CYP17 genetic polymorphism in endometrial cancer: are only steroids involved?

被引：32

作者：

Berstein, LM ^{[1
]}

Imyanitov, EN ^{[1
]}

Gamajunova, VB ^{[1
]}

Kovalevskij, AJ ^{[1
]}

Kuligina, ES ^{[1
]}

Belogubova, EV ^{[1
]}

Buslov, KG ^{[1
]}

Karpova, MB ^{[1
]}

Togo, AV ^{[1
]}

Volkov, ON ^{[1
]}

Kovalenko, IG ^{[1
]}

机构：

[1] NN Petrov Oncol Res Inst, Lab Oncoendocrinol, St Petersburg 197758, Russia

来源：

CANCER LETTERS | 2002年 / 180卷 / 01期

基金：

俄罗斯基础研究基金会;

关键词：

P450c17; steroid 17 alpha-hydroxylase/17,20-lyase (CYP17); polymorphism; androgen; estrogen; insulinemia; risk of endometrial cancer;

D O I：

10.1016/S0304-3835(02)00019-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Initiation and/or promotion of endometrial cancer is known to be associated with estrogen and androgen (androstenedione) excess as well as with hyperinsulinemia/insulin resistance. It is possible that some allelic polymorphisms of the genes involved in steroidogenesis or steroid metabolism contribute to endometrial cancer susceptibility. We evaluated here the role of CYP17 biallelic (MspAI) polymorphism in 114 endometrial cancer patients compared with 182 healthy women. Our data demonstrated that A2/A2 CYP17 genotype, considered on the basis of initial breast cancer studies as 'unfavorable', was under-represented in endometrial cancer group (odds ratio 0.48, 95% confidence interval 0.25-0.89) that confirmed results of two other recent investigations. Carriers of this genotype were characterized by having lower blood insulin (by 120 min of oral glucose tolerance test 36.7 +/- 3.9 muU/ml vs. 90.4 +/- 16.7 muU/ml in postmenopausal women with A1/A1 genotype, P = 0.04) and C-peptide levels (after night fasting 575.2 +/- 78.3 pg/ml vs. 978.9 +/- 115.7 pg/ml, respectively, P = 0.04). No significant difference was found between the mean concentrations of testosterone, dehydroepiandrosterone sulfate and estradiol concentrations in patients-carriers of separate CYP17 genotypes. Thus, CYP17 polymorphism (namely, carrying the 'normal' A1/A1 genotype) might be one of the risk factors for endometrial cancer development. A1/A1 CYP17 variant may be associated with untraditional (nonsteroidal) pathways that calls for corresponding preventive measures in high-risk groups. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

引用

页码：47 / 53

页数：7

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