الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Colorectal cancer is considered as one of the most common digestive system malignancies that exhibits higher morbidity and mortality all over the world. Its prevalence rate is increasing largely in the recent decades especially in the developing countries. The etiology of colorectal cancer is not clearly understood, it is a multifactorial disease. Many factors could share in the pathogenesis of colorectal cancer such as genetic defects and environmental risk factors. About 5% to 10% of people who develop colorectal cancer have inherited gene defects that cause the disease.
Many epidemiological studies have focused on the role of diet, environmental pollution, obesity, alcohol intake, social stress, tobacco smoking and high consumption of red meat (especially processed meat), low consumption of fruits, vegetables, dietary fibers, and sedentary life style as possible risk factors.
Recently, many studies indicated the important role of environmental factors, including trace elements of heavy metals , these studies proved the strong association between the increased level of environmental pollution and colorectal cancer development assessed by the increased levels of different trace elements such as lead, cadmium, manganese and copper in patients with colorectal cancer compared to healthy controls. These factors could affect DNA and lead to genetic defects by generation of reactive oxidative species (ROS) which causes ineffective DNA repair and leading to carcinogenesis. This gives an alarm for the importance of increasing the public health awareness about environmental risk factors.
Nayak, Bhat, Upadhyay, & Udupa, (2003) and Emre et al., (2013) had proved the previously mentioned relationship. Another case control study was conducted by Sohrabi et al., (2018) had proved the increased levels of heavy metals in the cancerous tissue of colorectal cancer patients compared to the normal neighboring tissue in the same patients and it was statistically significant,( p< 0.05).
So, the present study aimed to measure the level of lead and copper in colorectal cancer patients and healthy controls and to measure the level of lead and copper in drinking water samples consumed by cases and healthy controls. It aimed also to identify environmental risk factors of colorectal cancer then to determine the relation between identified environmental risk factors and level of lead and copper in colorectal cancer patients.
The study was conducted at the oncology and nuclear medicine department of Alexandria Main University Hospital. Cases were colorectal cancer patients attending the oncology outpatient clinic, and controls were healthy individuals matched to cases on age and sex. The sample size was 50 subjects: 25 cases and 25 controls. A structured interviewing predesigned questionnaire was administered to participants and was used to collect data from cases and controls. Data included: personal and socio-demographic data, medical history, lifestyle, dietary habits, indoor and outdoor environmental exposures.
Anthropometric measurements were done and a heparinized blood sample was drawn from each participant to measure the level of lead and copper by flame atomic absorption spectrometry after wet digestion of the heparin plasma samples. Appropriate statistical procedures were then applied to process the data, and the following results were obtained:
• High household crowding index (2+) was detected in (56%) of the cases compared to (16%) of controls. Cases had 6.68 times more risk to develop colorectal cancer compared to controls (OR=6.682; 95% CI: 1.1769 – 25.245). It was noted that about (80%) of cases were having lower income compared to (20%) of controls that had an impact on the increased risk of cases to develop colorectal cancer 16 times more than controls (OR=16.0; 95% CI: 4.0 – 63.975).
• Regarding educational level, there was a significant difference between cases and controls. The cases with low education (illiterate) were 9.5 more risk to develop colorectal cancer than controls (OR=9.5; 95% CI: 1.579 – 57.16). On the other side, the cases with secondary /above intermediate education had 5.4 more risk to develop colorectal cancer compared to controls (OR=5.4; 95% CI: 1.059 – 27.833).
• Concerning the presence of comorbid diseases, it was found that cases with comorbidities(diabetes, hypertension and irritable bowel diseases) were 4.75 times more risk to develop colorectal cancer than those who do not (OR=4.75; 95% CI: 1.406 – 16.051). The risk of developing colorectal cancer was higher in cases using medications 4 times more than controls (OR=4.33; 95% CI: 1.235 – 15.21). It was noted that 32% of the cases were diabetic and hypertensive compared to only 20% of controls.
• It was found that cases who were exposed to environmental tobacco smoke (ETS) had about 8 times more risk to develop colorectal cancer than controls (OR=7.944; 95% CI: 1.884 – 33.498).
• Cases who used insecticides with high rate had 5.46 times more risk to develop colorectal cancer than those who don’t use insecticides of control group (OR=5.46; 95% CI: 1.627-18. 352).
• Drinking water considered being one of the main sources of trace heavy metals. It was detected that (72%) of cases who had drinking water problems (changing the color or odor, turbid water, and inadequate water source) had 13.5 times more risk to develop colorectal cancer compared to controls (p<0.05), (OR=13.5; 95% CI: 3.395 – 53.682) .
