Risk of Colon Cancer With No Family History
Colorectal Cancer: Risk Factors and Recommendations for Early on Detection
Am Fam Physician. 1999 Jun 1;59(11):3083-3092.
Related Editorial
Article Sections
- Abstruse
- Classification of Hazard and Screening Recommendations
- Future Directions
- References
Spurred by mounting evidence that the detection and treatment of early-stage colorectal cancers and adenomatous polyps can reduce bloodshed, Medicare and some other payors recently authorized reimbursement for colorectal cancer screening in persons at average adventure for this malignancy. A collaborative group of experts convened by the U.S. Agency for Wellness Care Policy and Research has recommended screening for average-risk persons over the age of l years using ane of the post-obit techniques: fecal occult blood testing each year, flexible sigmoidoscopy every five years, fecal occult blood testing every twelvemonth combined with flexible sigmoidoscopy every v years, double-contrast barium enema every five to 10 years or colonoscopy every ten years. Screening of persons with risk factors should begin at an earlier age, depending on the family history of colorectal cancer or polyps. These recommendations augment the colorectal cancer screening guidelines of the American University of Family Physicians. Recent advances in genetic research accept made it possible to identify persons at high risk for colorectal cancer because of an inherited predisposition to develop this malignancy. These patients require aggressive screening, usually past lower endoscopy performed at an early historic period. In some patients, genetic testing can guide screening and may exist cost-effective.
Cancer of the colon and rectum is 2d only to lung cancer as the leading cause of cancer-related deaths in the United States.ane In 1997, an estimated 131,000 Americans were diagnosed with colorectal cancer, and 55,000 died of the illness.1 Without undergoing screening or taking preventive action, approximately one in 17 persons in this country will develop colorectal cancer at some point in life.
Recent research has shown that advisable screening and treatment can alleviate much of the suffering associated with colorectal cancer and reduce the number of deaths caused by this malignancy. Evidence is mounting that detecting and removing adenomatous polyps tin can prevent the development of colorectal adenocarcinoma and that detecting and treating early-stage cancers can lower the mortality rate for colorectal cancer.2–6 Both polyps and early on-phase cancers are usually asymptomatic. Compared with these lesions, cancers that have grown big enough to cause symptoms have a much worse prognosis. This dissimilarity highlights the need for screening in asymptomatic persons.
Past fifty years of age, well-nigh persons at average risk for colorectal cancer should begin regular screening for polyps and malignancies.7,eight Yet, screening or handling should be instituted as early as puberty in the substantial number of persons who are at increased take a chance of colorectal cancer because of an inherited predisposition to the illness. As a issue of the advances in genetic research that have occurred in the past xv years, inherited forms of colorectal cancer are meliorate understood, and the populations that require endoscopic or genetic screening early in life are existence defined.
The effectiveness of colorectal cancer screening has been a subject of controversy. In 1995, the U.South. Preventive Services Task Forcefulness (USPSTF) reversed earlier position statements and endorsed screening with fecal occult blood testing and sigmoidoscopy for asymptomatic persons at average risk for colorectal cancer.ix,10 The recommendations for periodic health examinations developed by the American Academy of Family Physicians (AAFP) annotation the need to screen all adults fifty years of age and older, every bit well as adults forty years and older who accept a family unit history of colorectal cancer.8 The AAFP recommendations used the 1995 USPSTF Guide to Clinical Preventive Services as a starting point. The AAFP guidelines indicate that screening can be performed with fecal occult blood testing (annually), sigmoidoscopy, colonoscopy or barium enema. Because of perceived lack of scientific evidence, the AAFP recommendations purposely exclude frequency of colorectal cancer screening.
Several years ago, the U.South. Bureau for Health Care Policy and Inquiry (AHCPR) convened a collaborative group of experts representing the American College of Gastroenterology, the American Gastroenterological Clan, the American Guild of Colon and Rectal Surgeons, the American Society for Gastrointestinal Endoscopy and the Social club of American Gastrointestinal Endoscopic Surgeons to critically evaluate the available evidence on colorectal cancer screening and develop advisable clinical do guidelines.7 These guidelines have been endorsed by the American Cancer Society (ACS) and the Crohn'southward and Colitis Foundation of America, and they provide the framework for this review.seven,11
Classification of Risk and Screening Recommendations
- Abstract
- Classification of Risk and Screening Recommendations
- Time to come Directions
- References
The cornerstone for determining a patient'southward gamble of developing colorectal cancer is the family unit history. Failure to properly investigate a patient'due south family history of colorectal neoplasia can lead to inappropriate and inadequate treatment of both the patient and other family members who may be at risk.
