Article Search
검색
검색 팝업 닫기

Metrics

Help

  • 1. Aims and Scope

    Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE

  • 2. Editorial Board

    Editor-in-Chief + MORE

    Editor-in-Chief
    Yong Chan Lee Professor of Medicine
    Director, Gastrointestinal Research Laboratory
    Veterans Affairs Medical Center, Univ. California San Francisco
    San Francisco, USA

    Deputy Editor

    Deputy Editor
    Jong Pil Im Seoul National University College of Medicine, Seoul, Korea
    Robert S. Bresalier University of Texas M. D. Anderson Cancer Center, Houston, USA
    Steven H. Itzkowitz Mount Sinai Medical Center, NY, USA
  • 3. Editorial Office
  • 4. Articles
  • 5. Instructions for Authors
  • 6. File Download (PDF version)
  • 7. Ethical Standards
  • 8. Peer Review

    All papers submitted to Gut and Liver are reviewed by the editorial team before being sent out for an external peer review to rule out papers that have low priority, insufficient originality, scientific flaws, or the absence of a message of importance to the readers of the Journal. A decision about these papers will usually be made within two or three weeks.
    The remaining articles are usually sent to two reviewers. It would be very helpful if you could suggest a selection of reviewers and include their contact details. We may not always use the reviewers you recommend, but suggesting reviewers will make our reviewer database much richer; in the end, everyone will benefit. We reserve the right to return manuscripts in which no reviewers are suggested.

    The final responsibility for the decision to accept or reject lies with the editors. In many cases, papers may be rejected despite favorable reviews because of editorial policy or a lack of space. The editor retains the right to determine publication priorities, the style of the paper, and to request, if necessary, that the material submitted be shortened for publication.

Search

Search

Year

to

Article Type

Editorial

Split Viewer

Can Statin Prevent the Risk of Colorectal Cancer in Patients with Inflammatory Bowel Disease?

Hyun Joo Jang

Department of Gastroenterology, Hallym University School of Medicine, Hwasung, Korea

Correspondence to: Hyun Joo Jang (https://orcid.org/0000-0003-4424-1968)
Department of Gastroenterology, Hallym University School of Medicine, 7 Keunjaebong-gil, Hwaseong 18450, Korea
Tel: +82-31-8086-2450, Fax: +82-31-8086-2029, E-mail: jhj1229@hallym.or.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gut Liver 2019;13(2):138-139. https://doi.org/10.5009/gnl19003

Published online March 15, 2019, Published date March 31, 2019

Copyright © Gut and Liver.

The risk for dysplasia and colorectal cancer (CRC) is increased in patients with long-standing ulcerative colitis (UC) and extensive Crohn’s disease (CD). CRC is one of important causes of death in patients with inflammatory bowel disease (IBD). Patients with long-standing UC and colonic CD have about 1- to 6-fold increase in lifetime risk of CRC compared to the general population.1 The risk factors for IBD-associated CRC include: prolonged duration of colitis, extent and severity of colitis, coexistence of primary sclerosing cholangitis (PSC), and family history of CRC.2 Oncogenic mechanism of IBD-related CRC has been known that chronic or repeated inflammation to the intestinal mucosa leads to the development of CRC via low- and high-grade dysplasia.

There is a controversial issue about whether statins have chemopreventive potentials against CRC, but it still remains a debate. Statins, one of cholesterol-lowering drugs, are used to prevent and treat cardiovascular diseases. Some experimental results recently suggest that statins provide an additional chemopreventive effect by inducing apoptosis, inhibiting angiogenesis, increasing the antitumor effects of several cytokines, and preventing metastasis.3,4 Two recent meta-analyses including 40 and 42 individual studies suggested a risk reduction of CRC among statin users.5,6

Statins reduce synthesis of cholesterol in liver and reduce the level of serum cholesterol by 3-hydroxy-3-methylglutaryl-coenzyme A reductase which is a rate-limiting enzyme in the mevalonate pathway. Its downstream mevalonate products (such as isoprenoid molecules, farnesyl pyrophosphate and geranyl-geranyl pyrophosphate) are necessary for post-translational modification and isoprenylation of a variety of proteins such as Ras and RhoA, which are important for cell growth, cell proliferation, angiogenesis or cell migration.7 These proteins are over-expressed in CRC and are associated with tumor invasion. Statin induces apoptosis and suppresses the β subunits of insulin-like growth factor 1 receptor (IGF-1R) and IGF-1-induced ERK/Akt activation.3 Non HMG-CoA reductase-mediated effects of statins may be through inhibition of inflammation, angiogenesis and cell adhesion, and an antioxidant effect.

