© Springer International Publishing Switzerland 2015
Omer Engin (ed.)Colon Polyps and the Prevention of Colorectal Cancer10.1007/978-3-319-17993-3_1313. Colon Cancer Risk and Prevention
(1)
Surgery Department, Buca Seyfi Demirsoy State Hospital, Izmir, Turkey
(2)
Emergency Department, Buca Seyfi Demirsoy State Hospital, Izmir, Turkey
(3)
Surgery Department, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
(4)
Surgery Department, Tepecik Training and Research Hospital, Izmir, Turkey
Definition of Cancer
Every day, thousands of cells die and thousands of cells proliferate in our bodies. This cell proliferation is not unlimited. Cells take their place in the normal structure depending on macroscopic and microscopic anatomic features of an organ. Cancer develops as the result of mutation of the genes that are responsible for the differentiation and regulation of cell growth. Multiple genes are affected in most tumors. Tumor suppressor genes may lose their function or oncogenes may be activated as a result [1]. Cell proliferation is uncontrolled and unlimited in cancer; it does not comply with the features of the tissue or organ and continues to grow by impairing the structure of the organ. This proliferation exceeds the limits of the organ and continues to proceed toward neighboring organs. After reaching a certain size, a cancer needs vessels for nutrition. Angiogenesis is the main requirement for tumorigenesis. Vascular endothelial growth factor A takes part in this process [2]. All organs and tissues of the body have blood and lymph vessels. Cancer cells grow and impair the wall structure of these vessels. The cells that enter the vessels proceed to distant organs via the vascular structure, reside there, and begin to proliferate, which leads to distant metastasis.
Breast cancer is the most commonly diagnosed and most fatal type of cancer among women. Lung cancer is the most common and most fatal type of cancer among men. Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. CRC occurs more frequently in Australia, New Zealand, Europe, and North America; it is less common in Africa and South Central Asia [3, 4].
Risk Factors in Colorectal Cancer
Family history, inflammatory bowel diseases (Crohn’s disease, ulcerative colitis), diabetes mellitus, smoking, alcohol use, meat and processed meat consumption, and the presence of adenomatous polyps are risk factors for CRC. Aspirin use, multivitamin use (supplemental folate and calcium), physical activity, calcium, and milk consumption may reduce CRC risk [5, 6].
Factors Increasing Risk for CRC
Family History
CRC risk is high among people with a family history of CRC and colorectal adenoma (CRA). Risk is very high among the relatives of patients diagnosed with CRC [7]. The risk is higher in first-degree relatives of patients with CRC and lower in second- and third-degree relatives [8]. CRC incidence and mortality were shown to decrease through removal of polyps that are detected in the course of colonoscopy screenings in individuals with a family history of CRC [9]. The American College of Gastroenterology (ACG), American Society of Gastrointestinal Endoscopy (ASGE), and American Gastroenterology Association (AGA) recommend colonoscopy screening every 5 years after age 40 for first-degree relatives of patients diagnosed with colon cancer before the age of 60. The ASGE and AGA recommend colonoscopy screening after age 40 and ACG recommends colonoscopy after age 50 for first-degree relatives of patients whose colon cancer was detected after age 60 [10].
Ergül et al. conducted a study in Ankara, Turkey. They performed screening colonoscopies in people who were older than 40 and had a family history of CRC in a first-degree relative. Eighty subjects participated in the study, and lesions were detected in 27.5 % of them. Distribution of the lesions were as follows: neoplastic lesions in 12 cases, cancer in 2, high-risk adenoma in 10, villous or tubulovillous adenoma in 6, tubular adenoma >10 mm in 4, low-risk lesions in 24, low-risk adenoma in 19, and hyperplastic polyps in 5. Most (approximately half) of the lesions were located in the rectosigmoid colon, followed by the descending and transverse colon. A few pathologies were detected in the right hemicolon. The authors recommended screening colonoscopy after age 40 and suggested that screening may decrease the incidence of colon cancer [10].
Hereditary Syndromes
History of Previous Treatment for Certain Cancers
Colorectal cancer risk was reported to be increased in patients who have a history of testicular cancer and prostate cancer. Radiotherapy may be the reason for this. The rectum is exposed to radiation in the course of radiotherapy. The American Cancer Society recommends earlier screening for these patients who have increased risk for CRC, as radiotherapy directly applied on the abdomen is among the risk factors that increase CRC risk [11, 12].
