Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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Relationship between XRCC1 Polymorphism and Acute Complication of Chemoradiation Therapy in the Patients with Colorectal Cancer

대장, 직장암 환자에서 화학방사선치료의 급성 부작용과 XRCC1 유전자 다형성과의 상관관계

  • Kim Woo-Chul (Department of Radiation Oncology, Inha University College of Medicine) ;
  • Hong Yun-Chul (Department of Preventive Medicine, Seoul National University College of Medicine) ;
  • Choi Sun-Keun (Department of Surgery, Inha University College of Medicine) ;
  • Woo Ze-Hong (Department of Surgery, Inha University College of Medicine) ;
  • Nam Jeong-Hyun (Department of Clinical Research Center, Inha University College of Medicine) ;
  • Choi Gwang-Seong (Department of Clinical Research Center, Inha University College of Medicine) ;
  • Lee Moon-Hee (Department of Clinical Research Center, Inha University College of Medicine) ;
  • Kim Soon-Ki (Department of Clinical Research Center, Inha University College of Medicine) ;
  • Song Sun-U. (Department of Clinical Research Center, Inha University College of Medicine) ;
  • Loh John-Jk (Department of Radiation Oncology, Inha University College of Medicine)
  • 김우철 (인하대학교 의과대학 방사선종양학교실) ;
  • 홍윤철 (서울대학교 의과대학 예방의학교실) ;
  • 최선근 (인하대학교 의과대학 일반외과학교실) ;
  • 우제홍 (인하대학교 의과대학 일반외과학교실) ;
  • 남정현 (인하대학교 의과대학 임상중앙연구소) ;
  • 최광성 (인하대학교 의과대학 임상중앙연구소) ;
  • 이문희 (인하대학교 의과대학 임상중앙연구소) ;
  • 김순기 (인하대학교 의과대학 임상중앙연구소) ;
  • 송순욱 (인하대학교 의과대학 임상중앙연구소) ;
  • 노준규 (인하대학교 의과대학 방사선종양학교실)
  • Published : 2006.03.01
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Abstract

Purpose: It is well known from clinical experience that acute complications of chemoradiation therapy vary from patients to patients. However, there are no known factors to predict these acute complications before treatment starts. The human XRCC1 gene is known as a DNA base excision repair gene. We investigated the possibilities of XRCC1 gene polymorphisms as a predictor for the acute complications of chemoradiation therapy in colorectal cancer patients. Materials and Methods: From July 1997 to June 2003, 86 colorectal cancer patients (71 rectal cancer, 13 sigmoid colon cancer and 2 colon cancer patients) were treated with chemoradiation therapy at the Department of Radiation Oncology, Inha University Hospital. Twenty-two patients were in stage B, 50 were in stage C, 8 were in stage D and 6 patients were unresectable cases. External radiation therapy was delivered with 10MV X-ray at a 1.8 Gy fraction per day for a total dose of radiation of $30.6{\sim}59.4 Gy$ (median: 54 Gy). All the patients received 5-FU based chemotherapy regimen. We analyzed the acute complications of upper and lower gastrointestinal tract based on the RTOG complication scale. The initial and lowest WBC and platelet count were recorded during both the RT period and the whole treatment period. Allelic variants of the XRCC1 gene at codons 194, 280 and 399 were analyzed in the lymphocyte DNA by performing PCR-RFLP. Statistical analyses were carried out with the SAS (version 6.12) statistical package. Results: When all the variables were assessed on the multivariate analysis, recurrent disease revealed the factors that significantly correlated with upper gastrointestinal acute complications. Arg399Gln polymorph isms of the XRCC1 gene, the radiation dose and the frequencies of chemotherapy during radiation therapy were significantly correlated with lower gastrointestinal complications. Arg399Gln polymorph isms also affected the decrease of the WBC and platelet count during radiation therapy. Conclusion: Although the present sample size was too small for fully evaluating this hypothesis, this study suggests that Arg399Gln polymorph isms of the XRCC1 genes may be used as one of the predictors for acute complications of chemoradiation therapy in colorectal cancer patients.

목적: 방사선치료와 항암제치료의 급성부작용은 환자 개인에 따라 차이가 많다는 것은 임상경험을 통하여 널리 알려져 있다. 그러나 아직 이를 미리 예측할 수 있는 인자로 알려진 것은 없다. XRCC1 유전자는 DNA base-excision repair에 관여하는 유전자로 알려져 있다 저자들은 대장 직장암 환자를 대상으로 방사선치료와 항암제치료로 인한 급성부작용과 XRCC1 유전자의 다형성이 관련이 있는지를 알아보고자 본 연구를 수행하게 되었다. 대상 및 방법: 1997년 7월부터 2003년 6월까지 인하대학교병원에서 치료를 받은 대장 직장암 환자 85명을 대상으로 하였다. 대장암이 2명, 5자결장암이 13명, 직장암이 71명이었다 병기는 B기가 22명, C기가 50명, D기가 8명이었고 절제 불가능한 경우가 6명이었다 방사선치료 범위는 골반강만 조사된 경우가 81명, extended field로 조사된 경우가 5명이었고 방사선량은 일일 1.8 Gy로 주 5회 조사하여 총 $30.6 Gy{\sim}59.4 Gy$ (중앙값: 54 Gy)를 조사하였다. 항암제치료는 전 환자에서 5FU를 근간으로 한 약제를 투여받았고 방사선 치료기간 중에 시행된 횟수는 1회가 24명, 2회가 45명이었고 17명은 동시에 투여 받지는 않았다. 치료의 급성부작용은 상부위장관과 하부위장관으로 나누어 기록하였고 증상이 전혀 없는 경우를 0, 증상이 있으나 투약이 필요하지 않은 경우를 1, 투약이 필요한 경우를 2, 투약에도 불구하고 증상이 심하여 치료의 휴식 또는 입원을 한 경우를 3으로 분류하였고 전 치료기간 중 최초, 최저 수치와 방사선치료기간 중 최초, 최저 백혈구, 혈소판 수치를 조사하였다. 환자의 동의 하에 혈액을 채취하여 림프구를 분리한 후 DNA를 추출하여 PCR-RFLP 방법으로 XRCC1 유전자의 코돈 194, 280, 399번 위치의 다형성을 분석하였다. 통계는 Chi-square, t-test, logistic regression, ANOVA를 사용하였다. 결과: 다변량 분석결과 상부위장관 부작용에 영향을 미치는 인자는 재발유무였고, 하부위장관의 부작용에 영향을 미치는 인자는 XRCC1 339 다형성, 방사선량, 방사선 중 항암제횟수 순이었다. 방사선 치료 중 백혈구 감소에 영향을 미치는 인자는 XRCC1 399 다형성, 194 다형성이었고, 혈소판 감소에 영향을 미치는 인자는 진단명, XRCC1 399 다형성이었다. 결론: 대장 직장암 환자에서 방사선치료와 항암제의 치료에 따른 정상조직의 급성부작용을 예측하는데 XRCC1 유전자의 코돈 399번의 다형성이 사용될 가능성이 있을 것으로 생각된다.

Keywords

References

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