AVERAGE RISK
As indicated in Tabular array one,7 most persons who develop colorectal cancer accept no identifiable risk factors. Persons considered to be at average risk for colorectal cancer do not fit whatever of the higher chance categories. Specifically, they are asymptomatic and have no personal history of colorectal cancer or adenomatous polyps, no family history of colorectal neoplasia, no inflammatory bowel affliction and no unexplained anemia.
TABLE 1
Incidence of Colorectal Cancer by Run a risk Category
| Average take chances (sporadic; no identifiable risk factor) | 75 % |
| Family history of colorectal cancer | 15 to 20 % |
| Hereditary nonpolyposis colorectal cancer | 3 to 8 % |
| Familial adenomatous polyposis | 1 % |
| Ulcerative colitis | 1 % |
Screening Recommendations. The AHCPR panel recommended that, beginning at the age of 50 years, persons at average risk for colorectal cancer undergo one of the post-obit screening regimens:
-
Fecal occult blood testing annually.
-
Flexible sigmoidoscopy every five years.
-
Fecal occult blood testing annually and flexible sigmoidoscopy every 5 years.
-
Double-contrast barium enema every v to ten years.
-
Colonoscopy every ten years.
Although the panel stated that all of these screening strategies are acceptable options, each strategy has unique strengths and weaknesses (Tabular array 2).vii
TABLE 2
Summary of Characteristics of Screening Tests Discussed in the AHCPR Report*
| Screening method | Overall performance | Complexity† | Potential effectiveness | Show of effectiveness | Screening test risk |
|---|---|---|---|---|---|
| Fecal occult blood test | Intermediate for cancers | Lowest | Lowest | Strongest | Lowest |
| Low for polyps | |||||
| Flexible sigmoidoscopy | High for up to one one-half of the colon | Intermediate | Intermediate | Intermediate | Intermediate |
| Fecal occult claret exam plus flexible sigmoidoscopy | Same every bit for flexible sigmoidoscopy | Intermediate | Intermediate | Intermediate | Intermediate |
| Double-contrast barium enema | Loftier | High | Loftier | Weakest | Intermediate |
| Colonoscopy | Highest | Highest | Highest | Weakest | Highest |
The fecal occult blood test is a nonspecific exam that fails to detect many small cancers and precancerous lesions.12 Nonetheless, several large, randomized, controlled trials have shown that annual or biannual testing for fecal occult claret followed past complete diagnostic evaluation of the colon (primarily with colonoscopy) in patients with a positive test reduces the number of deaths caused by colorectal cancer.3,13,14
When performed appropriately, the fecal occult blood test involves the sampling of atraumatically obtained stool from three consecutive bowel movements in a patient who has not ingested reddish meat, aspirin, not-steroidal anti-inflammatory drugs, turnips, horseradish or vitamin C for two days before the examination and throughout the examination period.7,15
A major drawback to fecal occult blood testing as a screening technique is poor compliance. Only 38 to 60 percent of patients in the large trials completed all planned tests.3,13,14 Use of the examination in the full general population is estimated to exist lower.16 Testing of stool obtained traumatically during a digital rectal exam is of unproven value.17 The ACS and other experts recommend that almanac fecal occult blood testing be accompanied by flexible sigmoidoscopy every five years.xi
The effectiveness of sigmoidoscopy as a screening tool depends on its ability to observe cancers and adenomatous polyps in the distal colon of asymptomatic patients at average chance for colorectal cancer who have a negative fecal occult blood test. If the sigmoidoscopic examination detects polyps, colonoscopy should exist strongly considered considering almost one 3rd of such patients have neoplastic lesions in the proximal colon.eighteen Randomized controlled trials take non proved that sigmoidoscopy reduces the mortality rate for colorectal cancer, although case-control studies accept shown a benefit.ii,vi,19 The Prostate, Lung, Colon and Ovary Trial, which is being supported by the National Cancer Institute (NCI), is currently evaluating the effectiveness of flexible sigmoidoscopy in a randomized, controlled setting; notwithstanding, mortality data are not expected to get available until 2008.7
The efficacy of barium enema in preventing deaths from colorectal cancer has not been evaluated in a controlled trial. Nonetheless, effectiveness tin can be inferred from the fact that detecting polyps and early-stage cancers by other methods reduces the incidence of colorectal cancer equally well as the number of deaths from this malignancy. Double-contrast barium enema detects l to fourscore percent of polyps less than 1 cm in size, lxx to 90 percentage of polyps larger than ane cm and fifty to fourscore percent of stage I and II adenocarcinomas.20–23 Unmarried-column barium enema is less sensitive than double-dissimilarity barium enema. Thus, if unmarried-column barium enema is used as a screening tool, it should be combined with flexible sigmoidoscopy.seven The major limitation of barium enema as a screening method is that patients require colonoscopy if lesions are detected.