Night Shift Work
Colon cancer risk was reported to be increased in women who work the night shift for 3 days weekly for 15 years. Melatonin concentration is suggested to be a factor in this risk. More studies are required on this subject [13].
Presence of Multiple Primary Cancers
Multiple primary tumors may develop in a patient concurrently or at different times and are reported as 0.7–11.7 % of all carcinomas. The risk for secondary cancer is 1.29-fold greater in patients with primary tumors compared with healthy people. Multiple primary tumors are seen more in elderly people (>65). These may be divided as synchronous and metachronous. If the second tumor is detected within 6 months following the diagnosis of the first tumor, it is defined as a synchronous tumor; if detected 6 months or more after the diagnosis of the primary tumor it is a metachronous tumor. A total of 75 patients (32 female, 43 male) who had double primary tumors were analyzed in the study of Dogu et al. Primary tumors in these patients were as follows: 22 breast cancer, 15 larynx cancer, 8 colorectal cancer, 5 prostate cancer, 3 bladder cancer, and 3 lymphoma. The second primary cancers were as follows: 22 non-small-cell lung cancer and mesothelioma and 16 gastrointestinal cancers (5 colorectal carcinoma). In 14 patients, both primary and secondary tumors were breast cancer [14].
Age
Incidence of colon cancer increases with age. It is most common between 60 and 75 years. Ninety percent of new cases and 94 % of deaths are seen above age 50 [15].
Inflammatory Bowel Diseases
Coexistence of chronic inflammation and cancer have shown by studies on inflammatory bowel disease and colon cancer. Colon cancer development risk increased five to sevenfold among subjects with chronic ulcerative colitis or Crohn’s disease. This risk is accepted to increase after 8 years of disease. Cancer risk increases as duration of inflammation increases [16, 17]. CRC risk increased 2.4-fold in patients with ulcerative colitis. Male gender, being diagnosed with ulcerative colitis at an early age, and extensive colitis lead to an increase in cancer risk [18]. The risk for CRC in inflammatory bowel diseases has changed over time with developments in treatment methods. Jess et al. stated that cancer risk tended to decrease as a result of developments in the treatment of inflammatory bowel diseases [19]. Nowacki et al. reported that CRC risk was still high despite development in modern treatment methods in ulcerative colitis. Primary sclerosing cholangitis is a risk factor for CRC and dysplasia in patients with Crohn’s disease [20].
Diabetes
CRC risk was reported to be 30 % higher in patients with diabetes mellitus compared with those without diabetics. This risk is valid both for males and females. Type 2 diabetes carries such risk factors for carcinogenesis as hyperinsulinemia, insulin resistance, hyperglycemia, and hypertriglyceridemia. Insulin may stimulate cell proliferation directly through insulin receptors or insulin-like growth factor (IGF)-1 receptor. Insulin, C-peptide (a marker of insulin secretion), or elevated IGF-1 was shown to increase CRC risk. Prolonged intestinal transit time may also increase CRC risk. Colonic mucosa is exposed to potential carcinogenesis and fecal bile acids longer due to prolonged intestinal transit time. Fecal bile acids were shown to promote CRC in animal models. Some studies have shown that mortality due to CRC was increased in diabetic patients; however, this risk could not be detected in other studies [21]. Endogenous hyperinsulinemia is a potential risk factor for CRC. Yang et al. reported that chronic insulin treatment increased CRC risk [22].
Smoking
Cigarette smoke contains many carcinogens. These carcinogens may lead to many changes in DNA and even irreversible injury and colon cancer. The colonic mucosa may be exposed to the carcinogens in cigarette smoke through blood circulation or ingestion of the saliva contaminated with smoke [23]. Smokers are known to have 18 % higher risk for colon cancer. Proximal colon cancer risk was reported to be higher than distal colon cancer risk in these individuals. However, a significant difference was not reported between distal and proximal cancer risk in other studies. Therefore, more aggressive colon cancer screening may be recommended in these individuals. The American College of Gastroenterology supports colorectal cancer screening earlier (at age 45 instead of 50) in heavy smokers [4, 23–26]. Smoking is among the causes of microvascular diseases that lead to tissue ischemia. Tissue ischemia may cause leakage of the anastomoses. Studies have reported that anastomosis leakage is higher after colon surgery among smokers [27, 28].
