Colorectal cancer in egypt: clinical, life-style, and socio-demographic risk factors

*Essam A. El-Moselhy
Community Medicine, Al-Azhar University , Egypt
Ahmed M. Hassan
General Surgery, Al-Azhar University , Egypt
Diaa M. El-Tiby
Tropical Medicine, Al-Azhar University , Egypt
Alaa Abdel-Wahed
Occupational And Industrial Medicine, Al-Azhar University , Egypt
Abd-Elnaser S. Mohammed
Community Medicine, Al-Azhar University , Egypt
Ayman Abd El-Aziz
Internal Medicine, Al-Azhar University , Egypt

*Corresponding Author:

Essam A. El-Moselhy
Community Medicine, Al-Azhar University
Egypt

Published on: 2017-04-14

Abstract

Aim: To determine the clinical, life-style, and socio-demographic risk factors of CRC in Egypt.

Patients and Methods: A hospital-based, case-control study design was used. One hundred sixty patients with CRC and 300 healthy subjects were recruited in this study. An interviewing form and clinical examinations were used to collect data.

Results: Significant medical and family risk factors were obesity, DM, bowel habit change, inflammatory bowel disease (IBD), precancerous colonic lesions, no NSAIDs use, no HRT use, cholecystectomy, and family history of CRC (ORs=2.12, 2.13, 1.97, 4.91, 5.46, 3.69, 6.3, 3.84, and 8.88; respectively). Significant dietary risk factors were high red and processed meats intake, low white meat intake, high fat intake, dairy products, low fibers, low fruits and vegetables, and high salty/spicy foods, (ORs=5.12, 2.17, 5.59, 2.58, 2.79, 3.05, and 2.5; respectively). Significant social life-style risk factors were smoking, caffeine, alcohol, and no physical activity (ORs=1.58, 4.17, 6.6, and 4.87; respectively). Significant health care risk factor was no compliance with medical follow up (OR=1.85). Significant socio-demographic risk factors were age ≥60 year, male gender, single status, urban residence, higher education, professional occupations, and high social status (ORs=2.08, 2. 45, 1.87, 1.95, 1.99, 1.76, and 1.73; respectively).

Keywords

Colorectal Cancer, Clinical, Life Style, Socio Demographic, Risk factors, Egypt

Introduction

Colorectal cancer (CRC) is cancer of the colon and rectum. It arises from the mucosal lining the colon, rectum or both (1).

CRC affects all racial and ethnic groups (2). It is the third most commonly diagnosed cancer after lung and breast worldwide. The highest rates (~60.0%) are found in developed regions and countries e.g. Europe, North America, and Australia. The lowest rates are found in developing areas e.g. Africa and South-Central Asia. Over 1.2 million new CRC cases and 608,700 deaths estimated to be occurred worldwide in (2008), accounting for 8.0% of all cancer deaths, making it the fourth most common cause of death from cancer (1).

In the US, CRC is the fourth most common cancer diagnosed. It is estimated that in (2014) there was 136,830 new cases of and 50,310 deaths from CRC, second only to lung cancer (3).

In Egypt, CRC contributes 6.5% of all cancers (4). Further, the National Cancer Institute registry, Cairo University for the years (2002)- (2003) (5) cleared CRC was among the most common cancers registered (6th); it was 4.2% in males and 3.8% in females (6). Also, CRC is not uncommon in Egypt; it was diagnosed in 14.0% of all patients who undergone colonoscopies (7).

CRC is most often found in those aged 50 years or older worldwide (2). A population-based study in Garbiah, Egypt has shown high rates of CRC in patients aged 40 years and younger. These rates were slightly higher than rates of the same age group in the United States (8). CRC affects both men and women (2). It is the third most common cancer in men (663,000 cases, 10.0% of the total) and the second in women (570,000 cases, 9.4% of the total) worldwide (1). In Egypt, low rates of CRC (6.9/100,000 for males and 5.1/100,000 for females) were reported by the Middle East Cancer Consortium in the period of (1999)-(2001) (9). Also, low rates were reported from Garbiah Cancer Registry in Egypt for period from (2000)-(2002); age standardized incidence rates (ASRs) were 6.5/100,000 for males and 4.2/100,000 for females (8).