• Concerning the type of water pipes in houses of cases, it was found in(56%) had old water pipes in their houses compared to only (8%)of controls(p<0.01), and they had 14.6 more risk to develop colorectal cancer than those with new plastic water pipes,(OR=14.6; 95% CI: 2.82 – 75.954).
• Regarding the assessment of waste water problems, it was detected that (36%) of cases had problems in waste water in the areas of their residence compared to (8%) of controls (p<0.01), with 13.5 times more risk to develop colorectal cancer than those who do not of the control group, (OR=13.5; 95% CI: 1.556 – 117.137).
• When asking about the fuel source used in houses, it was detected that (52%) of cases were using butane as a fuel source compared to (8%) of controls, (p<0.05) and they had 12 times more risk to develop colorectal cancer than those who use natural gas (OR=12; 95% CI: 23.407 – 64.495).
• It was detected that cases who worked >7 hrs. /day had 33 more risk to develop colorectal cancer than control group (OR=33; 95% CI: 4.74 – 229.65). This could be explained by excess exposure to harmful risk factors in work place for long time.
• It was estimated that cases with exposure history to noise and excess vibrations had 39 times more risk to develop colorectal cancer than controls. Also it was noted that about 48%of cases were working as drivers and in industry compared to 12%of controls (p<0.01), this may explain the impact of air pollution on health after long exposure time (OR=39; 95% CI: 4. 022 –378.199). cases who were exposed to chemical risk factors had 11 times more risk to develop colorectal cancer than controls (OR=11; 95% CI: 2.157 – 56.094) .
• Regarding the assessment of harmful effect of chronic exposure to outdoor environmental risk factors especially air pollution caused by industrial exhausts, firing garbage and accumulation of solid waste in many residential areas ,it was noted that the risk of colorectal cancer development in cases lived nearby mobile phone stations, cases were 9 times of higher risk than controls (OR=9.33; 95% CI: 1.052 – 82.780), and it was detected that cases lived nearby waste dustbins were 4 times more risk to develop colorectal cancer than controls,(OR=4.125; 95% CI: 0.961 – 17.04) and it was estimated that the cases lived nearby area of firing
Garbage had 11 times more risk to develop colorectal cancer than controls,(OR=11.294; 95% CI: 1.29 – 98.889).
• Concerning the dietary habits, it was found that cases with excess consumption of carbonated beverages (64%) compared to (28%)of controls p=0.01 had 4.57 times more risk to develop colorectal cancer,(OR=4.57; 95% CI: 1.383 – 15.109)
• It was noted that mean concentration of heparin plasma Pb level in cases was (0.45±0.048)mg/L, and it is double the value of mean concentration of Pb in controls (0.21±0.25)mg/L, about 64% of the cases with lead level (> 0.164 mg/L), had about 4 times more risk to develop colorectal cancer compared to 32% of controls with lead level less than (0.164 mg/L (OR=3.778; 95% CI: 1.170 – 12.194).
• It was detected that 56% of the cases with copper level (>1.3 mg/L) had high copper% had 3 times more risk to develop colorectal cancer compared to 28% of controls with copper level less than(1.3 mg/L) (OR=3.273; 95% CI: 1.008 – 10.621). There was a significant positive correlation between the levels of lead and copper in cases.
• It was noted that 72% of the cases had high lead level in drinking water (> 0.061mg/L) had 10 times more risk to develop colorectal cancer compared to 20% of controls with water lead less than( 0.061 mg/L)(OR=10.286; 95% CI: 2.67- 38.215).
• It was noted that 17% of the cases had high copper in drinking water (> 0.012mg/L) had 11 times more risk to develop colorectal cancer compared to 4% of controls with water copper less than (0.012mg/L) (OR=10.286; 95% CI: 2.864 – 43.464).
• By performing a multivariate stepwise logistic regression analysis, four factors showed significant association with colorectal cancer. Lead level (Pb) level (>0.164) mg /L, passive smoking, living nearby waste dustbins and the type of wall covering paints (old oily paints) (OR= 31.057 (95% CI: 1.549 -622.588), OR= 32.2(95% CI: 0.625-52.024, OR= 9.354 (95% CI: 1.02-85.786), OR=83 (95%CI: 1.279-5419. Respectively).
In conclusion, it was evident from the results that colorectal cancer is multi-factorial disease, where many risk factors interact and contribute to its development. The current study showed that the environmental exposures and the possible etiological mechanisms in colorectal cancer development would allow us to reduce the incidence and prevalence rates and better health care policies would be adapted to improve early detection of the disease. Also it would be reflected on the economic side presented in saving economic resources and opportunities for patients, families, employers and society and avert the substantial burden of the disease.