What are the Risks for Relatives of Patients With Colorectal Cancer?

Close relatives of people with colorectal cancer (CRC) have a significant increase in prevalence of advanced neoplasms and should be screened for cancer, according to the March issue of Gastroenterology.

Relatives of patients with CRC have been shown to be at increased risk for colorectal neoplasms, but little is known about the prevalence of advanced neoplasms among asymptomatic siblings of patients with CRC.

Siew Ng et al. determined the prevalence of advanced colorectal neoplasms in 374 siblings of patients with CRC (from 237 families) compared to 374 matched siblings of subjects without a family history of CRC.

“We were interested in the question of what one would expect to find upon colonoscopy of close relatives [of a person] found to have CRC,” said Siew Ng in a video abstract.

The prevalence of advanced neoplasms was 7.5% among siblings of patients, compared with 2.9% among controls. The prevalence of adenomas larger than 10 mm was also higher among siblings of patients than in controls (5.9% vs 2.1%), as was the presence of colorectal adenomas (31.0% vs 18.2%). The risk of advanced neoplasm appeared higher when the index case had CRC of the distal colon. Interestingly, 6 siblings of patients with CRC developed an adenocarcinoma, compared with none of the control siblings.

In an editorial that accompanies the article, Antoni Castells and Francis Giardiello say that the findings show that increased risk is not limited to CRC but also to premalignant lesions. These data clearly support the need to include these high-risk individuals in specific CRC screening programs.

Familial risk of CRC depends mainly on the number of relatives, kinship, and age at cancer diagnosis. Castells and Giardiello explain that if you have 2 or more first-degree relatives who have had CRC, your risk is consistently higher than if you have only 1 first-degree relative who has had the cancer. CRC in second- or third-degree relatives also increases the likelihood of developing this neoplasm, but only by about 50% more than the general population.

These data could provide the basis for planning family-specific screening approaches and extend the benefits of colonoscopic polypectomy.

One strength of the study is that it included siblings of adenoma- and cancer-free patients; the siblings were asymptomatic and had been matched closely to siblings of cancer patients. Including this control group helped the authors avoid a biased estimate of the association with family history, and removed acquired or environmental components of the association. Previous studies included consecutive patients who had undergone colonoscopy as controls—many of whom had bowel symptoms and were therefore not a good control population.

Like previous studies, Ng et al. found that advanced neoplasms and colorectal adenomas were more prevalent in men than in women. However, they also found that when the index case was female, siblings were at a greater risk advanced neoplasms—an observation that requires confirmation in larger studies.

Little is known about the pathogenic mechanisms of these “nonsyndromic familial CRCs”. Susceptibility is likely to involve low-penetrance genetic alterations, so genetic tests might be developed to help physicians assess cancer risk and optimize diagnostic, therapeutic, and preventive approaches. Castells and Giardiello propose that improved genotype–phenotype characterization of patients with CRC, based on numbers or combinations of low-penetrance risk alleles, could provide further information about risk and improve screening strategies.

Read the article online.
Ng SC, Lau JYW, Chan FKL, et al. Increased risk of advanced neoplasms among asymptomatic siblings of patients with colorectal cancer. Gastroenterology 2013;144:544–550.

Read the accompanying editorial.
Castells A, Giardiello FM. Familial colorectal cancer screening: so close, so far. Gastroenterology 2013;144:492–494.