There are limited studies investigating the chemopreventive effect of statins against CRC in IBD patients. One study showed that long-term statin use was associated with a reduced risk of both IBD-associated CRC (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.01 to 0.78) and non-IBD CRC (OR, 0.49; 95% CI, 0.39 to 0.62).8 The limitations of this study were recall bias and misclassifications based on self-reporting data. It also did not report disease duration, location of disease, medications, extent of disease and severity. Another recent study of Ananthakrishnan et al.9 showed that statin use was associated with about 60% of risk reduction of CRC in a large cohort including 11,000 IBD patients based on ICD-9 codes.

In previous issue of Gut and Liver, Shah et al.10 reported that statin use was not associated with lower rates of dysplasia or CRC in IBD patients undergoing surveillance colonoscopies. There was no significant difference in low-grade dysplasia, high-grade dysplasia or CRC development during follow-up between the statin exposed and non-exposed groups. Propensity score analysis did not change the overall findings. The main strengths of this study are as follows: the results of this study provided detailed information of their IBD history, disease duration, the extent of disease, and histologic activity. This study also analyzed statin exposure and occurrence of any dysplasia, and therefore any neoplastic transformation among IBD colitis patients undergoing surveillance colonoscopies for longstanding colitis or PSC-related colitis. However, there are some limitations of this study. This study included insufficient numbers of patients and the low overall rates of dysplasia and CRC to prove differences. The results of this study did not analyze the name, duration and dose of statin. Statins exert different effects depending on cell line, the type of statin being used, concentration of statin, and duration of exposure of cells to statins in experimental environment. The retrospective design of this study also limits to control unmeasured and measured confounders.

In summary, statin use as chemopreventive agents in IBD patients remains controversial. Well-designed and large prospective studies would be needed to prove the chemopreventive role of statin in IBD patients.

No potential conflict of interest relevant to this article was reported.

  1. Jess T, Gamborg M, Matzen P, Munkholm P, Sørensen TI. Increased risk of intestinal cancer in Crohn’s disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol 2005;100:2724-2729.
    Pubmed CrossRef
  2. Stidham RW, Higgins PD. Colorectal cancer in inflammatory bowel disease. Clin Colon Rectal Surg 2018;31:168-178.
    Pubmed KoreaMed CrossRef
  3. Jang HJ, Hong EM, Park SW, et al. Statin induces apoptosis of human colon cancer cells and downregulation of insulin-like growth factor 1 receptor via proapoptotic ERK activation. Oncol Lett 2016;12:250-256.
    Pubmed KoreaMed CrossRef
  4. Guruswamy S, Rao CV. Multi-target approaches in colon cancer chemoprevention based on systems biology of tumor cell-signaling. Gene Regul Syst Bio 2008;2:163-176.
    Pubmed KoreaMed
  5. Lytras T, Nikolopoulos G, Bonovas S. Statins and the risk of colorectal cancer: an updated systematic review and meta-analysis of 40 studies. World J Gastroenterol 2014;20:1858-1870.
    Pubmed KoreaMed CrossRef
  6. Liu Y, Tang W, Wang J, et al. Association between statin use and colorectal cancer risk: a meta-analysis of 42 studies. Cancer Causes Control 2014;25:237-249.
    Pubmed CrossRef
  7. Kobayashi Y, Banno K, Kunitomi H, et al. Is antidyslipidemic statin use for cancer prevention a promising drug repositioning approach?. Eur J Cancer Prev. Epub 2018 Nov 8. https://doi.org/10.1097/CEJ.000000000000049
    Pubmed CrossRef
  8. Samadder NJ, Mukherjee B, Huang SC, et al. Risk of colorectal cancer in self-reported inflammatory bowel disease and modification of risk by statin and NSAID use. Cancer 2011;117:1640-1648.
    Pubmed KoreaMed CrossRef
  9. Ananthakrishnan AN, Cagan A, Cai T, et al. Statin use is associated with reduced risk of colorectal cancer in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2016;14:973-979.
    Pubmed KoreaMed CrossRef
  10. Shah SC, Glass J, Giustino G, et al. Statin exposure is not associated with reduced prevalence of colorectal neoplasia in patients with inflammatory bowel disease. Gut Liver 2019;13:54-61.
    Pubmed KoreaMed CrossRef

