Skip to main content
Top

15-01-2018 | Colorectal cancer | Article

Diabetes, Obesity, and the Metabolic Syndrome as Prognostic Factors in Stages I to III Colorectal Cancer Patients

Journal: Journal of Gastrointestinal Cancer

Authors: Brianna Croft, Melissa Reed, Caitlyn Patrick, Natalie Kovacevich, Ioannis A. Voutsadakis

Publisher: Springer US

Abstract

Background

Attempts to introduce prognostic factors for survival outcomes in localized colorectal cancer patients receiving surgical treatment with or without adjuvant therapies, beyond the classic staging parameters, have been met with limited success. Obesity and diabetes mellitus are among the conditions that predispose to colorectal cancer but their value as prognostic markers once the disease is diagnosed is controversial.

Patients and Methods

This study examines the prognostic value of the components of metabolic syndrome in a retrospective series of colorectal cancer patients with stages I to III disease followed in a single center.

Results

Among the four components of the metabolic syndrome, only diabetes was independently associated with progression-free survival (PFS) while obesity, hypertension, and dyslipidemia were not. No associations of the metabolic syndrome (MS) or its components with overall survival (OS) were observed in multivariate analysis.

Conclusion

These data pinpoint to diabetes mellitus (DM) as a possible prognostic factor for PFS in localized colorectal cancer and further cast doubt for the value of obesity as measured by body mass index (BMI) on local stage colorectal cancer prognosis.
Literature
1.
Kinzler LW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell. 1996;87(2):159–70. https://​doi.​org/​10.​1016/​S0092-8674(00)81333-1.CrossRefPubMed
2.
Voutsadakis IA. Pathogenesis of colorectal carcinoma and therapeutic implications: the roles of the ubiquitin-proteasome system and Cox-2. J Cell Mol Med. 2007;11(2):252–85. https://​doi.​org/​10.​1111/​j.​1582-4934.​2007.​00032.​x.CrossRefPubMedPubMedCentral
3.
Ansary Moghaddam A, Woodward M, Huxley R. Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomark Prev. 2007;16:2533–47.CrossRef
4.
Yuhara H, Steinmaus C, Cohen SE, Corley DA, Tei Y, Buffler PA. Is diabetes mellitus an independent risk factor for colon cancer and rectal cancer? Am J Gastroenterol. 2011;106(11):1911–22. https://​doi.​org/​10.​1038/​ajg.​2011.​301.CrossRefPubMedPubMedCentral
5.
Voutsadakis IA Obesity and diabetes as prognostic factors in patients with colorectal cancer. Diab Metab Syndr. 2017;11(Suppl 1):S109–S114. https://​doi.​org/​10.​1016/​j.​dsx.​2016.​12.​018.
6.
Pais R, Silaghi H, Silaghi AC, et al (2009) Metabolic syndrome and risk of subsequent colorectal cancer. World J Gastroenterol 15:5141–5148.
7.
Sinicrope FA, Foster NR, Yothers G, Benson A, Seitz JF, Labianca R, et al. Body mass index at diagnosis and survival among colon cancer patients enrolled in clinical trials of adjuvant chemotherapy. Cancer. 2013;119(8):1528–36. https://​doi.​org/​10.​1002/​cncr.​27938.CrossRefPubMedPubMedCentral
8.
Yang Y, Mauldin PD, Ebeling M, Hulsey TC, Liu B, Thomas MB, et al. Effect of metabolic syndrome and its components on recurrence and survival in colon cancer patients. Cancer. 2013;119(8):1512–20. https://​doi.​org/​10.​1002/​cncr.​27923.CrossRefPubMed
9.
Amptoulach S, Gross G, Kalaitzakis E (2015) Differential impact of obesity and diabetes mellitus on survival after liver resection for colorectal cancer metastases. J Surg Res 199: 378–385.
10.
Ottaiano A, Nappi A, Tafuto S et al (2016) Diabetes and body mass index are associated with neuropathy and prognosis in colon cancer patients treated with capecitabine and oxaliplatin adjuvant chemotherapy. Oncologia 90: 36–42.
11.
Peng F, Hu D, Lin X, Chen G, Liang B, Zhang H, et al. Preoperative metabolic syndrome and prognosis after radical resection for colorectal for colorectal cancer: the Fujian prospective investigation of cancer (FIESTA) study. Int J Cancer. 2016;139(12):2705–13. https://​doi.​org/​10.​1002/​ijc.​30404.CrossRefPubMed
