Title

血紅素結合蛋白之基因變異型得以預測大腸直腸癌病患之存活情形

Translated Titles

Haptoglobin genotypes predict the survival of patients with colorectal cancer

DOI

10.6834/CSMU.2012.00001

Authors

賴泓誌

Key Words

血紅素結合蛋白 ; 大腸直腸癌 ; 存活率 ; haptoglobin ; colorectal cancer ; survival

PublicationName

中山醫學大學醫學研究所學位論文

Volume or Term/Year and Month of Publication

2012年

Academic Degree Category

碩士

Advisor

周明智

Content Language

繁體中文

Chinese Abstract

本研究旨在研究血紅素結合蛋白之基因多型性與大腸直腸癌之病人存活情形之關聯性。因故,本研究收集單一教學醫院之非轉移性大腸直腸癌病患並抽血保存於EDTA管中,進一步使用逆轉錄聚合酶鏈式反應確認血紅素結合蛋白之基因型分型。 從西元2005年一月至十一月共計62個非轉移性大腸直腸癌病患接受血紅素結合蛋白基因型之分析檢驗。因病例數太少無法分析故,排除五個Hp 1-1及二個Hp 2-0合子型病人,最後分析了29個Hp 2-1及27個Hp 2-2病人。根據年齡及腫瘤分期進行配對分析後發現具有Hp 2-2之病人其整體存活率較差(Hazard ratio (HR) 3.0; p = 0.028) 且疾病特定之存活較差(HR 3.5; p = 0.018)。 總結來說,本研究證實Hp2-2基因型與非轉移性的大腸直腸癌病患之較短的整體存活以及疾病特定之存活情形有顯著相關。具有Hp2-2基因型之非轉移性的大腸直腸癌病患的預後較差。

English Abstract

The objective of this study is to examine the correlation between genotype of haptoglobin and survival of patients with non-metastatic colorectal cancer. We evaluated cases of patients diagnosed with non-metastatic colorectal cancer at our hospital and collected blood samples. Further identification of haptoglobin genotyping based on polymerase chain reaction. From January 2005 to November 2005, totally 62 non-metastatic colorectal cancer patients was included. The patients with Hp1-1 (5 cases ) and Hp2-0 (2 cases)was not enrolled due to the small case number. Finally, 29 cases of Hp 2-1 and 27 cases of Hp 2-2 were enrolled. These patients were matched for analysis of the Hp genotype. Patients with the Hp2-2 genotype had significantly worse overall survival (Hazard ratio (HR) 3.0; p = 0.028) and disease-specific survival rates than patients with the Hp2-1 genotype (HR 3.5; p = 0.018). We demonstrated the correlation between Hp 2-2 genotype and shorter overall survival and disease-specific survival of patients with non-metastatic colorectal cancer significantly.

