How likely is it to test positive for a pathogenic variant with GeneMate®?

Two years ago, we wrote a blog post about what to expect after your GeneMate® test. We wrote that most people will test negative (no pathogenic variant), as pathogenic variants in genes associated with hereditary cancer are rare in the general population. 

Is this reflected in GeneMate® customer test results?

Yes - the majority of GeneMate® test results are negative. However, there are more who test positive for a pathogenic variant than we expected. Among those who underwent testing with GeneMate®, 8% tested positive for a pathogenic variant in one of the analyzed genes. We can consider this in comparison to the 10% of breast cancer patients who are estimated to carry a pathogenic variant contributing to their cancer development. The majority (91%) of our customers who have tested positive for a pathogenic variant are healthy, that is, they have not had cancer themselves.

Do customers that carry a pathogenic variant have anything in common?

Of those who tested positive, 35% had a known pathogenic variant in the family, which means that the probability of carrying a pathogenic variant themselves is significantly higher than in the normal population.

 As many as 83% had a family history of cancer, while the remaining 13% had no cancer in the family at all, or alternatively, did not know their family cancer history. A family history of breast cancer was present in as many as 70% of those with a pathogenic variant, often in combination with other types of cancer such, as ovarian and prostate cancer.

In which genes do we most commonly identify a pathogenic variant?

Given that most customers who tested positive had a family history of breast cancer, it is not entirely surprising that nearly half (48%) had a pathogenic variant in a gene associated with hereditary breast cancer. The majority of these had a pathogenic variant in either BRCA1, BRCA2, or CHEK2.

Thirty-five percent had a pathogenic variant in a gene associated with hereditary colorectal cancer. The majority of these had a pathogenic variant in MUTYH. This gene is inherited autosomal recessively and a person must therefore have a pathogenic variant in both copies of the gene to develop the disease. Thus, it is relatively common to be a healthy carrier of a pathogenic variant in MUTYH. 

The remaining 17% had a pathogenic variant in a gene associated with other types of cancer.