Metabolic syndrome and colorectal neoplasms: An ominous association

Trabulo, Daniel

doi:10.3748/wjg.v21.i17.5320

Cited by 31 publications

(34 citation statements)

References 39 publications

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“…Most CRCs are adenocarcinomas. CRC risk is associated with high BMI, and a 3% increase in risk with each unit of BMI has been estimated . The associations are stronger for men than for women, and for colonic cancers than for rectal cancers .…”

Section: Large Bowelmentioning

confidence: 99%

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Obesity and metabolic syndrome: pathological effects on the gastrointestinal tract

Feakins

2016

Histopathology

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Obesity is an increasingly common problem worldwide and a risk factor for a variety of gastrointestinal (GI) diseases, both non-neoplastic (e.g. gastro-oesophageal reflux and Barrett's oesophagus) and neoplastic (e.g. oesophageal adenocarcinoma, colorectal carcinoma, and gallbladder cancer). Furthermore, obesity is associated with worse GI cancer outcomes. Body mass index is a commonly used measure of fat accumulation, although specific patterns such as abdominal/central obesity and visceral fat quantity sometimes predict disease risk more accurately. Metabolic syndrome (MS) is a related condition characterized by central adiposity and insulin resistance. The reasons for the associations with neoplasia are diverse. Established cancer-related conditions that have a higher prevalence in overweight subjects include Barrett's oesophagus and gallstones. Preneoplastic lesions such as colorectal adenoma, colorectal serrated lesions and pancreatic intraepithelial neoplasia are also associated with obesity/MS. At the cellular level, adipocytes can release carcinogens such as adipokines, insulin-like growth factor, and vascular endothelial growth factor. Inflammatory cells constitute a further potential source of carcinogens; in obese subjects, their numbers are increased systemically and in adipose tissue. Animal studies have contributed additional information. For example, mice with a genetic predisposition to develop colorectal carcinoma given a high-fat diet have larger and more numerous intestinal adenomas than controls, and there may be demonstrably higher levels of mucosal oncogenic factors. The associations between obesity and GI disease are of variable strength, and the underlying mechanisms are incompletely understood, but it is clear that obesity and MS have a significant, potentially avoidable and often under-recognized impact on the population burden of GI disease.

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Section: Large Bowelmentioning

confidence: 99%

“…The associations are stronger for men than for women, and for colonic cancers than for rectal cancers . As for some other cancers, visceral fat may be more ‘dangerous’ than subcutaneous fat, and a better guide than BMI to the increased risk . Associations with MS are inconsistent, restricted to men, and often weak .…”

Section: Large Bowelmentioning

confidence: 99%

Obesity and metabolic syndrome: pathological effects on the gastrointestinal tract

Feakins

2016

Histopathology

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“…Both obesity and MetS represent important risk factors for development of colorectal cancer 46, 47. Environmental and metabolic factors interact with genetic predisposition in the pathogenesis of colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

ADIPOQ rs266729 G/C gene polymorphism and plasmatic adipocytokines connect metabolic syndrome to colorectal cancer

Divella

Daniele

Mazzocca³

et al. 2017

J. Cancer

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Background: ADIPOQ gene, which encode for Adiponectin (APN), is sited on chromosome 3q27 and linked to a susceptibility locus for metabolic syndrome (MetS). The ADIPOQ rs266729 G/C gene polymorphism is significantly associated with low APN levels and linked to susceptibility to develop cancer. In addition, decreased APN serum levels are linked with tumor development and progression and inversely associated with markers of inflammation. Here, we investigate the influence of APN rs266729 G/C polymorphism on adipocytokine circulating levels and their association with MetS in colorectal cancer patients (CRC).Methods: Blood samples from 105 CRC patients (50 women and 55 men) with and without MetS were genotyped for APN rs266729 G/C polymorphism by TETRA ARMS PCR. ELISA assay was used to measure plasma levels of APN and inflammatory TNF-α cytokine. Biochemical and anthropometric parameters of MetS were also analyzed.Results: We found that CRC patients (N=75) with genotype rs266729G/C or carriers of G allele were associated with a significantly increased risk of MetS development (OR =2.9) compared to those with CC genotype (N=30). Also, CG/GG genotypes were associated with significantly lower plasma APN levels and higher TNF-α levels in comparison to CC genotype (P=0.034) and APN levels were decreased in relation to BMI increases (P=0.001).Conclusions: Our findings show that APN rs266729 G/C polymorphism is associated with lower APN levels in CRC patients, indicating that decreased circulating levels of APN may be a determinant risk factor for CRC in MetS patients.

