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Japanese Journal of Clinical Oncology Advance Access published online on February 14, 2006
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyi231
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© 2006 Foundation for Promotion of Cancer Research
Received October 10, 2005
Accepted December 13, 2005

Original Article

MDR1 Polymorphisms Predict the Response to Etoposide-Cisplatin Combination Chemotherapy in Small Cell Lung Cancer

Ji Woong Sohn 1, Shin Yup Lee 1, Su Jung Lee 2, Eun Jin Kim 1, Seung Ick Cha 1, Chang Ho Kim 1, Jae-Tae Lee 3, Tae Hoon Jung 1, and Jae Yong Park 4 *

1 Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
2 Cancer Research Center, School of Medicine, Kyungpook National University, Daegu, Korea
3 Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
4 Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea; Cancer Research Center, School of Medicine, Kyungpook National University, Daegu, Korea

* To whom correspondence should be addressed.
Jae Yong Park, E-mail: jaeyong{at}kyungpook.ac.kr


  Abstract

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.

Keywords: MDR1; polymorphisms; chemotherapy response; small cell lung cancer.
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