AI treatment. Electrophoretic mobility shift and reporter gene assays confirmed the potential functional effects of these two SNPs on transcription regulation. These studies provide insight into the role of common genetic polymorphisms in CYP19 in variation in response to AIs by breast cancer patients.

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CYP19 gene polymorphism in endometrial cancer patients

Abstract: Thus, CYP19 polymorphism might be one of the genetic risk factors for endometrial cancer development.

Cited by 51 publications

References 7 publications

Human Aromatase: Gene Resequencing and Functional Genomics

Human Aromatase: Gene Resequencing and Functional Genomics

Polymorphisms in the CYP19A1 (Aromatase) Gene and Endometrial Cancer Risk in Chinese Women

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

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