High socioeconomic status (SES) is also associated with an increased risk for the development of CRC. It is estimated that CRC risk being about 30.0% increase in the lowest as compared with the highest SES quintile (10). The risk of developing CRC is influenced by both environmental and genetic factors (11). There is also evidence that life-style factors increase cancer risk and, if modified, could significantly reduce the cancer burden (12). The major risk factors that can be modified to decrease risk for many cancers include reducing tobacco use, increasing physical activity, controlling weight, improving diet, and limiting alcohol consumption (13). When defining the cancer prevention strategies used to modify these risk factors, it is also important to integrate genetic information that might play a role in determining the effectiveness for modifying the factor (14). So, due to the substantial effect of modifiable life-style factors on the most prevalent cancers, it has been estimated that 50.0% of cancer is preventable (15).

Patients and Methods

Study design: A hospital-based, case-control, analytic study design was used to perform this research. Administrative design: An approval to carry out this study in Al-Azhar University hospitals was taken from the managers of these hospitals.

Study settings and patients: A consecutive sample of 160 patients with CRC attending the General Surgery, Tropical Medicine, and Internal Medicine Clinics, Al-Azhar University Hospitals, Assiut and Cairo, seeking for medical advice or follow up were recruited in this study as a patients' group. Also, 300 apparently healthy subjects (relatives to other patients attending these clinics and free from any type of cancer) were enrolled as a control group in the present study.

Study tools: A specially designed comprehensive interviewing form contains data related to topic of the study was used to collect data from the patients and controls. Also, all of them had undergone anthropometric measurements; height (cm) and weight (kg) were measured with participants standing without the shoes and heavy garments. Body mass index (BMI) was calculated and classified according to WHO (16) classification. Participant who has taken pain relieving, non-steroidal anti-inflammatory drugs (NSAIDs) regularly during the last year he/she were included in the analysis. CRC classification: The modified Dukes' classification according to Astler-Coller's modification (17) was used for classifying the stage of CRC of the patients.

Ethical considerations: The study was approved by the Ethics Committee of Al-Azhar Faculty of Medicine. The purpose of the study and procedures were explained to the patients and controls. Consents of both of them were given before recruiting in the study and confidentiality and security were guaranteed for both of them.

Statistical analysis: The collected data were organized, tabulated and statistically analyzed using statistical package for social sciences (SPSS) version 20 (SPSS, Inc., Chicago, USA). For qualitative data, frequency and percent were calculated. Statistical analysis was performed between the two groups using odds ratio (OR) test to detect the risk factors. To determine the significance of OR, the 95% confidence interval (CI) or exact confidence limits (ECL) was used.

Results

Table (1) illustrates frequency distribution of CRC cases according to clinical and characteristic features. Age at diagnosis was divided to somewhat 3 equal values; 31.9%, 33.1%, and 35.0% in 3 age sectors; <40, 40-59, and ≥60 year, respectively. Rectal bleeding, chronic severe constipation/diarrhea, and intestinal obstruction were the most common presenting symptoms; 51.3%, 34.4%, and 21.9%; respectively. Site of CRC was the distal-, proximal- colon, and rectum among 45.6%, 33.8%, and 20.6% of cases, respectively. The histopathological diagnosis of CRC was adencarcinoma, mucoid carcinoma, and signet-ring cell carcinoma in 75.0%, 16.9%, and 8.1% of cases, respectively. Modified Astler-Coller staging was Dukes' B and C in 40.6% and 36.9%, of cases, respectively. Lastly, lymph node involvement was found in 50.6% of cases.