Colonoscopy is the merely screening technique that allows the detection and removal of pre-malignant lesions throughout the colon and rectum. Furthermore, it is the terminal common pathway for all positive screening tests. Although successful colonoscopy depends on the skill of the endoscopist to reach the cecum and to identify small lesions, this technique remains the aureate standard for evaluation of the colonic mucosa.7 The ability of colonoscopy to reduce deaths from colorectal cancer has been demonstrated indirectly through studies showing that the detection and removal of polyps reduces the incidence of colorectal cancer and that the detection of early on cancers lowers the bloodshed rate for this malignancy.two–6 Patients may be more likely to comply with screening colonoscopy considering no confirmatory examinations are required and, thus, just one bowel preparation is necessary.
The Office of Engineering science Assessment of the U.South. Congress plant that fecal occult blood testing, sigmoidoscopy, double-contrast enema and colonoscopy are about equally cost-constructive every bit screening strategies, with an estimated price of less than $20,000 per twelvemonth of life saved (bold that screening begins at the age of 50 years and is discontinued at the historic period of 85 years).7,24 Although cost-benefit analyses are exceedingly complex, this approximate is well inside the acceptable range of price-effectiveness by U.South. wellness standards and compares favorably with the cost-benefit judge for screening mammography in women over 50 years old.
Medicare Coverage. Since January 1, 1998, Medicare has covered colorectal cancer screening in persons at average risk for this malignancy who are over fifty years of age. Medicare does not reimburse the toll of screening colonoscopy in persons at average risk, but it does cover almanac fecal occult claret testing as well as flexible sigmoidoscopy or barium enema performed every four years.25 Reimbursement by other tertiary-party payors is variable.
Handling. Patients found to take adenomatous polyps should undergo colonoscopy and polypectomy; later 3 years, they should be reexamined past colonoscopy.seven,18,26 Patients establish to have cancer should undergo colonoscopy to search for synchronous lesions and should then receive standard treatment for the cancer.
Family HISTORY OF COLORECTAL CANCER OR ADENOMATOUS POLYPS
A family history of colorectal cancer or adenomatous polyps increases the risk of colorectal cancer. In general, closer familial relationships to affected relatives, younger age of affected relatives and larger numbers of affected relatives increase this risk.seven,27,28 A careful family unit history should always exist obtained to exclude one of the more well-defined inherited colorectal cancer syndromes, such every bit hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis. Every bit the molecular genetics of colorectal cancer come to be better understood, many patients with familial colorectal cancer may eventually be categorized as having distinct inherited syndromes (Table 3).7
TABLE 3
Screening Recommendations for Colorectal Cancer and Polyps
| Risk category | Screening method | Age to begin screening |
|---|---|---|
| Average take chances | Choose one of the post-obit: | l years |
| i. Fecal occult blood testing annually | ||
| 2. Flexible sigmoidoscopy every five years | ||
| three. Fecal occult blood testing annually and flexible sigmoidoscopy every five years* | ||
| 4. Double-contrast barium enema every five to 10 years† | ||
| v. Colonoscopy every 10 years | ||
| Family unit history | Cull i of the post-obit: | forty years or 10 years before cancer was diagnosed in the youngest affected family member, whichever is earlier |
| i. Colonoscopy every 10 years | ||
| 2. Double-contrast barium enema every five years | ||
| Hereditary nonpolyposis colorectal cancer | Colonoscopy every one to three years | 21 years |
| Genetic counseling | ||
| Consider genetic testing | ||
| Familial adenomatous polyposis | Flexible sigmoidoscopy or colonoscopy every i to two years | Puberty |
| Genetic counseling | ||
| Consider genetic testing | ||
| Ulcerative colitis | Colonoscopy with biopsies for dysplasia every i to two years | 7 to eight years after the diagnosis of pancolitis |
| 12 to fifteen years subsequently the diagnosis of left-sided colitis |
Screening Recommendations. The AHCPR panel recommended that persons who accept first-degree relatives with colorectal cancer or adenomatous polyps undergo screening for colorectal neoplasia starting time at 40 years of age or ten years earlier the age at which the diagnosis was fabricated in the afflicted relative, whichever is earlier.seven Because patients whose start-degree relatives developed colorectal cancer before the age of l years may be at higher gamble, consummate colonic evaluation with colonoscopy should be strongly considered. Patients who have a 2d-degree relative with colorectal cancer or a relative with adenomatous polyps diagnosed afterward the age of 60 years tin be screened in accordance with the recommendations for persons at boilerplate risk.vii
Medicare Coverage. Medicare covers screening colonoscopy in persons at high risk for colorectal cancer when the procedure is performed at least two years after the last screening colonoscopy or barium enema.25
Handling. Patients found to have adenomatous polyps should undergo colonoscopy and polypectomy; after three years, they should be reexamined by colonoscopy.7,26 Patients institute to have cancer should undergo colonoscopy to search for synchronous lesions and should then receive standard handling for the cancer. At nowadays, no data support total abdominal colectomy for patients with familial colorectal cancer who do not run into criteria for an inherited colorectal cancer.
