___________________________________________________________________________ Colorectal Cancer
(with propofol), recognition that malignancy is more common in the right colon with attenuated FAP, and the growing tendency to defer surgery for a number of years. Individuals testing negative for an otherwise known family mutation do not need FAP-oriented surveillance and can undergo average-risk population screening. In the case of families where no family mutation has been identified in an affected person, clinical surveillance is warranted [90; 96; 103]. Colon surveillance should not be stopped in carriers of an APC mutation who do not yet manifest polyps, because adenomas occasionally do not appear before the fourth and fifth decades of life. In some circumstances, full colonoscopy is preferred over the more limited sigmoidoscopy. Tolerability of endoscopic procedures among pediatric patients has improved with the use of deeper intravenous sedation [90; 96; 103]. Interventions . After an APC mutation is identified in a patient or member of their family, evaluation for polyposis by flexible sigmoidoscopy or colonoscopy begins promptly. In those showing polyps, the only effective management to prevent colorectal cancer is eventual colectomy. In patients with early-stage classic FAP, the surgeon, endoscopist, and patient/family may opt to delay surgery for several years in the interest of achieving social milestones. Carefully selected patients with attenuated FAP who show minimal polyp burden and are of advanced age may also defer decision-making about colectomy [111]. The timing of risk-reducing surgery is based on symptomatology and the number, size, and histology of polyps. Surveillance colonoscopy is not useful after numerous polyps have developed, because it is no longer possible to remove and biopsy all of them. It is appropriate for patients at this time to consult with a surgeon experienced with available options, including total colectomy and postcolectomy reconstruction techniques. Rectum-sparing surgery followed by sigmoidoscopic surveillance of the remaining rectum is an option for patients who wish to avoid total colectomy, provided they are able to understand the risks and consequences and to follow through with surveillance recommendations [111]. Familial Colorectal Cancer Many families exhibit aggregation of colorectal cancer and/ or adenomas in the absence of known or identifiable genetic susceptibility factors; this is termed familial colorectal cancer [113]. The presence of colorectal cancer in more than one family member may be caused by hereditary factors, shared environmental risk factors, or even chance. Familial colorectal cancer accounts for 20% of all colorectal cancer cases [114]. In the general population, 7% to 10% of individuals have a first-degree relative with colorectal cancer and 14% to 20% have either a first-degree or a second-degree relative with colorectal cancer [90; 96; 103]. A simple family history of colorectal cancer (i.e., colorectal cancer in one or more close relatives, known hereditary colon cancer absent) confers a two- to six- fold increase in risk, with degree of risk influenced by family member’s age of colorectal cancer onset, the number of affected
relatives, closeness of the genetic relationship, and whether colorectal cancer has occurred across generations. A positive family history of colorectal cancer appears to increase the risk of colorectal cancer earlier in life such that at 45 years of age, the annual incidence is more than three times higher than in average-risk people; at age 70 years, the risk is similar to that in average-risk individuals [115]. The incidence in individuals 35 to 40 years of age is about the same as that of an average- risk person at 50 years of age. There is no evidence to suggest that colorectal cancer in people with one affected first-degree relative is more likely to be proximal or more rapidly progressive [90; 96; 103]. Although controlled comparisons have not been performed of genetic screening in persons with modest family history of colorectal cancer, expert opinion is fairly consistent that colorectal cancer screening should begin earlier in life (35 to 40 years of age, when risk magnitude approximates that of an individual 50 years of age) [115]. Screening in persons with average risk of colorectal cancer should begin at 50 years of age with repeat screening every 10 years. Increased risk with greater extent of family history warrants room for clinical judgment in favor of even earlier screening based on family history, and shortening the frequency of screening interval to every five years. There is no empirical or logical support to initiate colorectal cancer screening 10 years younger in age than the family member with youngest age of colorectal cancer detection [90; 116]. Other Genetic Factors In addition to FAP and Lynch syndrome, several rare genetic syndromes confer an increased risk for colorectal cancer, including [90; 96]: • Peutz-Jeghers syndrome: STK11/LKB1 gene • Juvenile polyposis syndrome: SMAD4/DPC4 and BMPR1A genes • Cowden syndrome: PTEN gene • Ruvalcaba-Myhre-Smith syndrome: PTEN gene • Hereditary mixed polyposis syndrome Factors that Suggest Hereditary Colorectal Cancer Predisposition Syndrome With the exception of autosomal recessive inheritance with MYH -associated polyposis, all gene mutations known to cause colorectal cancer predisposition are inherited in an autosomal dominant fashion [113]. Thus, family characteristics consistent with autosomal dominant inheritance of cancer predisposition are important to identify because they indicate high risk and possibly the presence of a cancer-predisposing mutation. Factors that suggest a hereditary colorectal cancer predisposition syndrome include [111; 113]: • Vertical transmission (i.e., presence of a genetic predisposition in sequential generations) of cancer predisposition in autosomal dominant conditions • Inheritance risk of 50% for both men and women because when a parent carries an autosomal dominant
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