Drug-Metabolizing Enzyme Polymorphisms Predict Clinical Outcome in a Node-Positive Breast Cancer Cohort

DeMichele, Angela; Aplenc, Richard; Botbyl, Jeffrey; Colligan, Theresa; Wray, Lisa; Klein-Cabral, Melissa; Foulkes, Andrea S.; Gimotty, Phyllis A.; Glick, John H.; Weber, Barbara; Stadtmauer, Edward A.; Rebbeck, Timothy R.

doi:10.1200/jco.2005.06.208

Cited by 45 publications

(25 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistently with our observation, patients with low drug metabolizing genotypes with acute myeloid leukemia, esophageal cancer, lung cancer, or breast cancer exhibited reduced survival rates in some studies (39)(40)(41)(42). This might be attributable to a higher rate of toxicity-related deaths.…”

Section: ------------------------------------------------------------supporting

confidence: 88%

Comprehensive analysis of excision repair complementation group 1, glutathione S-transferase, thymidylate synthase and uridine diphosphate glucuronosyl transferase 1A1 polymorphisms predictive for treatment outcome in patients with advanced gastric cancer treated with FOLFOX or FOLFIRI

Seo

Kwon²,

Oh³

et al. 2009

Oncol Rep

View full text Add to dashboard Cite

Abstract. Oxaliplatin and irinotecan have proven effective in the treatment of gastric cancer. We attempted to determine whether single nucleotide polymorphisms in ERCC1, GST, TS and UGT1A1 predicted overall survival in gastric cancer patients receiving FOLFOX and/or FOLFIRI chemotherapy. Total genomic DNA was extracted from the whole blood of patients. The PCR-restriction fragment length polymorphism technique was applied in order to detect the known variant sites of ERCC1, GST, TS and UGT1A1. The response rate of FOLFOX (N=75) was 24%. Grade 3-4 neutropenia and neurotoxicity were observed at frequencies of 34.7 and 16%, respectively. TTP and OS of first-line administration of FOLFOX (N=35) were 3.1 months (95% CI, 0.1-6.1 months) and 13.9 months (95% CI, 12.2-15.6 months), respectively. Only the GSTM1 positive genotype exhibited a significantly better time to progression (P=0.023). However, significant genotypic variation of TS, GST and ERCC1, which was assumed to affect the activity of oxaliplatin, was not observed to affect RR, toxicity and overall survival. The response rate of FOLFIRI (N=74) was 23%. Grade 3-4 neutropenia and diarrhea were observed in 55.4 and 9.5% of cases, respectively. TTP and OS of first-line administration of FOLFIRI (N=33) was 4.9 months (95% CI, 3.5-6.4 months) and 19.0 months (95% CI, 8.5-29.5months). The low expression type (2R/2R, 2R/3C and 3C/3C) of TS was associated with a high incidence of grade ≥3 neutropenia. However, significant genotypic variation of UGT1A1, which was assumed to affect irinotecan toxicity, was not observed to affect RR, toxicity or survival. In this study, the GSTM1 positive genotype evidenced a significantly better time to progression in cases of advanced gastric cancer being treated with FOLFOX. The low expression type (2R/2R, 2R/3C and 3C/3C) of TS was associated with a high incidence of grade ≥3 neutropenia in cases of advanced gastric cancer treated with FOLFIRI.

show abstract

Section: ------------------------------------------------------------supporting

confidence: 88%

Comprehensive analysis of excision repair complementation group 1, glutathione S-transferase, thymidylate synthase and uridine diphosphate glucuronosyl transferase 1A1 polymorphisms predictive for treatment outcome in patients with advanced gastric cancer treated with FOLFOX or FOLFIRI

Seo

Kwon²,

Oh³

et al. 2009

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…In line with the present study of BC, previous investigations of Hodgkin's lymphoma, ovarian cancer, colorectal cancer, and even BC have also found the same improved survival rates when lymph node status was associated with polymorphic forms of GSTT1, GSTM1, and GSTP1 (Khedhaier et al, 2003;Huang et al, 2003;Hohaus et al, 2005;DeMichele et al, 2005;Beeghly et al, 2006;Holley et al, 2006;Kweekel et al, 2008;Kolwijck et al, 2009;Jones et al, 2009;Khrunin et al, 2010).…”

Section: Discussionsupporting

confidence: 76%

GSTT1, GSTM1, and GSTP1 polymorphisms as a prognostic factor in women with breast cancer

