Screening for colorectal cancer in patients with a family history of colorectal cancer or advanced polyp

INTRODUCTION — 

A family history of colorectal cancer (CRC) can increase the risk that an individual will develop CRC over a lifetime. Familial CRC is a result of interactions among genetic and lifestyle factors; the amount of increased risk varies widely depending on specifics of the family history [1]. For a small proportion of people, genetic predisposition is the dominant risk factor. For most people, lifestyle factors (eg, diet, exercise, smoking, and obesity) are stronger risk factors [2,3].

This topic review describes the assessment of CRC risk using information obtained from the family history and CRC screening approaches based on the level of risk due to family history.

Strategies for screening of average-risk patients, tests available for screening, other CRC risk factors, CRC prevention strategies, and molecular genetics of CRC are described separately:

●(See "Screening for colorectal cancer: Strategies in patients at average risk".)

●(See "Tests for screening for colorectal cancer".)

●(See "Epidemiology and risk factors for colorectal cancer".)

●(See "Molecular genetics of colorectal cancer".)

ASSESSING RISK DUE TO FAMILY HISTORY — 

A family history of CRC is common. Among the general population, 5 to 10 percent of United States adults aged 20 to 79 years report having a first-degree relative (FDR), defined as a close blood relative (ie, parent, full sibling, or child) with CRC [4]. Some countries have higher rates, with a study from the Netherlands finding that 11.7 percent of adults aged 30 to 70 years reported at least one FDR with CRC [5].

Each component of the family history (eg, recognized familial genetic syndromes, the number of FDRs with CRC and their ages at diagnosis, and the family history of documented advanced adenomas or serrated lesions) helps to determine whether the patient's risk of CRC is increased and the magnitude of the impact of the family history on the individual's risk of developing CRC.

Familial colorectal cancer history (non-syndromic) — The family history should include the number of FDRs with CRC and their ages at diagnosis. Just knowing that there is some family history, without determining age of onset, degree of relatedness, and number of affected family members, is not a strong predictor of who will develop CRC.

For most people, if a family member had CRC, it was a "nonsyndromic familial" (also called "familial") CRC, rather than a high-risk, genetically heritable familial cancer syndrome. Meta-analyses of case-control and cohort studies showed that patients with a positive family history of CRC in FDRs have a 1.87-fold risk (95% CI 1.68-2.09) of developing CRC and an increased risk of adenoma (pooled odds ratio [OR] 1.67, 95% CI 1.46-1.91), nonadvanced adenoma (pooled OR 1.35, 95% CI 1.21-1.51), advanced adenoma (pooled OR 1.66, 95% CI 1.46-1.88), and advanced neoplasia (pooled OR 1.58, 95% CI 1.44-1.73), compared with those without a family history [6,7]. The magnitude of risk is highest if there are multiple FDRs with CRC or an FDR who developed CRC before age 50 years [8-12]. Estimates of these risks are shown in a figure (figure 1) [9]. Among patients who have CRC, 25 percent have a family history that placed them at increased risk [13].

A study of screening colonoscopy among people aged 45 to 75 years found that 11 percent of people with an FDR with CRC had advanced neoplasia, compared with 6 percent of those without an FDR with CRC (OR 2.41, 95% CI 1.69-3.43) [14]. Other studies have found similar results and suggest that risk is somewhat higher if the index case was female or had distal CRC [15]. In another study, risk for CRC was greater for relatives of patients with colon, rather than rectal, cancer [10].

Although CRC occurring only in distant relatives has been associated with an increased risk of CRC in family members, the magnitude of the increase in risk (relative risk [RR] 1.82, 95% CI 1.47-2.25) is not large enough to warrant more screening than is recommended for the general population [9,10].

Family polyp history — Having an FDR with an adenomatous colon polyp increases the patient's risk for adenoma and CRC [16-20]. Several studies suggest that a family history of an advanced adenoma increases risk of CRC, regardless of the relative's age at diagnosis [21]. Representative examples include the following:

●A systematic review found that having an FDR with an adenoma was associated with CRC (RR 1.99, 95% CI 1.55-2.55), compared with having no family history of adenoma [4]. However, the magnitude of risk due to a family polyp history may have been overestimated because of increased efforts to look for cancer in families who already have a history of colorectal neoplasia.

●In a subsequent population-based, case-control study of 60,800 patients with CRC and 333,753 matched controls, having an FDR with a colorectal polyp was associated with a higher risk of CRC (OR 1.40, 95% CI 1.35-1.45), with the highest risk for relatives with advanced adenomas [22].

●Similarly, in a retrospective study of 126,936 adults who underwent colonoscopy, having an FDR with adenoma (RR 1.35, 95% CI 1.25-1.46) or advanced adenoma (RR 1.68, 95% CI 1.29-2.18) or a second-degree relative with adenoma (RR 1.15, 95% CI 1.07-1.23) was associated with CRC, compared with no family history of adenoma [21].

High-risk familial colorectal cancer syndromes — A small proportion of people with a family history of CRC have one of the high-risk genetically heritable familial cancer syndromes that substantially increase the risk of CRC. Some of these syndromes increase the risk of other cancers too. A pattern suggesting the possibility of a high-risk genetically heritable familial cancer syndrome (eg, Lynch syndrome [hereditary nonpolyposis colorectal cancer] or familial adenomatous polyposis [FAP]) may become apparent when obtaining a family history. Patients may recognize the name of an inherited syndrome, if asked.

●Lynch syndrome – Lynch syndrome-related cancers often occur at an early age (commonly in the 30s and 40s, with median onset at age 61 years in mutation-positive relatives) (figure 2) [23,24]. Lynch syndrome is characterized by a strong family history (eg, multiple family members, across generations, developing CRC and other cancers at an early age). However, CRC patients without obvious family histories can still have the syndrome and carry a pathogenic variant in a Lynch syndrome gene [25].

With Lynch syndrome, polyps have an increased tendency to develop into CRC and an increased rate of progression to CRC. Although polyps do not occur more frequently than in the general population, they can occur at an early age [26].

Lynch syndrome is caused by autosomal dominant, variably penetrant genetic mutations, whose penetrance depends on the specific mutation mismatch repair gene in the family. Genetic testing for Lynch syndrome is warranted if an FDR has been diagnosed with Lynch syndrome. Although genetic testing for Lynch syndrome is widely recommended for patients diagnosed with CRC, this testing is not universally performed [27]. Additionally, the patient may be unaware of an FDR's diagnosis. Indications for testing for Lynch syndrome are described separately. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis", section on 'Indications for germline testing'.)

Lynch syndrome and related cancers are described separately. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis" and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Cancer screening and management".)

●FAP – In the classic form of FAP, FAP-related cancers develop beginning in the 20s, and nearly 100 percent of people with FAP develop CRC, usually before age 50 years (figure 2). Hundreds to thousands of polyps occur throughout the colon, beginning as early as adolescence (picture 1). FAP is caused by autosomal dominant, highly penetrant genetic mutations. There is also an attenuated form of FAP that presents with fewer polyps, a slightly lower risk of CRC, and a later age of onset than seen in the classical form.

FAP and attenuated FAP are described separately. (See "Clinical manifestations and diagnosis of familial adenomatous polyposis" and "Familial adenomatous polyposis: Screening and management of patients and families", section on 'AFAP'.)

●MAP – Individuals with MUTYH-associated polyposis (MAP) have multiple colorectal adenomas and an estimated lifetime CRC risk of 70 to 90 percent. Approximately 60 percent of patients with MAP have CRC at presentation. MAP is an autosomal recessive polyposis syndrome. Among patients with CRC, <1 percent are homozygous for MAP.

The risk of CRC in individuals who are heterozygous for MAP (1 to 2 percent of the population) appears similar to that in the overall population [28,29]. However, the risk in MAP heterozygotes may depend on whether there is also a family history of CRC. In those with no family history of CRC, the lifetime risk of CRC is not significantly increased (5 to 7 percent) [30]. By contrast, in those with a family history of CRC in an FDR, the lifetime risk is 10 to 12.5 percent [30]. (See "MUTYH-associated polyposis".)

●Other genes that cause colonic adenomatous polyposis and confer an increased risk of CRC include POLE, POLD1, NTHL1, AXIN2, MLH3, MBD4, and GALNT12.

