The study was conducted to identify the risk factors for colorectal cancer. The discussion is based on the objectives, the review of literature and research hypotheses specified in this study.
5. 1 The objective of the study was to find the association between the case and control groups and various factors such as clinical variability, genetic, environmental, life style and dietary factors, and to identify significant risk factors of colo rectal cancer among the groups.
The chi square of the above specified objectives results report showed as below,
5. 1. 1. Clinical variability:
It includes factors like Diabetes mellitus, duration of DM, pregnancy, age at first pregnancy, number of live birth and duration of breast feeding.
5. 1. 1 (a). Diabetes mellitus
The analysis in table no 4. 2. 1(a) depicts association of the case and control group with their clinical variability like diabetes mellitus and duration of diabetes mellitus. With regard to Diabetes mellitus, there is a significant association between years of DM and CRC at the level of p <0. 05. With regard to duration of diabetes mellitus, there is a significant association between duration of DM and colo rectal cancer at the level of p <0. 05, and the corresponding odds ratio is 2. 48 (DM for more than 5 years was referred to less than or equal to 5 years of DM). This shows that patients with DM for more than 5 years are having 2. 48 times risk of developing colo rectal cancer. Mechanisms through which diabetes may be linked with the risk of colorectal cancer include the bowel transit times for diabetes patients is slower, this contribute increased exposure of colon on and rectal mucosa to carcinogenic substances, another mechanism involved is increased blood glucose level in diabetic patients elevates fecal bile acid concentrations which promotes CRC. This finding was consistent with the results of meta analysis conducted by Yuhara, h., et al (2011) from EMBASE and MEDLINE databases of case control and cohort studies, in december 2009, analysis of those studies depicted that DM was significantly associated CRC, also from the results of 11 studies in men and 10 studies in women, DM is an risk factor for CRC.
5. 1. 1 (b). Breast feeding
The analysis in table no 4. 2. 1(b), there is a significant association between duration of breast feeding and CRC at the level of p <0. 05 and its corresponding odds ratio is 0. 11(breast feeding more than 12 months was referred to feeding for less than or equal to 12 months). Thus Breast feeding for more than 12 months was protective against colo rectal cancer. The mechanism behind this factor is during breast feeding the estrodial level will fall. It is hypothesized that the estrogen causes cellular proliferation leading to CRC. Breast feeding result in lower lifetime estradiol exposure. Thus breast feeding reduces the risk of CRC. This finding was supported by Lo, AC., et al (2010) conducted a case control study on lifestyle, occupational and reproductive factors and risk of CRC in Egypt. Lifestyle information was obtained from 421 CRC patients and 439 hospital controls history of pesticides exposure, increased frequency of eating food directly from farms were associated with CRC risk and parous women who have 7 or more live births or breast fed for 19 months or more has a significant lower risk of CRC, thus results depicted that agricultural and industrial exposure were associated with CRC, whereas prolonged lactation and increased parity were inversely associated with CRC.
5. 1. 1(c). Past history of colo rectal polyps
With regard to colo rectal polyps, 4. 2. 1(c) shows there is a significant association between past history of colo rectal polyps and CRC at the level of p <0. 05. Dr. Bert Vogelstein Scientists IN Johns Hopkins, discovered the procees of progression of colo rectal polyps into CRC, it occurs due to mutation of genes or due to any chemical changes resulting. Due to this change Colo rectal polyps develops then gradually turns to CRC. The genetic mutation occurs due to chromosomal alteration thus reducing tumor suppressor genes like P53, K-ras and APC and initiating more tumor promoter genes.
Fig 5. 1. 1.(c). i. OVogelgramÓ showing colo rectal polyp transition into CRC
200903011304_3881_000Vogelgram shows, colo rectal adenoma is belived as precursor of CRC..
5. 1. 1. (d) Past history of other cancer
With regard to history of any other cancer, table no 4. 2. 1(c) shows there is a significant association between past history of other cancer and colorectal cancer at the level of p <0. 05. The mechanism behind this either by metastasize or due to side effects treatment modalities like chemotherapy or radiation therapy which leads to cancers in other site like colon, rectum etc.
