Positive association of polymorphisms in estrogen biosynthesis gene, CYP19A1, and metabolism, GST, in breast cancer susceptibility.
OBJECTIVE
This case-control study was conducted in order to evaluate the potential role of polymorphic genes encoding enzymes involved in estrogen biosynthesis (CYP19A1) and metabolism (GSTM1, GSTT1, and GSTP1), and their action in modulating individual susceptibility to breast cancer.


METHODS
Genomic DNA was extracted from blood samples of 101 patients with histological diagnosis of breast cancer and 121 healthy women. Genotyping analyses of CYP19A1 codon 39 Trp/Arg (T/C), GSTM1 and GSTT1 homozygous deletions, and GSTP1 codon 105 Ile/Val (A/G) were performed by polymerase chain reaction-based methods.


RESULTS
Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression. Significant statistical association of the TC/CC genotypes combined with breast cancer risk was found, with reference to TT genotype (OR=1.770; 95% CI=1.036-3.024; p=0.036). Also, CYP19A1 arginine allele in homozygosity or heterozygosity (TC/CC) was associated with a significant increased risk for breast cancer when associated to GSTM1 null genotype (OR=6.158; 95% CI=2.676-14.171; p<0.001) and GSTT1 null genotype (OR=4.870; 95% CI=2.216-10.700; p<0.001). The three-way combination of CYP19A1 TC/CC, GSTM1 null, and GSTT1 null polymorphism was related with significant increased risk for breast cancer (OR=11.429; 95% CI=3.590-36.385; p<0.001). Valine alleles compared with isoleucine alleles in codon 105 in GSTP1, in combination with CYP19A1 genotypes, were not associated with an increase of breast cancer development.


CONCLUSIONS
Our results suggest that the effect of CYP19A1 T/C polymorphism in susceptibility to breast cancer development can be modulated by the presence of GSTM1 and GSTT1, but not GSTP1.
CICS-UBI-Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Covilhã, Portugal. cramalhinho@fcsaude.ubi.pt
Ana Cristina Monteiro
AC
Ramalhinho
José Alberto
JA
Fonseca-Moutinho
Luiza Augusta Tereza Gil
LA
Breitenfeld Granadeiro
D000293:Adolescent; D000328:Adult; D000368:Aged; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D055815:Young Adult
D004967:Estrogens; D001141:Aromatase; C561410:CYP19A1 protein, human; D005982:Glutathione Transferase