Table (2) shows significant medical and family history risk factors for CRC are overweight/obese (OR=2.12, 95% CI: 1.41-3.2), history of DM (OR=2.13, 95% CI: 1.28-3.53), history of bowel habit change (OR=1.97, 95% CI: 1.26-3.09), history of inflammatory bowel disease (IBD) (OR=4.91, 95% CI: 2.42-10.07), history of IBD (OR=4.91, 95% CI: 2.42-10.07), history of precancerous colonic lesions (OR=5.46, 95% ECL:1.58-23.83), no regular use of NSAIDs (OR=3.69, 95% CI: 2.27-6.0), no use of hormone replacement therapy (HRT (OR=6.3, 95% CI: 3.36-11.99), cholecystectomy (OR=3.84, 95% CI: 1.57-9.59), and positive family history of CRC (OR=8.88, 95% ECL: 1.8-85.08], 1st degree relatives with CRC (OR=9.65, 95% ECL: 1.06-457.67), and other GIT cancers (OR=6.82, 95% ECL: 1.27-67.74).

Table (3) clarifies significant dietary life-style risk factors for CRC are history of high red and processed meats intake (OR=5.12, 95% CI: 3.08-8.53), low white meats intake (OR=2.17, 95% CI: 1.4-3.37), high animal fat intake (OR=5.59, 95% CI: 3.52-8.9), high dairy products, sour cream, and cheese intake (OR=2.58, 95% CI: 1.69-3.94), low fibers intake (OR=2.79, 95% CI: 1.82-4.29), low fruits and vegetables intake (OR=3.05, 95% CI: 1.82-5.11), high salty/spicy foods intake (OR=2.5, 95% CI: 1.65-3.79), current smoker (OR=1.58, 95% CI: 1.05-2.38), smoking index >20 cigarette/day (OR=1.66, 95% CI: 1.03-2.65), caffeine intake (OR=4.17 95% CI: 2.57-6.8), alcohol/beer use (OR=6.6, 95% ECL: 1.66-37.71), previous/current physically active (OR=4.87, 95% CI: 3.06-7.77), and no compliance with medical follow up (OR=1.85, 95% CI: 1.1-3.11).

Table (4) clears significant socio-demographic risk factors for CRC are age group ≥ 60 year (OR=2.08, 95% CI: 1.33-3.26), male gender [OR=2.45, 95% CI: 1.6-3.7], single marital status [OR=1.87, 95% CI: 1.01-3.48], urban residence (OR=1.95, 95% CI: 1.24-3.9), higher education level (secondary and university) (OR=1.99, 95% CI: 1.22-3.25), professional occupation level (OR=1.76, 95% CI: 1.01-3.07], and high social status (OR=1.73, 95% CI: 1.07-2.79)].

Discussion

The risk of developing CRC is influenced by genetic factors and acquired risk factors, including environmental exposures and comorbid medical conditions (11, 18).

In the present study, we cleared age at diagnosis of CRC was 31.9%, 33.1%, and 35.0% in age groups; <40, 40-59, and ≥60 year, respectively. CRC occurs predominantly in older patients, but its incidence rates in young patients are rising (19). In Egypt, there is an increasing incidence of CRC where it shares the feature of epidemiological characteristics of developing countries, which have higher incidence in young patients and cancer of rectum predominates (20). Gado, et al. (7) showed similar results; about 25.0%, 25.0%, and 50.0% of their CRC patients in the age groups <40, 40-5o, and 51-80 year respectively. Rectal bleeding, chronic severe constipation/diarrhea, and intestinal obstruction were the most common presenting symptoms; 51.3%, 34.4%, and 21.9%; respectively. Also, Gado, et al. (7) found similar results. Eisa, (21) observed rectal bleeding (53.9%), abdominal pain (42.7%), habit change (40.5%), and intestinal obstruction (11.2%) among her CRC patients. Site of CRC was the distal-, proximal- colon, and rectum among 45.6%, 33.8%, and 20.6% of cases, respectively. Again, Gado, et al. (7) reported similar results; distal colon (43.0%), proximal colon (36.0%), and rectum (21.0%). Eisa, (21) reported the site of CRC were rectum (42.7%), sigmoid (15.7%), left colon (10.1%), transverse colon (5.6%), and right colon (25.8%). The histo-pathological diagnosis of CRC patients was adencarcinoma (75.0%), mucoid carcinoma (16.9%), and signet-ring cell carcinoma (8.1%). Gado, et al. (7) reported similar results; adenocarcinoma (79%), mucoid carcinoma (14%), and signet-ring cell carcinoma (7%). Modified Astler-Coller staging was Dukes' B and C in 40.6% and 36.9%, of cases, respectively. Eisa, (21) noticed 42.7% and 33.7% of CRC patients were in Dukes' B and Dukes' C, respectively. Lymph node involvement was found in 50.6% of cases. Eisa, (21) noted a similar figure, 49.4%.

There are number of well-known correctable CRC risk factors (22). In this study, overweight/obesity (BMI: 25-≥30, OR=2.12) is significant risk factor for CRC. Evidence suggests a positive link between obesity and CRC risk, although whether weight loss can lead to CRC risk reduction is unclear (18). The association between body weight and CRC was recognized. The relative risk (RR) attributable to obesity was estimated to be significant (1.24 for men and 1.09 for women) (23). Various anthropometric variables such as BMI, waist circumference, and waist/hip ratio are suggested to be positively associated with colon cancer in both men and women (24). Common metabolic pathways linking obesity and CRC risk have been hypothesized, such as those of chronic inflammation, oxidative stress, and insulin resistance (18). On the other hand, Luo, et al. (25) found a significant statistical difference between CRC cases and controls regarding mean BMI, cases had a lower mean BMI.

DM was significant risk factor for CRC (OR=2.13). It may be associated with an elevated risk of CRC (26). A study showed a significantly increased risk of CRC in diabetic patients compared with non-diabetic controls (RR=1.30) (27). One explanation linking DM to CRC is hyperinsulinemia as insulin and insulin-like growth factor are important growth factors for colonic mucosal cells and stimulate colonic neoplastic cells (28). A relationship between serum levels of C-peptide and CRC risk was reported (29). Chronic insulin therapy may also increase the risk of CRC in diabetic patients. A study estimated that the age- and sex-adjusted risk of CRC associated with more than 1 year of insulin use was 2.1 (30).

In this study, we noted bowel habit change was significant risk factor for CRC (OR=1.97). This result is expected and accepted as many of these patients will develop IBD as this symptom is a cardinal symptom of it. Further, patients with chronic IBD involving the colon (ulcerative colitis (UC) and Crohn’s disease (CD)) are at increased risk for CRC. UC was significant risk factor for CRC (4.68). Several factors may influence the risk of CRC in IBD patients (31, 32). The severity of inflammation may also be an important marker of CRC risk (33). In UC, the risk of CRC depends on the duration and extent of disease. The risk is highest in those with extensive colitis, pancolitis, with a standardized incidence ratio of 2.4 in the US (34). Overall, the approximate cumulative incidence of CRC is 5%-10% after 20 years and 30% after 35 years of UC (31). However, the risk of CRC in patients with long-standing UC was not different from that of the general population, a finding that may be a reflection of the more aggressive surgical approach in Europe toward patients poorly responsive to medical treatment (35). In patients with UC and primary sclerosing cholangitis (PSC), CRC was more compared to those without PSC. Also, it is accepted that CRC in IBD is preceded by dysplastic changes. Thus, dysplasia may be a marker for coexisting and subsequent malignancy. There is agreement that the finding of high-grade dysplasia warrants prompt colectomy because of the high risk of synchronous CRC (11). Further, in UC patients there is high rate of progression from low-grade to high-grade dysplasia or CRC, estimated to be 53.0% at 5 years (36). However, Jess, et al. (37) hasn't shown such high rate of progression. Also, a history of CD was significant risk factor for CRC (OR=5.71). Studies have reported the risk of CRC in long-standing CD involving the colon is probably comparable to that of UC (32). The median duration of CD (15 year) prior to the diagnosis of CRC was comparable for UC (18 year) (11). Precancerous colonic lesions were significant risk factor for CRC (OR= 5.46). Andersen, et al. (38) cleared precancerous colonic lesions are associated with higher CRC risk. Zhivotovskiy, et al. (39) observed precancerous colonic lesions are significant risk factor for CRC (OR=5.25). Acromegaly was insignificant risk factor for CRC. There is evidence that colorectal adenomas occur with more in acromegalic patients (40). Acromegalic patients were more likely to have multiple and proximal adenomas. Reduced expression of the peroxisome proliferator-activated receptor gene has been implicated in these patients (11).

Non-regular use of NSAIDs was significant risk factor for CRC (OR=3.69). Theodoratou, et al. (41) cleared CRC cases signi?cantly taking NSAIDs regularly less than controls. Also, NSAIDs as aspirin have been shown to decrease colon cancer risk (42). Also, HRT non-use in women was significant risk factor for CRC (OR= 6.3). The association between HRT and CRC was supported by showing a reduction in risk of CRC in post-menopausal women. A 20.0% reduction in CRC risk in those who ever used HRT and 34.0% in the current users versus those who never used HRT (43). Also, Theodoratou, et al. (41) reported CRC cases signi?cantly taking HRT less than controls. HRT intake was strongly inversely associated with CRC. Possible biological mechanisms for an HRT effect on CRC risk include through the properties of exogenous oestrogens when there is decreased production of secondary bile acid in the colonic epithelium, reduced estrogen receptor gene methylation, inhibition of cell proliferation and increased vitamin D receptor activity (44, 45). However, at present, there is no strong experimental evidence to support the role of any speci?c biological pathway in modulating this effect of HRT intake on CRC risk (41). Cholecystectomy was significant risk factor for CRC (OR=3.84). A relation between cholecystectomy and right-sided colon cancer has been described. Patients who had undergone cholecystectomy showed a slightly increased risk of right-sided colon cancer but not left-sided cancer (46). Results of meta-analyses have supported this association with proximal colon cancers (47). Pelvic radiation therapy (PRT) was insignificant risk factor for CRC. PRT for prostate cancer correlated with an increased risk of rectal cancer (48).

ABO blood group was insignificant risk factor for CRC. It was noticed that an association between the ABO blood groups and CRC risk was not confirmed in series of studies across different populations and ethnicities (39, 49). Positive family history of CRC was a significant risk factor (OR=4.9), 1st degree relative(s) with CRC was a significant risk factor (OR=1.8), other GIT cancers were significant risk factors for CRC (OR=2.2). There is a great role of genetic predisposition in CRC development (39, 50). In well-defined inherited forms of CRC, e.g. familial polyposis and Lynch syndrome, the inherited genetic predisposition is decisive and the role of other factors may be limited or nonexistent (18, 50). Family history of colorectal cancer in any first-degree relatives slightly increased risk of rectal cancer (OR: 1.37, 95% CI: 1.02-1.85) (51). Luo, et al. (25) found a significant statistical difference between CRC cases and controls regarding 1st degree relative with CRC. Zhivotovskiy, et al. (39) cleared 4-fold risk increase in patients with family history of gastrointestinal cancers.

