Hormonal imbalance in two types of endometrial cancer and genetic polymorphism of steroidogenic enzymes.
OBJECTIVE
Modern data on endometrial cancer (EC) incidence demonstrate that it is one of the most prevalent gynecologic malignancies. It is possible that some allelic polymorphisms of the genes involved in steroidogenesis or steroid metabolism differently contribute into susceptibility to described types of this disease, namely to type I (which is considered to be hormone dependent) and type II.


METHODS
Distribution of allelic polymorphisms of CYP17 (17alpha-hydroxylase/17,20-lyase), CYP19 (aromatase), catechol-O-methyltransferase (COMT) and CYP1B1 (primarily, estrogen 4-hydroxylase) genes was compared totally in 156 endometrial cancer patients, approximately two-third of who belonged (on the basis of case history and some characteristics of host and tumor) to type I of the disease, and one-third to type II. Blood leukocytes were used as source of normal DNA for PCR-genotyping.


RESULTS
No differences were found in distribution of CYP17 and CYP1B1 genotypes between patients belonging to type I or II of the disease. On the other side, in case of CYP19, the ratio of incidence of A6A6 genotype to the frequency of A1A6 and A3A6 genotypes was higher in type II patients (1.0) than in type I patients (0.3). Besides, incidence of high activity (HH) COMT genotype was higher among patients with type I of disease than in patients with type II of it (33.3% versus 14.7%, OR=2.9, z=1.96, p=0.05) revealing tendency to the lower inactivation of catecholestrogens in the latter group.


CONCLUSIONS
It may be suggested that more aggressive clinically and frequently receptor-negative type II of endometrial cancer is associated with indirect signs of mainly intratumoral hyperproduction of estrogens (excess of CYP19 A6A6 genotype) without their sufficient inactivation into methoxyderivatives that warrants further study.
Berstein
Lev
L
Lab. Oncoendocrinology, N.N. Petrov Research Institute of Oncology, Pesochny, St. Petersburg 197758, Russia. levmb@endocrin.spb.ru
Zimarina
Tatjana
T
Imyanitov
Evgeny
E
Kovalevskij
Anatolij
A
Maximov
Sergei
S
Pujol
Pascal
P
Thijssen
Jos
J
D000328:Adult; D000368:Aged; D001141:Aromatase / Q000235:genetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
D012739:Gonadal Steroid Hormones; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D013254:Steroid 17-alpha-Hydroxylase; D002394:Catechol O-Methyltransferase