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Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 4, pp 843–851 | Cite as

Pharmacogenetic analysis of adjuvant FOLFOX for Korean patients with colon cancer

  • Kyung-Hun Lee
  • Hye Jung Chang
  • Sae-Won Han
  • Do-Youn Oh
  • Seock-Ah Im
  • Yung-Jue Bang
  • Sun Young Kim
  • Keun-Wook Lee
  • Jee Hyun Kim
  • Yong Sang Hong
  • Tae Won Kim
  • Young Suk Park
  • Won Ki Kang
  • Sang Joon Shin
  • Joong Bae Ahn
  • Gyeong Hoon Kang
  • Seung-Yong Jeong
  • Kyu Joo Park
  • Jae-Gahb Park
  • Tae-You KimEmail author
Original Article

Abstract

Purpose

Ethnic diversity of genetic polymorphism can result in individual differences in the efficacy and toxicity of cancer chemotherapy.

Methods

We analyzed 20 germline polymorphisms in 10 genes (TS, MTHFR, ERCC1, XPD, XRCC1, ABCC2, AGXT, GSTP1, GSTT1 and GSTM1) from prospectively enrolled 292 Korean patients treated with adjuvant oxaliplatin plus leucovorin plus 5-fluorouracil (FOLFOX) for colon cancer.

Results

In contrast to previous studies in Caucasians, neutropenia (grade 3–4, 60.5 %) was frequently observed, whereas only 16.4 % experienced grade 2 or more sensory neuropathy. Neutropenia was more frequent in MTHFR 677TT [adjusted odds ratio (OR) 2.32, 95 % confidence interval (CI) 1.19–4.55] and ERCC1 19007TT (adjusted OR 4.58, 95 % CI 1.20–17.40) genotypes. Patients harboring XRCC1 23885GG experienced less grade 2–4 neuropathy [adjusted OR 0.52, 95 % CI 0.27–0.99]. MTHFR 677TT (p = 0.002) and XRCC1 23885GG (p = 0.146) genotypes were also more prevalent in Koreans compared to Caucasians. TS ‘low’ genotype (adjusted HR 1.83, 95 % CI 1.003–3.34) was significantly related to shorter disease-free survival. Overall survival was not significantly different according to the polymorphisms.

Conclusions

Polymorphisms in MTHFR, XRCC1 and TS are related to toxicities and disease-free survival in patients with colon cancer. The ethnic differences in frequencies of genotypes may explain the ethnic difference in toxicity profile following adjuvant FOLFOX chemotherapy.

Keywords

Adjuvant chemotherapy Colon cancer Oxaliplatin Polymorphism Toxicity 

Notes

Acknowledgments

This research was supported by Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0093820) and by Future-based Technology Development Program (Nano Fields) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012-0001033).

Conflict of interest

None.

Supplementary material

280_2013_2075_MOESM1_ESM.tif (18.7 mb)
Supplementary Figure 1 Inter-ethnic difference of genotype frequency. The allele and genotype frequency data of the present study were compared with those selected from publicly available sources based on International HapMap Project (http://hapmap.org/). Utah residents with northern and western European ancestry (CEU) were defined as Europids. Japanese in Tokyo (JPT) and Han Chinese in Beijing (CHB) were defined as Asians. Because the frequency data for TS (28-bp repeat in enhancer region, 6-bp deletion in 3′ UTR), AGXT 154C > T, GSTT1 (null genotype) and GSTM1 (null genotype) were lacking, ethnic frequencies of each polymorphisms were selected from previously published studies (TIFF 19173 kb).
280_2013_2075_MOESM2_ESM.docx (31 kb)
Supplementary material 2 (DOCX 31 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Kyung-Hun Lee
    • 1
    • 2
  • Hye Jung Chang
    • 1
  • Sae-Won Han
    • 1
    • 2
  • Do-Youn Oh
    • 1
    • 2
  • Seock-Ah Im
    • 1
    • 2
  • Yung-Jue Bang
    • 1
    • 2
    • 3
  • Sun Young Kim
    • 4
  • Keun-Wook Lee
    • 5
  • Jee Hyun Kim
    • 5
  • Yong Sang Hong
    • 6
  • Tae Won Kim
    • 6
  • Young Suk Park
    • 7
  • Won Ki Kang
    • 7
  • Sang Joon Shin
    • 8
  • Joong Bae Ahn
    • 8
  • Gyeong Hoon Kang
    • 9
  • Seung-Yong Jeong
    • 10
  • Kyu Joo Park
    • 10
  • Jae-Gahb Park
    • 10
  • Tae-You Kim
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Internal MedicineSeoul National University HospitalChongno-Gu, SeoulKorea
  2. 2.Cancer Research InstituteSeoul National University College of MedicineSeoulKorea
  3. 3.Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and TechnologySeoul National UniversitySeoulKorea
  4. 4.Research Institute and HospitalNational Cancer CenterGoyangKorea
  5. 5.Department of Internal MedicineSeoul National University Bundang HospitalSeongnamKorea
  6. 6.Department of Internal Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  7. 7.Department of Internal Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  8. 8.Department of Internal Medicine, Severance HospitalYonsei University College of MedicineSeoulKorea
  9. 9.Department of PathologySeoul National University College of MedicineSeoulKorea
  10. 10.Department of Surgery, College of MedicineSeoul National UniversitySeoulKorea

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