Metabolic syndrome is associated with colorectal cancer in men

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Abstract

Aim of the study

We assessed the relation between metabolic syndrome (MetS) and its components and colorectal cancer.

Methods

We analysed data from a multicentre case–control study conducted in Italy and Switzerland, including 1378 cases of colon cancer, 878 cases of rectal cancer and 4661 controls. All cases were incident and histologically confirmed. Controls were subjects admitted to the same hospitals as cases with acute non-malignant conditions. MetS was defined according to the International Diabetes Federation criteria. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated by multiple logistic regression models, including terms for major identified confounding factors for colorectal cancer.

Results

With reference to each component of the MetS, the ORs of colorectal cancer in men were 1.27 (95% CI, 0.95–1.69) for diabetes, 1.24 (95% CI, 1.03–1.48) for hypertension, 1.14 (95% CI, 0.93–1.40) for hypercholesterolaemia and 1.26 (95% CI, 1.08–1.48) for overweight at age 30. The corresponding ORs in women were 1.20 (95% CI, 0.82–1.75), 0.87 (95% CI, 0.71–1.06), 0.83 (95% CI, 0.66–1.03) and 1.06 (95% CI, 0.86–1.30). Colorectal cancer risk was increased in men (OR = 1.86; 95% CI, 1.21–2.86), but not in women (OR = 1.13; 95% CI, 0.66–1.93), with MetS. The ORs were 2.09 (95% CI, 1.38–3.18) in men and 1.15 (95% CI, 0.68–1.94) in women with ⩾3 components of the MetS, as compared to no component. Results were similar for colon and rectal cancers.

Conclusion

This study supports a direct association between MetS and both colon and rectal cancers in men, but not in women.

Introduction

The metabolic syndrome (MetS) is characterised by a clustering of components associated with cardiovascular diseases (i.e. hyperglycaemia, obesity, hypertension and dyslipidaemia). Several definitions of the MetS have been proposed during the last decade,1, 2, 3 and experts of major organisations have recently agreed a joint scientific statement trying to unify its diagnostic criteria.4

Besides cardiovascular conditions, the MetS has more recently been associated to the risk of various cancers, including those of the colon and rectum, in a number of epidemiological studies.5, 6, 7, 8, 9, 10, 11, 12, 13, 14 The MetS might increase colorectal cancer risk through various biological mechanisms, particularly those related to insulin resistance.15 However, not all findings supported a relation between MetS and colorectal cancer,11, 12 and the results between studies were often inconsistent when the associations were examined by site (i.e. colon or rectum) and sex.

With reference to the components of the MetS, the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) report concluded that there is convincing evidence that greater body fat causes colorectal cancer.16 Further, increasing evidence shows that abdominal fat, and particularly visceral adiposity, is associated with increased risk of colorectal adenoma and cancer, independently of overall body mass index (BMI).16, 17 Several epidemiological studies conducted in different populations indicated diabetes as a risk factor for colorectal cancer.18, 19, 20, 21 On the other hand, most findings suggest that the association between hypertension and dyslipidaemia and colorectal cancer risk is – if any – modest.9, 12

To provide further information on the relation between MetS and its components and colorectal cancer, we analysed data from a case–control study conducted in Italy and Switzerland.

Section snippets

Patients and methods

Data were derived from a multicentre case–control study of colorectal cancer conducted in six Italian areas (the provinces of Pordenone and Gorizia in the north-east; the urban areas of Milan and Genoa and the province of Forlì in the North; Latina in the centre; and the urban area of Naples in the South) and in Canton Vaud, Switzerland, between 1992 and 2001. The general design of the investigation has already been described.22, 23 The study included 1378 cases of colon cancer (International

Results

Table 1 gives the distribution of cases and controls by age, study centre, education and occupational physical activity, separately for men and women. In men only, cases had more frequently than controls a high level of education and a low level of occupational physical activity.

Table 2 shows the distribution of colon and rectal cancer cases and controls according to the components of the MetS, separately by gender, and the corresponding ORs and 95% CIs. For colorectal cancer, the ORs in men

Discussion

The MetS, and particularly its underlying component hyperinsulinaemia, might influence colorectal cancer risk through several plausible biological mechanisms. By suppression of hepatic secretion of insulin-like growth factors (IGF)-binding protein-1, insulin enhances the levels of bioavailable IGF-1.24 IGF-1 stimulates cell proliferation and differentiation, inhibits apoptosis25 and increases production of vascular endothelial growth factors, important in tumour angiogenesis. Further, insulin

Financial support

This work was conducted with the contribution of the Italian Association for Cancer Research and the Italian League against Cancer.

Conflict of interest statement

None declared.

Acknowledgement

The authors thank Mrs. I. Garimoldi for editorial assistance.

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