HEREDITARY NONPOLYPOSIS COLORECTAL CANCER
As many equally 75 percent of patients with hereditary nonpolyposis colorectal cancer develop malignant affliction by the historic period of 65 years.29–32 This autosomal dominant syndrome is the outcome of germline mutations in mismatch repair genes (genes that code for proteins responsible for correcting errors during DNA replication). Patients with hereditary nonpolyposis colorectal cancer typically develop malignancy between the ages of 40 and 50 years. Near tumors occur proximal to the splenic flexure.
"Nonpolyposis" refers to the distinction between hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis (in which patients take hundreds of polyps). However, this term is somewhat misleading considering patients with the syndrome develop adenomatous polyps preceding the cancer. The progression from adenoma to carcinoma appears to be accelerated in patients who take hereditary nonpolyposis colorectal cancer compared with patients who take sporadic cancers. Thus, the recommended intervals between screening colonoscopies are short (i to 3 years).29 In addition, patients with hereditary nonpolyposis colorectal cancer tend to develop multiple colorectal cancers. Betwixt 30 and 50 percent of patients who undergo segmental colectomy for one cancer develop a 2nd cancer inside 10 to 15 years.29 Patients with hereditary nonpolyposis colorectal cancer are also at loftier chance for cancers of other organs, peculiarly the ovary and uterus.
Because gene carriers cannot all the same exist conclusively identified, the penetrance of colorectal cancer can only exist estimated (about xc percent).30 Furthermore, some patients in families with hereditary nonpolyposis colorectal cancer do not have identifiable germline mismatch repair gene mutations but withal develop colorectal cancer. For these reasons, the diagnosis of this hereditary syndrome in a family remains clinical and is based on the Amsterdam criteria33:
-
Colorectal cancer is present in three or more family members.
-
Ii generations are affected.
-
One affected person is a first-degree relative of another afflicted person.
-
1 person is diagnosed with cancer before the age of 50 years.
The Amsterdam criteria were originally developed to standardize the definition of hereditary nonpolyposis colorectal cancer for research purposes. However, the criteria neglect to identify patients who may be affected with the syndrome but take unknown or abbreviated family histories or patients who have a personal or family history of extracolonic malignancies associated with the syndrome. A recent NCI working grouping acknowledged the shortcomings of the Amsterdam criteria as clinical guidelines and published recommendations to expand the clinical suspicion of hereditary nonpolyposis colorectal cancer to a broader range of patients.32
Screening Recommendations. Expert panels convened by the AHCPR7 and the Cancer Genetics Studies Consortium (CGSC)29 recommended that persons who are members of a family that fits the clinical criteria for hereditary nonpolyposis colorectal cancer undergo colonoscopy at 20 to 25 years of age and every one to three years thereafter. In addition, these patients and their family members should be referred for genetic counseling. Germline testing for mismatch repair gene mutations can be considered, just the predictive value of such testing is but 50 to 80 percent.34 Therefore, regardless of the outcome of such testing, colonoscopy should be performed.
Treatment. Although prospective, randomized trials are lacking, the CGSC panel and others have made recommendations for the treatment of patients with hereditary non-polyposis colorectal cancer.29 Total intestinal colectomy with ileorectal anastomosis and endoscopic screening of the rectum should exist strongly considered for patients with this syndrome and colon cancer, every bit well every bit for selected gene mutation carriers who have multiple adenomatous polyps. Patients with rectal cancer should exist considered for total proctocolectomy. Selected gene mutation carriers (i.e., those unable to comply with frequent colonoscopic surveillance) can be considered for prophylactic colectomy, although the benefit of this arroyo has non yet been evaluated.
FAMILIAL ADENOMATOUS POLYPOSIS
Familial adenomatous polyposis is caused by an autosomal dominant defect in the adenomatous polyposis coli (APC) gene.35 Patients with this syndrome develop hundreds of adenomatous polyps as early on as puberty and ultimately develop colorectal cancer, unremarkably by 40 years of age.36,37 Patients who have familial adenomatous polyposis are too prone to develop a variety of extracolonic tumors, notably duodenal adenomas, duodenal carcinomas and desmoid tumors.36 Gene mutations occur spontaneously and account for the patients who are diagnosed with familial adenomatous polyposis merely do non have a family history of the syndrome.38 Attenuated familial adenomatous polyposis is a rare variant in which polyps and cancers develop later in life.39
The most commonly used genetic examination for familial adenomatous polyposis is an assay for a truncated poly peptide production of the mutated APC gene. As only about 80 pct of families with the syndrome take a mutation that produces a truncated poly peptide, the predictive value of testing at-hazard family unit members is greatest if the proband (affected relative) has a positive test.forty Because of the socioeconomic and emotional bug surrounding genetic testing for familial adenomatous polyposis, such testing should be performed simply after genetic counseling has taken place and informed consent has been obtained.twoscore
Screening Recommendations. Persons with a family unit history of familial adenomatous polyposis should undergo flexible sigmoidoscopy or colonoscopy at puberty.seven,41 Lower endoscopy should exist repeated every one to two years considering adenomatous polyps throughout the bowel mostly precede cancer. Genetic testing should be considered, especially in large families with many at-risk members; in such situations, genotyping may be more cost-effective than repeated endoscopy.41 If the proband has a positive truncated protein assay, at-adventure relatives who examination negative may be screened as average-take a chance persons.41
Treatment. Patients found to have polyposis should undergo total proctocolectomy. In most patients, intestinal continuity can be preserved with the structure of an ileal pouch–anal anastomosis. Total abdominal colectomy with ileorectal anastomosis can be considered, but only if the rectum is relatively gratis of polyps and the patient will comply with regular screening proctoscopy. Patients should also undergo endoscopic screening for duodenal adenomas.42
INFLAMMATORY BOWEL DISEASE
Over time, the risk of colorectal cancer increases in patients with ulcerative colitis.7 Patients with Crohn's colitis may as well be at increased hazard for colorectal cancer, although this association has been less well divers.
Screening Recommendations. Later on a menses of years, patients with ulcerative colitis are commonly screened every one to 2 years by colonoscopy and the procurement of multiple random biopsy samples to look for dysplasia. This screening is initiated seven to 8 years after the diagnosis of pancolitis and 12 to xv years after the diagnosis of left-sided colitis.7,43,44 However, only weak evidence shows that surveillance reduces mortality or is better than timing a colectomy according to the extent and duration of disease.vii,43,44
Treatment. Patients found to take dysplasia should be strongly considered for total proctocolectomy. In most patients, intestinal continuity can exist preserved with the structure of an ileal pouch–anal anastomosis.
Future Directions
- Abstract
- Classification of Run a risk and Screening Recommendations
- Future Directions
- References
It is troubling that so much free energy and expense are devoted to the cure of advanced or recurrent colorectal cancer in the U.s.a., but so trivial time and coin are expended on screening for polyps and early-stage cancers. Information technology is estimated that only 10 to xxx per centum of Americans over the historic period of l years undergo any type of regular screening for colorectal neoplasia16,45,46 (Figure i).7
Colorectal Cancer Screening and Surveillance
FIGURE 1.
Algorithm for colorectal cancer screening and surveillance in patients at boilerplate and increased risk for this malignancy.
Adapted with permission from Winawer SJ, Fletcher RH, Miller Fifty, Godlee F, Stolar MH, Mulrow CD, et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology 1997;112:594–642 [Published errata in Gastroenterology 1997;112:1060 and 1998;114:625].
Colorectal cancer has not received much publicity, even though information technology is the second leading crusade of cancer-related deaths in this country and even though information technology has a well-defined, identifiable and treatable precursor lesion—the adenomatous polyp. Both health care professionals and the public need to get more enlightened of the potential benefits of colorectal cancer screening.
As the genetics of inherited colorectal cancer syndromes become better understood, information technology will be possible to conclusively identify high-risk populations. It is of paramount importance that screening efforts be directed toward these populations. Genetic counselors are invaluable resources for educating afflicted patients and their family members and for helping to directly genetic testing.
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Copyright © 1999 by the American Academy of Family Physicians.
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