Colorectal Cancer A Literature Review - 2200 Words

Colorectal Cancer: A Literature Review (Dissertation Review Sample) Content: Literature ReviewColorectal cancer is a complex disease whose origin is likely multi-factorial in nature. In general, the etiology of CRCA remains unknown. Evidence from ecologic and migrant studies shows that environmental or lifestyle factors may play important roles in CRCA risk (Winawer et al., 2003). Generally, a diet that is high in red meat and fat (and usually low in fruit, vegetable, and fiber intake) appears to increase risk while high calcium, vegetable, fruit, fiber, and folate intake have been associated with decreased risk of colorectal cancer (Jemal et al., 2007). Decreased risk of CRCA and adenoma also has been observed among those with regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) (Cleveland Clinic). In addition, a physically active lifestyle and maintenance of normal body weight were associated with a decreased risk of CRCA (Benson, et al., 2004). Although environmental factors play a role in colorectal cancer risk, genetic factors obviously play a part in its etiology (Institute of Medicine).Given that both genetic and environmental factors play roles in colorectal cancer,failure to take into account both factors can lead to bias in the estimation of disease risk. With the application of genetic and molecular techniques in epidemiology, epidemiological research has allowed us to understand roles of both environmental exposures and genetic susceptibility in colorectal cancer etiology. This is the important step in understanding colorectal cancer etiology. Interest in the relationship between environmental exposures and genetic susceptibility on cancer risk is growing and a number of studies are currently underway to investigate these interactions. However, the literature on examining potential interactions between environmental and genetic factors on colorectal cancer risk is still sparse. Well-designed studies investigating these interactions would increase our understanding the etiology of ca ncer, which in turn could allow identification of high-risk groups in the general population. Eventually, this would lead to developing the most appropriate prevention or treatment regimes. We hope that this literature research paper will add valuable information to the literature.Selected Environmental FactorsDietDiet has been suggested to play an important role in the etiology of colorectalcancer. It has been estimated that differences in diet may account for most of thevariation among countries in the incidence of colorectal cancer (Ferrandez, et al., 2013). As stated before, numerous dietary factors have been associated with colorectal cancer risk including high intake of fat and meat intake, and low intake of vegetables, fruits, fiber, folate, calcium, and some antioxidants (Crucitti, et al., 2005). However, unlike results from ecological studies and laboratory experiments, findings from analytic epidemiological studies have beeninconsistent. Although much confusion remains, va rious mechanisms have beenproposed to explain the effects of dietary factors on colorectal carcinogenesis. Theseinclude modification of the putative damaging effects of bile acids on colonic mucosa,direct damage to DNA or act as growth factors by products of fat peroxidation, changesin colonic bacterial metabolism, and decreased protection due to inadequate antioxidants(Crucitti, et al., 2005).This inconsistency of the association between diet and colorectal cancer may dueto methodologic limitations, including a lack of variability in nutrient intakes in Westerncountries in which these epidemiologic studies are conducted (Coons, et al., 2000), and difficulty of study participants to recall past dietary intake with sufficient accuracy. Randommisclassification of nutrient intakes, possible biases related to psycho-behavioral traits ofresearch subjects (e.g., social desirability (Macran Kind 2003), recall bias of dietary intake according to disease status, undetected confounding, and other unidentified factors can combine to obscure true diet-disease relationships. In addition, the difference within populations ofindividual susceptibility to diet may contribute, in part, to this inconsistency. Thishypothesis is supported by studies showing that the risk of colorectal cancer is notincreased in the spouses of cases compared with that of the general population (Institute of Medicine),despite presumably similar exposures. Thus, the level of genetic susceptibility to dietary exposure may contribute to the variation in individual risk of cancer. Therefore, inabilityto stratify subjects by susceptibility may explain the lack of association of dietary factorswith colorectal cancer in many epidemiological studies.Fat and MeatEvidence from laboratory animal experiments has shown a positive associationbetween dietary fat or meat intake and colorectal cancer. In addition, this hypothesis was further supported by ecologic and migrant studies. A recent international correlati on study in 21 countries found a correlation coefficient of 0.62 between age-adjusted colon cancer incidence rates and total fat consumption. Dietary fat is thought to be one of the main risk factors on the basis of reports of positive associations between diet and colorectal cancer. However, analytic epidemiological evidence of dietary fat and colorectal cancer risk is inconclusive. Most early case-control studies have provided evidence for a relation between colorectal cancer and fat consumption. Cohort studies, however, have not provided supportive evidence for such an association. Four out of five cohort studies that studied dietary fat intake and colon cancer found no association, only one found an increased risk with fat intake. In this large cohortstudy, the Nurses Health Study, the highest quintile of total fat intake was associated with a 2-fold increase in risk of colon cancer compared with those in the lowest quintile (Willett et al., 2000).A recent pooled analysis includ ing 13 case-control studies reported that there was noassociation between total fat intake and risk of colorectal cancer. A number of studies have investigated the association between saturated or animal fat intake and colorectal cancer risk (5;75;76). Results from these studies have been inconsistent, but showed a stronger risk with animal fat than with total fat intake. Among these studies, 11 out of 19 studies showed some evidence of increased risk with higher intakes of animal fat, two of them showed a weak inverse association, and six of them found no association (Kievit van de Velde, 1990).Findings for specific foods produce stronger effects than nutrient-based results. For example, the Nurses Flealth Study reported that women who consumed red meat frequently had a 2.5-fold increase in colon cancer risk compared with those consumed meat rarely (Willett et al., 2000). A meta-analysis of 13 prospective studies has reported an increased risk of colorectal cancer with a daily inc rease of lOOg of all meat or red meat. However, several other large cohort studies showed no increase in colorectal cancer risk with meat consumption (Willett et al., 2000).Numerous case-control studies have investigated the association of meat intake and colorectal neoplasia (cancer or adenoma). As with the cohort studies, all estimates of risk are increased or null with higher intake of meat. In a recent meta-analysis of 32 case-control and 13 cohort studies of meat consumption and colorectal cancer, meat consumption is associated with a modest increase in colorectal cancer risk, particularly red meat and processed meat. In summary, findings support a stronger association of meat intake and colorectal cancer, while animal fat intake or specific fatty acids are possibly associated with an increased risk for colorectal cancer.Vegetables and FruitsDiets rich in vegetables, fruits or antioxidants may have a protective effect through reducing oxidative damage or inflammatory responses in the colon. For many years, a diet rich in vegetables and fruits has been associated with a reduced risk of colorectal cancer in observational studies. Numerous case-control studies have investigated the association of vegetables and fruits consumption and colorectal cancer risk. In a summary report, 17 out of 21 case-control studies reported a reduced colon cancer risk with high consumption of at least one category of vegetable or fruit. In addition, results from a recent meta-analysis including sixteen case-control studies reported that high intake of vegetables was associated with a combined odds ratio of 0.48 (95% Cl, 0.41-0.57) for colon cancer risk. Most, if not all, rectal cancer case-control studies have found a statistically significant inverse association for at least one vegetable or fruit category intake (94). However, some recent results of epidemiologic studies do not support the hypothesis of the protective role of vegetables and fruit on colorectalcancer that was r eported in earlier studies. Among seven cohort studies, five of them found no association for vegetables and fruits consumption and colorectal cancer risk (88;96-100), and two of them found an inverse association. On the other hand, a recently published large case-control study reported that vegetables, particularly dark green vegetables, reduced risk for colon cancer (102). Methodologic limitations in diet assessment could be one explanation for these conflicting results such as recall bias from case-control study, or self-reporting biases associated with the food frequency questionnaire (FFQ). For the null results from large cohort studies, it is possible that the range of vegetable and fruit intake within the prospective population is not wide enough to allow detecting a significant effect.Calcium and Vitamin DSeveral plausible biological mechanisms of a pro... Colorectal Cancer A Literature Review - 2200 Words Colorectal Cancer: A Literature Review (Dissertation Review Sample) Content: Literature ReviewColorectal cancer is a complex disease whose origin is likely multi-factorial in nature. In general, the etiology of CRCA remains unknown. Evidence from ecologic and migrant studies shows that environmental or lifestyle factors may play important roles in CRCA risk (Winawer et al., 2003). Generally, a diet that is high in red meat and fat (and usually low in fruit, vegetable, and fiber intake) appears to increase risk while high calcium, vegetable, fruit, fiber, and folate intake have been associated with decreased risk of colorectal cancer (Jemal et al., 2007). Decreased risk of CRCA and adenoma also has been observed among those with regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) (Cleveland Clinic). In addition, a physically active lifestyle and maintenance of normal body weight were associated with a decreased risk of CRCA (Benson, et al., 2004). Although environmental factors play a role in colorectal cancer risk, genetic factors obviously play a part in its etiology (Institute of Medicine).Given that both genetic and environmental factors play roles in colorectal cancer,failure to take into account both factors can lead to bias in the estimation of disease risk. With the application of genetic and molecular techniques in epidemiology, epidemiological research has allowed us to understand roles of both environmental exposures and genetic susceptibility in colorectal cancer etiology. This is the important step in understanding colorectal cancer etiology. Interest in the relationship between environmental exposures and genetic susceptibility on cancer risk is growing and a number of studies are currently underway to investigate these interactions. However, the literature on examining potential interactions between environmental and genetic factors on colorectal cancer risk is still sparse. Well-designed studies investigating these interactions would increase our understanding the etiology of ca ncer, which in turn could allow identification of high-risk groups in the general population. Eventually, this would lead to developing the most appropriate prevention or treatment regimes. We hope that this literature research paper will add valuable information to the literature.Selected Environmental FactorsDietDiet has been suggested to play an important role in the etiology of colorectalcancer. It has been estimated that differences in diet may account for most of thevariation among countries in the incidence of colorectal cancer (Ferrandez, et al., 2013). As stated before, numerous dietary factors have been associated with colorectal cancer risk including high intake of fat and meat intake, and low intake of vegetables, fruits, fiber, folate, calcium, and some antioxidants (Crucitti, et al., 2005). However, unlike results from ecological studies and laboratory experiments, findings from analytic epidemiological studies have beeninconsistent. Although much confusion remains, va rious mechanisms have beenproposed to explain the effects of dietary factors on colorectal carcinogenesis. Theseinclude modification of the putative damaging effects of bile acids on colonic mucosa,direct damage to DNA or act as growth factors by products of fat peroxidation, changesin colonic bacterial metabolism, and decreased protection due to inadequate antioxidants(Crucitti, et al., 2005).This inconsistency of the association between diet and colorectal cancer may dueto methodologic limitations, including a lack of variability in nutrient intakes in Westerncountries in which these epidemiologic studies are conducted (Coons, et al., 2000), and difficulty of study participants to recall past dietary intake with sufficient accuracy. Randommisclassification of nutrient intakes, possible biases related to psycho-behavioral traits ofresearch subjects (e.g., social desirability (Macran Kind 2003), recall bias of dietary intake according to disease status, undetected confounding, and other unidentified factors can combine to obscure true diet-disease relationships. In addition, the difference within populations ofindividual susceptibility to diet may contribute, in part, to this inconsistency. Thishypothesis is supported by studies showing that the risk of colorectal cancer is notincreased in the spouses of cases compared with that of the general population (Institute of Medicine),despite presumably similar exposures. Thus, the level of genetic susceptibility to dietary exposure may contribute to the variation in individual risk of cancer. Therefore, inabilityto stratify subjects by susceptibility may explain the lack of association of dietary factorswith colorectal cancer in many epidemiological studies.Fat and MeatEvidence from laboratory animal experiments has shown a positive associationbetween dietary fat or meat intake and colorectal cancer. In addition, this hypothesis was further supported by ecologic and migrant studies. A recent international correlati on study in 21 countries found a correlation coefficient of 0.62 between age-adjusted colon cancer incidence rates and total fat consumption. Dietary fat is thought to be one of the main risk factors on the basis of reports of positive associations between diet and colorectal cancer. However, analytic epidemiological evidence of dietary fat and colorectal cancer risk is inconclusive. Most early case-control studies have provided evidence for a relation between colorectal cancer and fat consumption. Cohort studies, however, have not provided supportive evidence for such an association. Four out of five cohort studies that studied dietary fat intake and colon cancer found no association, only one found an increased risk with fat intake. In this large cohortstudy, the Nurses Health Study, the highest quintile of total fat intake was associated with a 2-fold increase in risk of colon cancer compared with those in the lowest quintile (Willett et al., 2000).A recent pooled analysis includ ing 13 case-control studies reported that there was noassociation between total fat intake and risk of colorectal cancer. A number of studies have investigated the association between saturated or animal fat intake and colorectal cancer risk (5;75;76). Results from these studies have been inconsistent, but showed a stronger risk with animal fat than with total fat intake. Among these studies, 11 out of 19 studies showed some evidence of increased risk with higher intakes of animal fat, two of them showed a weak inverse association, and six of them found no association (Kievit van de Velde, 1990).Findings for specific foods produce stronger effects than nutrient-based results. For example, the Nurses Flealth Study reported that women who consumed red meat frequently had a 2.5-fold increase in colon cancer risk compared with those consumed meat rarely (Willett et al., 2000). A meta-analysis of 13 prospective studies has reported an increased risk of colorectal cancer with a daily inc rease of lOOg of all meat or red meat. However, several other large cohort studies showed no increase in colorectal cancer risk with meat consumption (Willett et al., 2000).Numerous case-control studies have investigated the association of meat intake and colorectal neoplasia (cancer or adenoma). As with the cohort studies, all estimates of risk are increased or null with higher intake of meat. In a recent meta-analysis of 32 case-control and 13 cohort studies of meat consumption and colorectal cancer, meat consumption is associated with a modest increase in colorectal cancer risk, particularly red meat and processed meat. In summary, findings support a stronger association of meat intake and colorectal cancer, while animal fat intake or specific fatty acids are possibly associated with an increased risk for colorectal cancer.Vegetables and FruitsDiets rich in vegetables, fruits or antioxidants may have a protective effect through reducing oxidative damage or inflammatory responses in the colon. For many years, a diet rich in vegetables and fruits has been associated with a reduced risk of colorectal cancer in observational studies. Numerous case-control studies have investigated the association of vegetables and fruits consumption and colorectal cancer risk. In a summary report, 17 out of 21 case-control studies reported a reduced colon cancer risk with high consumption of at least one category of vegetable or fruit. In addition, results from a recent meta-analysis including sixteen case-control studies reported that high intake of vegetables was associated with a combined odds ratio of 0.48 (95% Cl, 0.41-0.57) for colon cancer risk. Most, if not all, rectal cancer case-control studies have found a statistically significant inverse association for at least one vegetable or fruit category intake (94). However, some recent results of epidemiologic studies do not support the hypothesis of the protective role of vegetables and fruit on colorectalcancer that was r eported in earlier studies. Among seven cohort studies, five of them found no association for vegetables and fruits consumption and colorectal cancer risk (88;96-100), and two of them found an inverse association. On the other hand, a recently published large case-control study reported that vegetables, particularly dark green vegetables, reduced risk for colon cancer (102). Methodologic limitations in diet assessment could be one explanation for these conflicting results such as recall bias from case-control study, or self-reporting biases associated with the food frequency questionnaire (FFQ). For the null results from large cohort studies, it is possible that the range of vegetable and fruit intake within the prospective population is not wide enough to allow detecting a significant effect.Calcium and Vitamin DSeveral plausible biological mechanisms of a pro...