Oliveira¹,

Rodrigues²,

Santos³

et al. 2014

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. The glutathione S-transferase (GST) family comprises phase-II cellular detoxification enzymes that catalyze the conjugation of chemotherapy drugs to glutathione and act on the apoptotic pathway. The aim of this study was to determine whether polymorphisms of the GSTT1, GSTM1, and GSTP1 genes are associated with different rates of overall survival (OS) and disease-free survival (DFS) after neoadjuvant chemotherapy in the management of locally advanced breast cancer, using either simple or combined analyses, and in relation to the posttherapy axillary lymph node status. Forty women with invasive ductal carcinoma of the breast submitted to neoadjuvant chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide were genotyped for GSTT1, GSTM1, and GSTP1. Comparisons were performed for the three genes, either isolated or in pairs, in polymorphic or wild-type combinations. Finally, the OS and DFS of patients were analyzed with 2522 A.L. Oliveira et al.©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (2): 2521-2530 (2014) respect to axillary lymph node status and with respect to wild-type or polymorphic presentations of each gene. No statistically significant difference in OS and DFS was evident between women with wildtype or polymorphic forms of the genes, either isolated or in pairs, after neoadjuvant chemotherapy. By contrast, after treatment, lymph node-negative women had better OS and DFS only in the presence of polymorphisms of GSTP1, and improved DFS only in the presence of the polymorphic types of GSTT1 and GSTM1 compared to women with positive lymph nodes. The presence of polymorphic forms of GSTP1, GSTM1, and GSTT1 was crucial to conferring better OS and DFS among women with negative axillary lymph nodes.

show abstract

“…Additionally, Mathijssen et al (2004) showed that CYP3A4 phenotype, as assessed by midazolam clearance, is statistically significantly associated with irinotecan pharmacokinetics. With respect to the already described CYP3A genotypes, a combination of CYP3A4, CYP3A5, GSTM1 and GSTT1 genotypes was shown to influence the probability of treatment failure after high-dose adjuvant chemotherapy for node-positive breast cancer (DeMichele et al, 2005). Table 3 also shows other important anticancer agents metabolized by CYP3A4, including taxanes, vinca-alkaloids and new drugs such as imatinib and gefitinib.…”

Section: P450 Pharmacogenetics C Rodriguez-antona and M Ingelman-sundmentioning

confidence: 99%

Cytochrome P450 pharmacogenetics and cancer

2006

View full text Add to dashboard Cite

The cytochromes P450 (CYPs) are key enzymes in cancer formation and cancer treatment. They mediate the metabolic activation of numerous precarcinogens and participate in the inactivation and activation of anticancer drugs. Since all CYPs that metabolize xenobiotics are polymorphic, much emphasis has been put on the investigation of a relationship between the distribution of specific variant CYP alleles and risk for different types of cancer, but a consistent view does not yet exist. This is to a great extent explained by the fact that the CYPs involved in activation of precarcinogens are in general not functionally polymorphic. This is in contrast to CYPs that are active in drug biotransformation where large interindividual differences in the capacity to metabolize therapeutic drugs are seen as a consequence of polymorphic alleles with altered function. This includes also some anticancer drugs like tamoxifen and cyclophosphamide metabolized by CYP2D6, CYP2C19 and CYP2B6. Some P450 forms are also selectively expressed in tumours, and this could provide a mechanism for drug resistance, but also future therapies using these enzymes as drug targets can be envisioned. This review gives an upto-date description of our current knowledge in these areas.

show abstract

Drug-Metabolizing Enzyme Polymorphisms Predict Clinical Outcome in a Node-Positive Breast Cancer Cohort

Abstract: Combined genotypes at CYP3A4, CYP3A5, GSTM1, and GSTT1 influence the probability of treatment failure after high-dose adjuvant chemotherapy for node-positive breast cancer.

Cited by 45 publications

References 24 publications

Comprehensive analysis of excision repair complementation group 1, glutathione S-transferase, thymidylate synthase and uridine diphosphate glucuronosyl transferase 1A1 polymorphisms predictive for treatment outcome in patients with advanced gastric cancer treated with FOLFOX or FOLFIRI

Comprehensive analysis of excision repair complementation group 1, glutathione S-transferase, thymidylate synthase and uridine diphosphate glucuronosyl transferase 1A1 polymorphisms predictive for treatment outcome in patients with advanced gastric cancer treated with FOLFOX or FOLFIRI

GSTT1, GSTM1, and GSTP1 polymorphisms as a prognostic factor in women with breast cancer

Cytochrome P450 pharmacogenetics and cancer

Contact Info

Product

Resources

About