Original Article
The Pharmacogenomics Journal (2006) 6, 189–193. doi:10.1038/sj.tpj.6500365; published online 10 January 2006
Estrogen-metabolizing gene polymorphisms in the assessment of female hormone-dependent cancer risk
O N Mikhailova1, L F Gulyaeva1, A V Prudnikov1, A V Gerasimov2 and S E Krasilnikov2
- 1Institute of Molecular Biology and Biophysics, Novosibirsk, Russia
- 2Regional Clinical Oncological Hospital, Novosibirsk, Russia
Correspondence: Dr ON Mikhailova, Department of Molecular Mechanisms of Carcinogenesis, Institute of Molecular Biology and Biophysics, Siberian Branch of the Russian Academy of Medical Sciences, Timakov Str. 2, Novosibirsk, 630117, Russia. E-mail: pharmacogenomics@ngs.ru
Received 5 May 2005; Revised 21 November 2005; Accepted 21 November 2005; Published online 10 January 2006.
Abstract
Allelic variants of cytochrome P450: CYP1A1, CYP1A2, CYP19 (Aromatase) and II-phase enzyme Sulfotransferase (SULT1A1) genes are associated with a high risk of hormone-dependent cancers. We estimated a frequency of these allelic variants in the female Caucasian population of the Novosibirsk region of Russia and their association with the elevated risk of ovarian and endometrial cancer. A DNA bank of gynecologic oncology patients, patients with benign gynecologic diseases and healthy women was created, and the following single nucleotide polymorphisms (SNPs) were examined: CYP1A1 M1 polymorphism, that is, T264
C transition in the 3'-noncoding region; CYP1A2*1F polymorphism, that is, C734
A transversion in CYP1A2 gene; C
T transition (Arg264Cys) in exon 7 of CYP19; SULT1A1*2 polymorphism, that is, G638
A transition (Arg213His) in SULT1A1 gene. A positive correlation of C allele of CYP1A2*1F and G allele of SULT1A1*2 with hormone-dependent cancers in women was found. Thus, these genes are appropriate candidates for studying the contribution of genetic factors to endocrine disorder and environmentally determined diseases susceptibility. In contrast, no association of CYP19 and CYP1A1 polymorphisms with increased cancer risk was revealed.
Keywords:
SNP, drug metabolizing enzymes, polymorphism, endometrial cancer, ovarian cancer
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