A single-nucleotide polymorphism in the MDR1 gene as a predictor of response to neoadjuvant chemotherapy in breast cancer.
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.


METHODS
Ninety-six patients with locally advanced breast carcinoma were enrolled. Genotyping of exon 26 of the MDR1 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).


CONCLUSIONS
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.
George
Joseph
J
Department of Surgery, Jawaharlal Institute of Post-graduate Medical Education and Research (JIPMER), Puducherry -605006, India. josephegeorge@gmail.com
Dharanipragada
Kadambari
K
Krishnamachari
Srinivasan
S
Chandrasekaran
Adithan
A
Sam
Soya Sisy
SS
Sunder
Elangovan
E
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil