Springerplus. 2013 Sep 11;2:450. doi: 10.1186/2193-1801-2-450. eCollection 2013.

Associations between null mutations in GSTT1 and GSTM1, the GSTP1 Ile(105)Val polymorphism, and mortality in breast cancer survivors.

SpringerPlus

Catherine Duggan, Rachel Ballard-Barbash, Richard N Baumgartner, Kathy B Baumgartner, Leslie Bernstein, Anne McTiernan

PMID: 24083102 PMCID: PMC3786079 DOI: 10.1186/2193-1801-2-450

Abstract

PURPOSE: Here we assessed associations between null mutations in glutathione-S-transferase (GST)T1 and GSTM1 genes, and the rs1695 polymorphism in GSTP1 (Ile(105)Val), 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.

METHODS: We 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.

RESULTS: Participants with ER-negative tumors were more likely to be GSTT1 null (χ(2)=4.52; P=0.03), and African American women were more likely to be GSTM1 null (χ(2)=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.

CONCLUSIONS: GSTM1 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.

Keywords: Breast cancer survival; GSTM1; GSTP1; GSTT1; Glutathione-S-transferases; Mortality; Polymorphisms

References

1. Ann Oncol. 2012 Jul;23(7):1750-6 - PubMed
2. Neurosci Lett. 2003 Jan 30;337(1):5-8 - PubMed
3. J Clin Oncol. 2003 May 15;21(10):1961-6 - PubMed
4. Cancer Res. 2002 Jun 1;62(11):3052-7 - PubMed
5. Cancer Res. 2000 Oct 15;60(20):5621-4 - PubMed
6. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7293-7 - PubMed
7. Breast Cancer Res Treat. 2009 Mar;114(1):155-67 - PubMed
8. Atherosclerosis. 2003 Dec;171(2):265-72 - PubMed
9. Arch Biochem Biophys. 1999 Jun 1;366(1):89-94 - PubMed
10. Cancer Res. 2001 Oct 1;61(19):7130-5 - PubMed
11. J Clin Oncol. 2009 Jul 20;27(21):3437-44 - PubMed
12. Atherosclerosis. 2006 Feb;184(2):404-12 - PubMed
13. Mutat Res. 2001 Oct 1;482(1-2):21-6 - PubMed
14. Cancer. 2005 Jan 1;103(1):52-8 - PubMed
15. Breast Cancer Res Treat. 2010 Jul;122(1):281-5 - PubMed
16. Cancer Epidemiol Biomarkers Prev. 1997 Sep;6(9):733-43 - PubMed
17. Pharmacology. 2000 Sep;61(3):154-66 - PubMed
18. Breast Cancer Res. 1999;1(1):81-7 - PubMed
19. IARC Sci Publ. 1999;(148):231-49 - PubMed
20. Biochem Biophys Res Commun. 2000 Nov 11;278(1):258-62 - PubMed
21. Breast Cancer Res Treat. 2007 Sep;105(1):45-54 - PubMed
22. Breast Cancer Res Treat. 2008 Sep;111(1):93-101 - PubMed
23. J Biol Chem. 1997 Apr 11;272(15):10004-12 - PubMed

Publication Types

• Journal Article

Grant support

• N01 PC067010/PC/NCI NIH HHS/United States
• R25 CA094880/CA/NCI NIH HHS/United States
• M01 RR000037/RR/NCRR NIH HHS/United States
• N01 CN005228/CN/NCI NIH HHS/United States
• M01 RR000997/RR/NCRR NIH HHS/United States