Skip to main content

Advertisement

SpringerLink
Log in

Risk of colon cancer recurrence in relation to diabetes

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Purpose

To describe the association between diabetes and colon cancer recurrence.

Methods

We conducted a cohort study at two integrated health care delivery systems in the United States. Using tumor registry data, we identified patients aged ≥ 18 years when diagnosed with stage I–IIIA adenocarcinomas of the colon during 1995–2014. Pre-existing diabetes was ascertained via diagnosis codes. Medical records were reviewed for eligibility and to abstract recurrence and covariate information. Recurrence was ascertained beginning 90 days after the end of colon cancer treatment (i.e., cohort entry). Recurrence of any cancer or a new primary cancer at any site was a secondary outcome. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for the associations between diabetes at cohort entry and study outcomes.

Results

Among the 1,923 eligible patients, 393 (16.7%) had diabetes at cohort entry. Diabetes was not associated with recurrence (HR 0.87; 95% CI 0.56–1.33) or with any subsequent cancer (HR 1.09; 95% CI 0.85–1.40). When the definition of recurrence included second primary colorectal cancer, risk was non-significantly higher in patients with diabetes than without diabetes.

Conclusions

The risk of colon cancer recurrence appears to be similar in patients with and without diabetes at diagnosis.

Impact

Future studies should evaluate the association between diabetes and colorectal cancer outcomes, especially second primary colon cancers, in larger populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bullard KM, Cowie CC, Lessem SE, Saydah SH, Menke A, Geiss LS, Orchard TJ, Rolka DB, Imperatore G (2018) Prevalence of diagnosed diabetes in adults by diabetes type—United States, 2016. MMWR Morb Mortal Wkly Rep 67(12):359–361. https://doi.org/10.15585/mmwr.mm6712a2

    Article  PubMed  PubMed Central  Google Scholar 

  2. Cossor FI, Adams-Campbell LL, Chlebowski RT, Gunter MJ, Johnson K, Martell RE, McTiernan A, Simon MS, Rohan T, Wallace RB, Paulus JK (2013) Diabetes, metformin use, and colorectal cancer survival in postmenopausal women. Cancer Epidemiol 37(5):742–749. https://doi.org/10.1016/j.canep.2013.04.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dehal AN, Newton CC, Jacobs EJ, Patel AV, Gapstur SM, Campbell PT (2012) Impact of diabetes mellitus and insulin use on survival after colorectal cancer diagnosis: the Cancer Prevention Study-II Nutrition Cohort. J Clin Oncol 30(1):53–59. https://doi.org/10.1200/jco.2011.38.0303

    Article  PubMed  Google Scholar 

  4. Garrett CR, Hassabo HM, Bhadkamkar NA, Wen S, Baladandayuthapani V, Kee BK, Eng C, Hassan MM (2012) Survival advantage observed with the use of metformin in patients with type II diabetes and colorectal cancer. Br J Cancer 106(8):1374–1378. https://doi.org/10.1038/bjc.2012.71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Singh PP, Shi Q, Foster NR, Grothey A, Nair SG, Chan E, Shields AF, Goldberg RM, Gill S, Kahlenberg MS, Sinicrope FA, Sargent DJ, Alberts SR (2016) Relationship between metformin use and recurrence and survival in patients with resected stage iii colon cancer receiving adjuvant chemotherapy: results from North Central Cancer Treatment Group N0147 (Alliance). Oncologist 21(12):1509–1521. https://doi.org/10.1634/theoncologist.2016-0153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. González N, Prieto I, del Puerto-Nevado L, Portal-Nuñez S, Ardura JA, Corton M, Fernández-Fernández B, Aguilera O, Gomez-Guerrero C, Mas S, Moreno JA, Ruiz-Ortega M, Sanz AB, Sanchez-Niño MD, Rojo F, Vivanco F, Esbrit P, Ayuso C, Alvarez-Llamas G, Egido J, García-Foncillas J, Ortiz A, Consortium DCC (2017) 2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications. Oncotarget 8(11):18456–18485. https://doi.org/10.18632/oncotarget.14472

