Sex- and site-specific differences in colorectal cancer risk among people with type 2 diabetes

Overbeek, Jetty A.; Kuiper, Josephina G.; Heijden, Amber A. W. A. van der; Labots, Mariëtte; Haug, Ulrike; Herings, Ron M. C.; Nijpels, Giel

doi:10.1007/s00384-018-3191-7

Cited by 27 publications

(26 citation statements)

References 29 publications

(51 reference statements)

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“…Statin users had a decreased risk of colorectal cancer compared with nonstatin users ( 13 ). Patients with diabetes, consistent with Overbeek et al ( 22 ), have an increased risk of developing colorectal cancer; however, the study did not account for smoking status nor BMI in estimating models as we did. Unlike Mamtani et al, we found an increased total serum cholesterol to be associated with an increased hazard of colorectal cancer similar to another study ( 13 , 23 ).…”

Section: Discussionsupporting

confidence: 65%

The Association Between Phosphodiesterase-5 Inhibitors and Colorectal Cancer in a National Cohort of Patients

Sutton

Magagnoli

Cummings

et al. 2020

Clinical and Translational Gastroenterology

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INTRODUCTION: To examine the association between phosphodiesterase-5 (PDE-5) inhibitor use and incidence of colorectal cancer among patients with erectile dysfunction treated in the Veterans Affairs (VA) Healthcare System. METHODS: A retrospective cohort study using the Veterans Affairs Informatics and Computing Infrastructure was conducted, with data spanning January 2001–December 2016. Patients were followed up from index until (i) the first diagnosis of colorectal cancer, (ii) death, or (iii) the end of study period. Statistical analyses evaluated demographics and baseline characteristics between cohorts (PDE-5 exposed or not) and the effect of additional dosages of each specific PDE-5 inhibitor using adjusted multivariate Cox proportional hazards models. RESULTS: A total of 221,538 patients met the study inclusion criteria, 192,691 patients in the PDE-5 cohort and 29,227 patients in the never use PDE-5 cohort. The multivariate Cox proportional hazards model results revealed that the those who had any exposure to a PDE-5 inhibitor have an 18% lower hazard of colorectal cancer (adjusted hazard ratio [HR] = 0.816, 95% confidence interval [CI] = 0.754–0.882). For each additional 100-mg dosage of sildenafil and 10-mg dosage of tadalafil, the hazard of colorectal cancer is reduced by 2.4% (adjusted HR = 0.976, 95% CI = 0.973–0.979) and 1.7% (adjusted HR = 0.983, 95% CI = 0.972–0.996), respectively. DISCUSSION: PDE-5 inhibitor usage in patients with erectile dysfunction is associated with a lower hazard of colorectal cancer compared with patients not exposed to PDE-5 inhibitors.

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Section: Discussionsupporting

confidence: 65%

The Association Between Phosphodiesterase-5 Inhibitors and Colorectal Cancer in a National Cohort of Patients

Sutton

Magagnoli

Cummings

et al. 2020

Clinical and Translational Gastroenterology

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“…Site-speci c difference of CRC risk among people with T2DM has been reported previously [22]. TP53 mutation was observed in distal colon and rectal tumors at higher frequencies, while it was observed in proximal tumors at lower frequencies [23].…”

Section: Discussionsupporting

confidence: 58%

Diabetes associated with abnormal p53 immunohistochemical patterns in colorectal cancer

