Glucose Intolerance and Cancer Risk: A Community-Based Prospective Cohort Study in Shanghai, China

Abstract

BackgroundCancer becomes the leading cause of premature death in China. Primary objective of this study was to determine the major risk factors especially glucose intolerance for cancer prophylaxis.MethodsA cluster sampling method was applied to enroll 10,657 community-based adults aged 15-92 years in Shanghai, China in 2013. A structured questionnaire and physical examination were applied in baseline survey. Prediabetes was diagnosed using 75-g oral glucose tolerance test. After excluding 1433 subjects including 224 diagnosed with cancer before and 1 year after baseline survey, the remaining 9,224 subjects were followed-up to December 31, 2020.ResultsA total of 502 new cancer cases were diagnosed. The cancer incidence was 10.29, 9.20, and 5.95/1,000 person-years in diabetes patients, those with prediabetes, and healthy participants, respectively (p<0.001). The multivariate Cox regression analysis indicated that age, prediabetes and diabetes, were associated with an increased risk of cancer in those <65 years, the hazard ratios (95% confidence interval) for prediabetes and diabetes were, 1.49(1.09-2.02) and 1.51(1.12-2.02), respectively. Glucose intolerance (prediabetes and diabetes) were associated with increased risks of stomach cancer, colorectal cancer, and kidney cancer in those <65 years. Anti-diabetic medications reduced the risk of cancer caused by diabetes. The multivariate Cox analysis showed that age, male, <9 years of education, and current smoking were associated with increased risks of cancer in those ≥65 years independently.ConclusionsGlucose intolerance is the prominent cancer risk factor in adults <65 years. Lifestyle intervention and medications to treat glucose intolerance help prevent cancer in this population.

Cancer Evo–Dev: A Theory of Inflammation-Induced Oncogenesis

“…Inflammation-induced mutation, stemness, and changes in metabolism are common events in the evolutionary process of different cancer types caused by factors including chronic infection and metabolic syndrome ( 47 , 116 , 117 ). These common issues, including somatic mutation, epigenetic modification, activation of inflammation, and signaling pathway of stemness, could be the key events at the early stage of cancer evolution.…”

“…Pollution, metabolic syndrome, physical inactivity, and adverse psychosocial exposure also promote the development of cancers via inducing chronic low-grade inflammation (41)(42)(43)(44)(45)(46)(47)(48)(49). Environmental and psychosocial factors and nutrition contribute mostly, either with a causative or a promotional role to increased low-grade smoldering chronic inflammation, especially in aged population (44).…”

“…The development of metabolic syndrome is attributed to the chronic low-grade inflammation that occurs in metabolic tissues including the liver (45). People with glucose intolerance, sedentary behavior, obesity, and lower physical activity levels have higher levels of circulating inflammatory factors that have been associated with increased risks of different cancer types (liver, endometrial, colorectal, esophageal, renal, pancreatic, gastric cardia, ovarian, meningioma, postmenopausal breast, multiple myeloma, gallbladder, thyroid, and lung) (46)(47)(48). Inflammation can be classified as "good" and "bad" inflammation.…”

Krebsrisiko bei Prädiabetes und Typ-2-Diabetes mellitus

“…Ursächlich werden von vielen Experten insbesondere die Diabetes-und die Adipositaspandemie mit ins Feld geführt [17,32,43,45]. Prädiabetes und T2D steigern das Darmkrebsrisiko im Allgemeinen auf bis das Zweifache [6,12,19,46], bei Erwachsenen unter 65 auf bis das Fünffache [45]. Oftmals tritt der Prädiabetes aber nicht isoliert auf, sondern ist vergesellschaftet mit weiteren Komponenten des metabolischen Syndroms.…”

“…Als Ursache gelten steigende Prävalenzen des Barrett-Ösophagus, der Refluxkrankheit, von übermäßigem Körpergewicht als auch von Prädiabetes und T2D [76]. Beide sind Risikofaktoren für Adenokarzinome der Speiseröhre, des ösophagogastralen Übergangs und der Magenkardia [6,12,14,77,78].…”