BACKGROUND: Germline genetic polymorphisms in certain genes are associated with response to anthracycline- and taxane-based neoadjuvant chemotherapy in breast cancer (BC). Recent evidence has indicated that microRNA (miRNA) let-7 expression is associated with response to chemotherapeutics. This study aims to evaluate the potential role of let-7 miRNA-related single nucleotide polymorphisms (mirSNPs) in the prediction of pathologic complete response to taxane- and platinum-based neoadjuvant chemotherapy in locally advanced breast cancer (LABC). METHODS: We genotyped the SNPs that reside in and around miRNA let-7 binding sites of two target genes: hypoxia-inducible factor 1 subunit alpha inhibitor (HIF1AN) and claudin 12 (CLDN12). The distribution frequencies of the SNPs were genotyped in LABC patients who received taxane- and platinum-based neoadjuvant chemotherapy. Associations among tumour-relevant biomarkers, genotype and pathological complete response (pCR) were evaluated using Student's t-test for continuous variables and the chi-square or Fisher's exact tests for non-categorical variables. The modified odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated by a multivariate logistic regression analysis to explore the association of genotype with pCR. RESULTS: For rs11292, which is located in the 3'-untranslated region (UTR) of HIF1AN, significant differences were detected in codominant, dominant and overdominant models between the patients who achieved pCR and those who did not (non-pCR) (P<0.05) in a multivariate analysis. For rs1017105, which is located in the 3'-UTR of CLDN12, significant differences were observed in the recessive model between the pCR and non-pCR patients with luminal-type BC. CONCLUSIONS: Let-7-related mirSNPs could predict pathologic complete response to taxane- and platinum-based neoadjuvant chemotherapy in LABC, which suggests the potential role of variants of miRNA let-7-related gene networks as predictive markers in a clinical setting.
BACKGROUND: Germline genetic polymorphisms in certain genes are associated with response to anthracycline- and taxane-based neoadjuvant chemotherapy in breast cancer (BC). Recent evidence has indicated that microRNA (miRNA) let-7 expression is associated with response to chemotherapeutics. This study aims to evaluate the potential role of let-7 miRNA-related single nucleotide polymorphisms (mirSNPs) in the prediction of pathologic complete response to taxane- and platinum-based neoadjuvant chemotherapy in locally advanced breast cancer (LABC). METHODS: We genotyped the SNPs that reside in and around miRNA let-7 binding sites of two target genes: hypoxia-inducible factor 1 subunit alpha inhibitor (HIF1AN) and claudin 12 (CLDN12). The distribution frequencies of the SNPs were genotyped in LABC patients who received taxane- and platinum-based neoadjuvant chemotherapy. Associations among tumour-relevant biomarkers, genotype and pathological complete response (pCR) were evaluated using Student's t-test for continuous variables and the chi-square or Fisher's exact tests for non-categorical variables. The modified odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated by a multivariate logistic regression analysis to explore the association of genotype with pCR. RESULTS: For rs11292, which is located in the 3'-untranslated region (UTR) of HIF1AN, significant differences were detected in codominant, dominant and overdominant models between the patients who achieved pCR and those who did not (non-pCR) (P<0.05) in a multivariate analysis. For rs1017105, which is located in the 3'-UTR of CLDN12, significant differences were observed in the recessive model between the pCR and non-pCR patients with luminal-type BC. CONCLUSIONS: Let-7-related mirSNPs could predict pathologic complete response to taxane- and platinum-based neoadjuvant chemotherapy in LABC, which suggests the potential role of variants of miRNA let-7-related gene networks as predictive markers in a clinical setting.
Entities:
Keywords:
Locally advanced breast cancer (LABC); miRNA let-7; miRNA-related single nucleotide polymorphisms (mirSNPs); neoadjuvant chemotherapy; pathologic complete response
Authors: Valentina Guarneri; Kristine Broglio; Shu-Wan Kau; Massimo Cristofanilli; Aman U Buzdar; Vicente Valero; Thomas Buchholz; Funda Meric; Lavinia Middleton; Gabriel N Hortobagyi; Ana M Gonzalez-Angulo Journal: J Clin Oncol Date: 2006-03-01 Impact factor: 44.544
Authors: Lin He; J Michael Thomson; Michael T Hemann; Eva Hernando-Monge; David Mu; Summer Goodson; Scott Powers; Carlos Cordon-Cardo; Scott W Lowe; Gregory J Hannon; Scott M Hammond Journal: Nature Date: 2005-06-09 Impact factor: 49.962
Authors: J A van der Hage; C J van de Velde; J P Julien; M Tubiana-Hulin; C Vandervelden; L Duchateau Journal: J Clin Oncol Date: 2001-11-15 Impact factor: 44.544
Authors: Valerie B Sampson; Nancy H Rong; Jian Han; Qunying Yang; Virginie Aris; Patricia Soteropoulos; Nicholas J Petrelli; Stephen P Dunn; Leslie J Krueger Journal: Cancer Res Date: 2007-10-15 Impact factor: 12.701
Authors: Ern Yu Tan; Leticia Campo; Cheng Han; Helen Turley; Francesco Pezzella; Kevin C Gatter; Adrian L Harris; Stephen B Fox Journal: Breast Cancer Res Date: 2007 Impact factor: 6.466