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

Spurdle, Amanda B.; Fahey, Paul; Chen, Xiaoqing; McGuffog, Lesley; kConFab, _; Easton, Douglas F.; Peock, Susan; Cook, Margaret; Embrace,; Simard, Jacques; Inherit,; Rebbeck, Tim; Antoniou, Antonis C.; Chenevix-Trench, Georgia

doi:10.1007/s10549-009-0601-0

Cited by 8 publications

(4 citation statements)

References 19 publications

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“…CIMBA presently comprises 42 groups from across Europe, US, Australia and Asia. Of the candidate genes that have been investigated as modifiers of BRCA1 and BRCA2 (for example TP53 , MDM2 , AURKA , and others (Osorio et al., 2009; Spurdle et al., 2006, 2009a, 2009b; Sinilnikova et al., 2009; Johnatty et al., 2009; Rebbeck et al., 2009a; Couch et al., 2007)) the association of only one SNP, in the 5′untranslated region of RAD51 , with BRCA2 mutation carriers has been confirmed where rare homozygotes were at a threefold increased risk of developing breast cancer (HR 3.18, 95% CI 1.39–7.27, p = .0007) (Antoniou et al., 2007). RAD51 is involved in double‐stranded DNA repair and interacts with both BRCA1 and BRCA2 (Scully et al., 1997; Chen et al., 1999; Wong et al., 1997).…”

Section: Genetic Modifiers Of Brca1 and Brca2‐related Breast Cancermentioning

confidence: 99%

Genetic susceptibility to breast cancer

et al. 2010

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Genetic susceptibilityAetiology of breast cancer BRCA1/2 mutation carriers Pathology A B S T R A C TGenetic and lifestyle/environmental factors are implicated in the aetiology of breast cancer. This review summarizes the current state of knowledge on rare high penetrance mutations, as well as moderate and low-penetrance genetic variants implicated in breast cancer aetiology. We summarize recent discoveries from large collaborative efforts to combine data from candidate gene studies, and to conduct genome-wide association studies (GWAS), primarily in breast cancers in the general population. These findings are compared with results from collaborative efforts aiming to identify genetic modifiers in BRCA1 and BRCA2 carriers. Breast cancer is a heterogeneous disease, and tumours from BRCA1 and BRCA2 carriers display distinct pathological characteristics when compared with tumours unselected for family history. The relationship between genetic variants and pathological subtypes of breast cancer, and the implication of discoveries of novel genetic variants to risk prediction in BRCA1/2 mutation carriers and in populations unselected for mutation carrier status, are discussed. ª 2010 Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies. IntroductionBoth non-genetic and genetic factors are involved in the aetiology of breast cancer. Non-genetic factors include menstrual and reproductive history, body mass index, alcohol intake and physical activity. The genetic component of the disease is reflected on a tendency to cluster in families, although this could also reflect shared life-style and environment. A measure of this familial clustering is the familial relative risk (FRR), defined as the ratio of the risk of disease for a relative of an affected individual to that for the general population. FRR for breast cancer varies both with age of cancer diagnosis of the index case and the age of the relative (Familial breast cancer, 2001;Pharoah et al., 2000). For example, FRR decreases

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Section: Genetic Modifiers Of Brca1 and Brca2‐related Breast Cancermentioning

confidence: 99%

Genetic susceptibility to breast cancer

et al. 2010

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“…The mammalian cytosolic GSTs comprise 6 classes of dimeric isoenzymes alpha (α), mu (μ), pi (π), theta (τ), zeta (ζ) and omega (ω). GST-μ, GST-τ, and GST-π are encoded by the GSTM1 , GSTT1 , and GSTP1 genes, respectively; and these 3 genes have been studied in association with genetic susceptibility to cancer (Strange & Fryer 1999; Spurdle et al 2010). …”

Section: Introductionmentioning

confidence: 99%

Associations between null mutations in GSTT1 and GSTM1, the GSTP1 Ile105Val polymorphism, and mortality in breast cancer survivors

et al. 2013

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PurposeHere we assessed associations between null mutations in glutathione-S-transferase (GST)T1 and GSTM1 genes, and the rs1695 polymorphism in GSTP1 (Ile105Val), and risk of breast cancer-specific (n=45) and all-cause (n=99) mortality in a multiethnic, prospective cohort of 533 women diagnosed with stage I-IIIA breast cancer in 1995–1999, enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study.MethodsWe measured the presence of the null mutation in GSTT1 and GSTM1, and the rs1695 polymorphism in GSTP1 by polymerase chain reaction. We assessed associations between breast-cancer specific and all-cause mortality using Cox proportional hazards models.ResultsParticipants with ER-negative tumors were more likely to be GSTT1 null (χ2=4.52; P=0.03), and African American women were more likely to be GSTM1 null (χ2=34.36; P<0.0001). Neither GSTM1 nor GSTT1 null mutations were associated with breast cancer-specific or all-cause mortality. In a model adjusted for body mass index, race/ethnicity, tumor stage and treatment received at diagnosis, the variant Val allele of rs1695 was associated with increased risk of all-cause (HR=1.81, 95% CI 1.16-2.82, P=0.008), but not breast cancer-specific mortality. The GSTT1 null mutation was associated with significantly higher levels of C-reactive protein.ConclusionsGSTM1 and GSTT1 null genotypes had no effect on outcome; however the variant allele of rs1695 appears to confer increased risk for all-cause mortality in breast-cancer survivors.Given the limited sample size of most studies examining associations between GST polymorphisms with breast cancer survival, and the lack of women undergoing more contemporary treatment protocols (treated prior to 1999), it may be helpful to re-examine this issue among larger samples of women diagnosed after the late 1990s, who all received some form of chemotherapy or radiotherapy.

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“…Another study has shown that the c.1518C>T variant in BARD1, a BRCA1 interactor, increases the risk of BC [15], while a possible role of ZBRK1 variants/haplotypes and ZNF350 promoter variants in intermediate BC risk has been suggested [16,17]. Other BRCA1/2 interactors were also studied, many having no effect on BC predisposition [18,19].…”

Section: Non-linear Progressionmentioning

confidence: 99%