Alcohol Use
Alcohol consumption is among the risk factors for cancer development in humans. Alcohol intake is related to cancers of the oral cavity, pharynx, larynx, esophagus, liver, female breast, and colorectum. Alcohol consumption-related colorectal cancer risk is similar among males and females. The results of the meta-analysis published by Fedirko et al. in 2011 are interesting. They divided alcohol consumption into mild, moderate, and severe. People who drank 50 g/day alcohol or more were defined as heavy drinkers and had a 52 % higher risk of CRC development. People drinking 12.6–49.9 g alcohol daily were defined as moderate drinkers and had a 21 % greater risk. Mild drinkers, those consuming 12.5 g/day alcohol or less had 0–7 % higher risk than those who did not drink alcohol. These results indicate that cancer risk is associated with the dose of alcohol used. CRC risk increases as alcohol consumption increases. Alcohol consumption was reported as a risk factor for anastomosis leakage in patients who underwent resection and anastomosis because of cancer [28–32].
Red Meat and Processed Meat Consumption
Red meat and processed meat consumption increase CRC risk. Potential biologic mechanisms that may explain this increase were reported. Heterocyclic amines that are present in meat cooked at high temperature have potential mutagenic effects. The second mechanism is endogenous formation of N-nitroso compounds in the gastrointestinal tract. Endogenous nitroso compounds are formed dose-dependently. Nitrites and nitrates are used as preservers in food. They form exogenous nitrites. Exogenous nitrites act as endogenous nitrites. Cancer risk related to processed meats and red meats is moderate (2–30 %). Eating less than 500 g red meat weekly and avoiding processed meat is recommended [33–36].
Gall Bladder Diseases
Cholecystectomy has a moderate risk for colon cancer. This risk was not shown for rectum cancer. Biologic mechanisms related to intestinal exposure to bile may be responsible for this risk. Presence of gallstone increases colonic adenoma risk. Chiong et al. reported that cholelithiasis increased rectal cancer risk in their meta-analysis [37– 40].
Presence of Adenomatous Polyps
Presence of adenomatous polyps is a risk factor for colon cancer. Colonic adenomatous polyps have risk factors for malignant transformation. These risk factors may be classified as low- and high-risk factors:
High risk: Large size (especially >1.5 cm), sessile or flat, severe dysplasia, presence of squamous metaplasia, villous architecture, polyposis syndrome (multiple polyps)
Low risk: Small size (especially <1.0 cm), pedunculated, mild dysplasia, no metaplastic areas, tubular architecture, single polyp
Obesity
Obesity is considered to be responsible for colon cancer, postmenopausal breast cancer, endometrial cancer, and esophageal cancer [45]. Obesity increases the risk for colon cancer by 30–70 % in males. This ratio is lower in females. Visceral fat and abdominal obesity are reported to be more important than subcutaneous fat tissue for risk [46–49].
Leptin is released from adipose tissue and acts through binding its receptor. Circulating leptin concentration is directly proportional to adipose tissue mass of the body. Leptin primarily controls fat deposition and also stimulates cell proliferation and induces angiogenesis. Studies report that leptin may play a role in CRA development [50].
Metabolic syndrome is the clinical condition composed of three or more of the following components: high blood pressure, increased waist circumference, hypertriglyceridemia, low HDL cholesterol, and diabetes mellitus. Metabolic syndrome seems to be a risk factor for CRC in males; however, it is not a risk factor for females [51].
Infections
Helicobacter pylori may lead to gastritis, ulcer, and gastric neoplasia. H. pylori infection also is associated with greater risk for colonic adenomatous polyp development and cancer. Colon cancer risk may be up to 30 % higher compared with healthy individuals [52–54].
Schistosomiasis is a frequent parasitic disease in underdeveloped countries. It may be transmitted by drinking contaminated water and may cause reinfection. Chronic schistomiasis may lead to cystitis and fibrosis and increases bladder, liver, and rectum cancer risk [16].
Human papilloma virus (HPV) infection is related to cervical cancer. An association was detected between HPV infection and colorectal cancer by the meta-analysis of Damin et al. Bowel cancer risk increases tenfold among individuals with HPV infection [55, 56].
Human cytomegalovirus (HCMV) is a beta-herpes virus and may be seen endemically. It may lead to a life-threatening infection in immunosuppressed subjects. Harkins et al. showed that nucleic acids and proteins of HCMV might have been present in neoplastic cells in colorectal polyps and adenocarcinomas. This infection was reported to play an important role in the oncogenic pathway in colon cancer [57].
Organ Transplantation
Organ transplantation increases the risk for other organ cancers. In a study of Adami et al., colorectal cancer risk was reported to be increased fourfold among patients who undergo organ transplantation [58].