12.
You J, Liu W-Y, Zhu G-Q. Metabolic syndrome contributes to an increased recurrence risk of non-metastatic colorectal cancer. Oncotarget. 2015;6(23):19880–90. https://​doi.​org/​10.​18632/​oncotarget.​4166.CrossRefPubMedPubMedCentral
13.
Ahmadi A, Noroozi M, Pourhoseingholi MA, Hashemi-Nazari S-S. Effect of metabolic syndrome and its components on survival in colorectal cancer: a prospective study. J Renal Inj Prev. 2015;4(1):15–9. https://​doi.​org/​10.​12861/​jrip.​2015.​05.CrossRefPubMedPubMedCentral
14.
Zhu B, Wu X, Wu B, Pei D, Zhang L, Wei L. The relationship between diabetes and colorectal cancer prognosis: a meta-analysis based on the cohort studies. PLoS One. 2017;12(4):e0176068. https://​doi.​org/​10.​1371/​journal.​pone.​0176068.CrossRefPubMedPubMedCentral
15.
Meyerhardt JA, Niedzwiecki D, Hollis D, et al. Impact of body mass index and weight change after treatment on cancer recurrence and survival in patients with stage III colon cancer: findings from cancer and leukemia group B 89803. J Clin Oncol. 2008;26:4109–15.CrossRefPubMedPubMedCentral
16.
Dignam JJ, Poitre BN, Yothers G, et al. Body mass index and outcomes in patients who receive adjuvant chemotherapy for colon cancer. J Natl Cancer Inst. 2006;98(22):1647–54. https://​doi.​org/​10.​1093/​jnci/​djj442.CrossRefPubMed
17.
Siegel EM, Ulrich CM, Poole EM, Holmes RS, Jacobsen PB, Shibata D. The effects of obesity and obesity-related conditions on colorectal cancer prognosis. Cancer Control. 2010;17(1):52–7. https://​doi.​org/​10.​1177/​1073274810017001​07.CrossRefPubMed
18.
Sinicrope FA, Foster NR, Sargent DJ, O'Connell MJ, Rankin C. Obesity is an independent prognostic variable in colon cancer survivors. Clin Cancer Res. 2010;16(6):1884–93. https://​doi.​org/​10.​1158/​1078-0432.​CCR-09-2636.CrossRefPubMedPubMedCentral
19.
Anderson BJ, Wahlquist AE, Hill EG, Marshall DT, Kimchi ET, Staveley O'Carroll KF, et al. The impact of metabolic syndrome on outcome and response to neoadjuvant chemoradiation in locally advanced rectal cancer patients. Int J Surg. 2016;33:8–12. https://​doi.​org/​10.​1016/​j.​ijsu.​2016.​07.​011.CrossRefPubMedPubMedCentral
20.
Fransgaard T, Thygesen LC, Gögenur I. Metformin increases overall survival in patients with diabetes undergoing surgery for colorectal cancer. Ann Surg Oncol. 2016;23(5):1569–75. https://​doi.​org/​10.​1245/​s10434-015-5028-8.CrossRefPubMed
21.
Ramjeesingh R, Orr C, Bricks CS, et al. A retrospective study on the role of diabetes and metformin in colorectal cancer disease survival. Curr Oncol. 2016;23:e116–22.CrossRefPubMedPubMedCentral
22.
Mei Z-B, Zhang Z-J, Liu C, et al. Survival benefits of metformin for colorectal cancer patients with diabetes: a systematic review and meta-analysis. PLoS One. 2014;9(3):e91818. https://​doi.​org/​10.​1371/​journal.​pone.​0091818.CrossRefPubMedPubMedCentral
23.
Vigneri PG, Tirrò E, Pennisi MS, et al. The insulin/IGF system in colorectal cancer development and resistance to therapy. Front Oncol. 2015;5:230.CrossRefPubMedPubMedCentral
24.
Yao C, Su L, Shan J, Zhu C, Liu L, Liu C, et al. IGF/ STAT3/ NANOG/ slug signaling axis simultaneously controls epithelial-mesenchymal transition and stemness maintenance in colorectal cancer. Stem Cells. 2016;34(4):820–31. https://​doi.​org/​10.​1002/​stem.​2320.CrossRefPubMed
25.
Li H, Singh Batth I, Qu X, et al. IGF-IR signaling in epithelial to mesenchymal transition and targeting IGF-IR therapy: overview and new insights. Mol Cancer. 2017;16(6):6. https://​doi.​org/​10.​1186/​s12943-016-0576-5.CrossRefPubMedPubMedCentral
26.
Tudzarova S, Osman MA. The double trouble of metabolic diseases: the diabetes-cancer link. Mol Biol Cell. 2015;26(18):3129–39. https://​doi.​org/​10.​1091/​mbc.​E14-11-1550.CrossRefPubMedPubMedCentral