Genetic polymorphisms in oestrogen metabolic pathway and breast cancer: a positive association with combined CYP/GST genotypes.
The cytochrome P450 family (CYPs) and the glutathione S-transferase (GSTs) enzymes play an important role in the metabolism of environmental carcinogens and of oestrogen and can affect breast cancer risk. In this study we examine the role of the genes CYP1A1, CYP17, CYP2D6, GSTM1, GSTP1 and GSTT1 in breast cancer risk in Brazilian women. The study population consisted of 102 incident breast cancer cases and 102 healthy controls. Genotyping analyses were performed by PCR-based methods. A significant finding was observed between GSTP1 Ile-Val polymorphism and breast cancer risk (OR = 1.81; CI 95% = 1.04-3.16). A significant association was observed between women with 0-2 risk genotypes and those with 4 or more risk genotypes (OR = 2.42; CI 95% = 1.13-5.18) when the potential combined effects of the risk genotypes were examined. No significant differences between cases and controls were found correlating the genotypes and the clinical-histopathological parameters. In conclusion, in our population only GSTP1 was associated with breast cancer risk. However, when the genes were tested in combination, a significant association in the breast cancer risk was observed.
Torresan
C
C
Departamento de Genética, Universidade Federal do Paraná, Caixa Postal 19071, CEP 81531-970, Curitiba, Paraná, Brazil.
Oliveira
M M C
MM
Torrezan
G T
GT
de Oliveira
S F V
SF
Abuázar
C S
CS
Losi-Guembarovski
R
R
Lima
R S
RS
Urban
C A
CA
Cavalli
I J
IJ
Ribeiro
E M S F
EM
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D011110:Polymorphism, Genetic
D004967:Estrogens; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase