How can Orchid tell me about an embryo’s future risk for cancer?
Orchid has a couple of different ways to identify if an embryo is at a higher risk for developing cancer as a child or an adult. Both can identify a higher risk without having to screen a parent’s DNA.
In the first, Orchid uses genetic risk scores (GRS) to determine an embryo’s risk for developing either breast or prostate cancer. Click here to learn more about GRS, and here to learn about Orchid’s breast cancer GRS and here to learn about Orchid’s prostate cancer GRS.
The rest of this guide will focus on the second set of cancers that Orchid can identify–hereditary cancers.
Hereditary cancers–cancer risks that run in the family
People with hereditary cancer syndromes are at a higher risk for specific cancers. This increased risk is usually inherited from one parent.
The most well known of these is BRCA1/2, made famous by Angeline Jolie.
People with certain differences (or variants) in these genes can have a much higher risk for breast cancer. Instead of the usual 12%, some women can have up to a 70% chance of developing breast cancer. Or to put it another way, 7 out of 10 women with one of these variants will develop breast cancer in their lifetime.
Of course that means that 3 in 10 women will not develop breast cancer. Having a BRCA1/2 variant makes developing breast cancer more likely, it does not guarantee it. And breast cancer is not the only risk. People with BRCA1/2 variants have a higher chance of developing prostate, ovarian and other cancers as well.
There are many other less famous hereditary cancers that increase risk for cancer in both children and adults. Some examples include:
- Li-Fraumeni syndrome (brain, bone, and others)
- Retinoblastoma (eye)
- Neurofibromatosis type 1 and type 2 (brain, spine, nerves)
- Wilms' tumor (kidney)
- Fanconi anemia (leukemia)
- BRCA1/2 (breast, ovary, prostate)
- Lynch syndrome (colon, uterus)
- PTEN Hamartoma tumor syndrome (breast, thyroid, kidney)
- Familial adenomatous polyposis (colon, small intestine)
- Von Hippel-Lindau disease (kidney, pancreas)
Around 3% of the U.S. population has a hereditary cancer variant
Individually, hereditary cancers are rare. For example, one of the most common hereditary cancers is associated with the BRCA1/BRCA2 genes. It is estimated that 1 in 500 U.S. women has a variant in one of these genes that increases their risk for breast cancer.
However, when totaled up they become more common. Around 3% of the population is thought to be at increased cancer risk because of hereditary cancer. And 12% of childhood and 5-10% of adult cancers are due to hereditary cancer.
How hereditary cancer is passed down
In most cases, if a parent has hereditary cancer, each of their children has a 50% chance of inheriting it.
It is this high risk that causes many parents who know they have hereditary cancer to undergo in vitro fertilization (IVF) and have their embryos screened. Parents can then choose to implant embryos that do not carry variants associated with hereditary cancer.
The most common embryo screen used for this purpose is called PGT-M. It is limited because it can only look for a single variant that runs in a particular family.
What this means is that one of the parents has to know the exact variant that they could pass down to their child. To know this, the parent has to be genetically screened beforehand.
An Orchid embryo test is different. It analyzes 90 genes at once to look for most of the known variants associated with hereditary cancer. In other words, it can identify variants that parents did not know they carried.
It is important to note that if a variant like this is found in an embryo, it most likely means that one of the parents has it as well. Which means one parent is at a higher risk for developing cancer.
Knowing you have hereditary cancer can save your life
It is absolutely critical that people know if they have hereditary cancer or not. Knowing can save their life. Let’s take a closer look at one of these hereditary cancers–Lynch syndrome.
People with DNA variants that can lead to Lynch syndrome can have up to an 80% chance of developing colon cancer in their lifetime. While this is a scary number, people with Lynch syndrome can do something about this risk.
For example, by getting annual colonoscopies at a young age, they can catch precancerous polyps and have them removed before they turn cancerous. The cancer can be prevented before it gets established.
If they didn’t know they had Lynch syndrome, they would have developed colon cancer before their first colonoscopy. Genetic testing saved their life.
Orchid’s complete hereditary cancer set of genes
Below is the list of the genes that Orchid analyzes to identify hereditary cancer. The genes and the disease-causing variants were curated by independent ClinGen Gene Curation Expert Panels. Orchid reports on the three strongest categories of variants–definitive, moderate, and strong.
ALK, APC, ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, BUB1B, CDC73, CDH1, CDK4, CDKN1B, CDKN2A, CEBPA, CEP57, CHEK2, COL7A1, CYLD, DDB2, DDX41, DIS3L2, DKC1, EGFR, ELANE, EPCAM, ERCC2, ERCC3, ERCC4, ERCC5, EXT1, EXT2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FH, FLCN, GATA2, GREM1, ITK, KIT, MAX, MEN1, MET, MLH1, MLH3, MSH2, MSH3, MSH6, MTAP, MUTYH, NBN, PALB2, PDGFRA, PHOX2B, PMS2, POLH, PRKAR1A, PRSS1, PTCH1, RAD51C, RAD51D, RB1, RECQL4, RET, RHBDF2, RUNX1, SBDS, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMARCA4, SMARCB1, SMARCE1, SUFU, TERT, TGFBR1, TMEM127, TP53, VHL, WAS, WRN, WT1, XPA, XPC