5. 1. 1.(e) History of constipation
With regard to constipation, table no 4. 2. 1(c) shows a significant association between constipation and CRC at the level of p <0. 01and the corresponding odds ratio was 11. 5(patients with the history of constipation was referred with patients without history of constipation), this suggests that patients with the history of constipation are 11. 5 times risk of developing CRC. The postulated causal link between constipation and increased colorectal cancer risk is that constipation causes longer transit times and which increase the duration of contact between the mucosa of colon and rectum and carcinogens like bile acids. This finding was supported by Nicholas., et al (2011) conducted a case control study among 28, 854 patients with chronic constipation and 86, 562 controls without chronic constipation, results showed both colo rectal cancer and benign neoplasm were more prevalent among chronic constipation patients also analyses the risk of developing colo rectal cancer among patients with chronic constipation, was 1. 78 times and risk of developing benign tumors was 2. 7 times higher.
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5. 1. 2. Genetic factors:
5. 1. 2(a). Family history of colorectal polyps
The analysis in table 4. 2. 2 depicts association between family history of colo rectal polyps and CRC at the level of p <0. 05.
5. 1. 2(b). Family history of CRC
The analysis in table 4. 2. 2 shows there is a significant association between family history of CRC and CRC at p <0. 05.
5. 1. 2(c). Family history of CRC
The analysis in table 4. 2. 2 depicts significant association between family history of cancer and CRC at p <0. 001, the corresponding odds ratio was 17. 4(patients with family history of cancer was referred with patients without family history of cancer). This shows that family history of cancer increases the risk of getting CRC by 17. 4 times. These finding was supported by Johns, LE., et al (2001) conducted a systematic review and meta-analysis of familial CRC risk in UK among 27 case control and cohort studies, weighted average was calculated from relative risk of all these studies result shows pooled estimates of relative risk as follows: a first-degree relative with CRC 2. 25 (95% CI = 2. 00-2. 53), colon 2. 42 (95% CI = 2. 20-2. 65), and rectal 1. 89 (95% CI = 1. 62-2. 21) cancer; parent with CRC 2. 26 (95% CI = 1. 87-2. 72); sibling with CRC 2. 57 (95% CI = 2. 19-3. 02); more than one relative with CRC 4. 25 (95% CI = 3. 01-6. 08); relative diagnosed with CRC before age 45, 3. 87 (95% CI = 2. 40-6. 22); and a relative with colo rectal adenoma 1. 99 (95% CI = 1. 55-2. 55), thus this study provides a strong evidence that CRC is more among those with family history of CRC and colo rectal adenoma. The mechanism behind all the above genetic factors involves, there are certain Colon Cancer Genes , mutations of these genes known to cause predisposition to CRC and are inherited in an autosomal dominant fashion or autosomal recessive fashion. Inheritance risk is 50% for both males and females. When a parent carries an autosomal dominant genetic predisposition, each child has a 50% chance of inheriting the predisposition. The risk is the same for both male and female children.
5. 1. 3. Lifestylefactors:
5. 1. 3(a). Smoking
Table no 4. 2. 3(a) shows association of smoking and CRC. With regard to smoking status, shows, there is a significant association between smoking status and CRC at p <0. 01. With regard to forms of smoking, there is a significant association between forms of smoking and CRC at p <0. 001. Odds ratio is 6. 7(beedi smokers referred to other forms of smokers). Thus it is evident that beedi smokers are 6. 7 times risk of developing CRC. With regard to duration of smoking, there is a significant association between duration of smoking and colo rectal cancer at p < 0. 01. With regard to frequency of smoking, there is a significant association between frequency of smoking and Colo rectal cancer at p <0. 01, Odds ratio is 3(smoking more than 6 times per day was referred to smoking less than or equal to 6 times per day). This shows that smokers who smokes more than 6 times are 3 times risk of developing colorectal cancer. The mechanism of smoking towards its causation of CRC involves: Tobacco and nicotine present in cigarettes are carcinogens disseminated throughout your body while inhaling, this mutate the cells and causes cellular changes that lead to cancer of colon or rectum and the bits of tobacco swallowed result in mixing up of chemicals with saliva which ends up in the colon, thus these carcinogens comes direct contact with mucosa of colon or rectum resulting in cancer. This result was supported by Phipps, AI., et al (2011) conducted a case control study samples were selected from 13 countries of USA during the year 1998-2007 who were diagnosed to have CRC and selected by registry of epidemiology, surveillance and End result cancer through telephone. Information was collected regarding history of smoking and alcohol consumption. The result showed CRC related mortality was higher among smokers than non smokers.
