CYP17 polymorphism in the groups of distinct breast cancer susceptibility: comparison of patients with the bilateral disease vs. monolateral breast cancer patients vs. middle-aged female controls vs. elderly tumor-free women.
The CYP17 gene encodes an enzyme involved in several critical steps of steroidogenesis. The promoter region of the CYP17 displays a single-nucleotide polymorphism, which is suspected to modulate the expression of the gene and thus may contribute in the interindividual variations of hormonal background. In agreement with this functional hypothesis, the MspA1+ allele (designated as A2) of the CYP17 was shown to render an increased risk of breast cancer (BC). However, the latter observation was disputed by a series of negative reports. Here, we re-evaluated the role of CYP17 MspA1 polymorphism in the BC susceptibility, using a non-traditional design of a case-control study. In addition to randomly selected 183 BC patients and 107 female middle-aged donors, we examined the groups with apparently extreme characteristics of either BC risk or BC resistance, namely the 57 bilateral breast cancer (biBC) patients and 75 elderly (>/=75 years old) tumor-free women. Neither BC nor biBC patients showed increased prevalence of 'unfavorable' A2 allele as compared with the non-affected cohorts. Moreover, the A2 variant was not significantly associated with the tumor size, nodal involvement and menopausal status in the patients either with the monolateral or bilateral disease. Thus, our data argue against the earlier reported role of the CYP17 in BC predisposition and progression. In addition, usual distribution of the CYP17 alleles in the elderly group indicates a neutral effect of this polymorphism on the longevity in females.
Kuligina
E S
ES
N.N. Petrov Institute of Oncology, Pesochny-2, 189646, St. Petersburg, Russia.
Togo
A V
AV
Suspitsin
E N
EN
Grigoriev
M Y
MY
Pozharisskiy
K M
KM
Chagunava
O L
OL
Berstein
L M
LM
Theillet
C
C
Hanson
K P
KP
Imyanitov
E N
EN
D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
D013254:Steroid 17-alpha-Hydroxylase