Article

Editorial

Gut and Liver 2019; 13(2): 138-139

Published online March 31, 2019 https://doi.org/10.5009/gnl19003

Copyright © Gut and Liver.

Can Statin Prevent the Risk of Colorectal Cancer in Patients with Inflammatory Bowel Disease?

Hyun Joo Jang

Department of Gastroenterology, Hallym University School of Medicine, Hwasung, Korea

Correspondence to:Hyun Joo Jang (https://orcid.org/0000-0003-4424-1968)
Department of Gastroenterology, Hallym University School of Medicine, 7 Keunjaebong-gil, Hwaseong 18450, Korea
Tel: +82-31-8086-2450, Fax: +82-31-8086-2029, E-mail: jhj1229@hallym.or.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Body

The risk for dysplasia and colorectal cancer (CRC) is increased in patients with long-standing ulcerative colitis (UC) and extensive Crohn’s disease (CD). CRC is one of important causes of death in patients with inflammatory bowel disease (IBD). Patients with long-standing UC and colonic CD have about 1- to 6-fold increase in lifetime risk of CRC compared to the general population.1 The risk factors for IBD-associated CRC include: prolonged duration of colitis, extent and severity of colitis, coexistence of primary sclerosing cholangitis (PSC), and family history of CRC.2 Oncogenic mechanism of IBD-related CRC has been known that chronic or repeated inflammation to the intestinal mucosa leads to the development of CRC via low- and high-grade dysplasia.

There is a controversial issue about whether statins have chemopreventive potentials against CRC, but it still remains a debate. Statins, one of cholesterol-lowering drugs, are used to prevent and treat cardiovascular diseases. Some experimental results recently suggest that statins provide an additional chemopreventive effect by inducing apoptosis, inhibiting angiogenesis, increasing the antitumor effects of several cytokines, and preventing metastasis.3,4 Two recent meta-analyses including 40 and 42 individual studies suggested a risk reduction of CRC among statin users.5,6

Statins reduce synthesis of cholesterol in liver and reduce the level of serum cholesterol by 3-hydroxy-3-methylglutaryl-coenzyme A reductase which is a rate-limiting enzyme in the mevalonate pathway. Its downstream mevalonate products (such as isoprenoid molecules, farnesyl pyrophosphate and geranyl-geranyl pyrophosphate) are necessary for post-translational modification and isoprenylation of a variety of proteins such as Ras and RhoA, which are important for cell growth, cell proliferation, angiogenesis or cell migration.7 These proteins are over-expressed in CRC and are associated with tumor invasion. Statin induces apoptosis and suppresses the β subunits of insulin-like growth factor 1 receptor (IGF-1R) and IGF-1-induced ERK/Akt activation.3 Non HMG-CoA reductase-mediated effects of statins may be through inhibition of inflammation, angiogenesis and cell adhesion, and an antioxidant effect.

There are limited studies investigating the chemopreventive effect of statins against CRC in IBD patients. One study showed that long-term statin use was associated with a reduced risk of both IBD-associated CRC (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.01 to 0.78) and non-IBD CRC (OR, 0.49; 95% CI, 0.39 to 0.62).8 The limitations of this study were recall bias and misclassifications based on self-reporting data. It also did not report disease duration, location of disease, medications, extent of disease and severity. Another recent study of Ananthakrishnan et al.9 showed that statin use was associated with about 60% of risk reduction of CRC in a large cohort including 11,000 IBD patients based on ICD-9 codes.