Additional high-risk hereditary syndromes that increase CRC risk (eg, juvenile polyposis syndrome, Cowden syndrome, Li-Fraumeni syndrome, Peutz-Jeghers syndrome, serrated [hyperplastic] polyposis syndrome, and others detected by cancer gene panels) are discussed separately. (See "Juvenile polyposis syndrome" and "PTEN hamartoma tumor syndromes, including Cowden syndrome" and "Li-Fraumeni syndrome" and "Peutz-Jeghers syndrome: Clinical manifestations, diagnosis, and management" and "Overview of colon polyps", section on 'Serrated polyposis syndrome' and "Next-generation DNA sequencing (NGS): Principles and clinical applications", section on 'Cancer screening and management'.)

When to assess family history — Assessment of family history of CRC or colon polyps among FDRs should begin at the initial visit. Although there are no studies addressing the frequency of reassessment, some clinicians reassess every three to five years as long as the patient is eligible for continued screening based on age and any comorbidities.

We assess family history before age 40 years to identify patients who warrant screening earlier than the usual starting age for average-risk patients, and those who also warrant genetic testing.

We periodically reassess the family history because family history evolves over time. Family members may develop cancers that affect the suggested frequency of screening for the patient. As an example, a study using a United States population-based cancer registry found that at age 30 years, 2.1 percent of participants met criteria for more aggressive screening based upon a family history of CRC, whereas at age 50 years, 7.1 percent met the criteria for high-risk screening [31]. (See 'Approach to enhanced screening' below.)

Obtaining a family history of CRC to guide screening may be cost-effective, with a cost per year of life gained similar to that of other widely accepted technologies [32,33]. However, family history is often not elicited or incorporated into patient care. In a survey of patients aged 35 to 55 years, 39 percent reported that they had not been asked about family history, 46 percent with a strong family history did not know they should be screened at an earlier age, and 55 percent with a strong family history had not received appropriate screening [34].

Limitations of narrative histories and prediction tools — The patient's age, family size (which, if small, can mask recognition of a genetic mutation as the cause of cancer in a family), as well as the possibility of uncertain paternity, should be taken into account when interpreting a narrative history or results from a prediction tool.

Studies show that a patient's report of family history may be inaccurate. In a population-based study in Connecticut, people were asked about CRC family history among FDRs and SDRs, and a sample of the responses was confirmed using registries, Medicare databases, medical records, and death records. The sensitivity of patient report about their relatives was 27.3 percent, with a positive predictive value (PPV) of 53.5 percent overall (86 percent for FDRs and 44 percent for SDRs) [35]. In another study, comparing patient self-reports of their own polyp history with medical record data, the positive predictive value for self-reported polyp was 80.9 percent and the negative predictive value was 85.8 percent [36].

Prediction tools are not commonly used to assess the impact of family history on CRC risk. Concerns about such tools include a lack of data supporting their clinical utility and uncertainty about whether they would materially alter recommendations for screening compared with using risk ascertainment approaches currently described in clinical practice guidelines.

APPROACH TO ENHANCED SCREENING — 

For patients who have a family history of CRC or documented advanced adenoma or serrated lesion but do not have a high-risk, genetically heritable familial cancer syndrome, we use information obtained during family history to guide which patients should undergo enhanced screening, the age to initiate screening, and the frequency and types of screening test to choose. Relevant information includes the age and number of first-degree relatives (FDRs) diagnosed. Our approach is consistent with 2024 guidelines from the National Comprehensive Cancer Network [37].

There are no randomized, controlled trials of screening in people with a family history of CRC to determine the optimal screening program. Screening recommendations for people with a family history of CRC are based upon extrapolation from evidence of effectiveness in average-risk people, modified by knowledge of how a family history affects the biology of colon polyp formation and progression to CRC. (See "Screening for colorectal cancer: Strategies in patients at average risk".)

Indications for enhanced screening — We suggest enhanced screening for CRC for individuals with FDRs who have a documented diagnosis of any of the following at any age:

●CRC

●Documented advanced polyp with ANY of the following:

•Advanced adenoma

-Adenoma size ≥1 cm

-Adenoma with high-grade dysplasia

-Adenoma with villous or tubulovillous histology

•Advanced serrated lesion

-Sessile serrated polyp (SSP) ≥1 cm

-Traditional serrated adenoma ≥1 cm

-SSP with cytologic dysplasia

If the only family history is an FDR with a polyp not clearly documented as an advanced adenoma or serrated lesion, we follow screening strategies for patients at average risk. (See 'Family polyp history' above and "Screening for colorectal cancer: Strategies in patients at average risk".)