5. 1. 3(b). Alcoholism
Table 4. 2. 3(b) depicts association of alcoholism and CRC. With regard to type of alcohol intake, there is a significant association between type of drinkers and colo rectal cancer at p < 0. 01. Odds ratio is 10. 66(regular drinkers referred to other type of drinkers). This shows that regular drinkers are 10. 66 times risk of developing colorectal cancer. The mechanism involved is described as follows, those bacteria in colon and rectum, converts alcohol into acetaldehyde, a carcinogen. Alcohol may also slow the body's capacity to break down and eliminate some chemicals which are harmful. Alcohol also lowers the intestine's ability to absorb folate from diet. Low folate levels may have a role in the causation of CRC.. This finding was supported by Fedirko, T., et al (2011) conducted a meta analysis of published study on alcohol drinking and CRC risk, 27 cohort and 34 case control studies depicted that there is a strong evidence for an association between alcohol drinking of > 1 drink/day and CRC, the relative risk (RR) were 1. 52 (95% CI 1. 27-1. 81) for heavy drinkers, RR were 1. 21 (95% CI 1. 13-1. 28) for moderate drinkers.
5. 1. 3 (c) . Exercise
Table 4. 2. 3(c) shows significant association of habit of exercise and CRC at p level <0. 001 and the corresponding Odds ratio is 0. 25(those who perform exercise referred to those who do not). This implies that performing exercise is a protective factor against the development of CRC.
5. 1. 3 (d). BMI
Table 4. 2. 3(c) shows significant association of BMI and CRC at p < 0. 01, its corresponding odds ratio is2. 85 (obese referred to others). This shows that those who are obese have 2. 85 times risk of developing CRC. A number of mechanisms have been proposed to account for the association of obesity with CRC risk. Some of the hypothesis involves, Excess Fat tissue produces large amount of estrogen, and this high levels of estrogen have association with the CRC risk. Obese people often have increased levels of insulin-like growth factor-1 (IGF-1) and insulin in blood, this promote the development of CRC. Fat cells produces hormones like adipokines which stimulates or inhibits growth of cell, this hormone is more in obese which promote cell proliferation, whereas adiponectin, which have anti proliferative effects which is less in obese. This finding was supported by Zhao, Z., et al (2012) conducted a case control study on alcohol drinking and obesity in relation to CRC during the year 1999-2003 in Canada. Cases (702) and controls (717) were selected. Self administered questionnaire assessing health and life style variables was given result showed among obese individuals (BMI> 30), intake of alcohol was associated with CRC risk, the corresponding odds ratio was 2. 2, (95% CI: 1. 2 -4) with respect to those who does not took alcoholic. The study results concluded that those who are obese and took 3 or more types of alcoholic drinks have 3. 4 fold higher risk of developing CRC with respect to those who do not took alcohol.