Topic Category 醫藥衛生 > 醫藥總論
醫學院 > 醫學研究所
Reference
  1. 1. Andrew P. Levy. et al. Antioxidants & Redox Signaling. 2010; 12(2): 293-304. “Haptoglobin: Basic and Clinical Aspects.”
    連結:
  2. 2. Marinković S, Baumann H. Mol Cell Biol 1990; 10: 1573-83. “Structure, hormonal regulation, and identification of the interleukin-6- and dexamethasone-responsive element of the rat haptoglobin gene.”
    連結:
  3. 3. Carter K, Worwood M. Int J Lab Hematol 2007; 29: 92-110. “Haptoglobin: a review of the major allele frequencies worldwide and their association with diseases.”
    連結:
  4. 6. Su YC, Chen YC, Li SC, Lee CC, Tung YT, et al. Clin Chem Lab Med 2009; 47(6): 745-749. “Deletion of Hpdel in healthy individuals and cancer patients in Taiwan.”
    連結:
  5. 7. Cid MC, Grant OS, Hoffman GS, Auerbach R, Fauci AS, et al. J Clin Invest 1993; 91: 977-85. “Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis.”
    連結:
  6. 10. Kymberley Carter, Mark Worwood. Int. Jnl. Lab. Hem. 2007, 29, 92–110. “Haptoglobin: a review of the major allele frequencies worldwide and their association with diseases.”
    連結:
  7. 12. Lee CC, Lin HY, Hung SK, Li DK, Su YC, et al. Int J of Bio Marker 2009; 24(1): 32-37. “Haptoglobin genotypes in nasopharyngeal carcinoma.”
    連結:
  8. 13. Awadallah SM, Atoum MF. Clin Chim Acta 2004; 341: 17-21. “Haptoglobin polymorphism in breast cancer patients from Jordan.”
    連結:
  9. 14. Lee CC, Lee MS, Ho HC, Hung SK, Su YC, et al. Clin Chem Lab Med 2009; 47(10): 1-7. “The prognostic utility of haptoglobin genotypes in squamous cell carcinoma of head and neck.”
    連結:
  10. 15. Lee CC, Ho HC, Lee MS, Hung SK, Su YC, et al. Clinica Chimica Acta 2009; 411: 1116-1121. “Expression of haptoglobin predict recurrence in head and neck squamous cell carcinoma.”
    連結:
  11. 17. Delanghe JR, Langlois MR, Boelaert JR, Van Acker J, Van Wanzeele F, van der Groen G, et al. AIDS 1998; 12: 1027-32. “Haptoglobin polymorphism, iron metabolism and mortality in HIV infection.”
    連結:
  12. 18. Van Vlierberghe H, Langlois M, Delanghe. J. Clin Chim Acta 2004; 345: 35-42. “Haptoglobin polymorphisms and iron homeostasis in health and in disease.”
    連結:
  13. 19. Chen LT, Whang-Peng. J. Clin Colorectal Cancer 2004; 4: 196-203. “Current status of clinical studies for colorectal cancer in Taiwan.”
    連結:
  14. 20. Bonetti A, Zaninelli M, Durante E, Fraccon AP, Franceschi T, Pasini F, et al. Tumori 2006; 92: 389-95. “Multiple-target chemotherapy (LV-modulated 5-FU bolus and continuous infusion, oxaliplatin, CPT-11) in advanced 5-FU-refractory colorectal cancer: MTD definition and efficacy evaluation. A phase Ι-II study.”
    連結:
  15. 22. Koch W, Latz W, Eichinger M, Gschwendner C, Teige B, et al. Clin Chem 2003; 49: 1937-40. “Haptoglobin gene subtyping by restriction enzyme analysis.”
    連結:
  16. 24. Fröhlander N, Stendahl U. Hum Hered 1988; 38: 180-2. “Haptoglobin groups in ovarian carcinoma.”
    連結:
  17. 25. Jayanthi M, Habibullah CM, Ishaq M, Ali H, Babu PS, et al. J Med Genet 1989; 26: 172-3. “Distribution of haptoglobin phenotypes in esophageal and gastric cancer.”
    連結:
  18. 26. Beckman G, Eklund A, Fröhlander N, Stjernberg N. Hum Hered 1986; 36: 258-60. “Haptoglobin groups and lung cancer.”
    連結:
  19. 27. Nevo S, Tatarsky I. Hum Genet 1986; 73: 240-4. “Serum haptoglobin types and leukemia.”
    連結:
  20. 28. Mahmud SM, Koushik A, Duarte-Franco E, Costa J, Fontes G, Bicho M, et al. Clin Chimica Acta 2007; 385: 67-72. “Haptoglobin phenotype and risk of cervical neoplasia: a case-control study.”
    連結:
  21. 29. Benkmann HG, Hansenn HP, Ovenbeck R, Goedde HW. Human Hered 1987; 37: 290-3. “Distribution of alpha-1-antitrypsin and haptoglobin phenotypes in bladder cancer patients.”
    連結:
  22. 31. Gutteridge JM. Biochim Biophys Acta 1987; 917: 219-23. “The antioxidant activity of haptoglobin towards haemoglobin-stimulated lipid peroxidation.”
    連結:
  23. 32. Lim YK, Jenner A, Ali AB, Wang Y, Hsu SI, Chong SM, et al. Kidney Int 2000; 58: 1033-44. “Haptoglobin reduces renal oxidative DNA and tissue damage during phenylhydrazine-induced hemolysis.”
    連結:
  24. 33. Thomas L. Haptoglobin/Hämopexin. In: Thomas L, editor. Labor and Diagnose, 4th ed. Marburg: Medizinische Verlagsgesellschaft 1992:813-20.
    連結:
  25. 34. Na N, Delanghe JR, Taes YE, Torck M, Baeyens WR, et al. Clin Chim Acta 2006; 365: 319-24. “Serum vitamin C concentration is influenced by haptoglobin polymorphism and iron status in Chinese.”
    連結:
  26. 35. Weinberg ED. Eur J Cancer Prev 1996; 5: 19-36. “The role of iron in cancer.”
    連結:
  27. 36. Toyokuni S. Free Rad Biol Med 1996; 20: 553-66. “Iron-induced carcinogenesis: the role of redox regulation.”
    連結:
  28. 37. de Kleijn DP, Smeets MB, Kemmeren PP, Lim SK, Velema E, et al. FASEB J 2002; 16: 1123-5. “Acute phase protein haptoglobin is a cell migration factor involved in arterial restructuring.”
    連結:
  29. 4. Langlois MR, Delanghe JR. Clin Chem 1996; 42: 1589-600. “Biological and clinical significance of haptoglobin polymorphism in humans.”
  30. 5. Michel R. Langlois, JoRIs R. Delanghe. ClinicalChemistiy 1996; 42(10): 1589-1600. “Biological and clinical significance of haptoglobin polymorphism in humans.”
  31. 8. Lange V. Der. Anthropol Anz 1992; 50: 281-302. “Review: Haptoglobin Polymorphismus-nicht nur eine genetische Markierungshilfe.”
  32. 9. Barclay R. Med Lab Sd 1985: 42: 166-77. “The role of iron in infection.”
  33. 11. Bettendorf A, Colonna J, Kleisbauer JP. Nouv Presse Med. 1980; 9(44): 3359-60. “Haptoglobin groups in the course of primary bronchial cancer.”
  34. 16. Li SC, Chen YC, Wei CK, Lin CH, Su YC, et al. J. Chinese Oncol. Soc. 2009; 25(3): 175-183. “Haptoglobin polymorphism in breast cancer.”
  35. 21. Koch W, Latz W, Eichinger M, Roguin A, Levy AP, Schömig A, Kastrati A. Clin Chem 2002; 48: 1377-82. “Genotyping of the common haptoglobin Hp 1/2 polymorphism based on PCR.”
  36. 23. Dobryszycka W, Warwas M. Neoplasma 1983; 30: 169-72. “Haptoglobin types in ovarian tumors.”
  37. 30. Sadrzadeh SM, Graf E, Panter SS, Hallaway PE, Eaton JW. J Biol Chem 1984; 256: 14354-6. “Hemoglobin. A biologic fenton reagent.”