PURPOSE: Genetic variants of ABCB1 gene contributed to cancer susceptibility and interindividual differences in chemotherapy response. Therefore, we investigated the relevance between genetic variations in ABCB1 gene and both risk and clinical outcomes of breast carcinoma. METHODS: A case-control study was performed on the SNPs C3435T, C1236T and G2677T/A in 1,173 Chinese breast carcinoma patients and 1,244 age- and sex-matched controls. These SNPs were typed by PCR-restriction fragment length polymorphism assays. RESULTS: We found the following: (1) ABCB1 C3435T, G2677T/A variants and haplotype 3435T-1236T-2677T significantly increased the risk of breast carcinoma [adjusted OR (95 % CI): 1.281 (1.021-1.285), 1.326 (1.182-1.487) and 1.707 (1.498-1.945), respectively]. (2) A significantly enhanced therapeutic response was observed in both C3435T variants and haplotype 3435T-1236T-2677T after neoadjuvant anthracycline-based chemotherapy (n = 148) [adjusted OR (95 % CI): 2.695 (1.172-6.211) and 8.064 (1.085-58.823), respectively]. (3) Cox proportional hazards regression models showed that the hazards ratio (HR) for progression-free survival (PFS) associated with C3435T CC genotype was 1.664 (95 % CI: 1.022-2.708, P = 0.041). Kaplan-Meier curve showed that C3435T CC carriers had a poor prognosis than those with CT/TT carriers after anthracycline-based chemotherapy (P = 0.043, n = 762). Furthermore, ABCB1 C3435T variants showed a significantly prolonged both PFS and overall survival (OS) in patients with triple-negative (ER-/PR-/HER2-) status (P = 0.001 and P = 0.016, respectively; n = 135). In addition, there was a significantly longer OS in patients with HER2-negative status who had G2677T/A variants (P = 0.036, n = 487). However, we did not find statistically significant association between C1236T genotypes and the risk or prognosis of breast carcinoma. CONCLUSIONS: These results suggest that ABCB1 gene C3435T, G2677T/A variations and haplotype 3435T-1236T-2677T relate to the risk and clinical outcomes of breast carcinoma and may function as candidate molecular markers of anthracycline chemosensitivity in breast carcinoma.
PURPOSE: Genetic variants of ABCB1 gene contributed to cancer susceptibility and interindividual differences in chemotherapy response. Therefore, we investigated the relevance between genetic variations in ABCB1 gene and both risk and clinical outcomes of breast carcinoma. METHODS: A case-control study was performed on the SNPs C3435T, C1236T and G2677T/A in 1,173 Chinese breast carcinomapatients and 1,244 age- and sex-matched controls. These SNPs were typed by PCR-restriction fragment length polymorphism assays. RESULTS: We found the following: (1) ABCB1C3435T, G2677T/A variants and haplotype 3435T-1236T-2677T significantly increased the risk of breast carcinoma [adjusted OR (95 % CI): 1.281 (1.021-1.285), 1.326 (1.182-1.487) and 1.707 (1.498-1.945), respectively]. (2) A significantly enhanced therapeutic response was observed in both C3435T variants and haplotype 3435T-1236T-2677T after neoadjuvant anthracycline-based chemotherapy (n = 148) [adjusted OR (95 % CI): 2.695 (1.172-6.211) and 8.064 (1.085-58.823), respectively]. (3) Cox proportional hazards regression models showed that the hazards ratio (HR) for progression-free survival (PFS) associated with C3435T CC genotype was 1.664 (95 % CI: 1.022-2.708, P = 0.041). Kaplan-Meier curve showed that C3435T CC carriers had a poor prognosis than those with CT/TT carriers after anthracycline-based chemotherapy (P = 0.043, n = 762). Furthermore, ABCB1C3435T variants showed a significantly prolonged both PFS and overall survival (OS) in patients with triple-negative (ER-/PR-/HER2-) status (P = 0.001 and P = 0.016, respectively; n = 135). In addition, there was a significantly longer OS in patients with HER2-negative status who had G2677T/A variants (P = 0.036, n = 487). However, we did not find statistically significant association between C1236T genotypes and the risk or prognosis of breast carcinoma. CONCLUSIONS: These results suggest that ABCB1 gene C3435T, G2677T/A variations and haplotype 3435T-1236T-2677T relate to the risk and clinical outcomes of breast carcinoma and may function as candidate molecular markers of anthracycline chemosensitivity in breast carcinoma.
Authors: Chava Kimchi-Sarfaty; Andrew H Marple; Shiri Shinar; Avraham M Kimchi; David Scavo; M Isabella Roma; In-Wha Kim; Adam Jones; Mili Arora; John Gribar; David Gurwitz; Michael M Gottesman Journal: Pharmacogenomics Date: 2007-01 Impact factor: 2.533
Authors: Jennifer D Brooks; Sharon N Teraoka; Leslie Bernstein; Lene Mellemkjær; Kathleen E Malone; Charles F Lynch; Robert W Haile; Patrick Concannon; Anne S Reiner; David J Duggan; Katherine Schiermeyer; Jonine L Bernstein; Jane C Figueiredo Journal: Cancer Causes Control Date: 2013-06-18 Impact factor: 2.506
Authors: Douglas Vivona; Luciene Terezina Lima; Alice Cristina Rodrigues; Carolina Tosin Bueno; Greyce Kelly Steinhorst Alcantara; Luiza Saldanha Ribeiro Barros; Vania Tiestsche DE Moraes Hungria; Carlos Sérgio Chiattone; Maria DE Lourdes Lopes Ferrari Chauffaille; Elvira Maria Guerra-Shinohara Journal: Oncol Lett Date: 2014-02-07 Impact factor: 2.967