Metabolic Syndrome and Colorectal Cancer: A Cross-Sectional Survey

Metabolic syndrome is a complex metabolic disease characterized by central obesity, impaired glucose tolerance, hypertension and dyslipidemia (Wang et al., 2005; Chiu et al., 2007; Pelucchi et al., 2010; Siddiqui, 2011). Metabolic syndrome is a most common risk factor for cardiovascular disease and Non-Insulin Dependent Diabetes Mellitus (NIDDM) (Sturmer et al., 2006; Rigo et al., 2009; Siddiqui, 2011). Prevalence of metabolic syndrome in Western countries is rising sharply (Pais et al., 2009). In the United States, the prevalence of metabolic syndrome has been estimated at 24% and 23% in men and women, respectively (Ahmed et al., 2006). This rate have been reported between 24.6% and 30.9% in Europe countries (Pais et al., 2009). Increasing prevalence of metabolic syndrome is not only in the West but also Asian countries are faced with increasing due to changing lifestyles (Wang et al., 2005; Chiu et al., 2007). Apart from the metabolic syndrome is a risk factor for cardiovascular disease, there is epidemiological evidence indicating that metabolic syndrome also increases the risk of colorectal cancer (CRC) (Morita et al., 2005; Chiu et al., 2007; Tsilidis et al., 2010). Various studies indicated that


Introduction
Metabolic syndrome is a complex metabolic disease characterized by central obesity, impaired glucose tolerance, hypertension and dyslipidemia (Wang et al., 2005;Chiu et al., 2007;Pelucchi et al., 2010;Siddiqui, 2011). Metabolic syndrome is a most common risk factor for cardiovascular disease and Non-Insulin Dependent Diabetes Mellitus (NIDDM) (Sturmer et al., 2006;Rigo et al., 2009;Siddiqui, 2011). Prevalence of metabolic syndrome in Western countries is rising sharply (Pais et al., 2009). In the United States, the prevalence of metabolic syndrome has been estimated at 24% and 23% in men and women, respectively (Ahmed et al., 2006). This rate have been reported between 24.6% and 30.9% in Europe countries (Pais et al., 2009). Increasing prevalence of metabolic syndrome is not only in the West but also Asian countries are faced with increasing due to changing lifestyles (Wang et al., 2005;Chiu et al., 2007).
Apart from the metabolic syndrome is a risk factor for cardiovascular disease, there is epidemiological evidence indicating that metabolic syndrome also increases the risk of colorectal cancer (CRC) (Morita et al., 2005;Chiu et al., 2007;Tsilidis et al., 2010). Various studies indicated that
Abdominal obesity is considered as one of the major components of metabolic syndrome which in many cases is caused due to physical inactivity (Siddiqui, 2011). Obesity may lead to CRC development by different mechanisms (Siddiqui, 2011). Several studies have shown that body mass index ≥30 has significant association with CRC (Giovannucci, 2003;Slattery et al., 2004;Frezza et al., 2006). Other components of metabolic syndrome including total cholesterol, high density lipoprotein cholesterol (HDL-c), and triglycerides may play role in development of CRC (Tsilidis et al., 2010). Although the exact mechanism is unknown but several studies have emphasized the role of dyslipidemia on CRC development (Schoen et al., 1999;Chung et al., 2006).
Hypertension is another component of metabolic syndrome (Cameron et al., 2004). There is no epidemiologic evidence to suggest that hypertension is a risk factor for colon adenomas and possibly CRC and only few studies have introduced hypertension as an independent risk factor for CRC (Ahmed et al., 2006). Despite the strong association between metabolic syndrome and CRC, there is little information about this issue in Iran. As a first step to provide further information, we decided to evaluate prevalence of metabolic syndrome and its components in patients with CRC.

