AGA releases BRCA risk guidance



BRCA carrier status alone should not influence screening recommendations for colorectal cancer or pancreatic ductal adenocarcinoma, according to an American Gastroenterological Association clinical practice update.

Relationships between BRCA carrier status and risks of pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) remain unclear, reported lead author Sonia S. Kupfer, MD, AGAF, of the University of Chicago, and colleagues.

“Pathogenic variants in BRCA1 and BRCA2 have ... been associated with variable risk of GI cancer, including CRC, PDAC, biliary, and gastric cancers,” the investigators wrote in Gastroenterology. “However, the magnitude of GI cancer risks is not well established and there is minimal evidence or guidance on screening for GI cancers among BRCA1 and BRCA2 carriers.”

According to the investigators, personalized screening for CRC is well supported by evidence, as higher-risk individuals, such as those with a family history of CRC, have been shown to benefit from earlier and more frequent colonoscopies. Although the value of risk-based screening is less clear for other types of GI cancer, the investigators cited a growing body of evidence that supports screening individuals at high risk of PDAC.

Still, data illuminating the role of BRCA carrier status are relatively scarce, which has led to variability in clinical practice.

“Lack of accurate CRC and PDAC risk estimates in BRCA1 and BRCA2 leave physicians and patients without guidance, and result in a range of screening recommendations and practices in this population,” wrote Dr. Kupfer and colleagues.

To offer some clarity, they drafted the present clinical practice update on behalf of the AGA. The recommendations are framed within a discussion of relevant publications.

Data from multiple studies, for instance, suggest that BRCA pathogenic variants are found in 1.3% of patients with early-onset CRC, 0.2% of those with high-risk CRC, and 1.0% of those with any type of CRC, all of which are higher rates “than would be expected by chance.

“However,” the investigators added, “this association is not proof that the observed BRCA1 and BRCA2 pathogenic variants play a causative role in CRC.”

The investigators went on to discuss a 2018 meta-analysis by Oho et al., which included 14 studies evaluating risk of CRC among BRCA carriers. The analysis found that BRCA carriers had a 24% increased risk of CRC, which Dr. Kupfer and colleagues described as “small but statistically significant.” Subgroup analysis suggested that BRCA1 carriers drove this association, with a 49% increased risk of CRC, whereas no significant link was found with BRCA2.

Dr. Kupfer and colleagues described the 49% increase as “very modest,” and therefore insufficient to warrant more intensive screening, particularly when considered in the context of other risk factors, such as Lynch syndrome, which may entail a 1,600% increased risk of CRC. For PDAC, no such meta-analysis has been conducted; however, multiple studies have pointed to associations between BRCA and risk of PDAC.

For example, a 2018 case-control study by Hu et al. showed that BRCA1 and BRCA2 had relative prevalence rates of 0.59% and 1.95% among patients with PDAC. These rates translated to a 158% increased risk of PDAC for BRCA1, and a 520% increase risk for BRCA2; but Dr. Kupfer and colleagues noted that the BRCA2 carriers were from high-risk families, so the findings may not extend to the general population.

In light of these findings, the update recommends PDAC screening for BRCA carriers only if they have a family history of PDAC, with the caveat that the association between risk and degree of family involvement remains unknown.

Ultimately, for both CRC and PDAC, the investigators called for further BRCA research, based on the conclusion that “results from published studies provide inconsistent levels of evidence.”

The investigators reported no conflicts of interest.

SOURCE: Kupfer SS et al. Gastroenterology. 2020 Apr 23. doi: 10.1053/j.gastro.2020.03.086.

Next Article: