Screening strategies for people with a family history of colorectal cancer
Background[edit source]
A family history of colorectal cancer means a person’s probability of developing colorectal cancer could be several times higher than that of someone without a family history (see Colorectal cancer risk according to family history) However, family history in itself is not a good predictor of colorectal cancer,[1] because the increased risk is applied to an average risk of colorectal cancer that is very low (lifetime risk approximately 5%), resulting in an absolute risk in those with a family history that is still low. Nevertheless, family history can be used to stratify people without a diagnosis or symptoms of colorectal cancer into risk categories in which the number of expected colorectal cancers or adenomas is high enough to warrant more intensive screening than the average population. Based on this, the current practice in Australia and in many other countries is to have more intensive or frequent screening for those with stronger family history. The majority of screening guidelines recommend biennial faecal occult blood test (FOBT) or 10-yearly colonoscopy for the lowest risk category, 5-yearly colonoscopy for the middle risk category and annual or biennial (every two years) colonoscopy for the highest risk category which includes those with high risk familial syndromes.[2][3] The majority of screening guidelines recommend screening to begin at age 50 for all risk categories or 10 years before the youngest age of colorectal cancer diagnosis in a relative.
Risk categories are defined in Colorectal cancer risk according to family history.
Previous Australian guidelines[4] recommended colonoscopy for people at moderately increased risk (category 2) and people at high risk (category 3) due to family history. Recommendations for category 2 included 5-yearly colonoscopy beginning at age 50 years (or 10 years earlier than youngest age of relative at diagnosis) and consideration of faecal occult blood testing (FOBT) between colonoscopies.[4] Recommendations for category 3 were based on family risk profile according to a high-risk familial syndrome, and included flexible sigmoidoscopy every 1–2 years for familial adenomatous polyposis (FAP), and annually or at least once every two years beginning at age 25 years or five years earlier than the age at diagnosis of the earliest cancer in the family for Lynch syndrome.[4]
An alternative to recommending an increase in screening modality for people in higher risk categories, is to recommend screening to begin at an earlier age, under the assumption that increased risk due to family history applies to each age category. Screening regimens could be based on absolute risk – following a principle of ‘equal risk, equal screening’ – whereby, an individual with a strong family history starts screening at a younger age because their absolute risk reaches the screening threshold earlier than someone at lower risk based on family history.
Overview of evidence[edit source]
What is the effect of screening on risk of colorectal cancer incidence and mortality and how does it vary by family history (various categories)?
Guidance in this section is based on: the 2005 edition of this guideline[4]; the systematic reviews performed for the Colorectal cancer risk according to family history and the Evidence for benefit from population screening sections; selected subsequent articles and international guidelines; and consensus. Please see Guideline development process for more information.
It should be noted that the following recommendations are based on studies of cancer risk and on yield of lesions in screening studies, not on randomised controlled trials with colorectal cancer mortality as the outcome.
Effectiveness of screening in patients younger than 50 years[edit source]
One study was identified that evaluated the effectiveness of FOBT prior to age 50 years.[5] This study correlated the results of FOBT tests with colonoscopy findings in 6096 asymptomatic patients aged 40 and over in Taiwan. It reported that a single immunochemical FOBT test for colorectal cancer in patients aged 40–49 years had a 60% sensitivity with a positive predictive value of 7.1%.[5]
Absolute risk[edit source]
The 10-year risk of colorectal cancer for: the average risk population along with those at two-fold risk (both category 1); those at three- to six-fold increased risk (category 2); and those at seven- to ten-fold risk, can be calculated from population-based statistics (Table 5.4). The 10-year colorectal cancer risk for a 40 year-old at three-fold risk is the same as the 10-year colorectal cancer risk for a 35 year-old at seven-fold risk, which in turn is the same as the 10-year colorectal cancer risk for a 50 year-old at average risk. For people in category 2, the 10-year risk of colorectal cancer from age 50 is 3% or higher.
Table 5.4. Ten-year absolute risks of colorectal cancer (%) based on age and level of increased risk due to family history[edit source]
| Number of first-degree relatives with colorectal cancer |
Multiplication of population risk due to family history (RR) |
Age 30 | Age 35 | Age 40 | Age 45 | Age 50 |
|---|---|---|---|---|---|---|
| 0 | 0.9 | 0.07% | 0.12% | 0.25% | 0.5% | 0.9% |
| 1 | 2 | 0.15% | 0.29% | 0.59% | 1.1% | 1.9% |
| 2 | 3-6 | 0.30% | 0.60% | 1.20% | 2.2% | 3.8% |
| 3+ | 7-10 | 0.60% | 1.2% | 2.4% | 4.8% | 7.6% |
RR: relative risk; the risk of colorectal cancer relative to the average risk in the population. Estimates are based on the assumption that the relative risk is the same for all age groups.
The blue shaded cells represent risks at least as high as the risk of a 50 year-old at average risk who are recommended to begin 2-yearly iFOBT screening in this chapter.
The red shaded cells represent risks approximately 4% of higher that are recommended 5-yearly colonoscopy in this chapter.
Source: Incidence data from AIHW Australian colorectal cancer incidence for males and females combined for the year 2000.[6]
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Screening by risk category[edit source]
Category 1 — Those near average risk[edit source]
| Category | Family history | Screening recommendation |
|---|---|---|
| 1 | No first- or second-degree relative with colorectal cancer
One first-degree relative with colorectal cancer diagnosed at 55 years or older One first-degree and one second-degree with colorectal cancer diagnosed at 55 years or older |
iFOBT every 2 years
from age 50 to age 74 |
Sources: St John et al (1993)[7], Fuchs et al (1994)[8], Slattery et al (1994)[9], Bass et al (2008)[10], Schoen et al (2015)[11], Taylor et al (2011)[1], Lynch et al (2003)[12], Hall et al (1996)[13], Leu et al (2008)[14], Benhamiche-Bouvier et al (2000)[15], Sandhu et al (2001)[16], Aitken et al (1996)[17], Anderson et al (2003)[18]
Note: Relative risk is the ratio of the risk of developing colorectal cancer in a particular exposed group to the average risk in the whole population.
The yield of clinically significant lesions at screening colonoscopy is low (see Colorectal cancer risk according to family history).[17][19][20][21][22]
A number of organisations, including the American Cancer Society and the American Gastroenterological Association, do not consider that risk of colorectal cancer justifies more invasive screening than that recommended for the average population.[23][24] The 1997 Australian Health Technology Advisory Committee (AHTAC) Report on Colorectal Cancer Screening concluded that recommendations for people in this category should be the same as for the average-risk population.[25]
- See the evidence-based recommendation: For people with a family history of colorectal cancer who are assessed as having category 1 risk, iFOBT should be performed every 2 years from age 50 to age 74.
- See also the evidence-based recommendation on aspirin use for people aged 50–70 years who are at average risk of colorectal cancer.
Practice point
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For people with category 1 risk of colorectal cancer with one relative with colorectal cancer, iFOBT should be considered every 2 years from age 45, given the risk of colorectal cancer at this age is approximately equivalent to the population risk at age 50. |
Category 2 — Those at moderately increased risk[edit source]
| Category | Family history | Screening recommendation |
|---|---|---|
| 2 | One first-degree relative with colorectal cancer diagnosed under 55 years
Two first-degree relatives with colorectal cancer diagnosed at any age One first-degree relative and at least two second-degree relative with colorectal cancer diagnosed at any age |
iFOBT every 2 years from age 40 to age 49.
Colonoscopy every five years from age 50 to age 74. |
Sources: St John et al (1993)[7], Fuchs et al (1994)[8], Slattery et al (1994)[9], Bass et al (2008)[10], Schoen et al (2015)[11], Taylor et al (2011)[1], Lynch et al (2003)[12], Hall et al (1996)[13], Leu et al (2008)[14], Benhamiche-Bouvier et al (2000)[15], Sandhu et al (2001)[16], Aitken et al (1996)[17], Anderson et al (2003)[18]
Note: Relative risk is the ratio of the risk of developing colorectal cancer in a particular exposed group to the average risk in the whole population.
For people in this category, their risk of colorectal cancer is as high at age 40 as the average population is at age 50 (see Colorectal cancer risk according to family history). Their risk of colorectal cancer at age 40 is approximately 1%, which is equivalent to the risk for people in category 1 at age 50.
Accordingly, 2-yearly screening from age 40 is appropriate. By age 50 their 10-year colorectal cancer risk is approximately 4%, which is sufficiently high to warrant screening by 5-yearly colonoscopy.
| Practice point
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For people with category 2 risk of colorectal cancer:
|
| Practice point
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For people in category 2, CT colonography can be offered if colonoscopy is contraindicated (Dachman 2003). |
| Practice point
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Because of the possibility of Lynch syndrome, a complete family history should be taken and updated regularly, and the accuracy of the cancer diagnoses and polyp pathology should be checked carefully. |
| Practice point
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Category 2 can now be met by inclusion of relatives from both sides of the family. Genetic testing is not appropriate at present for people with category 2 risk. Tumour testing for Lynch syndrome-related changes, using immunohistochemistry and microsatellite instability, should be considered when any of the revised Bethesda criteria are met (see Lynch syndrome). |
| Practice point
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As with all forms of screening, those at risk should be carefully checked for the presence of symptoms that might be due to colorectal neoplasia. Where symptoms are present, appropriate diagnostic steps should be taken before entry into a screening program. |
Category 3 — those at potentially high risk[edit source]
| Category | Family history | Screening recommendation |
|---|---|---|
| 3 | At least three first-degree or second-degree relatives with colorectal cancer, with at least one diagnosed under 55 years
At least three first-degree relatives with colorectal cancer diagnosed at any age |
iFOBT every 2 years from age 35 to age 44.
Colonoscopy every five years from age 45 to age 74. |
Sources: St John et al (1993)[7], Fuchs et al (1994)[8], Slattery et al (1994)[9], Bass et al (2008)[10], Schoen et al (2015)[11], Taylor et al (2011)[1], Lynch et al (2003)[12], Hall et al (1996)[13], Leu et al (2008)[14], Benhamiche-Bouvier et al (2000)[15], Sandhu et al (2001)[16], Aitken et al (1996)[17], Anderson et al (2003)[18]
Note: Relative risk is the ratio of the risk of developing colorectal cancer in a particular exposed group to the average risk in the whole population.
The risk for some people with three (or more) relatives with colorectal cancer may be difficult to categorise, especially if all cases of colorectal cancer occur at an advanced age, are confined to one generation of the family, and if no-one in the family has had any of the extra-colonic cancers associated with Lynch syndrome.[26] If there is uncertainty about their mutation status, it may be safer to categorise people as having suspected (or possible) Lynch syndrome. New diagnoses of cancer in the family or results of microsatellite instability, immunohistochemical staining or genetic testing may clarify the situation.
For people in this category, their risk of colorectal cancer is as high at age 35 as the average population is at age 50 (see Colorectal cancer risk according to family history). Their risk of colorectal cancer at age 35 is approximately 1.2%, which is equivalent to the risk for people in category 1 at age 50.
Accordingly, 2-yearly iFOBT screening from age 35 is appropriate. By age 45 their 10-year colorectal cancer risk ranges from approximately above 4%, which is sufficiently high to warrant screening by 5-yearly colonoscopy.
| Practice point
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For people with category 3 risk of colorectal cancer:
|
| Practice point
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Category 3 can now be met by inclusion of relatives from both sides of the family. This is expected to increase the numbers in this category by approximately 50%. Referral to a genetic centre for hereditary cancer syndromes should be prioritised to those with family members with colorectal cancer from the same side of the family. |
| Practice point
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Screening recommendations no longer specify that screening should begin at 10 years younger than the age of first diagnosis of colorectal cancer in the family, as there is no published evidence to support this strategy. |
Evidence summary and recommendations[edit source]
| Evidence summary | Level | References |
|---|---|---|
| Category 1 - Those at or slightly above average risk
The yield of clinically significant lesions at screening colonoscopy is low, so average population screening is appropriate by biennial iFOBT from age 50 to 74 years. For those with one affected first-degree relative, 10 year risk at age 45 is about 1% so biennial iFOBT could be considered from age 45. |
II, III-2 | [17], [19], [20], [21], [22] |
| Category 2 - Those at moderately increase risk
The risk of colorectal cancer is as high at age 40 as the average population is at age 50, so population-based screening is appropriate until age 50. The 10-year risk of colorectal cancer from age 50 is approximately 4%, so five-yearly colonoscopy is justified from age 50. |
II, III-2 | [7], [9], [13], [15], [16], [17] |
| Category 3 - Those at potentially high risk
This group excludes those known to be, or suspected to have a cancer genetic syndrome based on tumour or genetic testing of relatives. The risk of colorectal cancer is as high at age 35 as the average population is at age 50, so population-based screening is appropriate till age 45. The 10-year risk of colorectal cancer from age 45 is at least 4%, so five-yearly colonoscopy is justified from age 45. |
II, III-2 | [27], [28], [29], [30] |
| Evidence-based recommendation
|
Grade |
|---|---|
 For people with a family history of colorectal cancer who are assessed as having category 1 risk, iFOBT should be performed every 2 years from age 50 to age 74. See Population screening for colorectal cancer. For those with one first-degree relative with colorectal cancer, iFOBT every two years from age 45 should be considered. |
C |
| Evidence-based recommendation
|
Grade |
|---|---|
For category 2 patients, offer iFOBT every 2 years starting at age 40, then colonoscopy every 5 years starting at age 50. CT colonography may be offered if colonoscopy is contraindicated. |
C |
| Evidence-based recommendation
|
Grade |
|---|---|
For category 3 patients, offer iFOBT every two years starting at age 35, then colonoscopy every five years starting at age 45. CT colonography may be offered if colonoscopy is contraindicated. |
C |
Health system implications[edit source]
Clinical practice[edit source]
Since the last guidelines, the National Bowel Cancer Screening Program has been funded with a phased roll-out. By 2019 it will offer all Australians free colorectal cancer screening from age 50-74 by biennial iFOBT. These guidelines recommend that all people in Category 1 avail themselves of this screening program which will be sufficient given their risk of colorectal cancer.
These guidelines differ from the previous guidelines12 in in a number of ways. There have been some changes in the family history inclusion criteria for category 2; the genetic syndromes have been removed from category 3 and as a consequence colonoscopy screening for category 3 is now five yearly; and for category 2 and category 3, screening begins with iFOBT before age 50, before transitioning to colonoscopy at a later age.
Resourcing[edit source]
Resources must be in place to support the continued expansion of the NBCSP to complete rollout of screening every two years (biennial screening) by 2020.
Barriers to implementation[edit source]
There may be some resistance to the change in recommendations which have been in use for over 10 years.
Discussion[edit source]
Unresolved issues[edit source]
The optimal age to stop screening is not known. Health economic research is needed to determine whether the benefits of iFOBT screening or colonoscopy screening beyond age 74 years outweigh the inherent risks. Further research is needed, such as observational studies and health economic research, to determine whether the youngest age of colorectal cancer diagnosis should be used as an indicator of the age to begin screening unaffected relatives. Previous guidelines have recommended screening 10 years younger than the age of the youngest relative at colorectal cancer diagnosis, but there is no evidence available to support this recommendation.
Only a small number of studies examined the performance of colorectal cancer screening before age 50. Guidance presented here is based on the few studies that provide sensitivity estimates for colorectal cancer for those younger than age 50 that are similar to sensitivity estimates for ages 50 and over.[5][31]
Studies currently underway[edit source]
We are not aware of any current clinical trial that would provide more data on this question.
Future research priorities[edit source]
Health economic research is needed to assess the cost effectiveness of screening for various categories of family history, evaluate the screening strategies and further examine the relationship between risk and age.
In the absence of trials and observational studies for the effectiveness of screening strategies in people at elevated risk of colorectal cancer due to family history, cost-effectiveness analysis is appropriate to determine screening guidelines for the risk categories
References[edit source]
- ↑ 1.0 1.1 1.2 1.3 Taylor DP, Stoddard GJ, Burt RW, Williams MS, Mitchell JA, Haug PJ, et al. How well does family history predict who will get colorectal cancer? Implications for cancer screening and counseling. Genet Med 2011 May;13(5):385-91 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21270638.
- ↑ Medical Advisory Secretariat. Fecal Occult Blood Test for Colorectal Cancer Screening: an evidence-based analysis. Toronto, Ontario: Canada: Ministry of Health and Long-Term Care; 2009.
- ↑ International Agency for Research on Cancer. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition: International Agency for Research on Cancer; 2010.
- ↑ 4.0 4.1 4.2 4.3 Australian Cancer Network Colorectal Cancer Guidelines Revision Committee. Clinical practice guidelines for the prevention, early detection and management of colorectal cancer. The Cancer Council Australia and Australian Cancer Network 2005.
- ↑ 5.0 5.1 5.2 Chen Y-Y, Chen T-H, Su M-Y, Ning H-C, Kuo C-J, Lin W-P, et al.. Accuracy of immunochemical fecal occult blood test for detecting colorectal neoplasms in individuals undergoing health check-ups. Advances in Digestive Medicine 2014 Sep;Volume 1, Issue 3, Pages 74–79 Available from: http://www.aidm-online.com/article/S2351-9797(14)00045-0/abstract.
- ↑ AIHW & Australasian Association of Cancer Registries. Cancer in Australia 2000. Cancer Series. Cat. no. CAN 18. Canberra: AIHW; 2003.
- ↑ 7.0 7.1 7.2 7.3 St John DJ, McDermott FT, Hopper JL, Debney EA, Johnson WR, Hughes ES. Cancer risk in relatives of patients with common colorectal cancer. Ann Intern Med 1993 May 15;118(10):785-90 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8470852.
- ↑ 8.0 8.1 8.2 Fuchs CS, Giovannucci EL, Colditz GA, Hunter DJ, Speizer FE, Willett WC. A prospective study of family history and the risk of colorectal cancer. N Engl J Med 1994 Dec 22;331(25):1669-74 Available from: http://www.ncbi.nlm.nih.gov/pubmed/7969357.
- ↑ 9.0 9.1 9.2 9.3 Slattery ML, Kerber RA. Family history of cancer and colon cancer risk: the Utah Population Database. J Natl Cancer Inst 1994 Nov 2;86(21):1618-26 Available from: http://www.ncbi.nlm.nih.gov/pubmed/7932826.
- ↑ 10.0 10.1 10.2 Bass AJ, Meyerhardt JA, Chan JA, Giovannucci EL, Fuchs CS. Family history and survival after colorectal cancer diagnosis. Cancer 2008 Mar 15;112(6):1222-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18219663.
- ↑ 11.0 11.1 11.2 Schoen RE, Razzak A, Yu KJ, Berndt SI, Firl K, Riley TL, et al. Incidence and mortality of colorectal cancer in individuals with a family history of colorectal cancer. Gastroenterology 2015 Nov;149(6):1438-1445.e1 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26255045.
- ↑ 12.0 12.1 12.2 Lynch KL, Ahnen DJ, Byers T, Weiss DG, Lieberman DA. First-degree relatives of patients with advanced colorectal adenomas have an increased prevalence of colorectal cancer. Clin Gastroenterol Hepatol 2003 Mar;1(2):96-102 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15017501.
- ↑ 13.0 13.1 13.2 13.3 Hall NR, Bishop DT, Stephenson BM, Finan PJ. Hereditary susceptibility to colorectal cancer. Relatives of early onset cases are particularly at risk. Dis Colon Rectum 1996 Jul;39(7):739-43 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8674364.
- ↑ 14.0 14.1 14.2 Leu M, Reilly M, Czene K. Evaluation of bias in familial risk estimates: a study of common cancers using Swedish population-based registers. J Natl Cancer Inst 2008 Sep 17;100(18):1318-25 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18780865.
- ↑ 15.0 15.1 15.2 15.3 Benhamiche-Bouvier AM, Lejeune C, Jouve JL, Manfredi S, Bonithon-Kopp C, Faivre J. Family history and risk of colorectal cancer: implications for screening programmes. J Med Screen 2000;7(3):136-40 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11126162.
- ↑ 16.0 16.1 16.2 16.3 Sandhu MS, Luben R, Khaw KT. Prevalence and family history of colorectal cancer: implications for screening. J Med Screen 2001;8(2):69-72 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11480446.
- ↑ 17.0 17.1 17.2 17.3 17.4 17.5 Aitken JF, Bain CJ, Ward M, Siskind V, MacLennan R. Risk of colorectal adenomas in patients with a family history of colorectal cancer: some implications for screening programmes. Gut 1996 Jul;39(1):105-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8881819.
- ↑ 18.0 18.1 18.2 Anderson JC, Attam R, Alpern Z, Messina CR, Hubbard P, Grimson R, et al. Prevalence of colorectal neoplasia in smokers. Am J Gastroenterol 2003 Dec;98(12):2777-83 Available from: http://www.ncbi.nlm.nih.gov/pubmed/14687832.
- ↑ 19.0 19.1 Grossman S, Milos ML. Colonoscopic screening of persons with suspected risk factors for colon cancer. I. Family history. Gastroenterology 1988 Feb;94(2):395-400 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3335314.
- ↑ 20.0 20.1 Luchtefeld MA, Syverson D, Solfelt M, MacKeigan JM, Krystosek R, Waller J, et al. Is colonoscopic screening appropriate in asymptomatic patients with family history of colon cancer? Dis Colon Rectum 1991 Sep;34(9):763-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/1914741.
- ↑ 21.0 21.1 Rex DK, Lehman GA, Ulbright TM, Smith JJ, Pound DC, Hawes RH, et al. Colonic neoplasia in asymptomatic persons with negative fecal occult blood tests: influence of age, gender, and family history. Am J Gastroenterol 1993 Jun;88(6):825-31 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8503374.
- ↑ 22.0 22.1 Hunt LM, Rooney PS, Hardcastle JD, Armitage NC. Endoscopic screening of relatives of patients with colorectal cancer. Gut 1998 Jan;42(1):71-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9505888.
- ↑ Smith RA, Cokkinides V, von Eschenbach AC, Levin B, Cohen C, Runowicz CD, et al. American Cancer Society guidelines for the early detection of cancer. CA Cancer J Clin 2002 Jan;52(1):8-22 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11814067.
- ↑ Winawer S, Fletcher R, Rex D, Bond J, Burt R, Ferrucci J, et al. Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence. Gastroenterology 2003 Feb;124(2):544-60 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12557158.
- ↑ Australian Health Technology Advisory Committee (AHTAC). Colorectal cancer screening: a report of the Australian Health Technology Advisory Committee. Canberra, Australia: Commonwealth Department of Health and Family Services; 1997 [cited 2016 Dec 15].
- ↑ Lynch HT, Riley BD, Weissman SM, Coronel SM, Kinarsky Y, Lynch JF, et al. Hereditary nonpolyposis colorectal carcinoma (HNPCC) and HNPCC-like families: Problems in diagnosis, surveillance, and management. Cancer 2004 Jan 1;100(1):53-64 Available from: http://www.ncbi.nlm.nih.gov/pubmed/14692024.
- ↑ Rhodes M, Bradburn DM. Overview of screening and management of familial adenomatous polyposis. Gut 1992 Jan;33(1):125-31 Available from: http://www.ncbi.nlm.nih.gov/pubmed/1310949.
- ↑ Lynch HT, Smyrk T. Hereditary nonpolyposis colorectal cancer (Lynch syndrome). An updated review. Cancer 1996 Sep 15;78(6):1149-67 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8826936.
- ↑ Järvinen HJ. Epidemiology of familial adenomatous polyposis in Finland: impact of family screening on the colorectal cancer rate and survival. Gut 1992 Mar;33(3):357-60 Available from: http://www.ncbi.nlm.nih.gov/pubmed/1314763.
- ↑ Järvinen HJ, Mecklin JP, Sistonen P. Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 1995 May;108(5):1405-11 Available from: http://www.ncbi.nlm.nih.gov/pubmed/7729632.
- ↑ Chen CH, Tsai MK, Wen CP. Extending Colorectal Cancer Screening to Persons Aged 40 to 49 Years With Immunochemical Fecal Occult Blood Test: A Prospective Cohort Study of 513,283 Individuals. J Clin Gastroenterol 2016 Oct;50(9):761-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26905605.
Appendices[edit source]
