Skip to main content

Impact of diabetes on overall and cancer-specific mortality in colorectal cancer patients

Abstract

Purpose

Diabetes is associated with increased risk of developing colorectal cancer (CRC), but its effect on overall and cancer-specific mortality in CRC patients has been little investigated. The aim of this study was to assess the influence of diabetes on overall and cancer-specific mortality in Italian CRC patients.

Methods

Cases of adult (≥15 years) CRC, diagnosed in 2003–2005, most followed-up to the end of 2008, were randomly selected from the Italian Cancer Registries database. Diabetic status, sex, age, tumor stage, subsite, treatment, morphology, and grade were obtained by consultation of patient clinical records. Poisson multivariable regression models, adjusted for potential confounding variables, were used to estimate hazard ratios (HRs) for all-cause and CRC-specific mortality, according to diabetic status.

Results

A total of 1,039 CRC cases with known fasting glucose or diabetic status, archived in 7 cancer registries, was analyzed. Compared to non-diabetics, diabetics (specific diagnosis or glucose ≥126 mg/dl) were older and less likely to receive adjuvant therapy. Diabetics were at higher risk of all-cause death [HR 1.41; 95 % confidence interval (CI) 1.18–1.70] and CRC death (HR 1.36; 95 % CI 1.11–1.67), with no differences by sex or subsite.

Conclusions

Diabetes was significantly associated with increased overall and CRC-specific mortality. Our findings indicate that diabetes is a negative prognostic factor for CRC and suggest that in patients with CRC, diabetes prevention and treatments that stabilize the condition and control its complications might reduce mortality. Further studies are required to ascertain the mechanisms linking diabetes to greater mortality in CRC patients.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  • Agresti A (2002) Categorical data analysis, 2nd edn. Wiley, New York

    Book  Google Scholar 

  • AIRTUM Working Group, Crocetti E, Buzzoni C (2009) New incidence and mortality data 2003–2005. Epidemiol e Prev 33:e1–3–e5–26

    Google Scholar 

  • Berrino F, Sant M, Verdecchia A, Capocaccia R, Hakulinen T, Esteve J (Eds) (1995) Survival of cancer patients in Europe. The EUROCARE study. IARC Scientific Publication No 132. International Agency for Research on Cancer, Lyon

  • Booth GL, Kapral MK, Fung K, Tu JV (2006) Relation between age and cardiovascular disease in men and women with diabetes compared with non-diabetic people: a population-based retrospective cohort study. Lancet 368:29–36

    PubMed  Article  Google Scholar 

  • 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 159:1160–1167

    PubMed  Article  Google Scholar 

  • De Marco MF, Janssen-Heijnen ML, van der Heijden LH, Coebergh JW (2000) Comorbidity and colorectal cancer according to subsite and stage: a population-based study. Eur J Cancer 36:95–99

    PubMed  Article  Google Scholar 

  • 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 1:53–59. doi:10.1200/JCO.2011.38.0303

    Article  Google Scholar 

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

    Article  Google Scholar 

  • EUROCARE (2013) Survival of cancer patients in Europe. http://www.eurocare.it. Accessed 01 March 2013

  • Ferlay J, Parkin DM, Steliarova-Foucher E (2010) Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46:765–781. doi:10.1016/j.ejca.2009.12.014

    PubMed  Article  CAS  Google Scholar 

  • Fritz A, Percy C, Jack A, Shanmugaratnam K, Sobin LH, Parkin MD, Whelan S (2000) International classification of disease for oncology (ICD-O), 3rd edn. World Health Organization, Geneva

    Google Scholar 

  • Gatta G, Ciccolallo L, Capocaccia R, Coleman MP, Hakulinen T, Møller H, Berrino F, EUROCARE Working Group (2003) Differences in colorectal cancer survival between European and US populations: the importance of sub-site and morphology. Eur J Cancer 39:2214–2222

    PubMed  Article  CAS  Google Scholar 

  • Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG, Yee D (2010) Diabetes and cancer: a consensus report. Diabetes Care 33:1674–1685. doi:10.2337/dc10-0666

    PubMed  Article  Google Scholar 

  • Gross CP, Guo Z, McAvay GJ, Allore HG, Young M, Tinetti ME (2006) Multimorbidity and survival in older persons with colorectal cancer. J Am Geriatr Soc 54:1898–1904

    PubMed  Article  Google Scholar 

  • Huang YC, Lin JK, Chen WS, Lin TC, Yang SH, Jiang JK, Chang SC, Lan YT, Wang HS, Liu CY, Yang YW, Teng HW (2011) Diabetes mellitus negatively impacts survival of patients with colon cancer, particularly in stage II disease. J Cancer Res Clin Oncol 137:211–220. doi:10.1007/s00432-010-0879-7

    PubMed  Article  Google Scholar 

  • 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:e55196. doi:10.1371/journal.pone.0055196

    PubMed  Article  CAS  Google Scholar 

  • Jullumstrø E, Kollind M, Lydersen S, Edna TH (2009) Diabetes mellitus and outcomes of colorectal cancer. Acta Oncol 48:361–367. doi:10.1080/02841860802637765

    PubMed  Article  Google Scholar 

  • Kaplan E, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481

    Article  Google Scholar 

  • Khandwala HM, McCutcheon IE, Flyvberg A, Friend KE (2000) The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev 21:215–244

    PubMed  Article  CAS  Google Scholar 

  • Landriscina M, Esposito F (2011) Insulin resistant conditions: a favorable milieu for aggressive drug-resistant malignancies. J Gastrointest Oncol 2:11–12. doi:10.3978/j.issn.2078-6891.2011.004

