$\require{mediawiki-texvc}$
  • 검색어에 아래의 연산자를 사용하시면 더 정확한 검색결과를 얻을 수 있습니다.
  • 검색연산자
검색연산자 기능 검색시 예
() 우선순위가 가장 높은 연산자 예1) (나노 (기계 | machine))
공백 두 개의 검색어(식)을 모두 포함하고 있는 문서 검색 예1) (나노 기계)
예2) 나노 장영실
| 두 개의 검색어(식) 중 하나 이상 포함하고 있는 문서 검색 예1) (줄기세포 | 면역)
예2) 줄기세포 | 장영실
! NOT 이후에 있는 검색어가 포함된 문서는 제외 예1) (황금 !백금)
예2) !image
* 검색어의 *란에 0개 이상의 임의의 문자가 포함된 문서 검색 예) semi*
"" 따옴표 내의 구문과 완전히 일치하는 문서만 검색 예) "Transform and Quantization"
쳇봇 이모티콘
안녕하세요!
ScienceON 챗봇입니다.
궁금한 것은 저에게 물어봐주세요.

논문 상세정보

초록

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.

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.

참고문헌 (36)

  1. Hoeller U. Borgmann K, Bonacker M, et al. Individual radiosensitivity measured with lymphocytes may be used to predict the risk of fibrosis after radiotherapy for breast cancer. Radiother Oncol 2003;69:137-144 
  2. Rudat V, Dietz A, Conradt C, Flentje M. In vitro radiosensitivity of primary human fibroblasts: lack of correlation with acute radiation toxicity in patients with head and neck cancer. Radiother Oncol 1997;43:181-188 
  3. Casse C. Hu YC, Ahrendt SA. The XRCC1 codon 399 Gln allele is associated with adenine guanine p53 mutations in non-small cell lung cancer. Mutat Res 2003;25:19-27 
  4. Caldecott KW, McKeown CK. Tucker JD, Ljunsquist S. Thompson LH. An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III. Mol Cell Biol 1994;14:68-76 
  5. Whitehouse CJ, Taylor RM, Thistlethwaite A. et al. XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 2001;104:107-117 
  6. Vidal AE, Boiteux S, Hickson ID, Radicella JP. XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions. EMBO J 2001;20:6530-6539 
  7. Lunn RM. Langlois RG, Hsieh LL. Thompson CI. Bell DA. XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res 1999;59:2557-2561 
  8. Shen NR. Zdzienicka MZ, Mohrenweiser H, Thompson LH. Thelen MP. Mutations in hamster single-strand break repair gene XRCC1 causing defective DNA repair. Nucleic Acids Res 1998;26:1032-1037 
  9. Churchill ME. Peak JG. Peak MJ. Correlation between cell-survival and DNA-strand break repair proficiency in the Chinese hamster ovary cell-lines AA8 and EM9 irradiated with 365-nm ultraviolet-a radiation. Photochem Photobiol 1991;53:229-236 
  10. Fernet M, Hall J. Genetic biomarkers of therapeutic radiation sensitivity. DNA Repair 2004;3:1237-1243 
  11. Huyck KD, Eijkeren MV, Claes K, et al. Radiation-induced damage to normal tissues after radiotherapy in patients treated for gynecologic tumors: association with single nucleotide polymorphisms in XRCC1, XRCC3, and OGG1 genes and in vitro chromosomal radiosensitivity in lvmphocytes. Int J Radiat Oncol Biol Phys 2005;62:1140-1149 
  12. Masson M, Niedergang C, Schreiber V, Muller S. Menissier-de Murcia J, de Murcia G. XRCC1 is specifically associated with poly(ADP-ribose)polymerase and negatively regulates its activity following DNA damage. Mol Cell Biol 1998; 18:3563-3571 
  13. Sak SC, Harnden P, Johnston CF. Paul AB, Kiltie AE. APE1 and XRCC1 protein expression levels predict cancer-specific survival following radical radiotherapy in bladder cancer. Clin Cancer Res 2005;11:6205-6211 
  14. Shen MR. Jones IM, Mohrenweiser H. Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res 1998;58:604-608 
  15. Thompson LH, Brookman KW, Jones NJ, Allen SA, Carrano AV. Molecular cloning of the human XRCC1 gene, which corrects defective DNA strand break repair and sister chromitid exchange. Mol Cell Biol 1990;10:6160-6171 
  16. Cox JD, Stetz J. Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995;31:1341-1346 
