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研究生:陳世偉
研究生(外文):Shih-Wei Chen
論文名稱:糖尿病患Thiazolidinediones使用與罹患大腸直腸癌的風險
論文名稱(外文):Use of Thiazolidinediones and the Risk of Colorectal Cancer in Patients with Diabetes: A nationwide, population-based, case-control study
指導教授:陳保中陳保中引用關係
口試委員:陳仲達謝蕙宜何文照
口試日期:2012-06-26
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2012
畢業學年度:100
語文別:英文
論文頁數:34
中文關鍵詞:胰島素增敏劑糖尿病大腸直腸癌
外文關鍵詞:ThiazolidinedionesDiabetesColorectal Cancer
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研究目的:
根據目前許多臨床前的動物實驗或細胞實驗的結果顯示,PPAR-γ agonists具有抑制大腸直腸癌的作用。本研究以合成的PPAR-γ agonists(Thiazolidinediones, TZDs)來評估PPAR-γ agonists的使用與大腸直腸癌發生的關係。

研究方法:
研究設計為利用台灣全民健保資料庫進行全國性人口為基礎的病例對照研究,病例個案選取為診斷糖尿病至少365天於2000至2008年被診斷為大腸直腸癌之新發生個案,並以性別、年齡和糖尿病的診斷年齡為配對條件,隨機選取對照組。於24,496符合資格的病例和對照個案中,以條件邏輯回歸分析法評估TZDs藥物的使用與大腸直腸癌風險的關係。並另外進行附加研究,評估TZDs藥物同時與低劑量aspirin或非類固醇類止痛藥(NSAIDs)併用對大腸直腸癌風險的關係。

研究結果:
與沒有使用TZDs藥物的人比較之下,有使用TZDs藥物的人其罹患大腸直腸癌的風險降低,odds ratio為 0.86 (95% CI, 0.79-0.94)。此外,TZDs藥物與低劑量aspirin或NSAIDs併用下,大腸直腸癌的風險仍然下降。

結論:
TZDs的使用會降低糖尿病人發生大腸直腸癌的風險,此結果值得進一步的研究來確認。

Objective
Pre-clinical data suggest that peroxisome proliferator-activated receptor gamma (PPARγ) agonists have antineoplastic effects in colorectal cancer. We aimed to assess the association between the use of synthetic PPARγ agonists, represented by thiazolidinediones (TZDs), and the risk of developing colorectal cancer.

Research Design and Methods
We conducted a nationwide, population-based, case-control study using the Taiwan National Health Insurance Research Database. Cases were defined as patients who were diagnosed with diabetes at least 365 days prior to a new diagnosis of colorectal cancer between 2000 and 2008. We randomly selected diabetic controls for each case, which were matched by gender, age, and the duration of diabetes. Among the 24,496 eligible cases and controls, we used conditional logistic regression to assess the risk of colorectal cancer in association with use of TZDs. An additional analysis was conducted to assess the effects of concomitant use of TZDs and low-dose aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of colorectal cancer.

Results
A decreased risk of colorectal cancer was observed in patients who had used TZDs compared with those who had never used TZDs (adjusted odds ratio, 0.86; 95% CI, 0.79-0.94). Furthermore, the benefit of a decreased colorectal cancer risk was also found with concomitant use of TZDs and low-dose aspirin or NSAIDs.

Conclusions
The use of TZDs may be associated with a decreased risk of colorectal cancer in patients with diabetes. Further studies are warranted to confirm our findings.

致謝………………………………………………i
摘要………………………………………………ii
Abstract………………………………………………iii
Chapter 1 Introduction………………………………………………1
Chapter 2 Research Design and Methods ………………………………………………3
2.1 Source population………………………………………………3
2.2 Cases and Controls………………………………………………5
2.3 Exposure assessment………………………………………………6
2.4 Statistical analyses………………………………………………7
Chapter 3 Results………………………………………………9
Chapter 4 Discussions………………………………………………12
Chapter 5 References………………………………………………20

Figure contents

Figure 1 Flow diagram of cases and controls selection...........................................26
Figure 2 Adjusted odds ratios for colorectal cancer treated with a combination of TZDs and low-dose aspirin (A) or a combination of TZDs and NSAIDs (B).................................................................................................................30
Figure 3 Meta-analysis of use of thiazolidinediones and the risk of colorectal cancer in patients with diabetes in previously reported studies and in this study..............................................................................................................31


Table contents

Table 1 Characteristics in Cases and Controls................................................27
Table 2 Use of TZDs and odds ratios of colorectal cancer among patients with diabetes...................................................................................................28
Table 3 Sensitivity test for adjusted odds ratios of colorectal cancer in potentially confounding drugs.............................................................................29

Appendix

Table 1 Use of TZDs, Aspirin, NSAIDs and odds ratios of colorectal cancer among patients with diabetes...................................................................................32
Table 2 Distribution between use of TZD and diagnosis of colorectal polyp before index date in cases and controls....................................................................33
Table 3 Subgroup analysis of TZD use and adjusted odds ratios of colorectal cancer among patients with diabetes........................................................................33
Table 4 Distribution of insulin-use in cases and controls.........................................34
Table 5 Subgroup analysis of TZD use and adjusted odds ratios of colorectal cancer among patients with diabetes........................................................................34

