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 ster oidogenesis. 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 backgrou nd. In agreement with this functional hypothesis, the MspA1+ allele (design ated as A2) of the CYP17 was shown to render an increased risk of breast ca ncer (BC). However, the latter observation was disputed by a series of nega tive reports. Here, we re-evaluated the role of CYP17 MspA1 polymorphism in the BC susceptibility, using a non-traditional design of a case-control st udy. In addition to randomly selected 183 BC patients and 107 female middle -aged donors, we examined the groups with apparently extreme characteristic s of either BC risk or BC resistance, namely the 57 bilateral breast cancer (biBC) patients and 75 elderly (greater than or equal to 75 years old) tum or-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, noda l involvement and menopausal status in the patients either with the monolat eral or bilateral disease. Thus, our data argue against the earlier reporte d role of the CYP17 in BC predisposition and progression. In addition, usua l distribution of the CYP17 alleles in the elderly group indicates a neutra l effect of this polymorphism on the longevity in females. (C) 2000 Elsevie r Science Ireland Ltd. All rights reserved.