5. 1. 4. Environmental factors
5. 1. 4 (a) . Dye exposure
Table 4. 2. 4(a) shows association of dye exposure and CRC. With regard to dye exposure, there is a significant association between dye exposure and colo rectal cancer at the level of p < 0. 05. The odds ratio is 8(dye exposure referred to not exposed to dye). This shows that those who are exposed to dye are at 8 times risk of developing colorectal cancer. With regard to duration of dye exposure, there is a significant association between dye exposure and CRC at p < 0. 05. This findings was supported by De Roos AJ et al (2005) conducted a case-cohort analysis on occupational exposures in China on Colorectal cancer incidence among female textile workers in Shanghai to investigate risks of colon and rectum cancers in relation textile industry exposures. Female employees from the Shanghai Textile Industry Bureau were selected as samples, estimate hazard ratios (HR) for colon and rectum cancers associated with duration of employment (e. g., 0, > 0 to <10, 10 to <20 years,> or = 20 years) in various jobs classified according to process type and exposures to specific agents. The findings indicated that certain long term exposures may pose increased risk of colorectal cancers, especially dyes and dye intermediates with colon cancer (> or = 20 years exposure versus never, HR= 3. 9; 95% CI: 1. 4-10. 6), and maintenance occupation (HR = 2. 3; 95% CI: 1. 0-5. 7) and metals exposure (HR = 2. 0; 95% CI: 1. 1-3. 6) with rectum cancer.
5. 1. 5. Dietary factors
5. 1. 5(a). shows association of intake of pulses and CRC. With regard to pulses intake, there is no significant association between type of pulses intake and CRC at the level of P < 0. 001. The corresponding odds ratio is 0. 07(daily pulses intake referred to others). This shows that daily intake of pulses is a protecting factor against colorectal cancer. This findings was supported by Sun, Z., et al (2012) conducted a case control study to identify the associations of CRC risk with dietary intake of total energy, protein, fat, carbohydrate, fiber, and alcohol in Canada. Totally 1760 cases were selected from population based cancer registries and 2481controls were selected from residents from each province. The tools used were family history questionnaire, food frequency questionnaire and personal history questionnaire, the results revealed that total energy intake is associated with increased risk of CRC ( OR is 1. 56, 95% CI; 1. 21-2. 01, p trend= 0. 02, 5th verses 1st quintile), for proteins inverse associations exist (OR: 0. 85, 95% CI: 0. 69-1. 00, p trend= 0. 06, 5th verses 1st quintile) for carbohydrates (OR: 0. 81, 95% CI: 0. 63-1. 00, p trend= 0. 05, 5th verses 1st quintile) and for fiber (OR: 0. 84, 95% CI: 0. 67-0. 99, p trend= 0. 04, 5th verses first quintile), thus presents evidence that high energy intake may increase the risk of CRC , whereas diets rich in protein, fiber and carbohydrates may reduce the risk of disease.
5. 1. 5 (b) . Vegetables
Table 4. 2. 5(b) shows association of intake of vagetables and CRC. With regard to intake of vegetables, there is a significant association between green vegetables and colo rectal cancer at p < 0. 001. This finding was supported by Banqu, M., et al (2012) conducted a hospital based case control study to determine the relationship between food groups, nutrient intake and risk of colorectal cancer in Spain, among 245 cases matched with 490 controls. The data was collected using a semi quantitative frequency food questionnaire, results revealed inverse association with CRC, for vitamin B6 (OR: 0. 26), vitamin D (OR: 0. 45), vitamin E (OR: 0. 42), poly unsaturated fatty acids(OR: 0. 57) and fiber diet(OR: 0. 40). Whereas carbohydrate (OR: 1. 82) were significantly associated with CRC risk. There are couples of theories to explain the protective effect of fibre in fruits and vegetables, Fibre help elimination products to travel through the bowel without causing any stagnationFibre enhances excretion of bile acids thus eliminating carcinogens quicklyLack of fibre in diet causes constipated. During constipation carcinogenic agents stays in contact with the bowel for a long time and increases CRC risk. Fruit and vegetables protects from CRC, as they contain antioxidants. Antioxidant protects the bowel wall from cell damage thus preventing CRC riskFolate which have anti carcinogenic property found more in vegetables.
