Cancer and environment
Colorectal cancer and environmental factors
Cancer is a group of diseases in which cells undergo uncontrolled division. These cells invade and destroy adjacent tissues and sometimes undergo metastasis thus spreading to other body locations by blood and lymph. Cancers are mainly associated to abnormalities of genetic materials in the cancerous cells. Scientists are discovering several factors both intrinsic and extrinsic which may contribute to cancer development. Today large number of cancers (2/3 of all cancers are somehow associated to environmental cause.(reference)
Environmental factors which include lifestyle choices such as smoking, diet, consistent sunlight exposure and sexual behaviors in addition to factors such as drugs, chemicals, workplace hazards, radiations, all of them contributing in a way or another to development of cancer or predisposing individuals who are subject to them. The importance of such environmental contributors is reassured by the fluctuating risk of cancer between different occupations and different countries upon different exposures.
Genes are considered a major player in cancer development thus leading to inheritable cancers and several genes were found to increase persons chance of getting cancers. Genes were also found to play a role in increasing susceptibility to certain environmental carcinogens. Thus, genes cannot be separated from environmental factors by which they are influenced.
Colorectal cancer which is considered the fourth (reference) most common cancer in the world and the third with respect to how deadly it is with respect to other cancers was found to develop from polyps inside the colon, polyps are benign growths which gets bigger as time passes , the development to malignancy was found to be associated with mutations in the Wnt signaling pathway (a deletion of a normal copy of APC adenomatous polyposis coli on chromosome 5 ,thus leaving a mutated tumor suppressor gene . In addition to that a mutant proto-oncogene (RAS) on chromosome 12 contribute to the malignancy with later deletion l mutation in the P53 tumor suppressor gene on chromosome 17.
All these mutation in addition to epigenetic modification of certain genes leads to such type of cancer ,leaving us with the question :
Could environmental factors play a role is such mutations and modification ,thus leading to CRC ?
Colon cancers which appear on the wall of the intestine were found to be curable by surgery however cancer which undergo metastasis are harder to cure and need chemotherapy.
Symptoms of this cancer depend on location and metastasis and may range from local simple discomfort to constitutional chronic bleeding.
Environmental factors may contribute in increasing the risk for developing colon cancer, these factors such as smoking, diet, physical inactivity, alcohol are few of the known risks that are associated to this type of cancer, while other factors such as calcium, vitamin D, folate, antioxidants and minerals may provide a protective effect
Tobacco products are considered responsible for about 1/3 of all cancer related death in the US every year. Eventhough we directly associates smoking with lung cancers, other cancers such as colorectal cancer may be related to smoking. cigarette smoke was found to contain about 100 substances which may cause caner. A study done by the American cancer society found that smoking women are 40% at a higher risk to die from colorectal cancer than nonsmoking women while smoking men are at 30% higher risk.
Epigenetic changes such as DNA methylation and microsatellite instability may provide possible cause of colorectal cancer in relation to exposure to smoke related substances
Diet , Physical inactivity and body weight
Studies are showing that heavy consumption of red meat and salt preserved foods may increase the risk to develop stomach and colorectal cancer, however people who consume fruits, vegetables, fish and high fiber diet are at lower risk of colorectal cancer (European perspective investigation of cancer and nutrition, 2005) and might be a protective factor.
According to a study done by Edward GIOVANNUCCI, rates of colorectal cancer increase as the level of economic development increase ( more meat in diet )
Being overweight is considered to be the most important cancer causing after tobacco, also physical inactivity was shown to account to 30% of major cancers and a decrease in the risk was found in active and athletic people. Physical activity was shown to be related to improving efficiency of free radicals searching enzymes, reducing triglyceride levels and improving insulin resistance.
He also found that excessive energy intake in respect to what is needed is an important factor that may cause colon cancer although this evidence is not strong since energy intake and usage cannot be precisely calculated. In addition to that, higher BMI (body mass index) may be associated with increase risk of colon cancer (Wu Ah, et al.). Estrogen was found to play a role in protection against Colon cancer (differences between premenopausal and postmenopausal women) (Terry PD et al., 2002). An approximate 30 to 50% decrease in colon cancer incidents was detected among physically active people and found that 3 to 4 hours of walking or jogging may put an individual in a better position with respect to colon cancer risk. (Martinez et al.,1997). To relate between obesity and colon cancer and to detect the underlying causes, a study was done by GIOVANNUCCI et al. and found that insulin resistance leading to hyperinsulinemia are risk factors of colon cancer because of the growth promoting ability of insulin which was later reassured by a study that found that diabetes mellitus is associated with higher risk of colon cancer. Also insulin like growth factor -1 was related to high colon cancer risk.
A study done by Bruce et al. showed that meat can deliver carcinogens such as N-nitroso compounds and heterocyclic amines which are produced after cooking. It was also found that meat upon cooking with olive oil and oxidants resistant fats prevent the effect of carcinogenesis thus although red meat possess some carcinogens, it may also provide protection. Upon experimentation done on mice, (Ahmed found that diet rich with poly unsaturated fatty acid has tumor suppression properties because of the effect of the fatty acid docosahexaionic acid that controls several genes responsible for angiogenesis. In addition to that and in the same study, corn oil rich diet lead to increased farnecyl protein transferase which is an enzyme known to catalyse farensylation of ras precursors. On the other hand, increased fish oil consumption decrease levels of FPTase thus preventing post trnasyaltional modification of ras thus resulting In reduction of colonic tumors. Fish oil was also found to protect from inflammation and fortify apoptosis in different mechanisms.
Because it is difficult to differentiate energy intake from dietary fat intake, it was hard to determine if carcinogenesis is due to increase calorie intake or due to fats. It has been hypothesized that iron found in meat may be associated to CRC due to facilitation of DNA methylation by increasing oxygen radical synthesis, but as we know, iron intake is essential dietary intake and cannot be reduced in diet.
fibers, which are, polysaccharides that don't undergo digestion in the small intestine (Insoluble fibers such as alpha-cellulose) stay for a short time in the intestine and thus reduce exposure to tumor promoters and carcinogens. Refind fibers was found to lack protective components that is originally found in plant cell walls such as suberin and lignin thus loosing their cancer protection ability due to loss of antioxidants properties. The effect on carcinogenesis by fibers was found to be related to the type of ingested fibers (graph)
According to the diet and cancer report, there is an evidence that alcoholic drinks increase the risk of developing CRC. Another study by smith et al., 2004 showed that people who drink more than 30 g. of alcohol in the day may have a slight increase in the risk for colorectal cancer. But this was not consistent with all types of spirits and beverages because wine was found to decrease the risk of CRC. A pooled analysis done in US , Canada and Finland showed that daily uptake of 45 g. of ethanol was associated in 40% increase in the risk of CRC. (Cho et al., 2004). On the other hand, the association between alcohol and colorectal cancer was present in smokers and absent in nonsmokers thus showing a combinatory effect of cigarettes and alcohol toward increasing the risk of CRC.
Calcium and vitamin D
A study done on animals (mice) lead to the conclusion that milk and calcium containing food in addition to Vitamin D prevents CRC by precipitating bile acids and fatty acids that over-irritate the epithelium of the colon which might be causes of tumorgenesis. In addition to that, calcium was found to block tumor promoting enzyme ornithine decarboxylase thus preventing CRC. (Armtsrong et al.). the role of calcium and vitamin D was found to be correlated as they both play a role in preventing carcinogenesis.
In humans, calcium bind to secondary bile acids and fatty acids in the colon (lamina) thus forming insoluble soaps reducing their growth and differentiation effect on the colon. Vitamin D also reduces colonic cell proliferation and induce differentiation via vitamin D receptors. A case control study by the Wisconsin University reassured that calcium uptake during 2 years before the interview had a protective effect on colorectal cancer. Vitamin D contribute to various signaling pathways (leading to cell cycle stoppage at the G0 G1 stage by upregulating P21 And p 27 and preventing the synthesis of polyamide needed for progression into the S phase of the cell cycle and reducing C-myc and C-phos oncogenic transcription factors in addition to blockage of Beta-catenin in APC and allowing mitosis by preventing apoptotic gene bcl-2. (Ahmed et al.)
Calcium, on the other hand, was found to activate protein kinase C and downstream cascades of cyclin D1…which may play a role in switching cancer off. (Ahmed et al.)
Vitamins and micronutrients
Studies on animals showed that tomato rich in beta-carotenene/retinol, vitamin E have a protective effect in rats at a risk of colorectal cancer (Loren et al.). polyphenolic flavonoids from plant origins| (vegetables and fruits|) were also found to be preventive to CRC.
Folate which is water soluble vitamin D was also found to modulate development of CRC, folate coenzymes which contribute to the formation of purines which are important for building nucleic acids and a deficiency in folate in replicating cells will cause a problematic DNA synthesis leading to cellular mutations and it was also hypothesized that specific site for DNA hypomethylation is the mechanism by which lack of folate causes CRC. Folate readministration to animals under study increase the level of P53 transcripts leading to adequate repair of DNA breaks.
Exposure to viruses especially human papilloma virus may be correlated to colorectal cancer (Bodaghi et al.) Presence of HPV DNA in colorectal cancer tissues suggested that HPV might be related to carcinogenesis of colorectal cancer, HPV 16 infections were found to be common in colorectal cancer tissues and adjacent non tumerous tissues which may relate to pathogenesis of CRC but the origin of HPV was not determined.
Women who start sexual intercourse and become sexually active at age 16 or younger or having multi sexual partners was found to possess increased level of CRC and infection HPV.
Racial and ethnic variables.
African Americans are