Non-alcoholic Steatohepatitis
Wong et al. reported the coexistence of non-alcoholic steatohepatitis with CRA and advanced neoplasm was high in their study conducted in 2011. These adenomas were reported to be more frequent in the right hemicolon. They recommended colorectal cancer screening in this high-risk group [59].
Factors That Decrease Risk
Aspirin Use
Prophylactic aspirin use is recommended for its cardiovascular benefits today, although it may lead to hemorrhagic complications [60]. Aspirin is known to reduce the incidence of and mortality associated with CRC. Aspirin use also reduces the recurrence of adenomatous polyps. The mechanism of action is not exactly known. Aspirin is an mTOR (mechanistic target of rapamycin) inhibitor and AMKP (adenosine monophosphate-activated protein kinase) activator. These mechanisms of action may be responsible for prevention of CRC development. Studies are available reporting that long-term (median 18 years) low-dose (75–300 mg daily) aspirin use reduces colon cancer incidence by 76 % and mortality by 65 %; however, such significant results could not be found for rectal cancer [60–62].
Statin Use
Statin is 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. Statin is widely used in the treatment of hypercholesterolemia. Some have reported that statin reduced colorectal cancer risk in case-control studies. However, the benefit of statin could not be shown in most cohort studies [63].
Biphosphonate Use
Biphosphonates are usually used for treatment of osteoporosis and bone metastasis caused by breast cancer. Studies are available reporting that more than 1 year biphosphonate use reduces CRC risk by 59 %. The mechanism of action is not fully known [64].
Folate Intake
Folate plays a role in DNA methylation and DNA synthesis and repair. Studies are available reporting that low dietary intake of folate increases CRC risk. Results have been obtained indicating that folate intake reduces colorectal cancer risk. Zschabgitz et al. reported that increased folate intake in the early post-fortification period could lead to a transient increase in CRC risk [65–68].
Calcium and Vitamin D
Calcium has been suggested to reduce CRC risk by joining with toxic secondary bile acids and ionizing fatty acids, forming an insoluble soap in the colonic lumen, or by reducing the proliferation of colonic mucosa and promoting cellular differentiation. Some studies have reported that vitamin D deficiency increases mortality risk in CRC; vitamin D intake reduces CRC risk [69–71].
Physical Activity
Physical activity reduces the risk for many cancer types, including breast, colon, endometrial, and prostate cancers. A healthy body weight is achieved by physical activity. Hormones are secreted more properly (sex hormones, insulin, and prostaglandins) and chronic diseases may improve (heart diseases, diabetes, osteoporosis, and hypertension). Lack of physical activity increases cancer risk by 9–19 %. Moderate to vigorous physical activity for 30–60 min 5 days per week is recommended for cancer prevention [72–75].
Other Factors That Decrease the Risk
Screening Programs
Screening programs were seen to have a significant effect in reducing CRC incidence and mortality. There is a consensus that CRC screening should begin at age 50. The adverse effects of colonoscopy are low; however, they are seen more in elderly patients due to comorbidities. Therefore, some guidelines recommend that screening should be stopped at age 75 and others recommend stopping at age 80. Medical history, family history, colorectal polyps, and chronic inflammatory bowel diseases are among the major risk factors for CRC. Familial adenomatous polyposis and hereditary nonpolyposis colorectal cancers (Lynch syndrome) are high-risk factors for CRC. Smoking increases polyp development [5].
Screening has the potential to prevent colorectal cancer, as the majority of CRCs develop from adenomatous polyps. Also, newly developing CRCs may be diagnosed in the early stage, when the chance for curative treatment is higher. CRCs usually develop slowly within 10–15 years and typically begin as a noncancerous polyp. Polyps may later transform into cancer. These types of polyps are defined as adenomatous polyps or adenoma. Ten percent of adenomas transform into cancer. Adenomas are quite frequent; one or more adenomas develop in a third to half of the population. Ninety-six percent of colorectal cancers are adenocarcinomas. The majority of these cancers develop from adenomatous polyps. Cancer begins in the colonic wall; after it develops, it tries to invade blood and lymph vessels and metastasized to the lymph nodes. Cancer metastasizes to the liver and spleen hematogenously, invading the neighbor organs and ovaries via extension and seeding in the abdominal cavity. Many staging systems are available for colon cancer. The TNM and SEER (Surveillance, Epidemiology, and End Result) staging systems are most frequently used.
