Serrated polyposis syndrome patients, relatives at risk of colorectal cancer

The risk of colorectal cancer (CRC) is heightened in patients with serrated polyposis syndrome (SPS) and their first-degree relatives (FDRs), according to a study, which confirms findings of other reports. In addition, those with sessile serrated lesions (SSL) are at higher of prostate cancer.

“Our study provides novel evidence that relatives of individuals with SSL with any adenoma on examination may have an increased CRC risk, and we propose earlier and closer colonoscopy surveillance, similar to relatives of known advanced adenoma,” the researchers said. “These findings may be considered for screening and postpolypectomy surveillance recommendations.”

Fifty-nine patients with SPS were identified from hereditary patient registries. Using clinical data linked to the Utah Population Database, the researchers also selected 754 sporadic SSL and 1,624 sex- and age-matched normal colonoscopy controls.

CRC, extracolonic, and any-site adenocarcinoma/carcinoma cancer risks were estimated in patients and their relatives using Cox models adjusted for the number of relatives, degree of relatedness, and person-years at risk.

The risk of CRC was 10-fold higher in patients with SPS (p=0.04) and fivefold in their FDRs (p=0.001) compared with controls. In addition, any-site adenoma/carcinoma risk was 2.6-fold greater in FDRs of SPS patients. [Am J Gastroenterology 2022;117:336-342]

Risks of other common extracolonic cancers were not increased among SPS and family members. However, FDRs, second-, and third-degree relatives of patients with both SSL and adenomatous polyps had 50-percent increased risk of CRC.

“Our study confirms an increased CRC risk in patients with SPS and in their FDRs and supports the existing recommendation of continued and early screening in SPS and in their FDRs,” the researchers said. [Fam Cancer 2013;12:669-673; Am J Gastroenterol 2012;107:770-778]

Increased surveillance

Earlier studies also reported an increased association of metachronous advanced adenomas and neoplasia in patients with sporadic SSL. Recent recommendations support closer surveillance in those with >3–4 SSLs, SSLs ≥10 mm, or with dysplasia. [Gastroenterology 2012;143:844-857; Gastroenterology 2020;158:1131-1153]

Of note, CRC risk in relatives of SSL patients has not been studied before. Although expert guidelines suggest that FDRs of patients with SSL ≥1 cm in size or with dysplasia may be considered for similar surveillance follow-up, no substantial data are available for this recommendation. [Gastroenterology 2017;153:307-323]

“Our study indicates that relatives of [patients with] SSL (irrespective of size, location, and dysplasia status) may carry a risk for CRC and may need increased surveillance if they also have a history of any associated adenomatous polyps,” the researchers said. “This is significant as currently only relatives of [patients with] advanced adenomas are suggested to undergo earlier and increased surveillance.”

Further long-term clinical outcome studies are warranted to generate concrete recommendations with regard to screening initiation age, surveillance interval, and number of serrated or adenomatous lesions increasing CRC risk.

The current study had certain limitations. First, clinical confirmation of SSLs was not available, and only a text-based search algorithm was used to determine sporadic SSL and associated adenoma. Second, the number of patients with SSL and no adenoma history was small relative to those with SSL and adenoma.

“We acknowledge that an SPS and SSL cohort followed prospectively over several years to study incident cancers is preferred to our retrospective cohort study design, and prospective studies of outcomes in these patients are needed,” the researchers said.