Materials and Methods
The present study was designed as a cross-sectional survey to assess the frequency of metabolic syndrome in CRC patients and compare clinicopathologic characteristics of patients with and without metabolic syndrome. This study was conducted on 200 patients with new diagnosis of CRC, according to pathology report, which were referred to Imam Hossein Hospital, Tehran, Iran, from 2008-2010.
Before the onset of study, the aim of this survey was explained to all eligible individuals and requested their participation. The individuals were informed that participation in the study was not compulsory and their information will preserved confidential.
After obtaining informed consent, patients' information including demographic data, history of chronic disease, behavioral habits (such as smoking, alcohol use) and family history of disease were collected through the interview with them. Patients' waist circumference, weight and height were measured and body mass index (BMI) was calculated for all of them. Blood pressure was measured using standard sphygmomanometers, after 5 min of rest, in a sitting position. Fasting blood sample was taken for determination of high density lipoprotein (HDL), triglyceride and serum glucose.
According to NCEP definition, patients were divided into two categories based: CRC patients with metabolic syndrome and CRC patients without metabolic syndrome. Then clinicopathological characteristics of both groups were evaluated and were compared with each other.
Continuous variables are presented as mean±standard deviation, and other parameters as frequency and percentage. Differences between groups were determined by χ 2 test and differences between means of groups were compared by independent samples T test. Statistical analysis was performed using SPSS software (version 13.0). A P-value of 0.05 or less was considered statistically significant and all reported P values were two sided. study, of which 115 (57.5%) and 85 (42.5%) cases were male and female, respectively. The mean age of patients was 57.1±13.9 years. Rectum was the most common site of tumor followed by descending colon, ascending colon, cecum and transverse colon. Patients' Clinicopathological features are shown in Table 1.

Results
Fasting blood glucose was higher than 110 mg/dl in 25% of cases. Hypertension was present in 36.5% of patients. 38.5% of patients had an elevated serum TG.24% of men and 33.5% of women had a low HDL cholesterol level and abdominal obesity, based on waist circumference, were reported 46% and 6% in women and men, respectively. Table 2 demonstrates the distribution of metabolic syndrome's components.
As shown in Table 2, a total of 72 CRC patients (36%) had met to metabolic syndrome criteria that 76% were women and 24% were men. 47 patients with metabolic syndrome had at least 3 NCEP criteria and 21 and 4 of

Discussion
The present study findings indicated that considerable percentage of patients with colorectal cancer, simultaneously suffer from metabolic syndrome. These observations will reinforce the hypothesis of association between metabolic syndrome and risk of CRC.
Our results showed that about 36% of CRC patients diagnosed with metabolic syndrome. This value is similar to what is obtained in Chiu et al. (2007) study, they reported that 150 of 418 CRC patients had metabolic syndrome according to NCEP-ATP III. In another study in Korea the frequency of metabolic syndrome in CRC patients was reported 17% (Kim et al., 2007). Given that the similarity of diagnostic criteria of metabolic syndrome in these studies, differences in reported rates may be due to different demographic characteristics of population under study or various laboratory methods for determination of components of metabolic syndrome.
Although some studies (Ahmed et al., 2006;Pelucchi et al., 2010) suggested that risk of CRC in men with metabolic syndrome is higher than women, but in current study we found that metabolic syndrome in women is most common than men. This difference perhaps not be a real difference but also may be due to gender distribution in population under study in this survey.
Obesity is considered one of the major components of metabolic syndrome that is measured by different indicators including body mass index and abdominal obesity. As mentioned above, 80% of women and 14% of men had abdominal obesity according to waist circumference that is in contrast with Plucchi et al. study (Pelucchi et al., 2010). Although given that high prevalence of obesity in Iranian women (Ayatollahi and Ghoreshizadeh, 2010), the findings of current study is reasonable.
As seen in result section, prevalence of metabolic syndrome components' in our study was relatively high. Reported values in other studies (Wang et al., 2005;Chiu et al., 2007;Safaee et al., 2009) is lower than our findings. Although it should be considered that study populations' in current survey were selected from CRC patients but individuals under study in mentioned reports were selected from colonoscopy candidate that generally were healthy patients.
Pathological characteristics of patients were not associated with metabolic syndrome. But similar to other studies (Chiu et al., 2007;Safaee et al., 2009) smoking habit was most common in metabolic syndrome patients. Because of alcohol use and opium consumption is considered a taboo in Iran, obtained percentages in this study is not very reliable.
Our study has to be interpreted taking its limitations into account. First, needed information was obtained from a one referral public center that demographic characteristics of patients that refer to this center may be different from population and therefore, the generalization of results should be done with caution. Second, design of study was as a cross sectional and there was a lack of healthy control group, for this reason, causal inference is not possible.
In conclusion, our findings indicated that the prevalence of metabolic syndrome in CRC patients is relatively high. Therefore, further analytical and multicentric studies are needed to better understand the role of metabolic syndrome in development of CRC. If this association confirms in future studies, metabolic syndrome patients should be considered in CRC screening programs.