Increasing prevalence of CRC in the Western World suggests that life-style factors are deeply involved in its etiology. The modification of these factors might reduce CRC risk (52). Role of nutrition and physical activity in modulating CRC risk is obvious. Dietary regimens characterized by high contents of fiber, vegetables, fruits, fish, poultry, and lower in red and processed meats seem to be protective against CRC. Also, it is clear that genetic-environmental interactions may ultimately determine the effects of genetic, nutritional, or environmental factors (18). There is a tendency to increase of CRC incidence in certain parts of the world where it was low. This might be caused by many factors as shift of dietary pattern and increase in smoking prevalence. The US is the only country where a decline of CRC incidence has been observed recently. Also, stabilizing of incidence has been noted in Canada and New Zealand (53). Countries where dietary patterns have become more westernized have seen a parallel incremental increase in CRC incidence (54). Also, immigrants from low-incidence regions who moved to high-incidence industrialized regions may incur an elevated lifetime risk for CRC compared with those who remain in the low-incidence regions (55). Kirkegaard, et al. (56) stated adherence to the recommendations for physical activity, smoking, alcohol intake, and diet may reduce CRC risk considerably, 23.0% of the cases might be attributable to lack of adherence to the five lifestyle recommendations.

High intake of red and processed meats was significant risk factor for CRC (OR=5.12). Dietary regimens characterized by low red and processed meats seem to be protective against CRC (18) and vice versa is correct diet high in animal red meat is associated with CRC (57, 58). A diet high in red meat content may be associated with increase CRC risk (59). Meat has been found to affect the intestinal homeostasis (60). Zhivotovskiy, et al. (39) showed excessive red meat consumption is significant risk factor for CRC and excessive intake of red meat products. Also, Mahfouz, et al. (58) cleared higher consumption of red meat (OR=57.1) and processed meat (OR= 2.4) were the most significant dietary CRC risk factors. On the other hand, Sanjoaquin, et al. (61) haven't found a significant relation between red meat intake and CRC. Although the data are not consistent, the bulk of evidence supports the view that red meat consumption is associated with an increased risk of CRC (62). Further, low white meat was significant risk factor for CRC (OR=2.17). Dietary regimens characterized by a high consumption of fish and poultry exert protective effects against CRC (18, 58). Mahfouz, et al. (58) cleared the most significant protective factors was fish (OR=0.38). Baena and Salinas (63) showed fish consumption may decrease CRC risk by 12.0%.

High intake of animal fat and dairy products, sour cream, and cheese were significant risk factors for CRC (OR=5.59 and 2.58, respectively). Arafa, et al. (57) found a diet high in saturated fat appeared to be associated with CRC. High animal fat and cholesterol intake might be associated with CRC development (59, 64). Subjects in the highest quartile of cholesterol consumption had a significantly higher risk of CRC compared with those in the lowest quartile (RR=3.26), even after adjusting for other variables as fruit and vegetable intake (63). Theodoratou, et al. (41) observed subjects who consumed a diet high in fat (including cholesterol, SFAs, MUFAs, tFAs, and tMUFAs) and low in n3PUFAs had a higher risk of CRC. Also, high intake of dairy products, sour cream, and cheese were significant risk factors for CRC (ORs= 2.8, 1.7, and 1.6; respectively). Zhivotovskiy, et al. (39) cleared excessive intake of these products is significant risk factors for CRC.

We observed low fibers intake was significant risk factor for CRC (OR= 2.79). Dietary regimens characterized by a high consumption of fiber seem to be protective against CRC (18, 58). Mahfouz, et al. (58) cleared the most significant protective factor was high fiber bread (OR=0.15). Baena, Salinas, et al. (63) showed intakes of more than 20 g/day of fiber is associated with a 25.0% reduction of CRC risk. Rye bread has a significant protection, particularly in combination with wheat bread. Consumption of rye bread and both rye and wheat bread were established as protective factors (OR=0.32, 95% CI: 0.21-0.5 and 0.07, 95% CI: 0.02-0.21; respectively) (39). Some studies have noted an inverse relation between dietary fiber consumption and risk of colorectal adenomas and/or CRC (65). Dietary fiber from vegetables, fruit and cereals are converted by colonic bacteria to short-chain fatty acids that had been found to affect intestinal inflammation in various ways (66).