This approach is consistent with guidance from the United States Multi-Society Task Force on Colorectal Cancer (MSTF), which states that, for the purposes of CRC screening, a documented history of an FDR with an advanced adenoma (adenoma ≥1 cm, with high-grade dysplasia, or with villous elements) or any adenomatous polyp or sessile serrated lesion (SSL) requiring surgical excision should be weighted the same as having an FDR with CRC [38]. In individuals with an FDR who had had a documented advanced serrated lesion (SSL ≥10 mm, SSL with cytologic dysplasia, or traditional serrated adenoma ≥10 mm), screening should be similar to that of a patient whose FDR had documented advanced adenoma. The MSTF no longer recommends that patients undergo intensified colon screening without clear documentation that an FDR's polyp was advanced [38]. (See "Overview of colon polyps", section on 'Sessile serrated polyps and traditional serrated adenomas' and "Overview of colon polyps", section on 'Serrated polyposis syndrome'.)

Age to begin screening — For enhanced screening, we initiate screening at age 40 years or 10 years before the youngest FDR's diagnosis. When the family history includes an FDR with an advanced polyp, we start screening at the age of diagnosis of the advanced polyp, if that is earlier. (See 'Indications for enhanced screening' above.)

Direct evidence from prospective studies that documents the benefits of this screening strategy is not available. However, the rationale for beginning screening at age 40 years or 10 years before the age of diagnosis of the youngest FDR is that CRCs in these patients may occur early in life, not uncommonly in the 40s or even the 30s (figure 3) [39]. The patient's risk at age 40 years is therefore generally comparable to an average-risk person's risk at age 45 years, which is the usual age at which average-risk people begin screening [40,41]. Relative risk is greatest in the 30s and 40s and decreases as a person ages (figure 4) [42,43]. Beginning to screen 10 years before the age the cancer was diagnosed in the affected relative takes into account the additional risk related to early-onset CRC in the family member.

How often to screen — In general, we screen with colonoscopy every five years in patients with indications for enhanced screening and a personal history of advanced polyps without high-risk endoscopic features for invasive cancer. In patients with enhanced screening due to a personal history of advanced adenomas or SSPs, we recommend repeating screening in three years, and then, if the subsequent colonoscopy is negative, in five years [37]. For people with a history of nonadvanced polyps, we screen every five years. For patients with no personal history of colon polyps, due to lack of evidence supporting a specific screening interval and based on expert opinion, we screen every five years [37].

There is evidence that colonoscopy for screening should be repeated at five-year intervals in people with a family history of CRC. In the Nurses' Health Study and the Health Professionals Follow-up Study, colonoscopy screening reduced CRC risk for only five years for those with an FDR with CRC [44]. For individuals with an FDR with CRC, CRC risk was reduced within five years of colonoscopy (hazard ratio [HR] 0.44 [95% CI, 0.30-0.66]); however, CRC risk returned essentially to baseline beyond five years (HR 0.91 [95% CI, 0.55-1.52]), whereas for average-risk individuals with a negative family history, there was no difference in CRC risk less than or more than five years after colonoscopy (HR 0.42 [95% CI, 0.35-0.51] and 0.43 [95% CI, 0.32-0.58], respectively). (See "Tests for screening for colorectal cancer", section on 'Colonoscopy'.)

If the patient declines colonoscopy, fecal immunochemical testing (FIT) or multitarget stool deoxyribonucleic acid (mt-sDNA) test is used for screening. (See "Tests for screening for colorectal cancer", section on 'Fecal immunochemical test (FIT) for blood'.)

