MDR1 single nucleotide polymorphism G2677T/A and haplotype are correlated with response to docetaxel-cisplatin chemotherapy in patients with non-small-cell lung cancer.
BACKGROUND
The multidrug resistance gene 1 (MDR1) encodes P-glycoprotein (P-gp), which plays an important role in mediating multidrug resistance to chemotherapeutic agents. MDR1 gene polymorphisms may have an impact on the expression and function of P-gp, thereby influencing the response to chemotherapy.


OBJECTIVE
To investigate whether the MDR1 2677 and 3435 genotypes are associated with the sensitivity of non-small-cell lung cancer (NSCLC) to docetaxel.


METHODS
In this study we investigated the potential association of MDR1 2677G>T at exon 21, 3435C>T at exon 26 and their haplotypes with chemotherapy response of 54 Han Chinese patients with NSCLC. The patients were treated with docetaxel-cisplatin.


RESULTS
The 2677 GG genotype was associated with a significantly better response to chemotherapy compared with the combined 2677 GT and TT genotype (p = 0.035). The 3435 CC genotype was also associated with a better response to chemotherapy compared with the combined 3435 CT and TT genotypes although the difference was not statistically significant (p = 0.123). Moreover, 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/A polymorphism and the 2677G-3435C haplotype are predictors of treatment response to docetaxel-cisplatin chemotherapy in NSCLC patients.
Pan
Ji-Hong
JH
Key Laboratory of the Ministry of Public Health for Biotech-Drug, Key Laboratory for Modern Medicine and Technology of Shandong Province, Shandong Medicinal and Biotechnology Center, Shandong Academy of Medical Sciences, Jinan, China. pjh933@yahoo.com.cn
Han
Jin-Xiang
JX
Wu
Jian-Mei
JM
Huang
Hai-Nan
HN
Yu
Qing-Zhong
QZ
Sheng
Li-Jun
LJ
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics; D002945:Cisplatin / Q000627:therapeutic use*; D000077143:Docetaxel; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043823:Taxoids / Q000627:therapeutic use*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin