Is Birt-Hogg-Dubé Syndrome (BHD) linked with colon cancer? This is a question we often receive at the BHD Foundation and does not have a simple answer. Colon cancer is one of the most common cancers in the western world and is thought to be largely linked to environmental factors such as diet and age. However specific genetic mutations increase the risk of developing colon cancer and it is yet to be proven whether folliculin (the gene mutated in BHD) is one of them. There are reports of BHD patients developing colon cancer, but current research is not conclusive on whether these cases are linked to BHD or it is just a coincidence. Investigating this link is important as it will help to inform colon cancer screening in the BHD community.
A recent paper by Sattler et al., analysed the frequency of colon cancer in 256 BHD patients compared to 519 non BHD patients(1). We spoke to the lead researcher and BHD expert Professor Steinlein about this paper and delved into why researchers may be getting different results and what needs to be done to provide further evidence on the link between colon cancer and BHD.
What inspired your research looking into the risk of colon cancer in BHD?
Elke Sattler, Dermatology, and I (Human Genetics) started Germany’s only interdisciplinary BHD outpatient clinic more than 10 years ago and, together with Zulfiya Syunyaeva (Pulmonology) we have by now collected nearly 100 mostly multiplex families. Our patients, finding information about possible associations between colorectal cancer and BHD on Google, are often asking about their risk for this tumor type. Furthermore, we always perform extensive pedigree analysis in our BHD families and observed a higher than expected rate of early onset colon cancer. Some months ago we therefore decided to systematically analyse our data.
What did you discover?
We first looked at the frequency of colorectal cancer and found it to be significantly more frequent in BHD patients than in controls. However, the difference between both groups was small, meaning we found only a moderate increase in risk. Such small differences are statistically not very robust and not all previously published studies reported the same effect. Much more important is our observation that in BHD families in which colorectal cancer occurred, it often occurred either at an unusually early age (i. e. before the age 50 years) or affected several family members. This is a pattern well known from HNPCC (hereditary non-polyposis colon cancer or Lynch syndrome), the most common hereditary colorectal cancer syndrome.
There is an ongoing discussion about whether there is a link between colon cancer and BHD and whether BHD patients should get screening. What are the challenges faced by researchers to answer these questions and how can we overcome them?
The biggest challenge will be the availability of a large number of clinically well characterized BHD families. During the last decade several of such samples have been collected by different research groups but sample sizes still need to be increased. There is also the possibility, that cancer risks differ between ethnic or regional backgrounds. It therefore most likely will take several more years to collect enough large BHD samples from different populations before the BHD research community will be able to give a final answer to the question about a possible association between colorectal cancer and BHD.
What message would you give to BHD patients who are concerned about developing colon cancer?
We are counselling our patients that after age 50 years the colon cancer risk is likely to be comparable to the age-related risk for this cancer type in the general population. However, there might be a small but significant risk for early onset colorectal cancer. We are therefore suggesting to start coloscopy at age 40 (or ten years before the first family member developed colorectal cancer in patients where there is a family history of colon cancer).
Are you working on any other BHD research projects currently and can you tell us a bit about them?
BHD is our main research focus and we are steadily increasing our sample of families. Most of our current research projects are focused on clinical aspects, especially possible associations between BHD and different cancer types but we are also in the planning stage for functional studies.
Altogether this study suggests that although there is not a significant increase in colon cancer, BHD patients may be at increased risk of developing colon cancer at a younger age. Because of this discovery Professor Steinlein advises caution and suggests that BHD patients start colon cancer screening from the age of 40 (10 years earlier than screening for the general population).
It must be noted that due to the variation in results investigating the link between colon cancer and BHD, recommendations may vary in different areas. We recommend discussing any queries regarding colon screening with your BHD doctor. If you would like assistance identifying a BHD specialist please contact us at contact@BHDsyndrome.org or search our interactive map.
The BHD Foundation sincerely thanks Professor Steinlein for discussing her paper with us and the BHD community. The research paper is not currently freely available. Please contact us at email@example.com if you have any questions regarding this research.
1. Sattler EC, Syunyaeva Z, Reithmair M, Dempke W, Steinlein OK. Colorectal cancer risk in families with Birt-Hogg-Dubé syndrome increased. Eur J Cancer. 2021 Jul 1;151:168–74.