Choosing a screening test — Colonoscopy is the preferred test for patients at higher-than-average risk, as defined above (see 'Indications for enhanced screening' above). Among screening tests, colonoscopy has the highest sensitivity for CRC and adenomas (figure 5). If the patient declines colonoscopy, we encourage screening with FIT or mt-sDNA stool testing [45]:

●Colonoscopy – Colonoscopy has better sensitivity than FIT stool testing for advanced adenomas and, in the majority of studies, for CRC as well [45,46]. In a meta-analysis, one-time FIT sensitivity for CRC was 79 percent and, for advanced adenoma, 30 percent [38,47,48]. In one study, in which the threshold for a "positive" FIT in a quantitative assay was set intentionally low (≥10 micrograms hemoglobin/gram of feces), annual FIT for three years detected all CRC but only 61 percent of advanced adenomas in FDRs of patients with CRC [45]. However, in another study, 572 asymptomatic individuals with a positive family history for CRC, but without a suspected or known familial polyposis syndrome or Lynch syndrome, underwent screening by both one colonoscopy and one FIT [46]. Endoscopists were blinded as to FIT results. FIT was found to have low sensitivity (adenoma 9.5 percent [95% CI, 5.7-15.3], advanced neoplasm 35.1 percent [95% CI, 20.7-52.6], and CRC 25.0 percent [95% CI, 1.3-78.1]). Among patients who were FIT-negative, colonoscopy detected 24 advanced neoplasms (4.7 percent of individuals who were FIT-negative) and three CRCs (0.6 percent of individuals who were FIT-negative).

●Noninvasive strategies – Patients who decline colonoscopy should undergo CRC screening with another screening test, preferably FIT or mt-sDNA. FIT should be performed annually, and mt-sDNA is performed every three years. The MSTF considers FIT to be a "tier 1" test for CRC screening that is the suggested alternative and is performed annually [38,47,48].

FIT or mt-sDNA stool test may be attractive alternatives because they are noninvasive [38,47,48]. However, maintaining the screening schedule can be a challenge because FIT should be repeated annually. A positive FIT or mt-sDNA stool test requires timely follow-up with a colonoscopy. (See "Tests for screening for colorectal cancer", section on 'Advantages and disadvantages'.)

Specifics of tests for screening for CRC are discussed separately. (See "Tests for screening for colorectal cancer", section on 'Fecal immunochemical test (FIT) for blood' and "Tests for screening for colorectal cancer", section on 'Colonoscopy' and "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Choosing a screening test'.)

●Combined strategies – Combining colonoscopy with FIT may be a reasonable alternative in persons with a family history of CRC. In a modeling study of multiple CRC screening strategies, colonoscopy every 10 years and biennial FIT between colonoscopies from ages 40 to 80 years was superior to colonoscopy every five years in those at both twofold and fourfold increased CRC risk [49]. The combined strategy prevented slightly more CRC deaths, was cost-saving, and gained more quality-adjusted life-years.

When to stop screening — For individuals ages 76 to 85 years, we individualize the decision to start or continue screening based on prior screening history, life expectancy, CRC risk, and patient preference. We discontinue screening after age 85. This approach is consistent with recommendations from the MSTF [38].

Although there is no direct evidence to guide when to end CRC screening among people with a family history, the MIcrosimulation SCreening ANalysis (MISCAN) colorectal cancer model suggested that CRC screening should end at age 79 among persons with one FDR diagnosed after age 50 and end at age 85 for persons with two or more FDRs diagnosed before age 40 [5], unless the patient has a life expectancy of less than 10 years. The MSTF suggests that discontinuation of screening can be considered when patients who are up to date with screening and have had negative screening tests, particularly colonoscopy, reach age 75 years [38]. Continuing to screen until age 80 or 85 years is reasonable because the absolute risk of CRC attributable to family history increases with age since the risk is cumulative [10,43]. For example, the risk of a 70-year-old developing CRC in the next 10 years is approximately 9 percent if that person has at least two FDRs with CRC, compared with 3 percent in the general population [10].

HIGH-RISK SYNDROME SCREENING — 

Enhanced colon cancer screening and consideration of genetic testing are warranted for patients with a personal or family history of certain high-risk genetic syndromes.

Cancer screening strategies, genetic testing, and CRC prevention for each of the following syndromes are discussed in detail separately:

●Lynch syndrome (hereditary nonpolyposis colorectal cancer) (see "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis" and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Cancer screening and management")

●Familial adenomatous polyposis (FAP) (picture 1) (see "Familial adenomatous polyposis: Screening and management of patients and families")

●MUTYH-associated polyposis (see "MUTYH-associated polyposis")

●Juvenile polyposis syndrome (see "Juvenile polyposis syndrome")

●Cowden syndrome (see "PTEN hamartoma tumor syndromes, including Cowden syndrome")

●Li-Fraumeni syndrome (see "Li-Fraumeni syndrome")

●Attenuated FAP (see "Familial adenomatous polyposis: Screening and management of patients and families")

●Peutz-Jeghers syndrome (see "Peutz-Jeghers syndrome: Clinical manifestations, diagnosis, and management")

●Serrated (hyperplastic) polyposis syndrome (see "MUTYH-associated polyposis")

RISK FACTOR MODIFICATION — 

We encourage individuals at increased risk due to a family history of CRC to modify their behavioral risk factors. This includes increasing physical activity, reducing red meat intake, smoking cessation, achieving and maintaining a normal body weight, and increasing plant-based foods in the diet, all of which are associated with a reduction in risk for CRC. We also discuss certain medications (eg, aspirin, nonsteroidal anti-inflammatory drugs) that may reduce the risk of CRC but may also increase the risk of bleeding [50]. These topics are discussed separately. (See "Epidemiology and risk factors for colorectal cancer", section on 'Protective factors' and "NSAIDs (including aspirin): Role in prevention of colorectal cancer" and "Aspirin in the primary prevention of cardiovascular disease and cancer", section on 'Colorectal cancer'.)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Screening for colorectal cancer".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Colon and rectal cancer screening (The Basics)")

●Beyond the Basics topic (see "Patient education: Screening for colorectal cancer (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Assessing for risk due to family history – One in four patients with colorectal cancer (CRC) has a family history of CRC. Only a few percent of individuals with CRC have a high-risk, genetically heritable familial cancer syndrome. (See 'Assessing risk due to family history' above.)

Familial CRC results from the interaction of genetic and environmental causes. Several genetic polymorphisms are statistically associated with CRC, but with the exception of high-risk genetic syndromes such as Lynch syndrome (previously called hereditary nonpolyposis colorectal cancer [HNPCC]), familial adenomatous polyposis (FAP), and MUTYH-associated polyposis, these genetic polymorphisms appear to account for little of the observed familial risk. (See 'Assessing risk due to family history' above.)

●Indications for enhanced screening – To identify individuals at increased risk of CRC, we ask all patients about their family history before age 40 years. Assessment of family history may be repeated every three to five years and interpreted keeping in mind family size (which, if small, can cause false-negative reports) and the possibility of uncertain paternity. (See 'Indications for enhanced screening' above.)

●High-risk familial CRC syndromes – The most common high-risk, genetically heritable familial cancer syndromes with elevated rates of CRC are Lynch syndrome (HNPCC) and FAP. Enhanced CRC screening, tailored specifically to the disease pattern of each cancer syndrome, and consideration of genetic testing are warranted for patients with a personal or family history of certain high-risk genetic syndromes. (See 'High-risk syndrome screening' above and 'High-risk familial colorectal cancer syndromes' above.)

●Approach to screening – There are no randomized, controlled trials of screening in people with a family history of CRC. Screening recommendations for these patients are extrapolated from studies and recommendations for average-risk individuals, observational studies of people with familial CRC, and the known biology of familial CRC. (See 'Approach to enhanced screening' above.)

•Individuals at highest risk due to high-risk familial CRC syndromes should be screened for CRC with colonoscopy at frequent, specified intervals based on current guidelines. (See 'High-risk syndrome screening' above.)

•For other patients with a family history of CRC, advanced adenoma, or advanced serrated lesion with high-risk features described above, we suggest enhanced rather than average-risk screening (Grade 2B). Enhanced screening consists of beginning screening at age 40 years or 10 years before the first-degree relative's diagnosis, whichever is earlier. We typically screen with a colonoscopy every five years. For patients who decline colonoscopy, alternative screening strategies include annual fecal immunochemical testing or a multitarget stool DNA test. (See 'Indications for enhanced screening' above.)

•Screening for patients at average risk for CRC is described separately. (See "Screening for colorectal cancer: Strategies in patients at average risk".)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Robert H Fletcher, MD, MSc, who contributed to earlier versions of this topic review.