MDR1 polymorphisms predict the response to etoposide-cisplatin combination chemotherapy in small cell lung cancer.
BACKGROUND
The MDR1 gene encodes P-glycoprotein (PGP), which plays an important role in mediating multidrug resistance to chemotherapeutic agents. Polymorphisms in the MDR1 gene may have an impact on the expression and function of PGP, thereby influencing the response to chemotherapy.


METHODS
We investigated the potential association of MDR1 polymorphisms (2677G>T at exon 21 and 3435C>T at exon 26) and their haplotypes with chemotherapy response in 54 small cell lung cancer (SCLC) patients who received a combination chemotherapy of etoposide-cisplatin.


RESULTS
The 3435 CC genotype was associated with a significantly better chemotherapy response compared with the combined 3435 CT and TT genotype (P = 0.025). The 2677 GG genotype was also associated with a better chemotherapy response compared with the combined 2677 GT and TT genotype, although it was not statistically significant. Consistent with the results of genotyping analyses, patients harboring the 2677G-3435C haplotype had a statistically significant better response to chemotherapy compared with those with the other haplotypes combined (P = 0.015).


CONCLUSIONS
Our findings suggest that the MDR1 2677G>T and 3435C>T polymorphisms can be used for predicting treatment response to etoposide-cisplatin chemotherapy in SCLC patients.
Sohn
Ji Woong
JW
Department of Internal Medicine, School of Medicine, Kyungpook National University, Samduk 2Ga 50, Daegu 700-412, Korea.
Lee
Shin Yup
SY
Lee
Su Jung
SJ
Kim
Eun Jin
EJ
Cha
Seung Ick
SI
Kim
Chang Ho
CH
Lee
Jae-Tae
JT
Jung
Tae Hoon
TH
Park
Jae Yong
JY
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005544:Forecasting; D019450:Genes, MDR; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005047:Etoposide; D002945:Cisplatin