Family history of CRC ups risk of adenoma, neoplasia

Individuals with a family history of colorectal cancer (CRC) are at greater risk of developing adenoma, nonadvanced adenoma (NAA), advanced adenoma (AA), and advanced neoplasia (AN), reveals a study.

A team of investigators searched the databases of PubMed, Web of Science, and Embase from inception through 9 May 2024 for observational studies exploring the relationship between family history of CRC in first-degree relatives (FDRs) and the risk of colorectal neoplasia. Furthermore, they chose adenoma, NAA, AA, and AN as main outcomes because of the available data.

Data synthesis was done using a random-effects model, and the robustness of results was evaluated through subgroup meta-analyses. Seventy-five studies, involving a total of 931,515 participants, met the inclusion criteria.

Pooled results showed that a family history of CRC significantly correlated with an elevated risk of adenoma (pooled odds ratio [OR], 1.67, 95 percent confidence interval [CI], 1.46‒1.91), NAA (pooled OR, 1.35, 95 percent CI, 1.21‒1.51), AA (pooled OR, 1.66, 95 percent CI, 1.46‒1.88), and AN (pooled OR, 1.58, 95 percent CI, 1.44‒1.73). [Am J Gastroenterol 2025;120:531-539]

Subgroup analyses revealed similar positive associations. Additionally, individuals with two or more affected FDRs had a greater risk of adenoma (pooled OR, 4.18, 95 percent CI, 1.76‒9.91), AA (pooled OR, 2.42, 95 percent CI, 1.72‒3.40), and AN (pooled OR, 2.00, 95 percent CI, 1.68‒2.38).

“The findings further strengthen the necessity and importance of an intensified screening strategy to individuals with a positive family history of CRC, which is very useful for related health resource allocation and policymaking,” the investigators said.

Inheriting risk

Other meta-analyses that examined the association between family history and CRC also found similar findings. [Clin Gastroenterol Hepatol 2019;17:2657-2667; Am J Gastroenterol 2018;113:1819-1827]

Individuals with several affected FDRs appear to have a higher chance of inheriting multiple risk variants than those with no or fewer affected FDRs, given the shared genetic background among FDRs. This potentially increases their risk of developing adenoma and CRC. [Clin Transl Gastroenterol 2021;12:e00301]

“The results suggest that a potential way to optimize traditional risk-scoring systems is by incorporating the number of affected FDRs into the model,” the investigators said. “Instead of the same assignment to those with a positive family history of CRC in screening practice, the number of affected FDRs may be able to differentiate risk population more precisely.” [Am J Gastroenterol 2018;113:1788-1800]

Unfortunately, subestimates by other factors of FDRs are limited, and subgroup analysis by age of affected FDRs was only carried out in AN. Further studies are warranted to improve understanding of the relationship across several subgroups.

CRC development

Globally, CRC is the second leading cause of death and the third most common cancer diagnosis. Its incidence and mortality have quickly risen in many economically transitioning countries over the years, presenting serious public health challenges. [CA Cancer J Clin 2021;71:209-249; Gut 2017;66:683-691]

“The development of CRC typically entails the accumulation of specific mutations, progressing pathologically from precancerous lesions, primarily adenomas, to invasive cancer,” according to the investigators. [Cell 1990;61:759-767]

“Within this way, AA represents the final stage of precancerous lesion and carries a significantly elevated transition rate to CRC, which is usually grouped with CRC as AN in screening-based studies because of the low prevalence of CRC and its potential malignancy,” they added. [Gut 2007;56:1585-1589]