Pooled analysis indicates that the GSTT1 deletion, GSTM1 deletion, and GSTP1 Ile105Val polymorphisms do not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers.
The GSTP1, GSTM1, and GSTT1 detoxification genes all have functional polymorphisms that are common in the general population. A single study of 320 BRCA1/2 carriers previously assessed their effect in BRCA1 or BRCA2 mutation carriers. This study showed no evidence for altered risk of breast cancer for individuals with the GSTT1 and GSTM1 deletion variants, but did report that the GSTP1 Ile105Val (rs1695) variant was associated with increased breast cancer risk in carriers. We investigated the association between these three GST polymorphisms and breast cancer risk using existing data from 718 women BRCA1 and BRCA2 mutation carriers from Australia, the UK, Canada, and the USA. Data were analyzed within a proportional hazards framework using Cox regression. There was no evidence to show that any of the polymorphisms modified disease risk for BRCA1 or BRCA2 carriers, and there was no evidence for heterogeneity between sites. These results support the need for replication studies to confirm or refute hypothesis-generating studies.
Spurdle
Amanda B
AB
Division of Genetics and Population Health, Queensland Institute of Medical Research, 300 Herston Rd, Herston 4006, Australia.
Fahey
Paul
P
Chen
Xiaoqing
X
McGuffog
Lesley
L
Easton
Douglas
D
Peock
Susan
S
Cook
Margaret
M
Simard
Jacques
J
Rebbeck
Tim R
TR
Antoniou
Antonis C
AC
Chenevix-Trench
Georgia
G
D019943:Amino Acid Substitution; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics; D005006:Ethnicity / Q000235:genetics / Q000706:statistics & numerical data; D005260:Female; D017353:Gene Deletion; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012306:Risk
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human