A Single-Nucleotide Polymorphism in the MDR1 Gene as a Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer

被引：54

作者：

George, Joseph ^{[1
]}

Dharanipragada, Kadambari ^{[1
]}

Krishnamachari, Srinivasan ^{[1
]}

Chandrasekaran, Adithan ^{[2
]}

Sam, Soya Sisy ^{[2
]}

Sunder, Elangovan ^{[3
]}

机构：

[1] Jawaharlal Inst Postgrad Med Educ & Res, Dept Surg, Pondicherry 605006, India

[2] Jawaharlal Inst Postgrad Med Educ & Res, Dept Pharmacol, Pondicherry 605006, India

[3] Jawaharlal Inst Postgrad Med Educ & Res, Dept Radiodiag, Pondicherry 605006, India

来源：

CLINICAL BREAST CANCER | 2009年 / 9卷 / 03期

关键词：

3435C > T; Chemoresistance; Exon; 26; T allele; MULTIDRUG-RESISTANCE; PREOPERATIVE CHEMOTHERAPY; C3435T POLYMORPHISM; TRANSPORTER; ALLELE; SUSCEPTIBILITY; ASSOCIATION; POPULATION; TUMORS; CELLS;

D O I：

10.3816/CBC.2009.n.026

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: The single-nucleotide polymorphism (SNP) 3435C > T in exon 26 of the MDR1 gene has been shown to correlate with the functioning of P-glycoprotein. We studied the frequency of SNP in exon 26 of the MDR1 gene in breast cancer and its role in predicting response to neoadjuvant chemotherapy in breast cancer. Patients and Methods: Ninety-six patients with locally advanced breast carcinoma were enrolled. Genotyping of exon 26 of the MDR 7 gene was performed, and computed tomography scans were performed before and after neoadjuvant chemotherapy. Response to 3 cycles of the 5-fluorouracil/doxorubicin/cyclophosphamide (FAC) regimen was assessed. The prevalence of SNP was compared with that of historical controls. Association of the response was compared with the genotypes. Results: The frequency of genotypes was different from that of healthy sex-matched historical controls. Prevalence of TT genotype was significantly increased in breast cancer patients (P = .025). The patients with TT genotype had 2.26 times the chance of responding to neoadjuvant chemotherapy when compared with patients with the CC genotype (P = .44). Conclusion: Significantly higher prevalence of 3435TT genotype in exon 26 of the MDR1 gene in patients with breast cancer might suggest the possibility of increased breast cancer susceptibility. The genotypes did not show any significant association to response to chemotherapy in the population studied.

引用

页码：161 / 165

页数：5

共 20 条

[1]

Calado RT, 2002, HAEMATOLOGICA, V87, P564

[2] BIOCHEMISTRY OF MULTIDRUG-RESISTANCE MEDIATED BY THE MULTIDRUG TRANSPORTER [J].

GOTTESMAN, MM ;

PASTAN, I .

ANNUAL REVIEW OF BIOCHEMISTRY, 1993, 62 :385-427

[3] Functional polymorphisms of the human multidrug-resistance gene:: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo [J].

Hoffmeyer, S ;

Burk, O ;

von Richter, O ;

Arnold, HP ;

Brockmöller, J ;

Johne, A ;

Cascorbi, I ;

Gerloff, T ;

Roots, I ;

Eichelbaum, M ;

Brinkmann, U .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (07) :3473-3478

[4]

Illmer T, 2002, CANCER RES, V62, P4955

[5]

Kafka A, 2003, INT J ONCOL, V22, P1117

[6] Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy [J].

Kuerer, HM ;

Newman, LA ;

Smith, TL ;

Ames, FC ;

Hunt, KK ;

Dhingra, K ;

Theriault, RL ;

Singh, G ;

Binkley, SM ;

Sneige, N ;

Buchholz, TA ;

Ross, MI ;

McNeese, MD ;

Buzdar, AU ;

Hortobagyi, GN ;

Singletary, SE .

JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (02) :460-469

[7] Polymorphism in the P-glycoprotein drug transporter MDR1 gene in colon cancer patients [J].

Kurzawski, M ;

Drozdzik, M ;

Suchy, J ;

Kurzawski, G ;

Bialecka, M ;

Górnik, W ;

Lubinski, J .

EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2005, 61 (5-6) :389-394

[8] Cancer pharmacogenomics: Powerful tools in cancer chemotherapy and drug development [J].

Lee, W ;

Lockhart, AC ;

Kim, RB ;

Rothenberg, ML .

ONCOLOGIST, 2005, 10 (02) :104-111

[9] Allele and genotype frequency of MDR1 C3435T in Tamilian population [J].

Ramasamy, Kesavan ;

Sam, Soya Sisy ;

Chandrasekaran, Adithan .

DRUG METABOLISM AND PHARMACOKINETICS, 2006, 21 (06) :506-508

[10] Correlation of polymorphism C3435T of the MDR-1 gene and the response of primary chemotherapy in women with locally advanced breast cancer [J].

Rodrigues, F. F. O. ;

Santos, R. E. ;

Melo, M. B. ;

Silva, M. A. L. G. ;

Oliveira, A. L. ;

Rozenowicz, R. L. ;

Ulson, L. B. ;

Aoki, T. .

GENETICS AND MOLECULAR RESEARCH, 2008, 7 (01) :177-183

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