    Article  PubMed  PubMed Central  Google Scholar 

  7. Giovannucci E, Michaud D (2007) The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology 132(6):2208–2225. https://doi.org/10.1053/j.gastro.2007.03.050

    Article  CAS  PubMed  Google Scholar 

  8. Cohen DH, Leroith D (2012) Obesity, type 2 diabetes, and cancer: the insulin and IGF connection. Endocr Relat Cancer 19(5):F27–F45. https://doi.org/10.1530/ERC-11-0374

    Article  CAS  PubMed  Google Scholar 

  9. Deng L, Gui Z, Zhao L, Wang J, Shen L (2012) Diabetes mellitus and the incidence of colorectal cancer: an updated systematic review and meta-analysis. Dig Dis Sci 57(6):1576–1585. https://doi.org/10.1007/s10620-012-2055-1

    Article  CAS  PubMed  Google Scholar 

  10. Onitilo AA, Engel JM, Glurich I, Stankowski RV, Williams GM, Doi SA (2012) Diabetes and cancer I: risk, survival, and implications for screening. Cancer Causes Control 23(6):967–981. https://doi.org/10.1007/s10552-012-9972-3

    Article  PubMed  PubMed Central  Google Scholar 

  11. Chang CK, Ulrich CM (2003) Hyperinsulinaemia and hyperglycaemia: possible risk factors of colorectal cancer among diabetic patients. Diabetologia 46(5):595–607. https://doi.org/10.1007/s00125-003-1109-5

    Article  CAS  PubMed  Google Scholar 

  12. Luo S, Li JY, Zhao LN, Yu T, Zhong W, Xia ZS, Shan TD, Ouyang H, Yang HS, Chen QK (2016) Diabetes mellitus increases the risk of colorectal neoplasia: an updated meta-analysis. Clin Res Hepatol Gastroenterol 40(1):110–123. https://doi.org/10.1016/j.clinre.2015.05.021

    Article  PubMed  Google Scholar 

  13. Luo W, Cao Y, Liao C, Gao F (2012) Diabetes mellitus and the incidence and mortality of colorectal cancer: a meta-analysis of 24 cohort studies. Colorectal Dis 14(11):1307–1312. https://doi.org/10.1111/j.1463-1318.2012.02875.x

    Article  CAS  PubMed  Google Scholar 

  14. Jiang Y, Ben Q, Shen H, Lu W, Zhang Y, Zhu J (2011) Diabetes mellitus and incidence and mortality of colorectal cancer: a systematic review and meta-analysis of cohort studies. Eur J Epidemiol 26(11):863–876. https://doi.org/10.1007/s10654-011-9617-y

    Article  PubMed  Google Scholar 

  15. Tsilidis KK, Kasimis JC, Lopez DS, Ntzani EE, Ioannidis JP (2015) Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ 350:g7607. https://doi.org/10.1136/bmj.g7607

    Article  PubMed  Google Scholar 

  16. Campbell PT, Newton CC, Patel AV, Jacobs EJ, Gapstur SM (2012) Diabetes and cause-specific mortality in a prospective cohort of one million U.S. adults. Diabetes Care 35(9):1835–1844. https://doi.org/10.2337/dc12-0002

    Article  PubMed  PubMed Central  Google Scholar 

  17. Larsson SC, Orsini N, Wolk A (2005) Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst 97(22):1679–1687. https://doi.org/10.1093/jnci/dji375

    Article  PubMed  Google Scholar 

  18. Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ (2004) Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol 159(12):1160–1167. https://doi.org/10.1093/aje/kwh161

    Article  PubMed  Google Scholar 

  19. Rao Kondapally Seshasai S, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, Whincup PH, Mukamal KJ, Gillum RF, Holme I, Njolstad I, Fletcher A, Nilsson P, Lewington S, Collins R, Gudnason V, Thompson SG, Sattar N, Selvin E, Hu FB, Danesh J, Emerging Risk Factors C (2011) Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 364(9):829–841. https://doi.org/10.1056/NEJMoa1008862

