When to Screen BRCA Carriers for Colorectal, Pancreatic Cancer

David A. Johnson, MD


August 10, 2020

This transcript has been edited for clarity.

Hello. I’m Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

Genetic testing for hereditary cancer syndromes has become very prevalent in our practices.

The risk for breast cancer and ovarian cancer is particularly driven by the presence of BRCA1 and BRCA2. Pathogenic variants of these genes are involved in double-stranded DNA break repair. BRCA1 and BRCA2 are associated with lifetime risks of up to 85% for breast cancer and 20%-40% for ovarian cancer.

Whether patients carry variations of these genes is also increasingly important to gastroenterologists. I know that I have been getting asked more and more often about testing for these. This is because BRCA1 and BRCA2 have been associated with an incremental risk for colon cancer, pancreatic ductal adenocarcinoma, and biliary and gastric cancers.

We should offer kudos to the American Gastroenterological Association (AGA) for its recently published clinical practice update on the role of these genes in colorectal and pancreatic cancer, the key take-home messages from which I’d like to share with you.

For colorectal cancer, the authors reviewed case-controlled and cohort studies, and also relied heavily on a meta-analysis that looked at 14 studies. They reported that BRCA carriers had a moderate but significant increased odds ratio (1.24) of developing colorectal cancer. However, a subset analysis indicated that it was only BRCA1 that really drove this, with a still relatively low odds ratio (1.49), whereas BRCA2 was not significant.

The authors’ expert recommendation was that we should not necessarily screen for BRCA carriers any more diligently or aggressively than we would for those with Lynch syndrome or first-degree relatives with this cancer, which confers a much higher risk. Instead, they should be kept in an average-risk category for surveillance, with any carriers showing signs of rectal bleeding or iron deficiency being recommended for earlier evaluation.

The guidelines essentially reported the reverse findings for pancreatic ductal adenocarcinoma, with BRCA2 seemingly the more dominant risk factor. In one study, the incremental risk was 20 times greater for BRCA2, compared with around five times greater for BRCA1. However, the authors of the guidelines noted that this study was limited by drawing from a single center and not correcting for ascertainment bias.

Nonetheless, the authors recommended careful screening of BRCA mutation carriers with a family history of pancreatic ductal adenocarcinoma. This is in agreement with recently published updated recommendations from the International Cancer of the Pancreas Screening Consortium, which came to a 93% consensus on offering screening at a center of excellence to BRCA2carriers with one first-degree relative or two relatives of any degree by pancreatic adenocarcinoma screening. They could not, however, reach a similar consensus on screening for BRCA1 carriers.

In conclusion, these AGA guidelines basically leave it up to you to decide when to screen in BRCA carriers. Family history is a key factor in determining which carriers to send for pancreatic ductal adenocarcinoma screening. When it comes to how that gets paid for, how it gets done, and what we do for subsequent screening for these patients, there are no answers.

This document provides us with excellent guidance but no definitive long-term answers. As a result, we’re left with clinical judgment.

Hopefully this overview has provided you with useful information for discussing this in a rational way with your patients. Use good clinical judgment and refer patients when appropriate.

I’m Dr David Johnson. Thanks for listening.

David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube