Insulin resistance and cancer: epidemiological evidence. Endocr Relat Cancer 19(5):F1-F8

Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
Cancer Science (Impact Factor: 3.52). 02/2010; 101(5):1073-9. DOI: 10.1111/j.1349-7006.2010.01521.x
Source: PubMed


Over the last 60 years, Japanese people have experienced a rapid and drastic change in lifestyle, including diet. Suspicions have been raised that so-called ‘Westernization’, characterized by a high-calorie diet and physical inactivity, is associated with increasing trends in the incidence of cancer of the colon, liver, pancreas, prostate, and breast, as well as type 2 diabetes. Epidemiological evidence from our prospective study, the Japan Public Health Center-based Prospective (JPHC) study, and systematic literature reviews generally support the idea that factors related to diabetes or insulin resistance are associated with an increased risk of colon (mostly in men), liver, and pancreatic cancers. These cancers are inversely associated with physical activity and coffee consumption, which are known to decrease the risk of type 2 diabetes. The suggested mechanism of these effects is that insulin resistance and the resulting chronic hyperinsulinemia and increase in bioavailable insulin-like growth factor 1 (IGF1) stimulate tumor growth. In contrast, associations with diabetes are less clear for cancer of the colon in women, and breast and prostate, which are known to be related to sex hormones. The effect of insulin resistance or body fat on sex-hormone production and bioavailability may modify their carcinogenic effect differently from cancers of the colon in men, and liver and pancreas. In conclusion, there is substantial evidence to show that cancers of the colon, liver, and pancreas are associated with insulin resistance, and that these cancers can be prevented by increasing physical activity, and possibly coffee consumption.
(Cancer Sci 2010; 101: 1073–1079)

