The Impact of Diabetes Mellitus on the Second Primary Malignancies in Colorectal Cancer Patients

Abstract

IntroductionAll colorectal cancer (CRC) survivors have an increased risk of developing second primary malignancies (SPMs). The association between diabetes mellitus (DM) and the risk of cancer is well known. However, the role of DM and its therapy in the development of SPMs in CRC patients is not well described.MethodsIn this single-institutional retrospective analysis we identified 1,174 colorectal carcinoma patients, median follow-up 10.1 years, (median age 63 years, 724 men). All patients over 18 years with histologically confirmed CRC who were admitted in the period 1.1. 2003- 31.12.2013 and followed-up till 31.12. 2018 at the Masaryk Memorial Cancer Institute (MMCI) were screened for eligibility. The exclusion criteria were CRC diagnosed at autopsy, lost to follow-up and high risk of development of SPMs due to hereditary cancer syndrome. Tumours are considered multiple primary malignancies if arising in different sites and/or are of a different histology or morphology group. Comparisons of the basic characteristics between the patients with SPM and the patients without SPM were performed as well as comparison of the occurrence of SPMs by the site of diagnosis between the DM and non-DM cohorts and survival analyses.ResultsA SPM was diagnosed in 234 (20%) patients, DM in 183 (15%) patients. DM was diagnosed in 22.6% of those with SPM vs. in 13.8% of those without SPM (p=0.001). The most common types of SPMs in DM patients were other CRC, kidney, lung, bladder and nonmelanoma skin cancer, but only carcinoma of the liver and bile duct tracts was significantly more common than in the group without DM. Although breast cancer was the second most common in the group with DM, its incidence was lower than in the group without DM, as well as prostate cancer. A significantly higher incidence of SPMs was found in older CRC patients (≥ 65 years) and in those with lower stage colon cancer and DM. No significant difference in DM treatment between those with and without a SPM was observed including analysis of type of insulin.ConclusionCRC patients with diabetes mellitus, especially those with older age, and early stages of colon cancer, should be screened for second primary malignancies more often than the standard population. Patients without DM have longer survival. According to the occurrence of the most common second malignancies, a clinical examination, blood count, and ultrasound of the abdomen is appropriate, together with standard breast and colorectal cancer screening, and lung cancer screening under certain conditions, and should be recommended in CRC survivors especially in patients with intercurrent DM, however the necessary frequency of screening remains unclear.

Improvement of Diabetes Mellitus After Colorectal Cancer Surgery: A Retrospective Study of Predictive Factors For Type 2 Diabetes Mellitus Remission and Overall Survival

“…Patients might benefit from dietary adjustments, sodium restriction, more exercise and lower alcohol consumption; therefore, T2DM might improve when the lifestyle of patients is modified after CRC surgery. Pre-existing T2DM patients have a higher rate of developing other second primary malignancies (30), and a worse overall survival after CRC surgery (11,30). A meta-analysis also reported decreased survival and increased risk of relapse in patients with concurrent CRC and T2DM (11).…”

“…Pre-existing T2DM patients have a higher rate of developing other second primary malignancies ( 30 ), and a worse overall survival after CRC surgery ( 11 , 30 ). A meta-analysis also reported decreased survival and increased risk of relapse in patients with concurrent CRC and T2DM ( 11 ).…”

Use of Hypolipidemic Drugs and the Risk of Second Primary Malignancy in Colorectal Cancer Patients

“…In a previous analysis, we showed that diabetes mellitus is a negative prognostic factor in CRC patients with an SPM [ 76 ], and our current analysis suggests that the use of statins or the treatment of hyperlipidemia itself might also be predictive of cancer patients’ outcomes. To the best of our knowledge, this is the first article evaluating the association between hypolipidemic treatment and the development of SPMs in colorectal cancer patients.…”

Clinical characteristics of second primary malignancies among first primary malignancy survivors: A single‑center study, 2005‑2020

“…Diabetes, hypertension and family history of malignancy were also analyzed in the present study and, in contrast to previous studies ( 37 , 38 ), no differences were observed in these factors according to whether the patients had an SPM or not. However, the proportion of patients with a biliary tract or thyroid disease was significantly higher for patients with an SPM than those without.…”