Significance of Family History in Colorectal Cancer
A family history of colorectal cancer significantly increases an individual's risk of developing colorectal cancer, with risk varying based on the number of affected relatives, their degree of relation, and their age at diagnosis. 1
Risk Stratification Based on Family History
- Individuals with one first-degree relative diagnosed with colorectal cancer have a relative risk of 1.72 (95% CI, 1.34-2.19) compared to those without a family history 1
- The risk is significantly higher when the affected first-degree relative was diagnosed at a younger age (<45-50 years) 1
- Having two or more first-degree relatives with colorectal cancer increases the relative risk to 4-6 times that of the general population 1
- Approximately 28% of patients with early-onset colorectal cancer (diagnosed before age 50) have a family history of colorectal cancer 1
- First-degree relatives of individuals with colorectal cancer are about 3 times more likely to develop advanced neoplasia than those without such family history (OR, 3.07; 95% CI, 1.5-6.3) 1
Screening Recommendations Based on Family History
- For individuals with one first-degree relative diagnosed with colorectal cancer at age ≥60 years, colonoscopy screening should begin at age 50 1
- For individuals with one first-degree relative diagnosed with colorectal cancer at age <60 years or two first-degree relatives with colorectal cancer at any age, colonoscopy screening should begin at age 40 or 10 years before the earliest diagnosis in the family, whichever comes first 1, 2
- Screening intervals should be every 5-10 years for those with a family history, with more frequent intervals (every 5 years) recommended for those with stronger family histories 1, 2
- A recent study showed that up to 16% of early-onset colorectal cancer could be prevented if colonoscopy was performed at the age recommended by guidelines based on family history 1
Genetic Considerations
- About 13% of early-onset colorectal cancer cases are associated with hereditary cancer syndromes such as Lynch syndrome 1
- All patients with early-onset colorectal cancer should undergo multigene germline panel testing, regardless of family history 1
- Validated risk assessment tools like the Colon Cancer Risk Assessment Tool and PREMM5 can help identify patients who would benefit from genetic testing 1
- Individuals with a family history pattern suggestive of Lynch syndrome should be considered for genetic counseling and testing 1, 2
Clinical Implications and Outcomes
- Family history of colorectal cancer is associated with decreased survival after colorectal cancer diagnosis, with a hazard ratio for cancer-specific mortality of 1.38 (95% CI, 1.02-1.86) compared to those without a family history 3
- The negative impact on survival is more pronounced in patients with two or more affected relatives (HR for cancer-specific mortality: 2.19,95% CI, 1.10-4.38) 3
- The deleterious effect of family history on survival appears to be limited to patients with advanced disease at presentation and cancers originating in the colon 3
Common Pitfalls and Caveats
- Family history information is often incomplete or inaccurate; verification of diagnosis and age of onset in affected relatives should be attempted when possible 2
- Screening recommendations should be further modified based on additional risk factors such as personal history of adenomas, inflammatory bowel disease, and lifestyle factors 1, 4
- The impact of family history may become less apparent over time as screening becomes more widespread, since effective screening reduces the incidence of colorectal cancer in those with family history 5
- The effectiveness of screening depends on quality indicators such as adequate bowel preparation, cecal intubation rates, withdrawal time, and adenoma detection rates 2, 6
- For individuals who decline colonoscopy, annual fecal immunochemical testing (FIT) should be offered as an alternative screening method 2