    Article  PubMed  PubMed Central  Google Scholar 

  20. Dowling RJ, Goodwin PJ, Stambolic V (2011) Understanding the benefit of metformin use in cancer treatment. BMC Med 9(1):33. https://doi.org/10.1186/1741-7015-9-33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kourelis TV, Siegel RD (2012) Metformin and cancer: new applications for an old drug. Med Oncol 29(2):1314–1327. https://doi.org/10.1007/s12032-011-9846-7

    Article  CAS  PubMed  Google Scholar 

  22. Zhang HH, Guo XL (2016) Combinational strategies of metformin and chemotherapy in cancers. Cancer Chemother Pharmacol 78(1):13–26. https://doi.org/10.1007/s00280-016-3037-3

    Article  CAS  PubMed  Google Scholar 

  23. Mills KT, Bellows CF, Hoffman AE, Kelly TN, Gagliardi G (2013) Diabetes mellitus and colorectal cancer prognosis: a meta-analysis. Dis Colon Rectum 56(11):1304–1319. https://doi.org/10.1097/DCR.0b013e3182a479f9

    Article  PubMed  PubMed Central  Google Scholar 

  24. Noh GY, Hwang DY, Choi YH, Lee YY (2010) Effect of diabetes mellitus on outcomes of colorectal cancer. J Korean Soc Coloproctol 26(6):424–428. https://doi.org/10.3393/jksc.2010.26.6.424

    Article  PubMed  PubMed Central  Google Scholar 

  25. Meyerhardt JA, Catalano PJ, Haller DG, Mayer RJ, Macdonald JS, Benson AB 3rd, Fuchs CS (2003) Impact of diabetes mellitus on outcomes in patients with colon cancer. J Clin Oncol 21(3):433–440. https://doi.org/10.1200/JCO.2003.07.125

    Article  PubMed  Google Scholar 

  26. Feng J, Zhou X, Mao W (2011) Prognostic analysis of colorectal cancer patients with diabetes mellitus in China—the experience of a single institution. Adv Clin Exp Med 20(4):473–480

    Google Scholar 

  27. Jeon JY, Jeong DH, Park MG, Lee JW, Chu SH, Park JH, Lee MK, Sato K, Ligibel JA, Meyerhardt JA, Kim NK (2013) Impact of diabetes on oncologic outcome of colorectal cancer patients: colon vs. rectal cancer. PLoS ONE 8(2):e55196. https://doi.org/10.1371/journal.pone.0055196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bae S, Wong HL, Tie J, Desai J, Field K, Kosmider S, Fourlanos S, Jones I, Skinner I, Gibbs P (2015) Impact of diabetes status and medication on presentation, treatment, and outcome of stage II colon cancer patients. J Cancer Epidemiol 2015:189132. https://doi.org/10.1155/2015/189132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhu B, Wu X, Wu B, Pei D, Zhang L, Wei L (2017) The relationship between diabetes and colorectal cancer prognosis: a meta-analysis based on the cohort studies. PLoS ONE 12(4):e0176068. https://doi.org/10.1371/journal.pone.0176068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chubak J, Ziebell R, Greenlee RT, Honda S, Hornbrook MC, Epstein M, Nekhlyudov L, Pawloski PA, Ritzwoller DP, Ghai NR, Feigelson HS, Clancy HA, Doria-Rose VP, Kushi LH (2016) The Cancer Research Network: a platform for epidemiologic and health services research on cancer prevention, care, and outcomes in large, stable populations. Cancer Causes Control 27(11):1315–1323. https://doi.org/10.1007/s10552-016-0808-4

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ross TR, Ng D, Brown JS, Pardee R, Hornbrook MC, Hart G, Steiner JF (2014) The HMO research network virtual data warehouse: a public data model to support collaboration. EGEMS (Washington, D.C.) 2(1):1049. https://doi.org/10.13063/2327-9214.1049

