title: 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.
abstract: 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.
authors.affiliation: Division of Genetics and Population Health, Queensland Institute of Medical Research, 300 Herston Rd, Herston 4006, Australia.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Spurdle
authors.forename: Paul
authors.initials: P
authors.lastname: Fahey
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Chen
authors.forename: Lesley
authors.initials: L
authors.lastname: McGuffog
authors.forename: Douglas
authors.initials: D
authors.lastname: Easton
authors.forename: Susan
authors.initials: S
authors.lastname: Peock
authors.forename: Margaret
authors.initials: M
authors.lastname: Cook
authors.forename: Jacques
authors.initials: J
authors.lastname: Simard
authors.forename: Tim R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench
mesh_terms: 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
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human