Low fruits and vegetables was significant risk factor for CRC (OR=3.05). Studies have shown a relation between diets low in fruits and vegetables and increased CRC risk (18, 57, 58, 67). Mahfouz, et al. (58) reported higher consumption of fruits and vegetable was significant protective (OR=0.02). Fiber, antioxidant vitamin, folic acid, micronutrient, and Phyto-chemical content in vegetables and fruits might own a protective effect. RR of CRC is about 0.5 when groups with the highest- and lowest- vegetable and fruit intake were compared (67). On the other hand, other studies haven't found this relation. Analysis of data showed no significant relation between fruits or vegetables intake and the incidence of CRC (68). Also, Schatzkin, et al. (69) found fiber supplementation had no significant protection on the development of adenomas in patients who had undergone colonoscopic polypectomy. Further, a meta-analysis of five studies cleared increased dietary fiber didn't appear to reduce the incidence or recurrence of colorectal adenoma over a 4-year period (24). Also, a meta-analysis of 13 cohort studies observed dietary fiber intake wasn't an independent risk factor for CRC (70). At present, the degree of protection from the consumption of vegetables, fruits, or dietary fiber remains unsettled (11). Tayyem, et al. (71) found consuming fruits and vegetables didn't significantly correlate with a lower CRC incidence.

High intake of salty and spicy foods was significant risk factor for CRC (OR= 2.5). Zhivotovskiy, et al. (39) reported spicy food consumption is significant risk factor for CRC (OR=2.87, 95% CI: 1.9-4.33). Also, they cleared high concentration of salt in the food is significant risk factor for CRC (OR=3.45, 95% CI: 1.68-7.1). Mahfouz, et al. (58) clarified higher consumption spicy foods (OR=4.2) was a significant risk factor. Current smoking was significant risk factor for CRC (OR=1.58). Further, smoking >20 cigarette/day slightly increase the risk significantly (OR=1.66). There is now sufficient evidence that tobacco smoking is a cause of CRC (72). Smoking has been associated with increased CRC incidence and mortality (58, 73). There is 38.0% increased risk of CRC for increase of 40 cigarette/day (74). Zhivotovskiy, et al. (39) showed smoking is significant risk factor for CRC (OR=2.13, 95% CI: 1.4-3.24). Also, Luo et al. (25) found significant statistical differences between CRC cases and controls regarding regular and passive smoking. Caffeine intake was significant risk factor for CRC (OR=4.17). The relation between caffeine consumption and CRC is unresolved. Giovannucci, (75) noticed a link between low rates of coffee consumption and an elevated CRC risk, but Michels et al. (68) didn't support this. Also, alcohol/ beer intake was significant risk factor for CRC (OR=6.6). A relation between heavy alcohol consumption and increased CRC risk had reported [39, 73]. Zhivotovskiy, et al. (39) found significant risk factors for CRC are alcohol drinking (OR=8.73), beer drinking (OR=9.24), and hard liquor consumption (OR=9.37). Cho et al. (76) estimated CRC risk was slightly increased (RR=1.41) in those who consumed alcohol >45 g/day. Harnack, et al. (77) showed risk increased to a lesser degree in those who consumed from 30-45 g/day. Baena and Salinas (63) showed intakes of moderate amounts of alcohol (25-30g/day) increase CRC risk. On the other hand, Luo, et al. (25) found no significant statistical difference between CRC cases and controls.