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    • "All environmental factors potentially involved in the occurrence of obesity, T2DM, insulin resistance Fetal malnutrition during pregnancy [46] [57] EDCs [76,80–85,87–89] Prenatal exposure to air pollution [26] [27] [28] T2DM [4] Insulin resistance [14] [16] [15] Acute pancreatitis Obesity [17] [110] Alcohol, current tobacco use [8] Hypertryglyceridemia [185] Organophosphorus pesticides [187] [188] [189] [190] [191] Hypercalcemia [186] Anticholinesterase insecticides [192] [193] Gallstones, biliary sludge [99] [7] Glyphosate [194] Organic solvents, pentachlorophenol [18] [195] Chronic pancreatitis Obesity [196] [21] Alcohol, current tobacco use [8] Celiac diasease [197] Occupational chemicals [19] [20] [21] Nutritional factors and rare metabolic factors [198] Pancreatic cancer Obesity [8,111–114,119,121,123,124] Current tobacco use [8] Chronic pancreatitis [199] Alcohol [8] Diabetes [200] Residence close to metal industries [24] Inherited familial disorders [201] [202] POPs [157] [158] [159] [160] [161] Long-life duration of obesity [119] Arsenic [167] [168] [169] [170] Insulin resistance [125] [126] Cadmium [171,169,172–175,123] Insulin-like growth factors and adipokines [127] [128] Lead [169] Fatty pancreas [135] Pancreatic islet/β-cell damage and dysfunction Nutritional conditions [203] Particulates of less than 10 μm (PM10) Maternally derived gut microbiota [204] Nitrogen oxides, non-methane organic volatile compounds (VOCs) [22] Variations of intestinal microbiota [205] [206] Bisphenol-A, phthalate [76] [77] [78] [79] Ozone and sulfate [207] Nitrates, nitrites, N-nitroso compounds, persistent organochlorine pollutants [208] [209] Chromium [210] Lead [211] EDCs, endocrine disrupting chemicals; POPs, persistent organic pollutants; T2DM, type 2 diabetes mellitus. rat F1 female offspring. "
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    ABSTRACT: The worldwide obesity epidemic is paralleled by a rise in the incidence of pancreatic disorders ranging from "fatty" pancreas to pancreatitis and cancer. Body fat accumulation and pancreatic dysfunctions have common pathways, mainly acting through insulin resistance and low-grade inflammation, frequently mediated by the epigenome. These mechanisms are affected by lifestyle and by the toxic effects of fat and pollutants. An early origin is common, starting in pediatric age or during the fetal life in response to nutritional factors, endocrine disruptor chemicals (EDCs) or parental exposure to toxics. A "fatty pancreas" is frequent in obese and is able to induce pancreatic damage. The fat is a target of EDCs and of the cytotoxic/mutagenic effects of heavy metals, and is the site of bioaccumulation of lipophilic and persistent pollutants related with insulin resistance and able to promote pancreatic cancer. Increased Body Mass Index (BMI) can act as independent risk factor for a more severe course of acute pancreatitis and obesity is also a well-known risk factor for pancreatic cancer, that is related with BMI, insulin resistance, and duration of exposure to the toxic effects of fat and/or of environmental pollutants. All these mechanisms involve gene-environment interactions through epigenetic factors, and might be manipulated by primary prevention measures. Further studies are needed, pointing to better assess the interplays of modifiable factors on both obesity and pancreatic diseases, and to verify the efficacy of primary prevention strategies involving lifestyle and environmental exposure to toxics
    European Journal of Internal Medicine 12/2014; 25(10):865-873. DOI:10.1016/j.ejim.2014.10.012 · 2.89 Impact Factor
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    • "Hyperinsulinemia occurs in presence of insulin resistance, a key pathophysiological mechanism linked to type 2 diabetes mellitus and obesity. There is substantial epidemiological evidence linking insulin resistance and cancer of the liver, colon and pancreas [39]. However, the association between hyperinsulinemia/insulin resistance and breast cancer has been controversial in humans. "
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    ABSTRACT: Objective This study was undertaken to evaluate the association between components defining insulin resistance and breast cancer in women. Study Design We conducted a systematic review of four databases (PubMed-Medline, EMBASE, Web of Science, and Scopus) for observational studies evaluating components defining insulin resistance in women with and without breast cancer. A meta-analysis of the association between insulin resistance components and breast cancer was performed using random effects models. Results Twenty-two studies (n = 33,405) were selected. Fasting insulin levels were not different between women with and without breast cancer (standardized mean difference, SMD −0.03, 95%CI −0.32 to 0.27; p = 0.9). Similarly, non-fasting/fasting C-peptide levels were not different between the two groups (mean difference, MD 0.07, −0.21 to 0.34; p = 0.6). Using individual odds ratios (ORs) adjusted at least for age, there was no higher risk of breast cancer when upper quartiles were compared with the lowest quartile (Q1) of fasting insulin levels (OR Q2 vs. Q1 0.96, 0.71 to 1.28; OR Q3 vs. Q1 1.22, 0.91 to 1.64; OR Q4 vs. Q1 0.98, 0.70 to 1.38). Likewise, there were no differences for quartiles of non-fasting/fasting C-peptide levels (OR Q2 vs. Q1 1.12, 0.91 to 1.37; OR Q3 vs. Q1 1.20, 0.91 to 1.59; OR Q4 vs. Q1 1.40, 1.03 to 1.92). Homeostatic model assessment (HOMA-IR) levels in breast cancer patients were significantly higher than in people without breast cancer (MD 0.22, 0.13 to 0.31, p<0.00001). Conclusions Higher levels of fasting insulin or non-fasting/fasting C-peptide are not associated with breast cancer in women. HOMA-IR levels are slightly higher in women with breast cancer.
    PLoS ONE 06/2014; 9(6):e99317. DOI:10.1371/journal.pone.0099317 · 3.23 Impact Factor
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    • "Metabolic syndrome and insulin resistance have been associated with increased risk of cancer, particular EAC [40-43]. This is mediated by adipokines and cytokines released by metabolically active visceral fat, which result in chronic hyperinsulinemia and increase risk of insulin-like growth factor-mediated carcinogenesis [44]. Exercise decreases visceral fat, lowering the level of carcinogenic adipocytokines, improves insulin sensitivity and reduces fasting insulin and C-peptide levels, and may decrease insulin-like growth factor-1 [12]. "
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    ABSTRACT: Background Physical activity has been inversely associated with risk of several cancers. We performed a systematic review and meta-analysis to evaluate the association between physical activity and risk of esophageal cancer (esophageal adenocarcinoma [EAC] and/or esophageal squamous cell carcinoma [ESCC]). Methods We conducted a comprehensive search of bibliographic databases and conference proceedings from inception through February 2013 for observational studies that examined associations between recreational and/or occupational physical activity and esophageal cancer risk. Summary adjusted odds ratio (OR) estimates with 95% confidence intervals (CI) were estimated using the random-effects model. Results The analysis included 9 studies (4 cohort, 5 case–control) reporting 1,871 cases of esophageal cancer among 1,381,844 patients. Meta-analysis demonstrated that the risk of esophageal cancer was 29% lower among the most physically active compared to the least physically active subjects (OR, 0.71; 95% CI, 0.57-0.89), with moderate heterogeneity (I2 = 47%). On histology-specific analysis, physical activity was associated with a 32% decreased risk of EAC (4 studies, 503 cases of EAC; OR, 0.68; 95% CI, 0.55-0.85) with minimal heterogeneity (I2 = 0%). There were only 3 studies reporting the association between physical activity and risk of ESCC with conflicting results, and the meta-analysis demonstrated a null association (OR, 1.10; 95% CI, 0.21-5.64). The results were consistent across study design, geographic location and study quality, with a non-significant trend towards a dose–response relationship. Conclusions Meta-analysis of published observational studies indicates that physical activity may be associated with reduced risk of esophageal adenocarcinoma. Lifestyle interventions focusing on increasing physical activity may decrease the global burden of EAC.
    BMC Gastroenterology 05/2014; 14(1):101. DOI:10.1186/1471-230X-14-101 · 2.37 Impact Factor
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