SEER
In situ: Preinvasive lesion. The lesion did not begin to invade the colorectal wall.
Local: Cancer is within the colonic wall. It has not invaded the neighboring tissues.
Regional: Cancer has invaded the neighboring tissues or lymph nodes.
Distant: Cancer has spread to other body parts (liver, lungs).
Ratio of cancer is 5 % among males and females in the United States.
Gender: Colorectal incidence and mortality is higher in males.
Prevention of Colorectal Cancer
Colorectal cancer is the second leading cause of cancer-related deaths. Colonoscopic screening may reduce CRC risk by 90 %. Another benefit of screening colonoscopy that it provides a chance for cure, which may not be possible when diagnosis occurs at an advanced stage. Studies are available reporting the incidence of adenomatous polyps as 25 % in males and 15 % in females at age 50. Most of these polyps are asymptomatic. Colonoscopy is important for prevention of colon cancer as it may detect and remove these polyps [87]. Changing lifestyle is reported to reduce CRC risk [88].
Fiber-rich feeding is reported to reduce CRC risk. Fibers are suggested to absorb and dilute carcinogens, modulate colonic transit time, alter bile acid metabolism, lower colonic pH, and increase short-chain fatty acid production. High intakes of fiber or vegetables is reported to decrease CRC risk by 40–50 %. However further studies are required. Red meat consumption is reported to increase CRC risk. Fish may be chosen as an alternative animal protein source. Reducing alcohol intake reduces CRC risk. Smoking should certainly be avoided. Obesity should be avoided. Studies have reported that participating in physical activity could reduce CRC risk by 24 %. Calcium is suggested to reduce CRC risk through binding toxic secondary bile acids [69, 88–91].
The most important risk factor for colon cancer is advanced age. Screening tests are of great importance for prevention of CRC. Precancerous lesions may be detected in the early stage, before cancer has developed. Cancer may be prevented via polypectomy in early stages.
Screening tests for CRC may be divided into two large groups:
1.
Stool tests: occult blood and exfoliated DNA
2.
Structural examinations: colonoscopy, virtual colonoscopy
Stool tests for occult blood include the guaiac test and fecal immunochemical test (FIT) [92]. The guaiac test measures the occult blood in stool. Some foods may affect this test, therefore, the following foods should not be consumed for at least for 3 days prior to the test: red meat, cantaloupe, uncooked broccoli, turnips, radishes, and horseradish. Some drugs, including vitamin C, aspirin, ibuprofen, and naproxen, may also affect test results. A negative test result indicates the absence of blood in the stool. A positive test result indicates that a nonvisual amount of blood is present in the stool. Studies are available reporting 11 % false positivity with a normal diet. False negative results may reach 48 % [93, 94].
The fecal immunochemical test (FIT) is a newer occult blood test. The test is performed with monoclonal antibodies developed against the beta subunit of human hemoglobin. A normal test result indicates the absence of blood in the feces. The sensitivity of the test is high; it is more sensitive than the guaiac test [95, 96].
The exfoliated DNA test may diagnose CRC and large adenomas with a high sensitivity. This provides early diagnosis and curability. Sessile serrated polyps larger than 1 cm may be diagnosed with this method [97, 98].
Colorectal screening is recommended for asymptomatic males and females after 50 years of age. However, colonoscopy should be performed if indicated, as stated in the Chap. 5 on colonoscopy.
Fecal occult blood test (FOBT), fecal immunochemical test (FIT), stool DNA test, flexible sigmoidoscopy, colonoscopy, double contrast barium enema (DCBE), and CT colonoscopy are recommended screening tests after 50 years of age. Flexible sigmoidoscopy or DCBE are recommended every 5 years and colonoscopy is recommended every 10 years after 50 years of age. CT colonoscopy may be performed every 5 years when colonoscopy cannot be performed. Screening options may vary depending on the risks, patient preference, and availability. FOBT and FIT may be performed once a year. The stool DNA test has been newly recommended and a certain interval is not yet available. Colonoscopy intervals may be more frequent if an adenomatous precancerous condition is detected on colonoscopy (see Chap. 5) [99–101].
Related posts:
Lower Gastrointestinal Tract Endoscopy in Pregnant Women
Preoperative, Intraoperative and Postoperative Management of Colonoscopic Procedure
Follow-Up of a Pregnant Patient During Colonoscopy
Colonoscopy and Infectious Disease
Colon Polyps and Radiologic Approach
Colonoscopy and Cardiovascular System
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