No physical activity was significant risk factor for CRC [OR=4.87]. Physical activity has been associated with reduced CRC risk (58, 18), Baena and Salinas (63) and the vice versa is correct; sedentary life-style is associated with CRC (57). Baena and Salinas (63) found regular physical activity reduces this risk by 24.0%. Mahfouz, et al. (58) cleared the most significant protective factor was physical activity (OR=0.001). The protection may be through decreasing inflammation, increasing the body’s metabolic efficiency and capacity, and reducing insulin resistance (78). Further, this effect may interact with high energy intake, obesity, and the metabolic syndrome (79). Sedentary workers had a significantly increased CRC risk compared with those engaged in light or heavy physical activity (80). In a meta-analysis of 16 cohort studies, individuals who were the most physically active were observed to have a 23.0%-24.0% lower r colon cancer risk than those who were less active. For rectal cancer, no statistically significant association was observed (81).

Health care behavior risk factor for CRC was no compliance with medical follow up for diseases (OR=1.85). This result is expected and accepted as this health care behavior might lead to increased risk of many diseases including CRC. Hawkes, et al. (82) noted positive behavioral change has the potential to impact on progression of CRC. Further, Bours, et al. (83) cleared dietary changes post-diagnosis were reported by 36.0% of the survivors. Motivation for dietary changes was mostly cancer-related (44.0% reported prevention of cancer recurrence as the main reason). We cleared age ≥60 year was significant risk factor for CRC (OR=2.08). Luo et al. (25) found no relation between CRC cases and controls regarding the mean age. Also, male gender was significant risk factor for CRC (OR=2.45). ASR was 6.5/100,000 for males and 4.2/100,000 for females (8). Eisa, (21) observed 58.4% and 41.6% of CRC patients were males and females, respectively. Luo, et al. (25) showed no relation between CRC cases and controls as regard gender. Further, single marital status was significant risk factor for CRC (OR=1.87). Again, Luo, et al. (25) reported no relation between CRC cases and controls regarding marital status. An urban residence was significant risk factor for CRC (OR=1.95). Nfonsam, et al. (84) stated patients in rural areas are more likely to present with a higher stage of CRC and are less likely to have their cancer adequately staged. This is likely due to lack of better access to health care, lack of awareness, and poor education and also inadequate specialists. Luo, et al. (25) showed insignificant statistical difference between CRC cases and controls regarding residence. A protective effect of Egyptian diet against cancer was suggested, a hypothesis currently believed to be valid for many Mediterranean Basin populations. The industrial revolution of the 19th century has passed by Egypt; rural Egypt has hardly changed in 3,000 years (85). The highest education and occupation status were significant risk factors for CRC (ORs=1.99 and 1.76, respectively). Luo, et al. (25) found significant statistical differences between CRC cases and controls regarding the education and occupation statuses. Also, they found a significantly statistical difference between CRC cases and controls regarding the occupation activity (no and light to moderate activities). Arafa, et al. (57) showed sedentary life-style appeared associated with CRC. Collectively, high social class was significant risk factor for CRC (OR=1.73). High socioeconomic status is associated with increased age, westernized life-style. So, it is a reason for CRC to be more significant problem for developed countries compared to developing (10). At the same time, Zhivotovskiy, et al. (39) noticed income exceeding twice the subsistence minimum is significant risk factor for CRC (OR=5.34, 95% CI: 3.35-8.53).

Limitations of the study

The most important limitations for this study are the relatively small number of cases (160) and controls (300). It is important to recruit more cases for verification of the suggestions. Also, risk factors of cancer of every part of the gut should be defined separately. So, large sample size is required. Lastly, risk factors must be clear and accurately defined. For this reason, we interviewed the patients and controls personally to evaluate their answers and get the most reasonable answers.

Conclusions and Recommendations

Risk factors of CRC are mostly preventable. The most important risk factors were obesity, DM, IBD, precancerous colonic lesions, and family history of CRC. Follow of healthful life-style in diet and physical activity were CRC protective factors. More studies should be conducted on big number of patients in different geographical areas in Egypt to understand the true epidemiology and situation of CRC in Egypt and to doubling of efforts to address high risk groups. Also, the need for a national prevention and control program and integration into health facilities is urgent. Screening with colonoscopic surveillance is recommended for at risk groups.

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