    PubMed  Google Scholar 

  • Lee L, Cheung WY, Atkinson E, Krzyzanowska MK (2011) Impact of comorbidity on chemotherapy use and outcomes in solid tumors: a systematic review. J Clin Oncol 29:106–117. doi:10.1200/JCO.2010.31.3049

    PubMed  Article  Google Scholar 

  • Lemmens VE, Janssen-Heijnen ML, Houterman S, Verheij KD, Martijn H, van de Poll-Franse L, Coebergh JW (2007) Which comorbid conditions predict complications after surgery for colorectal cancer? World J Surg 31:192–199

    PubMed  Article  Google Scholar 

  • 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 21:433–440

    PubMed  Article  Google Scholar 

  • Park SM, Lim MK, Shin SA, Yun YH (2006) Impact of prediagnosis smoking, alcohol, obesity, and insulin resistance on survival in male cancer patients: national Health Insurance Corporation Study. J Clin Oncol 24:5017–5024

    PubMed  Article  Google Scholar 

  • Polednak AP (2006) Comorbid diabetes mellitus and risk of death after diagnosis of colorectal cancer: a population-based study. Cancer Detect Prev 30:466–472

    PubMed  Article  Google Scholar 

  • Pollak M (2008) Insulin and insulin-like growth factor signaling in neoplasia. Nat Rev Cancer 8:915–928

    PubMed  Article  CAS  Google Scholar 

  • Roncucci L, Fante R, Losi L, Di Gregorio C, Micheli A, Benatti P, Madenis N, Ganazzi D, Cassinadri MT, Lauriola P, Ponz de Leon M (1996) Survival for colon and rectal cancer in a population-based cancer registry. Eur J Cancer 32:295–302

    Article  Google Scholar 

  • Schrag D, Cramer LD, Bach PB, Begg CB (2001) Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst 93:850–857

    PubMed  Article  CAS  Google Scholar 

  • Shonka NA, Anderson JR, Panwalkar AW, Reed EC, Steen PD, Ganti AK (2006) Effect of diabetes mellitus on the epidemiology and outcomes of colon cancer. Med Oncol 23:515–519

    PubMed  Article  Google Scholar 

  • Sobin LH, Wittekind CH (2002) Colon and rectum. In: Sobin LH, Wittekind CH (eds) Classification of malignant tumours, 6th edn. Wiley-Liss, Geneva, pp 72–76

  • StataCorp: Stata Statistical Software: Release 9 (2005) StataCorp LP. College Station, TX

  • Thomas RM, Sobin LH (1995) Gastrointestinal cancer. Cancer 75:154–170

    PubMed  Article  CAS  Google Scholar 

  • van de Poll-Franse LV, Houterman S, Janssen-Heijnen ML, Dercksen MW, Coebergh JW, Haak HR (2007) Less aggressive treatment and worse overall survival in cancer patients with diabetes: a large population based analysis. Int J Cancer 120:1986–1992

    PubMed  Article  Google Scholar 

  • van de Poll-Franse LV, Haak HR, Coebergh JW, Janssen-Heijnen ML, Lemmens VE (2012) Disease-specific mortality among stage I-III colorectal cancer patients with diabetes: a large population-based analysis. Diabetologia 55:2163–2172. doi:10.1007/s00125-012-2555-8

    PubMed  Article  Google Scholar 

  • Vrieling A, Kampman E (2010) The role of body mass index, physical activity, and diet in colorectal cancer recurrence and survival: a review of the literature. Am J Clin Nutr 92:471–490. doi:10.3945/ajcn.2010.29005

    PubMed  CAS  Google Scholar 

  • Will JC, Galuska DA, Vinicor F, Calle EE (1998) Colorectal cancer: another complication of diabetes mellitus? Am J Epidemiol 147:816–825

    PubMed  Article  CAS  Google Scholar 

  • Woodward M, Zhang X, Barzi F, Pan W, Ueshima H, Rodgers A, MacMahon S, Asia Pacific Cohort Studies Collaboration (2003) The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific region. Diabetes Care 26:360–366

    PubMed  Article  CAS  Google Scholar 

  • World Health Organization (2004) International classification of diseases (ICD) 10th revision, 2nd edn. World Health Organization, Geneva

    Google Scholar 

  • World Health Organization (2006) Definition and diagnosis of diabetes mellitus and intermediate hyperglicaemia report of aWHO/IDF consultation. World Health Organization, Geneva

    Google Scholar 

  • Yancik R, Wesley MN, Ries LA, Havlik RJ, Long S, Edwards BK, Yates JW (1998) Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients: a population-based study. Cancer 82:2123–2134

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank the Compagnia di San Paolo, the Fondazione Cariplo, Italy and the Centro Nazionale per la Prevenzione e il Controllo delle Malattie of the Italian Ministry of Health for supporting this research; Chiara Margutti for secretarial assistance; Carlotta Buzzoni and AIRTUM for contributing to study design and providing data; and Don Ward for help with the English.

Conflict of interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Francesca Bella.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bella, F., Minicozzi, P., Giacomin, A. et al. Impact of diabetes on overall and cancer-specific mortality in colorectal cancer patients. J Cancer Res Clin Oncol 139, 1303–1310 (2013). https://doi.org/10.1007/s00432-013-1439-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-013-1439-8

Keywords

  • Colorectal cancer
  • Cancer-specific mortality
  • Survival
  • Diabetes
  • Prognosis