1.Mangelsdorf DJ, Thummel C, Beato M, et al. The nuclear receptor superfamily: the second decade. Cell. 1995; 83: 835-839.
2.Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature. 2000; 405: 421-424.
3.Forman BM, Tontonoz P, Chen J, et al. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell. 1995; 83: 803-812.
4.Sarraf P, Mueller E, Jones D, et al. Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Nat Med. 1998; 4: 1046-1052.
5.Mansen A, Guardiola-Diaz H, Rafter J, et al. Expression of the peroxisome proliferator-activated receptor (PPAR) in the mouse colonic mucosa. Biochem Biophys Res Commun. 1996; 222: 844-851.
6.DuBois RN, Gupta R, Brockman J, et al. The nuclear eicosanoid receptor, PPARgamma, is aberrantly expressed in colonic cancers. Carcinogenesis. 1998; 19: 49-53.
7.Grommes C, Landreth G, Heneka M. Antineoplastic effects of peroxisome proliferator activated receptor γ agonists. The Lancet Oncology. 2004; 5: 419-429.
8.Tanaka T, Kohno H, Yoshitani S, et al. Ligands for peroxisome proliferator-activated receptors alpha and gamma inhibit chemically induced colitis and formation of aberrant crypt foci in rats. Cancer Res. 2001; 61: 2424-2428.
9.Osawa E, Nakajima A, Wada K, et al. Peroxisome proliferator-activated receptor γ ligands suppress colon carcinogenesis induced by azoxymethane in mice. Gastroenterology. 2003; 124: 361-367.
10.Kulke MH, Demetri GD, Sharpless NE, et al. A phase II study of troglitazone, an activator of the PPARgamma receptor, in patients with chemotherapy-resistant metastatic colorectal cancer. Cancer J. 2002; 8: 395-399.
11.Govindarajan R, Ratnasinghe L, Simmons DL, et al. Thiazolidinediones and the Risk of Lung, Prostate, and Colon Cancer in Patients With Diabetes. Journal of Clinical Oncology. 2007; 25: 1476-1481.
12.Koro C, Barrett S, Qizilbash N. Cancer risks in thiazolidinedione users compared to other anti-diabetic agents. Pharmacoepidemiology and Drug Safety. 2007; 16: 485-492.
13.Lewis JD, Capra AM, Achacoso NS, et al. Thiazolidinedione Therapy Is Not Associated With Increased Colonic Neoplasia Risk in Patients With Diabetes Mellitus. Gastroenterology. 2008; 135: 1914-1923.
14.Ferrara A, Lewis JD, Quesenberry CP, et al. Cohort Study of Pioglitazone and Cancer Incidence in Patients With Diabetes. Diabetes Care. 2011; 34: 923-929.
15.Monami M, Lamanna C, Marchionni N, et al. Rosiglitazone and Risk of Cancer: A meta-analysis of randomized clinical trials. Diabetes Care. 2008; 31: 1455-1460.
16.Lewis JD, Ferrara A, Peng T, et al. Risk of Bladder Cancer Among Diabetic Patients Treated With Pioglitazone: Interim report of a longitudinal cohort study. Diabetes Care. 2011; 34: 916-922.
17.Bureau of National Health Insurance. Available from: http://www.nhi.gov.tw/Resource/webdata/Attach_13767_1_National%20Health%20Insurance%20in%20Taiwan%202010.pdf Accessed October 20, 2011.
18.Chiang TL. Taiwan''s 1995 health care reform. Health Policy. 1997; 39: 225-239.
19.Lu JF, Hsiao WC. Does universal health insurance make health care unaffordable? Lessons from Taiwan. Health Aff (Millwood). 2003; 22: 77-88.
20.Institutes NHR. National Health Insurance Research Database. Available from: http://w3.nhri.org.tw/nhird/en/index.htm Accessed October 20, 2011.
21.WHO. The ATC and DDD system. Available from: http://www.whocc.no/atc_ddd_index/ Accessed October 20, 2011.
22.Xin X, Yang S, Kowalski J, et al. Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem. 1999; 274: 9116-9121.
23.Panigrahy D, Singer S, Shen LQ, et al. PPARgamma ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis. J Clin Invest. 2002; 110: 923-932.
24.Flossmann E, Rothwell PM. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet. 2007; 369: 1603-1613.
25.Rothwell PM, Wilson M, Elwin CE, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. 2010; 376: 1741-1750.
26.Smalley W, Ray WA, Daugherty J, et al. Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: a population-based study. Arch Intern Med. 1999; 159: 161-166.
27.Rostom A, Dube C, Lewin G, et al. Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med. 2007; 146: 376-389.
28.Ruder EH, Laiyemo AO, Graubard BI, et al. Non-steroidal anti-inflammatory drugs and colorectal cancer risk in a large, prospective cohort. Am J Gastroenterol. 2011; 106: 1340-1350.
29.Seshasai SR, Kaptoge S, Thompson A, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011; 364: 829-841.
30.Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and Cancer: A consensus report. Diabetes Care. 2010; 33: 1674-1685.
Blanquicett C, Roman J, Hart CM. Thiazolidinediones as anti-cancer agents. Cancer Ther. 2008; 6: 25-34.

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