In previous issue of Gut and Liver, Shah et al.10 reported that statin use was not associated with lower rates of dysplasia or CRC in IBD patients undergoing surveillance colonoscopies. There was no significant difference in low-grade dysplasia, high-grade dysplasia or CRC development during follow-up between the statin exposed and non-exposed groups. Propensity score analysis did not change the overall findings. The main strengths of this study are as follows: the results of this study provided detailed information of their IBD history, disease duration, the extent of disease, and histologic activity. This study also analyzed statin exposure and occurrence of any dysplasia, and therefore any neoplastic transformation among IBD colitis patients undergoing surveillance colonoscopies for longstanding colitis or PSC-related colitis. However, there are some limitations of this study. This study included insufficient numbers of patients and the low overall rates of dysplasia and CRC to prove differences. The results of this study did not analyze the name, duration and dose of statin. Statins exert different effects depending on cell line, the type of statin being used, concentration of statin, and duration of exposure of cells to statins in experimental environment. The retrospective design of this study also limits to control unmeasured and measured confounders.

In summary, statin use as chemopreventive agents in IBD patients remains controversial. Well-designed and large prospective studies would be needed to prove the chemopreventive role of statin in IBD patients.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

References

  1. Jess T, Gamborg M, Matzen P, Munkholm P, Sørensen TI. Increased risk of intestinal cancer in Crohn’s disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol 2005;100:2724-2729.
    Pubmed CrossRef
  2. Stidham RW, Higgins PD. Colorectal cancer in inflammatory bowel disease. Clin Colon Rectal Surg 2018;31:168-178.
    Pubmed KoreaMed CrossRef
  3. Jang HJ, Hong EM, Park SW, et al. Statin induces apoptosis of human colon cancer cells and downregulation of insulin-like growth factor 1 receptor via proapoptotic ERK activation. Oncol Lett 2016;12:250-256.
    Pubmed KoreaMed CrossRef
  4. Guruswamy S, Rao CV. Multi-target approaches in colon cancer chemoprevention based on systems biology of tumor cell-signaling. Gene Regul Syst Bio 2008;2:163-176.
    Pubmed KoreaMed
  5. Lytras T, Nikolopoulos G, Bonovas S. Statins and the risk of colorectal cancer: an updated systematic review and meta-analysis of 40 studies. World J Gastroenterol 2014;20:1858-1870.
    Pubmed KoreaMed CrossRef
  6. Liu Y, Tang W, Wang J, et al. Association between statin use and colorectal cancer risk: a meta-analysis of 42 studies. Cancer Causes Control 2014;25:237-249.
    Pubmed CrossRef
  7. Kobayashi Y, Banno K, Kunitomi H, et al. Is antidyslipidemic statin use for cancer prevention a promising drug repositioning approach?. Eur J Cancer Prev. Epub 2018 Nov 8. https://doi.org/10.1097/CEJ.0000000000000497
    Pubmed CrossRef
  8. Samadder NJ, Mukherjee B, Huang SC, et al. Risk of colorectal cancer in self-reported inflammatory bowel disease and modification of risk by statin and NSAID use. Cancer 2011;117:1640-1648.
    Pubmed KoreaMed CrossRef
  9. Ananthakrishnan AN, Cagan A, Cai T, et al. Statin use is associated with reduced risk of colorectal cancer in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2016;14:973-979.
    Pubmed KoreaMed CrossRef
  10. Shah SC, Glass J, Giustino G, et al. Statin exposure is not associated with reduced prevalence of colorectal neoplasia in patients with inflammatory bowel disease. Gut Liver 2019;13:54-61.
    Pubmed KoreaMed CrossRef
Gut and Liver

Vol.18 No.1
January, 2024

pISSN 1976-2283
eISSN 2005-1212

qrcode
qrcode

Share this article on :

  • line

Popular Keywords

Gut and LiverQR code Download
qr-code

Editorial Office