5. 1. 5 (c). Fruits
Table 4. 2. 5(c) shows association of intake of fruits and CRC risk. With regard to intake of fruits, there is a significant association between fruits and colo rectal cancer at p < 0. 01. The corresponding odds ratio was 0. 0075(fruit intake once per week referred to fruit intake more than or equal to 1 per week). This shows that the intake of fruits is a protective factor against CRC. This finding was supported by the case control study conducted by Annema, N., et al (2011) between June 2005 to august 2007 in Australia on effect of vegetable and fruit consumption and risk of CRC. The samples of the study comprises 834 cases and 939 controls, data collected using food frequency questionnaire results denoted intake of dark yellow vegetables and apples reduces CRC risk.
5. 1. 5 (d). Fish
Table 4. 2. 5(d) shows association of intake of fish and CRC risk. With regard to intake of fish, there is a significant association between fish intake and colo rectal cancer at p <0. 001. The odds ratio was 0. 67(those who take fish is referred to those who do not take fish). This proves that fish is a protective factor against colorectal cancer. The mechanism involved was explained by the following hypothesis, Intake of fish promotes immunity, the byproducts of immune mechanism like cytokines and eicosanoids fights against development of CRCFish contains considerably low fat content and is rich in lean protein and omega 3 fatty acids, which protects the bowel wall from mutation. The high content of omega 3 fatty acids, low fat content and presence of vitamins A and D in fish offers lot of the benefits and prevents CRC. This finding was supported by Geelen A ., et al(2007) conducted a meta-analysis of prospective cohort studies at Netherlands on intake of fish, n-3 fatty acids and CRC. The pooled relative risk 4 studies results showed CRC incidence as 0. 97 (95% CI, 0. 92, 1. 02) for extra fish consumption of 100 g a week, The pooled relative risk results from 14 studies were 0. 88 (95% CI: 0. 78, 1. 8), thus concluded that highest fish consumption lower the CRC incidence.
5. 1. 5(e) . Dairy products
Table 4. 2. 5(d) shows association of intake of dairy products and CRC risk, there is significant association between dairy products and CRC at p < 0. 001. The odds ratio is 0. 39(daily intake of dairy products referred to others). This implies that intake of dairy products everyday is a protectively factor against development of colorectal cancer. The mechanism of protective effects of dairy products from colo rectal cancer is: Calcium in dairy products has a lower risk of bowel cancer and prevents development of polyps. Vitamin D in dairy products also has an ant carcinogenic property. This finding was consistent with systematic review and meta analysis conducted by Aune, D., et al (2011) on effect of dairy products and CRC risk in UK, data collected by searching pub med database on prospective studies which were published until may 2010, totally 19 cohort studies were selected and their relative risk was 0. 83 for 400 g/day of dairy products, for 200 g/day of milk intake relative risk was 0. 91 , the relative risk for cheese intake of 50 g/day was 0. 96 thus the study concluded that milk and dairy products were associated with reduction in CRC risk.
5. 1. 5 (f). Beef intake
Table 4. 2. 5(e) shows significant association between intake of beef and colo rectal cancer, at p < 0. 01, the odds ratio was 1. 514(intake of beef referred to non intake of beef ). Thus intake of beef increases risk for developing colo rectal cancer by 1. 5 times.
5. 1. 5 (g). Mutton intake
Table 4. 2. 5(e) shows significant association between mutton intake and colo rectal cancer, at p < 0, its corresponding odds ratio was 3. 272(mutton intake referred to non intake). Thus it is evident that taking mutton increases risk of colorectal cancer by 3. 2 times.
This findings was supported by English DR et al., (2004) conducted a cohort study on effect of chicken, red meat and fish consumption over the risk of CRC in Australia, the samples included in the study was 37, 112 residents from Melbourne. The data’s were collected using food frequency questionnaire. After follow up of 9 years 283 colon and 169 rectal cancers were identified. The result showed, the hazard ratios of rectal cancer due to consumption of both fresh and processed red meat was 2. 0 (1. 2-4. 2; P for trend = 0. 07) and 2. 3 (1. 1-3. 4; P for trend = 0. 09), [95% confidence intervals (95% CI)], while hazard ratio of Chicken consumption was 0. 7; 95% CI, 0. 6-1. 0; P for trend = 0. 03), thus it is weakly associated with CRC risk and the study concluded that processed meat and red meat are strong risk factors in the causation of CRC.
The mechanism of red meat towards the causation of colo rectal cancer that have been tested experimentally are, That high-fat diets could promote carcinogenesis via insulin resistance or fecal bile acidsCooking meat at a high temperature forms carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbonsThat carcinogenic N-nitroso compounds are formed in meat and endogenouslyThat heme iron in red meat can promote carcinogenesis because it increases cell proliferation in the mucosa, through lipoperoxidation and/or cytotoxicity of fecal water. Nitrosation might increase the toxicity of heme in cured products.
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5. 1. 5 (h). Chicken intake
Table 4. 2. 5(f) shows significant association between chicken intake, cooked and grilled meat intake and CRC. With regard to intake of chicken, there is significant association of intake of chicken and CRC at p < 0. 001. With regard to intake of cooked meat, there is significant association between cooked and CRC at p < 0. 001. The mechanism behind this is poultry contains small amounts of nutrients such as selenium and calcium that have been associated with lower risk of colorectal neoplasia.
5. 1. 5 (i). Grilled meat
Table 4. 2. 5(g) shows significant association between chicken intake, cooked and grilled meat intake and CRC, there is significant association of grilled meat and CRC at p < 0. The corresponding odds ratio is 9. 11(grilled meat intake referred to non intake of grilled meat). Thus it is evident that intake of grilled meat increases the risk for CRC by 9 times. This findings was supported case control study by Rashmi Sinha et al.,(1999) on effect of grilled meat and Colorectal polyps risk at Bethesda, National Naval Medical Center during april 1994 to september 1996, samples includes 146l cases were diagnosed with colorectal polyps and 228 Controls who does not have colorectal adenomas, food frequency questionnaire was used for data collection information was collected regarding meat-cooking techniques, frequency and grams of meat consumed in a day , cooking methods and temperature of cooking meat. The study concluded that increased intake of red meat, high temperature utilized for cooking such as grilling are associated with colo rectal polyps. The mechanism behind this includes, combination of meat with intense heat produces substances in the muscle proteins of red meat, poultry and seafood react under high heat to form carcinogenic compounds called heterocyclic amines (HCAs). HCAs can damage the DNA of our genes and contribute to the process of cancer development in colon and rectum.
5. 1. 5 (j) . Fried meat intake
Table 4. 2. 5(h) shows association of intake of fried meat and CRC, there is significant association between fried meat, and CRC at p < 0. 001, the odds ratio was 1. 7(intake of fried foods more than or equal to 2 per week referred to intake less than 2 per week). Thus it is evident that intake of fried foods increases the risk of colorectal cancer by 1. 7 times.
5. 1. 5 (k). Preserved food intake
Table 4. 2. 5(h) shows association of intake of preserved foods and CRC, there is significant association between preserved food and colo rectal cancer at p < 0, the corresponding odds ratio is 12. 3(preserved food intake referred to non intake of preserved food), odds ratio is 12. 3(preserved food intake referred to non intake of preserved food), Thus it is evident that intake of preserved food increase the risk of CRC by 12 times. The mechanism of preservative foods towards the causation of colo rectal cancer includes, during preserving foods may be cured using nitrites or nitrates. These act as preservatives to prevent food from spoiling, and they also add colors to the meat. Nitrites and nitrates are not cancer-causing by themselves, but in certain conditions in the body they can be changed into by-products called N-nitroso compounds, such as nitrosamines and nitrosamides. N-nitroso compounds are associated with an increased risk of cancer. This findings was supported by cohort study conducted by Ann Chao et al., (2005) in America on effect of meat consumption and risk of CRC, the samples of the study comprises of 48 610 adults aged between 50 to 74 years and were residing in 21 selected states of America samples selected by the use of population-based cancer registries, information collected about meat consumption during 1982 and again in 1992/1993, 1667 CRC cases were identified during this follow up period. The study result depicted that consumption of both red and processed meat in large quantity was associated with risk of CRC. Thus illuminates red and processed meat as risk factors of CRC.