    Article  Google Scholar 

  32. Deyo RA, Cherkin DC, Ciol MA (1992) Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 45(6):613–619. https://doi.org/10.1016/0895-4356(92)90133-8

    Article  CAS  PubMed  Google Scholar 

  33. Bella F, Minicozzi P, Giacomin A, Crocetti E, Federico M, Ponz de Leon M, Fusco M, Tumino R, Mangone L, Giuliani O, Budroni M, Sant M (2013) Impact of diabetes on overall and cancer-specific mortality in colorectal cancer patients. J Cancer Res Clin Oncol 139(8):1303–1310. https://doi.org/10.1007/s00432-013-1439-8

    Article  PubMed  Google Scholar 

  34. Warren JL, Yabroff KR (2015) Challenges and opportunities in measuring cancer recurrence in the United States. J Natl Cancer Inst 107:8. https://doi.org/10.1093/jnci/djv134

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Dr. Elizabeth Trice Loggers for assistance with designing the medical record abstraction instrument and providing clinical input, and Lee Barr, Kate Burniece, and Angela Plata for reviewing medical records. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers R01CA172073 (Chubak) and R50CA211115 (Bowles). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The collection of cancer incidence data used in this study was supported by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center, which is funded by Contract No. N01-CN-67009 and N01-PC-35142 from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute with additional support from the Fred Hutchinson Cancer Research Center and the State of Washington. Funders did not participate in the design, data collection, manuscript drafting, or decision to submit the manuscript for publication.

Funding

Monica Fujii reports receiving funding from a research contracts awarded to Kaiser Permanente Washington Health Research Institute from Allergan, BioDelivery Sciences, Collegium, Daiichi Sankyo, Depomed, Egalet, Endo, Janssen, Mallinckrodt, Pernix, Pfizer, Purdue, and West-Ward. Denise Boudreau reports receiving funding from research contracts awarded to Kaiser Permanente Washington Health Research Institute from Allergan, BioDelivery Sciences, Collegium, Daiichi Sankyo, Depomed, Egalet, Endo, Janssen, Mallinckrodt, Pernix, Pfizer, Purdue, and West-Ward. Onchee Yu reports receiving funding from a research grant awarded to the Kaiser Permanente Washington Health Research Institute from Bayer.

Author information

Authors and Affiliations

  1. Kaiser Permanente Washington Health Research Institute, 1730 Minor Avenue, Suite 1600, Seattle, WA, 98101, USA

    Jessica Chubak, Onchee Yu, Rebecca A. Ziebell, Erin J. Aiello Bowles, Monica M. Fujii, Denise M. Boudreau & Lu Chen

  2. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA

    Jessica Chubak, Denise M. Boudreau & James S. Floyd

  3. Kaiser Permanente Colorado Institute for Health Research, Denver, CO, USA

    Andrew T. Sterrett, Jennifer M. Boggs, Andrea N. Burnett-Hartman & Debra P. Ritzwoller

  4. School of Pharmacy, University of Washington, Seattle, WA, USA

    Denise M. Boudreau

  5. Department of Medicine, School of Medicine, University of Washington, Seattle, WA, USA

    James S. Floyd

  6. Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Rebecca A. Hubbard

Authors
  1. Jessica Chubak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Onchee Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rebecca A. Ziebell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Erin J. Aiello Bowles
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrew T. Sterrett
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Monica M. Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jennifer M. Boggs
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andrea N. Burnett-Hartman
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Denise M. Boudreau
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. James S. Floyd
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Debra P. Ritzwoller
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Rebecca A. Hubbard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jessica Chubak.

Ethics declarations

Informed consent

For this type of study, formal consent is not required.

Research involving animals

This article does not contain any studies with animals performed by any of the authors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 20 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chubak, J., Yu, O., Ziebell, R.A. et al. Risk of colon cancer recurrence in relation to diabetes. Cancer Causes Control 29, 1093–1103 (2018). https://doi.org/10.1007/s10552-018-1083-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-018-1083-3

Keywords

Search

Navigation