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“…In contrast, traditional-onset patients were more likely to have features of the metabolic syndrome. This is important as each 5 unit increase in BMI increases CRC risk by 30% while type 2 Diabetes Mellitus increases risk by 29% and 34% in men and women respectively [22]. This indicates the need for improved preventative and management measures for these metabolic conditions in Ethiopia.…”

Section: Discussionmentioning

confidence: 99%

What are the Clinicopathological Features and Outcomes of Sporadic Colorectal Cancer (CRC) in an Ethiopian Cohort with focus on young-onset CRC?

Worku¹

2017

JCPCR

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What are the Clinicopathological Features and Outcomes of Sporadic Colorectal Cancer (CRC) in an Ethiopian Cohort with focus on young-onset CRC?2/7Copyright: ©2017 Worku et al.Group (ECOG) status, family history, tumour histopathology, management aims, treatments offered and outcomes of these interventions were sought. Mode of presentation was defined as elective if surgery and treatment was planned and arranged, or, emergency if patient underwent hospital admission for complications including large bowel obstruction, perforation or life threatening haemorrhage. Follow up of all patients was performed in order to identify recurrence rates. Tumour staging was recorded using the American Joint Committee on Cancer Staging System (AJCC) which supersedes Dukes Classification [14]. Right-sided lesions were defined as those from the cecum up to and including the hepatic flexure with transverse colon lesions recorded separately. Left-sided lesions included the splenic flexure and the descending colon but not the rectosigmoid junction. In cases of synchronous tumours, patients would be classified as multiple and not according to individual tumour location. Decisions on outcomes including stage of management (e.g. whether in remission or having progression etc) were based on whether treatment was curative or palliative in nature and were determined by discussions within an MDT setting.Permission for this study was granted by the head of the Oncology department Dr Tigeneh Wondemagagnehu and the Dean of the University of Addis Ababa Medical School, Dr Daniel Siefu. ResultsA total of 95 CRC cases were identified during the study period of which 85 were eligible for analysis (age range with the remainder excluded due to coding errors (Table 1). 44 patients were ≤40 years old (young-onset) with 73% between 30-39 years and 41 patients >40 years old (traditional-onset) with a Male: Female ratio of 1:1 and 1.41:1 respectively. Results are reported here as young/traditional-onset disease. Pathological staging was reported in 94% (n=80) with pT3 staging the most commonly reported (50%/51%) with 30% of young-onset cases exhibiting perineural/lymphovascular involvement. Appropriate nodal Assessment (>12 nodes) at biopsy was low having been performed in only 59%/56% of patients. Clinically, young-onset patients were more likely to present within 6 months of symptom onset (53%v39%) with 16% traditional-onset CRC patients presenting ≥24 months (range 24-39 months). Comorbid illness featured in 76% and 55% of traditional-onset and young-onset cases respectively. Of traditional-onset patients 33%(n=10) had features of the metabolic syndrome while 15%(n=3) youngonset had HIV. Performance status in the majority was ECOG 0/1 (77%/83%) with young-onset patients more likely to suffer functional limitation and were the only cases of ECOG V recorded (n=2). Family History featured in 9% and 5% of young and traditional-onset patients respectively however in the majority of individuals no history was recorded (52%v51%). In all patients with positi...

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Metabolic syndrome and colorectal neoplasms: An ominous association

Abstract: MS is positively associated with adenomas and colorectal cancer. However, there is not enough information in western European countries to justify screening in patients with MS. To our knowledge, no previous study has evaluated this association in Portuguese patients.

Cited by 31 publications

References 39 publications

Obesity and metabolic syndrome: pathological effects on the gastrointestinal tract

Obesity and metabolic syndrome: pathological effects on the gastrointestinal tract

ADIPOQ rs266729 G/C gene polymorphism and plasmatic adipocytokines connect metabolic syndrome to colorectal cancer

What are the Clinicopathological Features and Outcomes of Sporadic Colorectal Cancer (CRC) in an Ethiopian Cohort with focus on young-onset CRC?

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