Over the past 15 years we’ve learned that there are many hereditary cancer genes that, when mutated, increase the risk of cancer development. Not just BRCA1 and BRCA2 for hereditary breast and ovarian cancer. Not just the Lynch Syndrome genes and APC for hereditary colon cancer. Dozens of genes that, when mutated, cause different ranges of risks for different types of cancers.
But if my doctor just orders the gene panel I’m covered, right?
Wrong. These panels, and the technology used in each, vary from company to company, and the field is evolving and changing every day. Tomorrow we may discover a new cancer gene not previously included on panels. Or tomorrow we may learn that a gene included on past panels is not as significant as we thought, or has different implications than was once believed.
The best panel is the one that includes the most genes, correct?
Not necessarily. Many of the genes on the extended panels are rare and we have little data on what mutations in these genes mean. So, if you are found to carry a mutation in one of those genes, we may not know what it means for your risks or what options you should be offered, if any, in terms of surveillance and risk reduction. Sometimes extended testing raises more questions than it answers. We also may not know if that rare mutation or genetic variant is a red herring – and has nothing to do with the cancers in your family – or is truly causative.
If my panel comes back negative, it means I’m safe.
Unfortunately, this is not true. An Ashkenazi Jewish family with multiple cases of early-onset colorectal cancer across generations and family members with different types of polyps (including adenomas, hamartomas and serrated lesions) comes to mind. Affected members of this family had colorectal cancer panel testing for all of the usual suspects in terms of hereditary colon cancer risk (Lynch, APC, CDH1, CHEK2, etc), which included over a dozen genes. But after much searching and research testing, we learned they carried a mutation in a lesser-known gene called GREM1. This gene is not included in most panels, nor is it ready for routine clinical testing. Through a research study, we were able to test multiple members of several generations of this family and showed that the mutation segregated (traveled) with the cancers and polyps in the family.
The bottom line: if your personal and/or family history of cancer truly looks hereditary, a panel alone may not be the panacea. You need a detailed evaluation by a certified genetic specialist to determine which testing makes most sense for your family. If the suspicion of a hereditary cancer syndrome remains, even after appropriate testing, genetic counselors may be able to help enroll you in a research study.
Photos by Brainfood Clothing, via Flickr