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MGMT −535G>T polymorphism is associated with prognosis for patients with metastatic colorectal cancer treated with oxaliplatin-based chemotherapy

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Abstract

Purpose

The present study analyzed the polymorphisms of DNA repair genes and their impact on the response to chemotherapy and survival of patients with colorectal cancer.

Patients and methods

A total of 94 patients with recurrent or metastatic colorectal cancer treated with oxaliplatin-based combination chemotherapy were enrolled in the present study. The single nucleotide polymorphisms of 16 DNA repair genes were determined using a PCR–RFLP assay.

Results

During the median follow-up duration of 15.9 (2.1–53.0) months, 67 (71.3%) progressions and 29 (30.9%) deaths were observed. Among the 60 patients assessable for response, response to the oxaliplatin-based regimens was found in 27 (45%) patients (9 CR and 18 PR). In a logistic regression analysis adjusted to age, sex, primary site, disease status, and regimen, the POLR2C rs4937 and MSH2 rs3732183 polymorphisms were statistically associated with the response to the oxaliplatin-based chemotherapy. A multivariate survival analysis showed that the TT genotype of the MGMT (rs1625649) −535G>T polymorphism was found to correlate with a worse progression-free survival (PFS) than the combined GG + GT genotypes (HR = 3.137; 95% CI = 1.423–6.914; P = 0.005), which was also observed among the 60 evaluable patients (HR = 2.653; 95% CI = 1.101–6.392; P = 0.030) For the clinical parameters, curative resection was the most significant prognostic factor in a Cox model for PFS and overall survival (HR = 0.229 and 0.205; P < 0.001 and 0.001, respectively).

Conclusion

The MGMT −535G>T polymorphism (rs1625649) was found to be correlated with PFS in patients with advanced colorectal cancer treated with oxaliplatin-based chemotherapy.

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Acknowledgments

This work was supported by BioMedical Research Institute grant, Kyungpook National University Hospital (2008).

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Authors and Affiliations

  1. Department of Internal Medicine, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea

    Jee Hyun Park, Nung Soo Kim & Jae Yong Park

  2. Department of Oncology/Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 50 Samduk 2-Ga, Jung-Gu, Daegu, 700-721, Korea

    Yee Soo Chae, Jong Gwang Kim, Sang Kyun Sohn, Joon Ho Moon & Byung Woog Kang

  3. Department of Oncology, Daegu Catholic University Hospital, Daegu Catholic University School of Medicine, Daegu, Korea

    Hun Mo Ryoo & Sung Hwa Bae

  4. Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea

    Gyu Seog Choi & Soo-Han Jun

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  1. Jee Hyun Park
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  2. Nung Soo Kim
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  4. Yee Soo Chae
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  7. Joon Ho Moon
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  9. Hun Mo Ryoo
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  10. Sung Hwa Bae
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Corresponding authors

Correspondence to Yee Soo Chae or Jong Gwang Kim.

Additional information

Y. S. Chae and J. G. Kim contributed equally to this manuscript.

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Park, J.H., Kim, N.S., Park, J.Y. et al. MGMT −535G>T polymorphism is associated with prognosis for patients with metastatic colorectal cancer treated with oxaliplatin-based chemotherapy. J Cancer Res Clin Oncol 136, 1135–1142 (2010). https://doi.org/10.1007/s00432-010-0760-8

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  • DOI: https://doi.org/10.1007/s00432-010-0760-8

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