Metabolic syndrome and leptin are associated with adverse pathological features in male colorectal cancer patients

Healy, Laura; Howard, Julia; Ryan, Aoife M.; Beddy, Peter; Mehigan, Brian; Stephens, R. B.; Reynolds, John V.

doi:10.1111/j.1463-1318.2011.02562.x

Cited by 36 publications

(29 citation statements)

References 34 publications

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“…In addition to increasing CRC risk, plasma leptin and leptin receptor levels have been associated with more aggressive tumour phenotype 104 144. An additional study of 108 Chinese patients with CRC reported a significant association between leptin/Ob-R expression and T and TNM staging, lymph node metastasis, distant metastasis, differentiation, and increased expression of phosphorylated PI3K, Akt and mTOR protein, suggesting that leptin may regulate the proliferation and apoptosis of CRC through the PI3K/Akt/mTOR signalling pathway 145.…”

Section: Resultsmentioning

confidence: 99%

Obesity and colorectal cancer

Bardou

Barkun

Martel

2013

Gut

644

479

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Excess body weight, as defined by the body mass index (BMI), has been associated with several diseases and includes subjects who are overweight (BMI ≥ 25-29.9 kg/m(2)) or obese (BMI ≥ 30 kg/m(2)). Overweight and obesity constitute the fifth leading risk for overall mortality, accounting for at least 2.8 million adult deaths each year. In addition around 11% of colorectal cancer (CRC) cases have been attributed to overweight and obesity in Europe. Epidemiological data suggest that obesity is associated with a 30-70% increased risk of colon cancer in men, whereas the association is less consistent in women. Similar trends exist for colorectal adenoma, although the risk appears lower. Visceral fat, or abdominal obesity, seems to be of greater concern than subcutaneous fat obesity, and any 1 kg/m(2) increase in BMI confers additional risk (HR 1.03). Obesity might be associated with worse cancer outcomes, such as recurrence of the primary cancer or mortality. Several factors, including reduced sensitivity to antiangiogenic-therapeutic regimens, might explain these differences. Except for wound infection, obesity has no significant impact on surgical procedures. The underlying mechanisms linking obesity to CRC are still a matter of debate, but metabolic syndrome, insulin resistance and modifications in levels of adipocytokines seem to be of great importance. Other biological factors such as the gut microbiota or bile acids are emerging. Many questions still remain unanswered: should preventive strategies specifically target obese patients? Is the risk of cancer great enough to propose prophylactic bariatric surgery in certain patients with obesity?

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Section: Resultsmentioning

confidence: 99%

Obesity and colorectal cancer

Bardou

Barkun

Martel

2013

Gut

644

479

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“…In particular, it is well established that cancer cells undergo metabolic reprogramming to a glycolytic state to survive and maintain proliferation in a hostile environment and there is increasing evidence this warburg effect is promoted by oncogenes, including KRAS [53]. In CRC, leptin production has been associated with adverse outcome in male patients, associating with advanced disease, nodal status and venous invasion [54]. In another study, a metabolic gene signature able to predict patient's risk of relapse was shown to be associated with lower disease-free survival (HR 4.2 95% CI 1.79-9.88) [55].…”

Section: Phenotypic Characteristics -Metabolismmentioning

confidence: 99%

Colorectal cancer subtypes: Translation to routine clinical pathology

Roseweir

McMillan

Horgan

et al. 2017

Cancer Treatment Reviews

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Colorectal cancer (CRC) is the second most common cause of cancer death in Europe.Although outcomes have improved, it is clear that from a genomic standpoint CRC is not one disease, but a heterogeneous group of malignancies that arise within one organ. Given that different subtypes have different outcomes, the ability to subtype tumours in the clinic would be highly favourable, enabling optimal treatment for individual patients.In 2015, a consortium proposed four consensus subtypes for CRC (MSI immune, canonical, metabolic, and mesenchymal) based on six classifications systems reported to have prognostic value.However, genomic assessment of tumours is not readily translated into routine pathology with a need for standardisation and reproducibility of assessment. Immunohistochemistry is widely used in routine pathology, and would present a more readily translatable method for subtyping CRC tumours. Therefore, the literature was reviewed to characterise the genomic and phenotypic features associated with each subtype, with the aim of enabling subtyping of CRC to be taken forward into routine clinical practice.

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“…Stattin et al (2004) evidenced that an increasing level of leptin stimulates invasiveness of CRC in men, but not in women. Another study associated the aggressiveness of CRC tumor in male patients with high leptin levels and hypertension, raised plasma glucose, triglycerides, and high-density cholesterol levels (Healy et al, 2012). On the contrary, Ho et.…”

Section: Obesity-leptin and Adiponectinmentioning

confidence: 99%

“…A growing body of evidence indicates that the metabolic syndrome (MetS) and expression of various adipokines (leptin and adiponectin) associated with obesity plays a crucial role in the development of colorectal cancer (Hardwick et al, 2001;Hoda et al, 2007;Endo et al, 2011;Aleksandrova et al, 2012;Healy et al, 2012;Erkasap et al, 2013;Gialamas et al, 2013). In obese people, the elevated insulin level, the rapidly growing secretion of leptin, and decreased adiponectin levels altogether activate several signaling pathways that favor carcinogenesis and are associated with colon cancer development.…”

Section: Obesity-leptin and Adiponectinmentioning

confidence: 99%