  17. Borgmann K. Roper B, EI-Awady R, et al. Indicators of late normal tissue response after radiotherapy for head and neck cancer: fibroblasts, lymphocytes, genetics, DNA repair, and chromosome aberrations. Radiother Oncol 2002;64:141-152 
  18. Duell EJ, Wieneke JK, Cheng T J, et al. Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis 2000;21:965-971 
  19. Stoehlmacher J, Ghaderi V, lobal S, et al. A polymorphism of the XRCC1 gene predicts for response to platinum based treatment in advanced colorectal cancer. Anticancer Res 2001;21:3075-3079 
  20. Krajinovic M, Labuda D. Mathonnet G, et al. Polymorphisms in genes encoding drugs and xenobiotic metabolizing enzymes, DNA repair enzymes, and response to treatment of childhood acute lymphoblastic leukemia. Clin Cancer Res 2002;8:802-810 
  21. Moullan N. Cox DG, Angele S, Romenstaing P. Gerard JP. Hall J. Polymorphisms in the DNA repair gene XRCC1, breast cancer risk and response to radiotherapy. Cancer Epidemiol Biomarkers Prev 2003;12:1168-1174 
  22. Hu JJ, Smith TR, Miller MS, Lohman K, Case LD. Genetic regulation of ionizing radiation sensitivity and breast cancer risk. Environ Mol Mutagen 2002;39:208-215 
  23. Smith TR, Miller MS, Lohman K, et al. Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer. Cancer Lett 2003;190: 183-190 
  24. Hu JJ. Smith TR, Miller MS, Mohrenweiser HW, Golden A. Case LD. Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis 2001;22:917-922 
  25. Lee SG, Kim B. Choi J, Kim C. Lee I. Song K. Genetic polymorphisms of XRCC1 and risk of gastric cancer. Cancer Lett 2002;187:53-60 
  26. Caldecott KW. XRCC1 and DNA strand break repair. DNA Repair 2003;2:955-969 
  27. Wang Y. Spitz MR. Zhu Y. Dong Q, Shete S. Wu X. From genotype to phenotype: correlating XRCC1 polymorphisms with mutagen sensitivity. DNA Repair 2003;2:901-908 
  28. Liu D, O'Day SJ. Yang D, et al. Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. Clin Cancer Res 2005;11:1237-1246 
  29. Kiltie AE, Ryan AJ, Swindell R, et al. A correlation between residual radiation-induced DNA double-strand breaks in cultured fibroblasts and late radiotherapy reactions in breast cancer patients. Radiother Oncol 1999;51:55-65 
  30. Tuimala J, Szekely G, Gundy S, Hirvonen A, Norppa H. Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes: role in mutagen sensitivity. Carcinogenesis 2002;23:1003-1008 
  31. Oppitz U. Schulte S. Stopper H. et al. In vitro radiosensitivity measured in lymphocytes and fibroblasts by colony formation and comet assay: comparison with clinical acute reactions to radiotherapy in breast cancer patients. Int J Radiat Biol 2002;78:611-616 
  32. Zhou W, Liu G, Miller DP, et al. Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk. Cancer Epidemiol Biomarkers Prev 2003;12:359-365 
  33. Lunn RM. Langlois RG, Hsieh LL. Thompson CL, Bell DA. XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res 1999;59:2557-2561 
  34. Gurubhagavatula S, Liu G. Park S, et al. XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy. J Clin Oncol 2004;22:2519-2521 
  35. Gryk MR. Marintchev A. Maciejewski MW. Robertson A, Wilson SH. Mullen GP. Mapping of the interaction interface of DNA polymerase beta with XRCC1. Structure 2000;10:1709-1720 
  36. Lee JM. Lee YC. Yang SY, et al. Genetic polymorphisms of XRCC1 and risk of the esophageal cancer. Int J Cancer 2001;95:240-246 

이 논문을 인용한 문헌 (0)

  1. 이 논문을 인용한 문헌 없음

원문보기

원문 PDF 다운로드

  • ScienceON :

원문 URL 링크

  • 대한방사선종양학회 : 저널

원문 PDF 파일 및 링크정보가 존재하지 않을 경우 KISTI DDS 시스템에서 제공하는 원문복사서비스를 사용할 수 있습니다. (원문복사서비스 안내 바로 가기)

상세조회 0건 원문조회 0건

DOI 인용 스타일