Yang

et al. 2020

Preprint

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Background Previous study has suggested a link between diabetes and colorectal cancer (CRC), but the specific molecule for the link has not been well-understood. Abnormal p53 immunohistochemical (IHC) pattern is an accurate predictor for TP53 gene mutation. The present study aimed to investigate the relationship between type 2 diabetes mellitus (T2DM) and p53 IHC patterns in CRC. Methods We analyzed p53 protein expression of 742 cases of CRC with radical colectomy by immunohistochemistry. The patients were grouped into subsets of non-diabetes (n = 570) and diabetes (n = 172), and further divided into subgroups of 1 normal p53 IHC pattern (p53 wild type or WT) and 3 abnormal p53 IHC patterns which included heterogeneous pattern (HT), overexpression (OE) and complete absence (CA). Results The ratios of p53 abnormal pattern in groups of T2DM and non-T2DM were 70.9% and 50.9% (P < 0.001). Univariately, groups of both T2DM and prediabetes (FPG: 6.1 ~ 6.9 mmol/L) were significantly associated with abnormal p53 pattern, compared with normal FPG control (P < 0.05 and P < 0.001). Moreover, T2DM was significantly associated with abnormal p53 patterns in cases with microsatellite instability (MSI) stable (MSS)/MSI-low phenotype (P < 0.001) and distal colon/rectum location, but not in cases with MSI-high phenotype and proximal colon location (P > 0.05). Multivariate analysis retained the above significance. Furthermore, abnormal p53 IHC patterns were positively associated with risk of lymph node metastasis and high tumor-node-metastasis (TNM) stage of CRC, which suggested a link between the abnormal p53 IHC patterns and aggressive clinical outcome. Conclusion Diabetes is associated with risk of abnormal p53 IHC patterns in CRC. It was suggested that diabetes might influence carcinogenesis, progression and prognosis via inducing TP53 mutation and abnormal p53 expression in CRC.

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“…While the mediating factors for this sex difference need further study (e.g., history of GDM, which was outside of the scope of this review), the increased prevalence of diabetes among women in some LatAm countries would be expected to have implications for health and health care, and potentially future generations [ 267 – 269 ]. Since diabetes may increase women’s risk for CVD, including stroke [ 270 ], cognitive decline [ 271 , 272 ], or some cancers [ 273 , 274 ], timely and comprehensive preventive care for women of all ages would need to be prioritized.…”

Section: Additional Observationsmentioning

confidence: 99%

Current State of Diabetes Mellitus Prevalence, Awareness, Treatment, and Control in Latin America: Challenges and Innovative Solutions to Improve Health Outcomes Across the Continent

et al. 2020

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Purpose of Review Latin America is the scenario of great inequalities where about 32 million human beings live with diabetes. Through this review, we aimed at describing the current state of the prevalence, awareness, treatment, and control of diabetes mellitus and completion of selected guidelines of care across Latin America and identify opportunities to advance research that promotes better health outcomes. Recent Findings The prevalence of diabetes mellitus has been consistently increasing across the region, with some variation: higher prevalence in Mexico, Haiti, and Puerto Rico and lower in Colombia, Ecuador, Dominican Republic, Peru, and Uruguay. Prevalence assessment methods vary, and potentially underestimating the real number of persons with diabetes. Diabetes unawareness varies widely, with up to 50% of persons with diabetes who do not know they may have the disease. Glycemic, blood pressure, and LDL-C control and completion of guidelines to prevent microvascular complications are not consistently assessed across studies, and the achievement of control goals is suboptimal. On the other hand, multiple interventions, point-of-care/rapid assessment tools, and alternative models of health care delivery have been proposed and tested throughout Latin America. Summary The prevalence of diabetes mellitus continues to rise across Latin America, and the number of those with the disease may be underestimated. However, some local governments are embedding more comprehensive diabetes assessments in their local national surveys. Clinicians and public health advocates in the region have proposed and initiated various multi-level interventions to address this enormous challenge in the region. Keywords Latin America. Diabetes prevalence. Diabetes treatment. Control. Diabetes complications. Interventions. Health care This article is part of the Topical Collection on Diabetes Epidemiology

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Sex- and site-specific differences in colorectal cancer risk among people with type 2 diabetes

Cited by 27 publications

References 29 publications

The Association Between Phosphodiesterase-5 Inhibitors and Colorectal Cancer in a National Cohort of Patients

The Association Between Phosphodiesterase-5 Inhibitors and Colorectal Cancer in a National Cohort of Patients

Diabetes associated with abnormal p53 immunohistochemical patterns in colorectal cancer

Current State of Diabetes Mellitus Prevalence, Awareness, Treatment, and Control in Latin America: Challenges and Innovative Solutions to Improve Health Outcomes Across the Continent

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